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Hao Li

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DOI: 10.1136/svn-2017-000101
2017
Cited 2,151 times
Artificial intelligence in healthcare: past, present and future
Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI.
DOI: 10.1038/nature01789
2003
Cited 2,088 times
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
DOI: 10.48550/arxiv.1608.08710
2016
Cited 1,593 times
Pruning Filters for Efficient ConvNets
The success of CNNs in various applications is accompanied by a significant increase in the computation and parameter storage costs. Recent efforts toward reducing these overheads involve pruning and compressing the weights of various layers without hurting original accuracy. However, magnitude-based pruning of weights reduces a significant number of parameters from the fully connected layers and may not adequately reduce the computation costs in the convolutional layers due to irregular sparsity in the pruned networks. We present an acceleration method for CNNs, where we prune filters from CNNs that are identified as having a small effect on the output accuracy. By removing whole filters in the network together with their connecting feature maps, the computation costs are reduced significantly. In contrast to pruning weights, this approach does not result in sparse connectivity patterns. Hence, it does not need the support of sparse convolution libraries and can work with existing efficient BLAS libraries for dense matrix multiplications. We show that even simple filter pruning techniques can reduce inference costs for VGG-16 by up to 34% and ResNet-110 by up to 38% on CIFAR10 while regaining close to the original accuracy by retraining the networks.
DOI: 10.1021/jacs.5b03105
2015
Cited 1,473 times
Efficient Visible Light Nitrogen Fixation with BiOBr Nanosheets of Oxygen Vacancies on the Exposed {001} Facets
Even though the well-established Haber-Bosch process has been the major artificial way to "fertilize" the earth, its energy-intensive nature has been motivating people to learn from nitrogenase, which can fix atmospheric N2 to NH3 in vivo under mild conditions with its precisely arranged proteins. Here we demonstrate that efficient fixation of N2 to NH3 can proceed under room temperature and atmospheric pressure in water using visible light illuminated BiOBr nanosheets of oxygen vacancies in the absence of any organic scavengers and precious-metal cocatalysts. The designed catalytic oxygen vacancies of BiOBr nanosheets on the exposed {001} facets, with the availability of localized electrons for π-back-donation, have the ability to activate the adsorbed N2, which can thus be efficiently reduced to NH3 by the interfacial electrons transferred from the excited BiOBr nanosheets. This study might open up a new vista to fix atmospheric N2 to NH3 through the less energy-demanding photochemical process.
DOI: 10.1056/nejmoa1215340
2013
Cited 1,367 times
Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack
Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).
DOI: 10.1016/j.mattod.2017.07.006
2018
Cited 1,177 times
Recent advances in gas storage and separation using metal–organic frameworks
Gas storage and separation are closely associated with the alleviation of greenhouse effect, the widespread use of clean energy, the control of toxic gases, and various other aspects in human society. In this review, we highlight the recent advances in gas storage and separation using metal-organic frameworks (MOFs). In addition to summarizing the gas uptakes of some benchmark MOFs, we emphasize on the desired chemical properties of MOFs for different gas storage/separation scenarios. Greenhouse gases (CO2), energy-related gases (H2 and CH4), and toxic gases (CO and NH3) are covered in the review.
DOI: 10.1038/23716
1999
Cited 1,102 times
Notch signalling controls pancreatic cell differentiation
DOI: 10.1063/1.2982585
2008
Cited 1,098 times
Graphene segregated on Ni surfaces and transferred to insulators
We report an approach to synthesize high quality graphene by surface segregation and substrate transfer. Graphene was segregated from Ni surface under the ambient pressure by dissolving carbon in Ni at high temperatures followed by cooling down with various rates. Different cooling rates led to different segregation behaviors, strongly affecting the thickness and quality of the graphene films. Electron microscopy and Raman spectroscopy indicated that the graphene films synthesized with medium cooling rates have high quality crystalline structure and well-controlled thicknesses. The graphene films were transferred to insulating substrates by wet etching and found to maintain their high quality.
DOI: 10.1002/anie.201705628
2017
Cited 894 times
Oxygen Vacancy‐Mediated Photocatalysis of BiOCl: Reactivity, Selectivity, and Perspectives
Abstract Semiconductor photocatalysis is a trustworthy approach to harvest clean solar light for energy conversions, while state‐of‐the‐art catalytic efficiencies are unsatisfactory because of the finite light response and/or recombination of robust charge carriers. Along with the development of modern material characterization techniques and electronic‐structure computations, oxygen vacancies (OVs) on the surface of real photocatalysts, even in infinitesimal concentration, are found to play a more decisive role in determining the kinetics, energetics, and mechanisms of photocatalytic reactions. This Review endeavors to clarify the inherent functionality of OVs in photocatalysis at the surface molecular level using 2D BiOCl as the platform. Structure sensitivity of OVs on reactivity and selectivity of photocatalytic reactions is intensely discussed via confining OVs onto prototypical BiOCl surfaces of different structures. The critical understanding of OVs chemistry can help consolidate and advance the fundamental theories of photocatalysis, and also offer new perspectives and guidelines for the rational design of catalysts with satisfactory performance.
DOI: 10.1038/nbt.4127
2018
Cited 846 times
An in vivo model of functional and vascularized human brain organoids
Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.
DOI: 10.1126/science.aat0586
2018
Cited 764 times
Ethane/ethylene separation in a metal-organic framework with iron-peroxo sites
A preference for ethane Industrial production of ethylene requires its separation from ethane in a cryogenic process that consumes large amounts of energy. An alternative would be differential sorption in microporous materials. Most of these materials bind ethylene more strongly that ethane, but adsorption of ethane would be more efficient. Li et al. found that a metal-organic framework containing iron-peroxo sites bound ethane more strongly than ethylene and could be used to separate the gases at ambient conditions. Science , this issue p. 443
DOI: 10.1109/cvpr.2017.434
2017
Cited 721 times
High-Resolution Image Inpainting Using Multi-scale Neural Patch Synthesis
Recent advances in deep learning have shown exciting promise in filling large holes in natural images with semantically plausible and context aware details, impacting fundamental image manipulation tasks such as object removal. While these learning-based methods are significantly more effective in capturing high-level features than prior techniques, they can only handle very low-resolution inputs due to memory limitations and difficulty in training. Even for slightly larger images, the inpainted regions would appear blurry and unpleasant boundaries become visible. We propose a multi-scale neural patch synthesis approach based on joint optimization of image content and texture constraints, which not only preserves contextual structures but also produces high-frequency details by matching and adapting patches with the most similar mid-layer feature correlations of a deep classification network. We evaluate our method on the ImageNet and Paris Streetview datasets and achieved state-of-the-art inpainting accuracy. We show our approach produces sharper and more coherent results than prior methods, especially for high-resolution images.
DOI: 10.1038/84792
2001
Cited 703 times
Regulatory element detection using correlation with expression
DOI: 10.1016/j.immuni.2014.06.014
2014
Cited 696 times
Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4
Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
DOI: 10.1021/jacs.6b12850
2017
Cited 691 times
New Reaction Pathway Induced by Plasmon for Selective Benzyl Alcohol Oxidation on BiOCl Possessing Oxygen Vacancies
Selective organic transformation under mild conditions constitutes a challenge in green chemistry, especially for alcohol oxidation, which typically requires environmentally unfriendly oxidants. Here, we report a new plasmonic catalyst of Au supported on BiOCl containing oxygen vacancies. It photocatalyzes selective benzyl alcohol oxidation with O2 under visible light through synergistic action of plasmonic hot electrons and holes. Oxygen vacancies on BiOCl facilitate the trapping and transfer of plasmonic hot electrons to adsorbed O2, producing •O2– radicals, while plasmonic hot holes remaining on the Au surface mildly oxidize benzyl alcohol to corresponding carbon-centered radicals. The hypothesized concerted ring addition between these two radical species on the BiOCl surface highly favors the production of benzaldehyde along with an unexpected oxygen atom transfer from O2 to the product. The results and understanding acquired in this study, based on the full utilization of hot charge carriers in a plasmonic metal deposited on a rationally designed support, will contribute to the development of more active and/or selective plasmonic catalysts for a wide variety of organic transformations.
DOI: 10.1200/jco.1999.17.3.832
1999
Cited 681 times
Metastasis Stage, Adjuvant Treatment, and Residual Tumor Are Prognostic Factors for Medulloblastoma in Children: Conclusions From the Children's Cancer Group 921 Randomized Phase III Study
PURPOSE: From 1986 to 1992, “eight-drugs-in-one-day” (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm 2 of residual tumor, versus ≥ 1.5 cm 2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm 2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.
DOI: 10.1053/j.gastro.2016.11.018
2017
Cited 656 times
Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor−κB, and Up-regulating Expression of MicroRNA-21
Nearly 20% of the global cancer burden can be linked to infectious agents. Fusobacterium nucleatum promotes tumor formation by epithelial cells via unclear mechanisms. We aimed to identify microRNAs (miRNAs) induced by F nucleatum and evaluate their ability to promote colorectal carcinogenesis in mice.Colorectal cancer (CRC) cell lines were incubated with F nucleatum or control reagents and analyzed in proliferation and would healing assays. HCT116, HT29, LoVo, and SW480 CRC cell lines were incubated with F nucleatum or phosphate-buffered saline (PBS [control]) and analyzed for miRNA expression patterns and in chromatin immunoprecipitation assays. Cells were incubated with miRNAs mimics, control sequences, or small interfering RNAs; expression of reporter constructs was measured in luciferase assays. CRC cells were incubated with F nucleatum or PBS and injected into BALB/C nude mice; growth of xenograft tumors was measured. C57BL adenomatous polyposis colimin/+, C57BL miR21a-/-, and C57BL mice with full-length miR21a (controls) were given F nucleatum by gavage; some mice were given azoxymethane and dextran sodium sulfate to induce colitis and colon tumors. Intestinal tissues were collected and tumors were counted. Serum samples from mice were analyzed for cytokine levels by enzyme-linked immunosorbent assay. We performed in situ hybridization analyses to detect enrichment of F nucleatum in CRC cells. Fusobacterium nucleatum DNA in 90 tumor and matched nontumor tissues from patients in China were explored for the expression correlation analysis; levels in 125 tumor tissues from patients in Japan were compared with their survival times.Fusobacterium nucleatum increased proliferation and invasive activities of CRC cell lines compared with control cells. CRC cell lines infected with F nucleatum formed larger tumors, more rapidly, in nude mice than uninfected cells. Adenomatous polyposis colimin/+ mice gavaged with F nucleatum developed significantly more colorectal tumors than mice given PBS and had shorter survival times. We found several inflammatory factors to be significantly increased in serum from mice given F nucleatum (interleukin 17F, interleukin 21, and interleukin 22, and MIP3A). We found 50 miRNAs to be significantly up-regulated and 52 miRNAs to be significantly down-regulated in CRCs incubated with F nucleatum vs PBS; levels of miR21 increased by the greatest amount (>4-fold). Inhibitors of miR21 prevented F nucleatum from inducing cell proliferation and invasion in culture. miR21a-/- mice had a later appearance of fecal blood and diarrhea after administration of azoxymethane and dextran sodium sulfate, and had longer survival times compared with control mice. The colorectum of miR21a-/- mice had fewer tumors, of smaller size, and the miR21a-/- mice survived longer than control mice. We found RASA1, which encodes an RAS GTPase, to be one of the target genes consistently down-regulated in cells that overexpressed miR21 and up-regulated in cells exposed to miR21 inhibitors. Infection of cells with F nucleatum increased expression of miR21 by activating Toll-like receptor 4 signaling to MYD88, leading to activation of the nuclear factor-κB. Levels of F nucleatum DNA and miR21 were increased in tumor tissues (and even more so in advanced tumor tissues) compared with non-tumor colon tissues from patients. Patients whose tumors had high amounts of F nucleatum DNA and miR21 had shorter survival times than patients whose tumors had lower amounts.We found infection of CRC cells with F nucleatum to increase their proliferation, invasive activity, and ability to form xenograft tumors in mice. Fusobacterium nucleatum activates Toll-like receptor 4 signaling to MYD88, leading to activation of the nuclear factor-κB and increased expression of miR21; this miRNA reduces levels of the RAS GTPase RASA1. Patients with both high amount of tissue F nucleatum DNA and miR21 demonstrated a higher risk for poor outcomes.
DOI: 10.1126/science.273.5275.666
1996
Cited 628 times
Emergence of Preferred Structures in a Simple Model of Protein Folding
Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural regularities are related to high designability and evolutionary stability. We measure the designability of each compact structure by the number of sequences which can design the structure, i.e., which possess the structure as their nondegenerate ground state. We find that compact structures are drastically different in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These structures are found to have ``protein like'' secondary structure and even tertiary symmetries. In addition, they are also thermodynamically more stable than ordinary structures. These results suggest that protein structures are selected because they are easy to design and stable against mutations, and that such a selection simutaneously leads to thermodynamic stability.
DOI: 10.1152/jappl.1994.77.6.2740
1994
Cited 622 times
Validation of near-infrared spectroscopy in humans
Near-infrared (NIR) spectroscopy is a noninvasive technique that uses the differential absorption properties of hemoglobin to evaluate skeletal muscle oxygenation. Oxygenated and deoxygenated hemoglobin absorb light equally at 800 nm, whereas at 760 nm absorption is primarily from deoxygenated hemoglobin. Therefore, monitoring these two wavelengths provides an index of deoxygenation. To investigate whether venous oxygen saturation and absorption between 760 and 800 nm (760-800 nm absorption) are correlated, both were measured during forearm exercise. Significant correlations were observed in all subjects (r = 0.92 +/- 0.07; P < 0.05). The contribution of skin flow to the changes in 760-800 nm absorption was investigated by simultaneous measurement of skin flow by laser flow Doppler and NIR recordings during hot water immersion. Changes in skin flow but not 760-800 nm absorption were noted. Intra-arterial infusions of nitroprusside and norepinephrine were performed to study the effect of alteration of muscle perfusion on 760-800 nm absorption. Limb flow was measured with venous plethysmography. Percent oxygenation increased with nitroprusside and decreased with norepinephrine. Finally, the contribution of myoglobin to the 760-800 nm absorption was assessed by using 1H-magnetic resonance spectroscopy. At peak exercise, percent NIR deoxygenation during exercise was 80 +/- 7%, but only one subject exhibited a small deoxygenated myoglobin signal. In conclusion, 760-800 nm absorption is 1) closely correlated with venous oxygen saturation, 2) minimally affected by skin blood flow, 3) altered by changes in limb perfusion, and 4) primarily derived from deoxygenated hemoglobin and not myoglobin.
DOI: 10.1109/cvpr.2019.00589
2019
Cited 563 times
On the Continuity of Rotation Representations in Neural Networks
In neural networks, it is often desirable to work with various representations of the same space. For example, 3D rotations can be represented with quaternions or Euler angles. In this paper, we advance a definition of a continuous representation, which can be helpful for training deep neural networks. We relate this to topological concepts such as homeomorphism and embedding. We then investigate what are continuous and discontinuous representations for 2D, 3D, and n-dimensional rotations. We demonstrate that for 3D rotations, all representations are discontinuous in the real Euclidean spaces of four or fewer dimensions. Thus, widely used representations such as quaternions and Euler angles are discontinuous and difficult for neural networks to learn. We show that the 3D rotations have continuous representations in 5D and 6D, which are more suitable for learning. We also present continuous representations for the general case of the n-dimensional rotation group SO(n). While our main focus is on rotations, we also show that our constructions apply to other groups such as the orthogonal group and similarity transforms. We finally present empirical results, which show that our continuous rotation representations outperform discontinuous ones for several practical problems in graphics and vision, including a simple autoencoder sanity test, a rotation estimator for 3D point clouds, and an inverse kinematics solver for 3D human poses.
DOI: 10.1038/s41563-019-0573-3
2020
Cited 559 times
Robust axion insulator and Chern insulator phases in a two-dimensional antiferromagnetic topological insulator
The intricate interplay between nontrivial topology and magnetism in two-dimensional (2D) materials has led to the emergence of many novel phenomena and functionalities. An outstanding example is the quantum anomalous Hall (QAH) effect, which was realized in magnetically doped topological insulators (TIs) in the absence of magnetic field. Recently, the layered van der Waals compound MnBi2Te4 has been theoretically predicted and experimentally verified to be a TI with interlayer antiferromagnetic (AFM) order. It is a rare stoichiometric material with coexisting topology and magnetism, thus represents a perfect building block for complex topological-magnetic structures. Here we investigate the quantum transport behaviors of both bulk crystal and exfoliated MnBi2Te4 flakes in a field effect transistor geometry. In the 6 septuple layers (SLs) device tuned into the insulating regime, we observe a large longitudinal resistance and zero Hall plateau, which are characteristic of the axion insulator state. The robust axion insulator state occurs in zero magnetic field, over a wide magnetic field range, and at relatively high temperatures. Moreover, a moderate magnetic field drives a quantum phase transition from the axion insulator phase to a Chern insulator phase with zero longitudinal resistance and quantized Hall resistance h/e2 (h is the Plank constant and e is the elemental charge). These results pave the road for using even-number-SL MnBi2Te4 to realize the quantized topological magnetoelectric effect and axion electrodynamics in condensed matter systems.
DOI: 10.1021/acs.accounts.6b00523
2016
Cited 555 times
Solar Water Splitting and Nitrogen Fixation with Layered Bismuth Oxyhalides
ConspectusHydrogen and ammonia are the chemical molecules that are vital to Earth’s energy, environmental, and biological processes. Hydrogen with renewable, carbon-free, and high combustion-enthalpy hallmarks lays the foundation of next-generation energy source, while ammonia furnishes the building blocks of fertilizers and proteins to sustain the lives of plants and organisms. Such merits fascinate worldwide scientists in developing viable strategies to produce hydrogen and ammonia. Currently, at the forefronts of hydrogen and ammonia syntheses are solar water splitting and nitrogen fixation, because they go beyond the high temperature and pressure requirements of methane stream reforming and Haber–Bosch reaction, respectively, as the commercialized hydrogen and ammonia production routes, and inherit the natural photosynthesis virtues that are green and sustainable and operate at room temperature and atmospheric pressure. The key to propelling such photochemical reactions lies in searching photocatalysts that enable water splitting into hydrogen and nitrogen fixation to make ammonia efficiently. Although the past 40 years have witnessed significant breakthroughs using the most widely studied TiO2, SrTiO3, (Ga1–xZnx)(N1–xOx), CdS, and g-C3N4 for solar chemical synthesis, two crucial yet still unsolved issues challenge their further progress toward robust solar water splitting and nitrogen fixation, including the inefficient steering of electron transportation from the bulk to the surface and the difficulty of activating the N≡N triple bond of N2.This Account details our endeavors that leverage layered bismuth oxyhalides as photocatalysts for efficient solar water splitting and nitrogen fixation, with a focus on addressing the above two problems. We first demonstrate that the layered structures of bismuth oxyhalides can stimulate an internal electric field (IEF) that is capable of efficiently separating electrons and holes after their formation and of precisely channeling their migration from the bulk to the surface along the different directions, thus enabling more electrons to reach the surface for water splitting and nitrogen fixation. Simultaneously, their oxygen termination feature and the strain differences between interlayers and intralayers render the easy generation of surface oxygen vacancies (OVs) that afford Lewis-base and unsaturated-unsaturated sites for nitrogen activation. With these rationales as the guideline, we can obtain striking visible-light hydrogen- and ammonia-evolving rates without using any noble-metal cocatalysts. Then we show how to utilize IEF and OV based strategies to improve the solar water splitting and nitrogen fixation performances of bismuth oxyhalide photocatalysts. Finally, we highlight the challenges remaining in using bismuth oxyhalides for solar hydrogen and ammonia syntheses, and the prospect of further development of this research field. We believe that our mechanistic insights could serve as a blueprint for the design of more efficient solar water splitting and nitrogen fixation systems, and layered bismuth oxyhalides might open up new photocatalyst paradigm for such two solar chemical syntheses.
DOI: 10.1016/j.enchem.2019.100006
2019
Cited 549 times
Porous metal-organic frameworks for gas storage and separation: Status and challenges
Gases are widely used as energy resources for industry and our daily life. Developing energy cost efficient porous materials for gas storage and separation is of fundamentally and industrially important, and is one of the most important aspects of energy chemistry and materials. Metal-organic frameworks (MOFs), representing a novel class of porous materials, feature unique pore structure, such as exceptional porosity, tunable pore structures, ready functionalization, which not only enables high density energy storage of clean fuel gas in MOF adsorbents, but also facilitates distinct host-guest interactions and/or sieving effects to differentiate different molecules for energy-efficient separation economy. In this review, we summarize and highlight the recent advances in the arena of gas storage and separation using MOFs as adsorbents, including progresses in MOF-based membranes for gas separation, which could afford broader concepts to the current status and challenges in this field.
DOI: 10.1016/j.carbon.2012.02.046
2012
Cited 534 times
Polyamine-functionalized carbon quantum dots for chemical sensing
Polyamine-functionalized carbon quantum dots (CQDs) with high fluorescence quantum yield (42.5%) have been synthesized by the low temperature (<200 °C) carbonization of citric acid with branched polyethylenimine (BPEI) in one simple step. The obtained BPEI–CQDs are spherical graphite nanocrystals (average 6.2 nm in size) capped with abundant BPEI at their surfaces. It is the first report that CQDs are both amino-functionalized and highly fluorescent, which suggests their promising applications in chemical sensing.
DOI: 10.1039/c8mh01365a
2019
Cited 502 times
Advances in designs and mechanisms of semiconducting metal oxide nanostructures for high-precision gas sensors operated at room temperature
A comprehensive review on designs and mechanisms of semiconducting metal oxides with various nanostructures for room-temperature gas sensor applications.
DOI: 10.1038/s41557-020-0481-9
2020
Cited 488 times
Coupling N2 and CO2 in H2O to synthesize urea under ambient conditions
The use of nitrogen fertilizers has been estimated to have supported 27% of the world’s population over the past century. Urea (CO(NH2)2) is conventionally synthesized through two consecutive industrial processes, N2 + H2 → NH3 followed by NH3 + CO2 → urea. Both reactions operate under harsh conditions and consume more than 2% of the world’s energy. Urea synthesis consumes approximately 80% of the NH3 produced globally. Here we directly coupled N2 and CO2 in H2O to produce urea under ambient conditions. The process was carried out using an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets. This coupling reaction occurs through the formation of C–N bonds via the thermodynamically spontaneous reaction between *N=N* and CO. Products were identified and quantified using isotope labelling and the mechanism investigated using isotope-labelled operando synchrotron-radiation Fourier transform infrared spectroscopy. A high rate of urea formation of 3.36 mmol g–1 h–1 and corresponding Faradic efficiency of 8.92% were measured at –0.4 V versus reversible hydrogen electrode. Conventionally, urea is synthesized via two consecutive processes, N2 + H2 → NH3 followed by NH3 + CO2. Now, an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets has been shown to directly couple N2 and CO2 in H2O to produce urea under ambient conditions.
DOI: 10.1186/s12967-019-2058-1
2019
Cited 468 times
The role of collagen in cancer: from bench to bedside
Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.
DOI: 10.18632/oncotarget.1913
2014
Cited 460 times
Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer
Long non-coding RNAs (lncRNAs) play key roles in the progression and metastasis of some carcinomas.We previously showed that the expression of lncRNA H19 (H19) was higher in gastric cancer (GC) tissues than that in paired noncanerous tissues.However, the underlying mechanisms remain unclear.In this study, H19/miR-675 knockdown models in the MKN45 cell line and ectopic expression models in the SGC7901 cell line were established, and a coexpression network of H19 was generated to identify target genes by RIP and DLR.The results showed that overexpression of H19 promoted the features of GC including proliferation, migration, invasion and metastasis.An H19 co-expression network identified ISM1 as a binding protein of H19, and its expression was positively correlated with that of H19.CALN1 was identified as a target gene of miR-675 and its expression was negatively correlated with that of miR-675.H19 and MiR-675 function in a similar manner.However, H19 RNA actively binds to ISM1 and miR-675 targets CALN1.These differences suggest that H19 plays other roles besides encoding miR-675 in GC.Our results suggest that the effect of H19 in GC is mediated by the direct upregulation of ISM1 and the indirect suppression of CALN1 expression via miR-675.
DOI: 10.1109/iccv.2019.00780
2019
Cited 454 times
Soft Rasterizer: A Differentiable Renderer for Image-Based 3D Reasoning
Rendering bridges the gap between 2D vision and 3D scenes by simulating the physical process of image formation. By inverting such renderer, one can think of a learning approach to infer 3D information from 2D images. However, standard graphics renderers involve a fundamental discretization step called rasterization, which prevents the rendering process to be differentiable, hence able to be learned. Unlike the state-of-the-art differentiable renderers, which only approximate the rendering gradient in the back propagation, we propose a truly differentiable rendering framework that is able to (1) directly render colorized mesh using differentiable functions and (2) back-propagate efficient supervision signals to mesh vertices and their attributes from various forms of image representations, including silhouette, shading and color images. The key to our framework is a novel formulation that views rendering as an aggregation function that fuses the probabilistic contributions of all mesh triangles with respect to the rendered pixels. Such formulation enables our framework to flow gradients to the occluded and far-range vertices, which cannot be achieved by the previous state-of-the-arts. We show that by using the proposed renderer, one can achieve significant improvement in 3D unsupervised single-view reconstruction both qualitatively and quantitatively. Experiments also demonstrate that our approach is able to handle the challenging tasks in image-based shape fitting, which remain nontrivial to existing differentiable renderers. Code is available at https://github.com/ShichenLiu/SoftRas.
DOI: 10.1021/acsphotonics.6b00079
2016
Cited 449 times
Near-Infrared Photodetector Based on MoS<sub>2</sub>/Black Phosphorus Heterojunction
Two-dimensional (2D) materials present their excellent properties in electronic and optoelectronic applications, including in ultrafast carrier dynamics, layer-dependent energy bandgap, tunable optical properties, low power dissipation, high mobility, transparency, flexibility, and the ability to confine electromagnetic energy to extremely small volumes. Herein, we demonstrate a photodetector with visible to near-infrared detection range, based on the heterojunction fabricated by van der Waals assembly between few-layer black phosphorus (BP) and few-layer molybdenum disulfide (MoS2). The heterojunction with electrical characteristics which can be electrically tuned by a gate voltage achieves a wide range of current-rectifying behavior with a forward-to-reverse bias current ratio exceeding 103. The photoresponsivity (R) of the photodetector is about 22.3 A W–1 measured at λ = 532 nm and 153.4 mA W–1 at λ = 1.55 μm with a microsecond response speed (15 μs). In addition, its specific detectivity D* is calculated to have the maximum values of 3.1 × 1011 Jones at λ = 532 nm, while 2.13 × 109 Jones at λ = 1550 nm at room temperature.
DOI: 10.1136/gutjnl-2018-317609
2019
Cited 427 times
Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial
Objective To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. Methods In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18–35 years; body mass index &lt;28 kg/m 2 ; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. Results The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p&lt;0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p&lt;0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. Conclusion Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. Trial registration number NCT02355795 ; Results.
DOI: 10.1021/ja208658w
2011
Cited 426 times
High Performance Thermoelectrics from Earth-Abundant Materials: Enhanced Figure of Merit in PbS by Second Phase Nanostructures
Lead sulfide, a compound consisting of elements with high natural abundance, can be converted into an excellent thermoelectric material. We report extensive doping studies, which show that the power factor maximum for pure n-type PbS can be raised substantially to ∼12 μW cm–1 K–2 at >723 K using 1.0 mol % PbCl2 as the electron donor dopant. We also report that the lattice thermal conductivity of PbS can be greatly reduced by adding selected metal sulfide phases. The thermal conductivity at 723 K can be reduced by ∼50%, 52%, 30%, and 42% through introduction of up to 5.0 mol % Bi2S3, Sb2S3, SrS, and CaS, respectively. These phases form as nanoscale precipitates in the PbS matrix, as confirmed by transmission electron microscopy (TEM), and the experimental results show that they cause huge phonon scattering. As a consequence of this nanostructuring, ZT values as high as 0.8 and 0.78 at 723 K can be obtained for nominal bulk PbS material. When processed with spark plasma sintering, PbS samples with 1.0 mol % Bi2S3 dispersion phase and doped with 1.0 mol % PbCl2 show even lower levels of lattice thermal conductivity and further enhanced ZT values of 1.1 at 923 K. The promising thermoelectric properties promote PbS as a robust alternative to PbTe and other thermoelectric materials.
DOI: 10.1038/nnano.2015.96
2015
Cited 420 times
An artificial molecular pump
DOI: 10.1038/ng1291
2004
Cited 414 times
Comparing genomic expression patterns across species identifies shared transcriptional profile in aging
We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.
DOI: 10.1021/acs.est.7b00040
2017
Cited 398 times
Oxygen Vacancy Associated Surface Fenton Chemistry: Surface Structure Dependent Hydroxyl Radicals Generation and Substrate Dependent Reactivity
Understanding the chemistry of hydrogen peroxide (H2O2) decomposition and hydroxyl radical (•OH) transformation on the surface molecular level is a great challenge for the application of heterogeneous Fenton system in the fields of chemistry, environmental, and life science. We report in this study a conceptual oxygen vacancy associated surface Fenton system without any metal ions leaching, exhibiting unprecedented surface chemistry based on the oxygen vacancy of electron-donor nature for heterolytic H2O2 dissociation. By controlling the delicate surface structure of catalyst, this novel Fenton system allows the facile tuning of •OH existing form for targeted catalytic reactions with controlled reactivity and selectivity. On the model catalyst of BiOCl, the generated •OH tend to diffuse away from the (001) surface for the selective oxidation of dissolved pollutants in solution, but prefer to stay on the (010) surface, reacting with strongly adsorbed pollutants with high priority. These findings will extend the scope of Fenton catalysts via surface engineering and consolidate the fundamental theories of Fenton reactions for wide environmental applications.
DOI: 10.1016/j.rser.2020.109799
2020
Cited 390 times
Recent advances in carbon dioxide utilization
Carbon dioxide (CO2) is the major contributor to greenhouse gas (GHG) emissions and the main driver of climate change. Currently, CO2 utilization is increasingly attracting interest in processes like enhanced oil recovery and coal bed methane and it has the potential to be used in hydraulic fracturing processes, among others. In this review, the latest developments in CO2 capture, utilization, conversion, and sequestration are examined through a multi-scale perspective. The diverse range of CO2 utilization applications, including mineralization, biological utilization, food and beverages, energy storage media, and chemicals, is comprehensively presented. We also discuss the worldwide research and development of CO2 utilization projects. Lastly, we examine the key challenges and issues that must be faced for pilot-scale and industrial applications in the future. This study demonstrates that CO2 utilization can be a driver for the future development of carbon capture and utilization technologies. However, considering the amount of CO2 produced globally, even if it can be reduced in the near-to mid-term future, carbon capture and storage will remain the primary strategy and, so, complementary strategies are desirable. Currently, the main CO2 utilization industry is enhanced oil and gas recovery, but considering the carbon life cycle, these processes still add CO2 to the atmosphere. In order to implement other CO2 utilization technologies at a large scale, in addition to their current technical feasibility, their economic and societal viability is critical. Therefore, future efforts should be directed toward reduction of energy penalties and costs, and the introduction of policies and regulation encouraging carbon capture, utilization and storage, and increasing the public acceptance of the strategies in a complementary manner.
DOI: 10.1088/0957-4484/22/10/105708
2011
Cited 376 times
The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells
The objective of this study is to evaluate the effect of hydroxyapatite (HAP) nanoparticles with different surface charges on the cellular uptake behavior and in vitro cell viability and proliferation of MC3T3-E1 cell lines (osteoblast). The nanoparticles' surface charge was varied by surface modification with two carboxylic acids: 12-aminododecanoic acid (positive) and dodecanedioic acid (negative). The untreated HAP nanoparticles and dodecanoic acid modified HAP nanoparticles (neutral) were used as the control. X-ray diffraction (XRD) revealed that surface modifications by the three carboxylic acids did not change the crystal structure of HAP nanoparticles; Fourier transform infrared spectroscopy (FT-IR) confirmed the adsorption and binding of the carboxylic acids on the HAP nanoparticles' surfaces; and zeta potential measurement confirmed that the chemicals successfully modified the surface charge of HAP nanoparticles in water based solution. Transmission electron microscopy (TEM) images showed that positively charged, negatively charged and untreated HAP nanoparticles, with similar size and shape, all penetrated into the cells and cells had more uptake of HAP nanoparticles with positive charge compared to those with negative charge, which might be attributed to the attractive or repulsive interaction between the negatively charged cell membrane and positively/negatively charged HAP nanoparticles. The neutral HAP nanoparticles could not penetrate the cell membrane due to their larger size. MTT assay and LDH assay results indicated that as compared with the polystyrene control, greater cell viability and cell proliferation were measured on MC3T3-E1 cells treated with the three kinds of HAP nanoparticles (neutral, positive, and untreated), among which positively charged HAP nanoparticles showed the strongest improvement for cell viability and cell proliferation. In summary, the surface charge of HAP nanoparticles can be modified to influence the cellular uptake of HAP nanoparticles and the different uptake also influences the behavior of cells. These in vitro results may also provide useful information for investigations of HAP nanoparticle applications in gene delivery and intracellular drug delivery.
DOI: 10.1021/ja063328m
2006
Cited 370 times
Enantioselective Organocatalytic Tandem Michael−Aldol Reactions: One-Pot Synthesis of Chiral Thiochromenes
A highly enantioselective (S) diphenylpyrrolinol silyl ether promoted tandem Michael-aldol reaction of alpha,beta-unsaturated aldehydes with 2-mercaptobenzaldehydes has been developed. The method affords one-pot access to chiral and synthetically useful thiochromenes in high yields and high enantioselectivities from readily available compounds.
DOI: 10.3929/ethz-b-000461393
2018
Cited 365 times
Visualizing the Loss Landscape of Neural Nets
Neural network training relies on our ability to find good minimizers of highly non-convex loss functions. It is well known that certain network architecture designs (e.g., skip connections) produce loss functions that train easier, and well-chosen training parameters (batch size, learning rate, optimizer) produce minimizers that generalize better. However, the reasons for these differences, and their effect on the underlying loss landscape, is not well understood. In this paper, we explore the structure of neural loss functions, and the effect of loss landscapes on generalization, using a range of visualization methods. First, we introduce a simple filter normalization method that helps us visualize loss function curvature, and make meaningful side-by-side comparisons between loss functions. Then, using a variety of visualizations, we explore how network architecture affects the loss landscape, and how training parameters affect the shape of minimizers.
2016
Cited 362 times
Pruning Filters for Efficient ConvNets
The success of CNNs in various applications is accompanied by a significant increase in the computation and parameter storage costs. Recent efforts toward reducing these overheads involve pruning and compressing the weights of various layers without hurting original accuracy. However, magnitude-based pruning of weights reduces a significant number of parameters from the fully connected layers and may not adequately reduce the computation costs in the convolutional layers due to irregular sparsity in the pruned networks. We present an acceleration method for CNNs, where we prune filters from CNNs that are identified as having a small effect on the output accuracy. By removing whole filters in the network together with their connecting feature maps, the computation costs are reduced significantly. In contrast to pruning weights, this approach does not result in sparse connectivity patterns. Hence, it does not need the support of sparse convolution libraries and can work with existing efficient BLAS libraries for dense matrix multiplications. We show that even simple filter pruning techniques can reduce inference costs for VGG-16 by up to 34% and ResNet-110 by up to 38% on CIFAR10 while regaining close to the original accuracy by retraining the networks.
DOI: 10.1126/science.1169678
2009
Cited 355 times
A Ferroelectric Oxide Made Directly on Silicon
Metal oxide semiconductor field-effect transistors, formed using silicon dioxide and silicon, have undergone four decades of staggering technological advancement. With fundamental limits to this technology close at hand, alternatives to silicon dioxide are being pursued to enable new functionality and device architectures. We achieved ferroelectric functionality in intimate contact with silicon by growing coherently strained strontium titanate (SrTiO3) films via oxide molecular beam epitaxy in direct contact with silicon, with no interfacial silicon dioxide. We observed ferroelectricity in these ultrathin SrTiO3 layers by means of piezoresponse force microscopy. Stable ferroelectric nanodomains created in SrTiO3 were observed at temperatures as high as 400 kelvin.
DOI: 10.1038/12669
1999
Cited 354 times
Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9
DOI: 10.1039/c4ta00106k
2014
Cited 348 times
Na<sub>3</sub>V<sub>2</sub>(PO<sub>4</sub>)<sub>3</sub>@C core–shell nanocomposites for rechargeable sodium-ion batteries
Na<sub>3</sub>V<sub>2</sub>(PO<sub>4</sub>)<sub>3</sub>@C core–shell nanocomposites were synthesized and applied as electrode materials in rechargeable sodium batteries, showing remarkable rate capability and cyclability.
DOI: 10.1021/acscatal.6b02613
2016
Cited 343 times
Oxygen Vacancy Structure Associated Photocatalytic Water Oxidation of BiOCl
A central issue in understanding photocatalytic water splitting on a stoichiometric or defective nanostructured oxide surface is its adsorption mode and related reactivity. More than just improving the adsorption of water on oxide surfaces, we demonstrate in this work that surface oxygen vacancies (OVs) also offer a possibility of activating water toward thermodynamically enhanced photocatalytic water oxidation, while the water activation state, as reflected by its capability to trap holes, strongly depends on the structures of OVs. Utilizing well-ordered BiOCl single-crystalline surfaces, we reveal that dissociatively adsorbed water on the OV of the (010) surface exhibits higher tendency to be oxidized than the molecularly adsorbed water on the OV of the (001) surface. Analysis of the geometric atom arrangement shows that the OV of the BiOCl (010) surface can facilitate barrierless O–H bond breaking in the first proton removal reaction, which is sterically hindered on the OV of the BiOCl (001) surface, and also allow more localized electrons transfer from the OV to the dissociatively adsorbed water, leading to its higher water activation level for hole trapping. These findings highlight the indispensable role of crystalline surface structure on water oxidation and may open up avenues for the rational design of highly efficient photocatalysts via surface engineering.
DOI: 10.1021/ja403134b
2013
Cited 341 times
High Thermoelectric Performance via Hierarchical Compositionally Alloyed Nanostructures
Previous efforts to enhance thermoelectric performance have primarily focused on reduction in lattice thermal conductivity caused by broad-based phonon scattering across multiple length scales. Herein, we demonstrate a design strategy which provides for simultaneous improvement of electrical and thermal properties of p-type PbSe and leads to ZT ~ 1.6 at 923 K, the highest ever reported for a tellurium-free chalcogenide. Our strategy goes beyond the recent ideas of reducing thermal conductivity by adding two key new theory-guided concepts in engineering, both electronic structure and band alignment across nanostructure-matrix interface. Utilizing density functional theory for calculations of valence band energy levels of nanoscale precipitates of CdS, CdSe, ZnS, and ZnSe, we infer favorable valence band alignments between PbSe and compositionally alloyed nanostructures of CdS1-xSex/ZnS1-xSex. Then by alloying Cd on the cation sublattice of PbSe, we tailor the electronic structure of its two valence bands (light hole L and heavy hole Σ) to move closer in energy, thereby enabling the enhancement of the Seebeck coefficients and the power factor.
DOI: 10.1021/es404250a
2014
Cited 339 times
Detecting Free Radicals in Biochars and Determining Their Ability to Inhibit the Germination and Growth of Corn, Wheat and Rice Seedlings
Biochar can benefit human society as a carbon-negative material and soil amendment. However, negative biochar impacts on plant germination and growth have been observed, and they have not been fully explained. Therefore, protocols to avoid these risks cannot be proposed. We hypothesized that the free radicals generated during charring may inhibit plant germination and growth. Significant electron paramagnetic resonance (EPR) signals were observed in the biochars derived from several types of common biomass (corn stalk, rice, and wheat straws) and the major biopolymer components of biomass (cellulose and lignin), but not in the original materials, suggesting the ubiquitous presence of free radicals in biochars. EPR signal intensity increased with increasing pyrolysis temperature, and it was dominantly contributed by oxygen centered in the mixture of oxygen- and carbon-centered free radicals as the temperature increased. The free radicals in biochars induced strong ·OH radicals in the aqueous phase. Significant germination inhibition, root and shoot growth retardation and plasma membrane damage were observed for biochars with abundant free radicals. Germination inhibition and plasma membrane damage were not obvious for biochars containing low free radicals, but they were apparent at comparable concentrations of conventional contaminants, such as heavy metals and polyaromatic hydrocarbons. The potential risk and harm of relatively persistent free radicals in biochars must be addressed to apply them safely.
DOI: 10.1002/anie.200461959
2005
Cited 338 times
Direct, Highly Enantioselective Pyrrolidine Sulfonamide Catalyzed Michael Addition of Aldehydes to Nitrostyrenes
Just can't get enough: The highly versatile pyrrolidine sulfonamide organocatalyst 1, which has been used in α-aminoxylation and Mannich-type reactions, also mediates diastereo- and enantioselective Michael addition reactions of aldehydes and ketones to nitroolefins (see scheme).
DOI: 10.1039/c4nr04810e
2014
Cited 335 times
Sustainable molecular oxygen activation with oxygen vacancies on the {001} facets of BiOCl nanosheets under solar light
Oxygen vacancies on the {001} facets of BiOCl can sustainably activate molecular oxygen for organic pollutant removal under solar light.
DOI: 10.1109/tip.2012.2207397
2012
Cited 331 times
Multimodal Graph-Based Reranking for Web Image Search
This paper introduces a web image search reranking approach that explores multiple modalities in a graph-based learning scheme. Different from the conventional methods that usually adopt a single modality or integrate multiple modalities into a long feature vector, our approach can effectively integrate the learning of relevance scores, weights of modalities, and the distance metric and its scaling for each modality into a unified scheme. In this way, the effects of different modalities can be adaptively modulated and better reranking performance can be achieved. We conduct experiments on a large dataset that contains more than 1000 queries and 1 million images to evaluate our approach. Experimental results demonstrate that the proposed reranking approach is more robust than using each individual modality, and it also performs better than many existing methods.
DOI: 10.1021/ja073262a
2007
Cited 331 times
Organocatalytic Enantioselective Cascade Michael-Alkylation Reactions: Synthesis of Chiral Cyclopropanes and Investigation of Unexpected Organocatalyzed Stereoselective Ring Opening of Cyclopropanes
The development of efficient methods for the facile construction of important molecular architectures is a central goal in organic synthesis. An unprecedented organocatalytic asymmetric cascade Michael-alkylation reaction of alpha,beta-unsaturated aldehydes with bromomalonates has been developed. The process, efficiently catalyzed by chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine, serves as a powerful approach to the preparation of synthetically and biologically important cyclopropanes in high levels of enantio- and diastereoselectivities. Remarkably, the power of the cascade process is fueled by its high efficiency of the production of two new C-C bonds, two new stereogenic centers, and one quaternary carbon center in one single operation, which otherwise is difficult to achieve by traditional strategies. Moreover, the beauty of the cascade process is further underscored by the nature of the product formation depending on the reaction conditions. With the alternation of base from 2,6-lutidine (1.1 equiv), which is effective for the cyclopropanations, to NaOAc (4.0 equiv), the spontaneous ring-opening of cyclopropanes takes place to lead to stereoselective (E) alpha-substituted malonate alpha,beta-unsaturated aldehydes. A possible reaction mechanism, which involves a Michael-alkylation-retro-Michael pathway, is proposed and verified by experimental studies. This investigation represents the first example of an organocatalyst-promoted ring opening of the cyclopropanes, whereas such reactions have been intensively explored by Lewis acid-based catalysis.
DOI: 10.1073/pnas.0810114105
2008
Cited 322 times
CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit
Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody. Fifteen patients were selected on the basis of availability of suitable specimens for immunologic monitoring, and eight of these showed evidence of clinical benefit. Five of the eight patients with evidence of clinical benefit had NY-ESO-1 antibody, whereas none of seven clinical non-responders was seropositive for NY-ESO-1. All five NY-ESO-1 seropositive patients had clearly detectable CD4(+) and CD8(+) T cells against NY-ESO-1 following treatment with ipilimumab. One NY-ESO-1 seronegative clinical responder also had a NY-ESO-1 CD4(+) and CD8(+) T cell response, possibly related to prior vaccination with NY-ESO-1. Among five clinical non-responders analyzed, only one had a NY-ESO-1 CD4(+) T cell response and this patient did not have detectable anti-NY-ESO-1 antibody. Overall, NY-ESO-1-specific T cell responses increased in frequency and functionality during anti-CTLA-4 treatment, revealing a polyfunctional response pattern of IFN-gamma, MIP-1beta and TNF-alpha. We therefore suggest that CTLA-4 blockade enhanced NY-ESO-1 antigen-specific B cell and T cell immune responses in patients with durable objective clinical responses and stable disease. These data provide an immunologic rationale for the efficacy of anti-CTLA-4 therapy and call for immunotherapeutic designs that combine NY-ESO-1 vaccination with CTLA-4 blockade.
DOI: 10.1093/nar/gky357
2018
Cited 322 times
HPEPDOCK: a web server for blind peptide–protein docking based on a hierarchical algorithm
Protein-peptide interactions are crucial in many cellular functions. Therefore, determining the structure of protein-peptide complexes is important for understanding the molecular mechanism of related biological processes and developing peptide drugs. HPEPDOCK is a novel web server for blind protein-peptide docking through a hierarchical algorithm. Instead of running lengthy simulations to refine peptide conformations, HPEPDOCK considers the peptide flexibility through an ensemble of peptide conformations generated by our MODPEP program. For blind global peptide docking, HPEPDOCK obtained a success rate of 33.3% in binding mode prediction on a benchmark of 57 unbound cases when the top 10 models were considered, compared to 21.1% for pepATTRACT server. HPEPDOCK also performed well in docking against homology models and obtained a success rate of 29.8% within top 10 predictions. For local peptide docking, HPEPDOCK achieved a high success rate of 72.6% on a benchmark of 62 unbound cases within top 10 predictions, compared to 45.2% for HADDOCK peptide protocol. Our HPEPDOCK server is computationally efficient and consumed an average of 29.8 mins for a global peptide docking job and 14.2 mins for a local peptide docking job. The HPEPDOCK web server is available at http://huanglab.phys.hust.edu.cn/hpepdock/.
DOI: 10.1136/svn-2020-000457
2020
Cited 321 times
China Stroke Statistics 2019: A Report From the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations
China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age &lt;18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 063 892 (35.3%)) of the patients were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (699 513 (23.2%)) and new rural cooperative medical schema (489 361 (16.3%)). The leading risk factor was hypertension (67.4% for IS, 77.2% for ICH and 49.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.1% for IS, 31.4% for ICH and 25.2% for SAH). In-hospital death/discharge against medical advice rate was 8.3% for stroke inpatients, ranging from 5.8% for IS to 19.5% for ICH. The median and IQR of length of stay was 10.0 (7.0–14.0) days, ranging from 10.0 (7.0–13.0) in IS to 14.0 (8.0–22.0) in SAH. Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.77±0.21, 0.72±0.28 and 0.59±0.32, respectively.
DOI: 10.1101/gad.1564207
2007
Cited 319 times
Cell- and gene-specific regulation of primary target genes by the androgen receptor
The androgen receptor (AR) mediates the physiologic and pathophysiologic effects of androgens including sexual differentiation, prostate development, and cancer progression by binding to genomic androgen response elements (AREs), which influence transcription of AR target genes. The composition and context of AREs differ between genes, thus enabling AR to confer multiple regulatory functions within a single nucleus. We used expression profiling of an immortalized human prostate epithelial cell line to identify 205 androgen-responsive genes (ARGs), most of them novel. In addition, we performed chromatin immunoprecipitation to identify 524 AR binding regions and validated in reporter assays the ARE activities of several such regions. Interestingly, 67% of our AREs resided within approximately 50 kb of the transcription start sites of 84% of our ARGs. Indeed, most ARGs were associated with two or more AREs, and ARGs were sometimes themselves linked in gene clusters containing up to 13 AREs and 12 ARGs. AREs appeared typically to be composite elements, containing AR binding sequences adjacent to binding motifs for other transcriptional regulators. Functionally, ARGs were commonly involved in prostate cell proliferation, communication, differentiation, and possibly cancer progression. Our results provide new insights into cell- and gene-specific mechanisms of transcriptional regulation of androgen-responsive gene networks.
DOI: 10.1111/j.1467-8659.2008.01282.x
2008
Cited 319 times
Global Correspondence Optimization for Non‐Rigid Registration of Depth Scans
Abstract We present a registration algorithm for pairs of deforming and partial range scans that addresses the challenges of non‐rigid registration within a single non‐linear optimization. Our algorithm simultaneously solves for correspondences between points on source and target scans, confidence weights that measure the reliability of each correspondence and identify non‐overlapping areas, and a warping field that brings the source scan into alignment with the target geometry. The optimization maximizes the region of overlap and the spatial coherence of the deformation while minimizing registration error. All optimization parameters are chosen automatically; hand‐tuning is not necessary. Our method is not restricted to part‐in‐whole matching, but addresses the general problem of partial matching, and requires no explicit prior correspondences or feature points. We evaluate the performance and robustness of our method using scan data acquired by a structured light scanner and compare our method with existing non‐rigid registration algorithms.
DOI: 10.1016/j.molmed.2017.05.006
2017
Cited 313 times
Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective
Recent work has identified patterns of altered gene expression denoting molecular pathways operating in groups of SLE patients. Studies have identified local, organ-specific factors enabling or ameliorating SLE tissue damage, thereby dissociating autoimmunity and end-organ damage. Novel subsets of adaptive immune effectors, and the contributions of innate immune cells including platelets and neutrophils, are being increasingly recognized in lupus pathogenesis. Studies have revealed metabolic cellular aberrations, which underwrite cell and organ injury, as important contributors to lupus disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors. Novel observations have provided an improved understanding of the contribution of tissue-specific factors and associated damage, T and B lymphocytes, as well as innate immune cell subsets and their corresponding abnormalities. The intricate web of involved factors and pathways dictates the adoption of tailored therapeutic approaches to conquer this disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors. Novel observations have provided an improved understanding of the contribution of tissue-specific factors and associated damage, T and B lymphocytes, as well as innate immune cell subsets and their corresponding abnormalities. The intricate web of involved factors and pathways dictates the adoption of tailored therapeutic approaches to conquer this disease. a major species of anti-apoptotic cell antibodies in SLE serum; associated with disease activity. antibodies reacting with double-stranded (ds)DNA; these are highly diagnostic of SLE and are implicated in the pathogenesis of lupus nephritis. antibodies against phospholipids that are found in all living cells and cell membranes. an intracellular degradation process in which a cell digests itself. homozygous mice for three NZB/W-derived lupus susceptibility gene loci (Sle1, Sle2, Sle3) on the C57BL/6J background; animals develop systemic autoimmunity with fatal glomerulonephritis; model for SLE. mice harboring a blood dendritic cell antigen 2 (BDCA2)–diphtheria toxin receptor (DTR) fusion transgene; this enables efficient plasmacytoid dendritic cell (pDC) depletion in vivo after a single dose of diphtheria toxin. serine/threonine kinase implicated in T cell transcriptional regulation. by releasing cytokines, Th cells can help to suppress or regulate immune responses; they are essential for B cell antibody class-switching, the activation and growth of cytotoxic T cells, and for maximizing the bactericidal activity of phagocytes. a subunit of CD3 complex of the T cell receptor; helps to activate cytotoxic CD8+ and CD4+ helper T cells and is downregulated in many chronic inflammatory diseases. the first subcomponent of the C1 complex in the classical pathway of complement activation. a series of small proteins and protein fragments (>30) that lead to the stimulation of phagocytes to clear foreign and damaged material, proxy inflammation to attract additional phagocytes, and activate the cell-killing membrane attack complex. The complement system includes serum and serosal proteins, as well as cell membrane receptors. a reduction in the number of cells (blood); often observed in SLE patients. class IV disease, the most severe and most common subtype of lupus nephritis. More than 50% of glomeruli are involved. Lesions can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. catalyze the addition of a methyl group to DNA; they might contribute to aberrant epigenetic regulation in SLE. IgD−CD27− cells; these are age-related or autoimmune disease-associated. antigen-experienced CD4+ T cells found outside B cell follicles of secondary lymphoid organs such as lymph nodes, spleens, and Peyer's patches; eTfh cells are identified by constitutive expression of CXCR4. a crucial component of Fc receptors expressed on many inflammatory cells. Fc receptors are essential for the initiation or maintenance of immune responses. examination of a genome-wide set of genetic variants, in different individuals within a population, that are potentially associated with a given trait. mature B cells reside in germinal centers within lymphoid organs, central factories for the generation of affinity-matured B cells specialized in producing refined antibodies. enzymes that catalyze the removal of acetyl groups from histone proteins (epigenetic regulation). formed by the binding of an antibody to a soluble antigen. Their deposition in tissues (e.g., kidneys) causes damage and is a prominent feature of several autoimmune diseases. a CD28 superfamily costimulatory molecule that is expressed on activated T cells. proteins which regulate the transcription of interferons (IFNs) and are crucial for innate immunity. Dysregulation of IRF signaling might contribute to autoimmune diseases. interleukin produced by T cells, has essential roles in tolerance and immunity. produced by T helper cells; acts as a potent mediator of delayed-type immune reactions and inflammation. produced by activated T cells to regulate immune responses; strongly linked to inflammation and autoimmunity. mechanism by which B cell production of immunoglobulin is changed from one type to another. metabolite of the amino acid L-tryptophan. an autophagy-related process in which phagosomes become decorated with LC3 and are subsequently trafficked to the lysosome for degradation. subdomains of the plasma membrane containing high concentrations of cholesterol and glycosphingolipids. Signaling in these domains differs in T cells from patients with SLE and rheumatoid arthritis. low levels of lymphocytes in the blood. ubiquitous atypical serine/threonine kinase important for cellular processes including survival, growth, and proliferation. Aberrant mTOR signaling is involved in many diseases (including autoimmune). a small specialized macrophage subset residing in the marginal zone of the spleen; MZMs play a central role in the clearance of apoptotic cells to minimize the immunogenicity of autoantigens. constitute the glomerular mesangium and, with the mesangial matrix, form the vascular pole of the glomerulus. Their primary function is to remove trapped residues and aggregated protein from the basement membrane. mice homozygous for the lymphoproliferation spontaneous mutation (Faslpr) show systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, arthritis, and immune complex-induced glomerulonephrosis; model for SLE. networks of extracellular fibers that are primarily composed of DNA from neutrophils, and may provide a source of autoantigens in autoimmune diseases. these mice develop an autoimmune disease resembling human SLE: high levels of antinuclear antibodies, hemolytic anemia, proteinuria, and progressive immune complex glomerulonephritis (more pronounced in females). a subtype predominantly found in germinal centers that contain many phagocytized, apoptotic cells. immature B cells that divide rapidly and secrete antibodies (but less than plasma cells). effector B cells that secrete large volumes of antibodies. cells in the renal Bowman’s capsule that wrap around the capillaries of the glomerulus. Their primary function is to filter blood and retain large molecules (e.g., albumin). inhibitory T cell-surface receptor implicated in mechanisms of self-tolerance. It is an immune checkpoint against autoimmunity. ubiquitously expressed; regulates cellular function by dephosphorylating molecules such as Akt, p53, c-Myc and β-catenin. Deregulation of PP2A in T cells has been implicated in autoimmunity. lymphoid-specific intracellular phosphatase that acts as negative regulator of T cell receptor signaling. Mutations in its coding gene may be associated with autoimmune disorders including SLE. quantitative study of chemical processes involving metabolites. proteins involved in cytoskeletal reorganization and control of cell adhesion and migration, apoptosis, proliferation, and differentiation. a family of signaling intermediates in the Janus kinase (JAK)/STAT signaling pathway which initiate gene transcription. Gain-of-function or loss-of-function mutations of different STATs can lead to immunodeficiency, infections, or multiorgan autoimmunity. a group of type I transmembrane receptors. SLAM members appear to play crucial roles in multiple autoimmune diseases. variations in a single nucleotide occurring at a specific position in the genome, where each variation is present to some appreciable degree within a population. cellular mechanism by which the immune system adapts to new foreign elements. It involves a programmed process of mutation affecting the variable regions of immunoglobulin genes. a B cell subtype that is formed within germinal centers following antigen encounter (switched immunoglobulin receptor). T cells that display the distinctive γδ T cell receptor (TCR) on their surface (most T cells bear αβ chain TCRs); mostly expressed in mucosal sites; considered as ‘first line of defense' or ‘bridge between innate and adaptive immunity. functional ectopic lymphoid structures formed inside non-lymphoid tissues, presumed to have immune functions. a CD4+ T cell subset that provides IL-21-mediated help to B cells (Tfh cells express BCL6). the ability of the immune system to recognize and tolerate the body's own proteins and organs, avoiding attacks against ‘self’. play key roles in innate immunity; sense danger/damage signals, recognizing structurally conserved molecular patterns derived from microbes (e.g., pattern-recognition receptors). Endogenous TLR ligands, particularly nucleic acids, may contribute to the modulation of aberrant adaptive immunity (e.g., SLE). immature B cells residing in peripheral lymphoid tissues; are capable of differentiating into mature B cells.
DOI: 10.24963/ijcai.2017/504
2017
Cited 311 times
What to Do Next: Modeling User Behaviors by Time-LSTM
Recently, Recurrent Neural Network (RNN) solutions for recommender systems (RS) are becoming increasingly popular. The insight is that, there exist some intrinsic patterns in the sequence of users' actions, and RNN has been proved to perform excellently when modeling sequential data. In traditional tasks such as language modeling, RNN solutions usually only consider the sequential order of objects without the notion of interval. However, in RS, time intervals between users' actions are of significant importance in capturing the relations of users' actions and the traditional RNN architectures are not good at modeling them. In this paper, we propose a new LSTM variant, i.e. Time-LSTM, to model users' sequential actions. Time-LSTM equips LSTM with time gates to model time intervals. These time gates are specifically designed, so that compared to the traditional RNN solutions, Time-LSTM better captures both of users' short-term and long-term interests, so as to improve the recommendation performance. Experimental results on two real-world datasets show the superiority of the recommendation method using Time-LSTM over the traditional methods.
DOI: 10.1016/j.cej.2020.126863
2021
Cited 310 times
Fabrication of environmentally friendly Losartan potassium film for corrosion inhibition of mild steel in HCl medium
The present study aimed to find a suitable alternative for traditional and hazardous corrosion inhibitors. A green antihypertensive drug-Losartan potassium (LP) with superior corrosion protection ability was developed for the first time. Gravimetric method, potentiodynamic polarization, AC impedance, and scanning vibrating electrode technique (SVET) were combined to evaluate the corresponding inhibition performance towards Q235 steel in HCl medium. The results indicated that LP exhibited superior mixed-type corrosion protection to steel at different temperatures owing to the formation of compact and ordered LP-adsorption film on steel surface. Specifically, the inhibition performance values increased to 88.9%, 91.8%, and 92.0% for 5 mM LP at 298, 308, and 318 K, respectively. Meanwhile, N-Fe bond from X-ray photoelectronic spectroscopy (XPS) implied multiple anchoring interaction between steel and LP with nitrogen atoms as active sites. Based on DFT calculation and molecular dynamics (MD) simulation, the obtained low energy gap (ΔE) and high Ebinding values as well as radial distribution function (RDF) analysis represented strong chemisorption of LP on Fe substrate, which theoretically explained the favorable inhibition effectiveness of LP compound at molecular or atomic level.
DOI: 10.1038/ncb1767
2008
Cited 301 times
Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression
The kinase Plk1 regulates multiple processes during mitosis in mammalian cells. Chen and colleagues show that Plk1 also controls a transcriptional network required for orderly cell-cycle progression through Cdk1-dependent phosphorylation of the transcription factor FoxM1 Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability1,2,3,4. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis5. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1 (refs 6, 7, 8), controls a transcriptional programme that mediates Plk1-dependent regulation of cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1–FoxM1 interaction. Formation of the Plk1–FoxM1 complex allows for direct phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1 activity, which is required for expression of key mitotic regulators, including Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression.
DOI: 10.1021/acs.est.5b04042
2015
Cited 300 times
Degradation of <i>p</i>-Nitrophenol on Biochars: Role of Persistent Free Radicals
Generation of environmentally persistent free radicals (EPFRs) on solid particles has recently attracted increasing research interest. EPFRs potentially have high reactivity and toxicity. However, the impact of EPFRs on organic contaminant behavior is unclear. We hypothesized that EPFRs in biochars can degrade organic contaminants and play an important role in organic contaminant behavior. We observed obvious degradation of p-nitrophenol (PNP) in the presence of biochars, through the detection of NO3– as well as organic byproducts. The extent of PNP degradation was correlated to the intensity of EPR signals of biochar particles. tert-Butanol (a •OH scavenger) did not completely inhibit PNP degradation, indicating that •OH could not fully explain PNP degradation. The decreased PNP degradation after tert-butanol addition was better correlated with reduced PNP sorption on biochars. PNP degradation through the direct contact with EPFRs in biochar particles could be an important contribution to the PNP concentration reduction in the aqueous phase. The coating of natural organic matter analogue (tannic acid) on biochars did not considerably inhibit PNP degradation, suggesting the ability of biochars to degrade PNP in soil and natural water. Similar EPFR-promoted degradation was observed for five different types of biochars and one activated carbon, as well as one additional chemical (p-aminophenol). Therefore, organic chemical degradation by EPFRs in biochars can be a common process in the environment and should be incorporated in organic chemical fate and risk studies.
DOI: 10.1371/journal.pgen.0030094
2007
Cited 284 times
Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
The glucocorticoid receptor (GR) associates with glucocorticoid response elements (GREs) and regulates selective gene transcription in a cell-specific manner. Native GREs are typically thought to be composite elements that recruit GR as well as other regulatory factors into functional complexes. We assessed whether GR occupancy is commonly a limiting determinant of GRE function as well as the extent to which core GR binding sequences and GRE architecture are conserved at functional loci. We surveyed 100-kb regions surrounding each of 548 known or potentially glucocorticoid-responsive genes in A549 human lung cells for GR-occupied GREs. We found that GR was bound in A549 cells predominately near genes responsive to glucocorticoids in those cells and not at genes regulated by GR in other cells. The GREs were positionally conserved at each responsive gene but across the set of responsive genes were distributed equally upstream and downstream of the transcription start sites, with 63% of them >10 kb from those sites. Strikingly, although the core GR binding sequences across the set of GREs varied extensively around a consensus, the precise sequence at an individual GRE was conserved across four mammalian species. Similarly, sequences flanking the core GR binding sites also varied among GREs but were conserved at individual GREs. We conclude that GR occupancy is a primary determinant of glucocorticoid responsiveness in A549 cells and that core GR binding sequences as well as GRE architecture likely harbor gene-specific regulatory information.
DOI: 10.1001/jama.2016.8662
2016
Cited 282 times
Association Between<i>CYP2C19</i>Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack
Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel.To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack.Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012.Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone.The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome.Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction).Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment.clinicaltrials.gov Identifier: NCT00979589.
DOI: 10.1002/anie.201302586
2013
Cited 274 times
Quasi‐Solid‐State Rechargeable Lithium‐Ion Batteries with a Calix[4]quinone Cathode and Gel Polymer Electrolyte
Filled to capacity: Calix[4]quinone (C4Q) has eight available carbonyl groups for binding lithium ions (see picture). It can be exploited to prepare quasi-solid-state rechargeable lithium batteries with a poly(methyl acrylate)/poly(ethylene glycol) based gel polymer electrolyte and a LiClO4/DMSO loading. It shows an initial discharge capacity of 422 mA h g−1 and a capacity retention of 379 mA h g−1 after 100 cycles. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
DOI: 10.1093/nsr/nwaa089
2020
Cited 274 times
High-Chern-number and high-temperature quantum Hall effect without Landau levels
The quantum Hall effect (QHE) with quantized Hall resistance of h/νe2 started the research on topological quantum states and laid the foundation of topology in physics. Since then, Haldane proposed the QHE without Landau levels, showing nonzero Chern number |C| = 1, which has been experimentally observed at relatively low temperatures. For emerging physics and low-power-consumption electronics, the key issues are how to increase the working temperature and realize high Chern numbers (C > 1). Here, we report the experimental discovery of high-Chern-number QHE (C = 2) without Landau levels and C = 1 Chern insulator state displaying a nearly quantized Hall resistance plateau above the Néel temperature in MnBi2Te4 devices. Our observations provide a new perspective on topological matter and open new avenues for exploration of exotic topological quantum states and topological phase transitions at higher temperatures.
DOI: 10.1088/0964-1726/25/2/027001
2016
Cited 273 times
Magnetic actuated pH-responsive hydrogel-based soft micro-robot for targeted drug delivery
For drug delivery in cancer therapy, various stimuli-responsive hydrogel-based micro-devices have been studied with great interest. Here, we present a new concept for a hybrid actuated soft microrobot targeted drug delivery. The proposed soft microrobot consists of a hydrogel bilayer structure of 2-hydroxyethyl methacrylate (PHEMA) and poly (ethylene glycol) acrylate (PEGDA) with iron (II, III) oxide particles (Fe3O4). The PHEMA layer as a pH-responsive gel is used for a trapping and unfolding motion of the soft microrobot in pH-varying solution, and the PEGDA-with-Fe3O4 layer is employed for the locomotion of the soft microrobot in the magnetic field. The bilayer soft microrobot was fabricated by a conventional photolithography procedure and its characteristics were analyzed and presented. To evaluate the trapping performance and the motility of the soft microrobot, test solutions with different pH values and an electromagnetic actuation (EMA) system were used. First, the soft microrobot showed its full trapping motion at about pH 9.58 and its unfolding motion at about pH 2.6. Second, the soft microrobot showed a moving velocity of about 600 μm s−1 through the generated magnetic field of the EMA system. Finally, we fabricated the real anti-cancer drug microbeads (PCL-DTX) and executed the cytotoxicity test using the mammary carcinoma cells (4T1). The viability of the 4T1 cells treated with the proposed microrobot and the PCL-DTX microbeads decreased to 70.25 ± 1.52%. The result demonstrated that the soft microrobot can be moved to a target position by the EMA system and can release a small amount of beads by the pH variation and the robot exhibited no toxicity to the cells. In the future, we expect that the proposed soft microrobot can be applied to a new tumor-therapeutic tool that can move to a target tumor and release anti-tumor drugs.
DOI: 10.1109/iccv48922.2021.00570
2021
Cited 270 times
PlenOctrees for Real-time Rendering of Neural Radiance Fields
We introduce a method to render Neural Radiance Fields (NeRFs) in real time using PlenOctrees, an octree-based 3D representation which supports view-dependent effects. Our method can render 800×800 images at more than 150 FPS, which is over 3000 times faster than conventional NeRFs. We do so without sacrificing quality while preserving the ability of NeRFs to perform free-viewpoint rendering of scenes with arbitrary geometry and view-dependent effects. Real-time performance is achieved by pre-tabulating the NeRF into a PlenOctree. In order to preserve view-dependent effects such as specularities, we factorize the appearance via closed-form spherical basis functions. Specifically, we show that it is possible to train NeRFs to predict a spherical harmonic representation of radiance, removing the viewing direction as an input to the neural network. Furthermore, we show that PlenOctrees can be directly optimized to further minimize the reconstruction loss, which leads to equal or better quality compared to competing methods. Moreover, this octree optimization step can be used to reduce the training time, as we no longer need to wait for the NeRF training to converge fully. Our real-time neural rendering approach may potentially enable new applications such as 6-DOF industrial and product visualizations, as well as next generation AR/VR systems. PlenOctrees are amenable to in-browser rendering as well; please visit the project page for the interactive online demo, as well as video and code: https://alexyu.net/plenoctrees.
DOI: 10.1002/adma.201804504
2018
Cited 269 times
Sulfuration of an Fe–N–C Catalyst Containing Fe<i><sub>x</sub></i>C/Fe Species to Enhance the Catalysis of Oxygen Reduction in Acidic Media and for Use in Flexible Zn–Air Batteries
During the preparation of atomically dispersed Fe-N-C catalysts, it is difficult to avoid the formation of iron-carbide-containing iron clusters ("Fex C/Fe"), along with the desired carbon matrix containing dispersed FeNx sites. As a result, an uncertain amount of the oxygen reduction reaction (ORR) occurs, making it difficult to maximize the catalytic efficiency. Herein, sulfuration is used to boost the activity of Fex C/Fe, forming an improved system, "FeNC-S-Fex C/Fe", for catalysis involving oxygen. Various spectroscopic techniques are used to define the composition of the active sites, which include Fe-S bonds at the interface of the now-S-doped carbon matrix and the Fex C/Fe clusters. In addition to outstanding activity in basic media, FeNC-S-Fex C/Fe exhibits improved ORR activity and durability in acidic media; its half-wave potential of 0.821 V outperforms the commercial Pt/C catalyst (20%), and its activity does not decay even after 10 000 cycles. Interestingly, the catalytic activity for the oxygen evolution reaction (OER) simultaneously improves. Thus, FeNC-S-Fex C/Fe can be used as a high-performance bifunctional catalyst in Zn-air batteries. Theoretical calculations and control experiments show that the original FeNx active centers are enhanced by the Fex C/Fe clusters and the Fe-S and C-S-C bonds.
DOI: 10.1103/physrevlett.121.250505
2018
Cited 268 times
12-Photon Entanglement and Scalable Scattershot Boson Sampling with Optimal Entangled-Photon Pairs from Parametric Down-Conversion
Entangled photon sources with simultaneously near-unity heralding efficiency and indistinguishability are the fundamental elements for scalable photonic quantum technologies. We design and realize a degenerate entangled-photon source from an ultrafast pulsed laser pumped spontaneous parametric down-conversion (SPDC), which show simultaneously ~97% heralding efficiency and ~96% indistinguishability between independent single photons. Such a high-efficiency and frequency-uncorrelated SPDC source allows generation of the first 12-photon genuine entanglement with a state fidelity of 0.572(24). We further demonstrate a blueprint of scalable scattershot boson sampling using 12 SPDC sources and a 12*12-modes interferometer for three-, four-, and five-boson sampling, which yields count rates more than four orders of magnitudes higher than all previous SPDC experiments. Our work immediately enables high-efficiency implementations of multiplexing, scattershot boson sampling, and heralded creation of remotely entangled photons, opening up a promising pathway to scalable photonic quantum technologies.
DOI: 10.1145/1618452.1618521
2009
Cited 264 times
Robust single-view geometry and motion reconstruction
We present a framework and algorithms for robust geometry and motion reconstruction of complex deforming shapes. Our method makes use of a smooth template that provides a crude approximation of the scanned object and serves as a geometric and topological prior for reconstruction. Large-scale motion of the acquired object is recovered using a novel space-time adaptive, non-rigid registration method. Fine-scale details such as wrinkles and folds are synthesized with an efficient linear mesh deformation algorithm. Subsequent spatial and temporal filtering of detail coefficients allows transfer of persistent geometric detail to regions not observed by the scanner. We show how this two-scale process allows faithful recovery of small-scale shape and motion features leading to a high-quality reconstruction. We illustrate the robustness and generality of our algorithm on a variety of examples composed of different materials and exhibiting a large range of dynamic deformations.
DOI: 10.1103/physrevlett.124.070501
2020
Cited 259 times
Sending-or-Not-Sending with Independent Lasers: Secure Twin-Field Quantum Key Distribution over 509 km
Twin field quantum key distribution promises high key rates at long distance to beat the rate distance limit. Here, applying the sending or not sending TF QKD protocol, we experimentally demonstrate a secure key distribution breaking the absolute key rate limit of repeaterless QKD over 509 km, 408 km ultra-low loss optical fibre and 350 km standard optical fibre. Two independent lasers are used as the source with remote frequency locking technique over 500 km fiber distance; Practical optical fibers are used as the optical path with appropriate noise filtering; And finite key effects are considered in the key rate analysis. The secure key rates obtained at different distances are more than 5 times higher than the conditional limit of repeaterless QKD, a bound value assuming the same detection loss in the comparison. The achieved secure key rate is also higher than that a traditional QKD protocol running with a perfect repeaterless QKD device and even if an infinite number of sent pulses. Our result shows that the protocol and technologies applied in this experiment enable TF QKD to achieve high secure key rate at long distribution distance, and hence practically useful for field implementation of intercity QKD.
DOI: 10.1039/c5nr00228a
2015
Cited 258 times
Artificial nacre-like papers based on noncovalent functionalized boron nitride nanosheets with excellent mechanical and thermally conductive properties
Artificial nacre-like papers with excellent mechanical and thermally conductive properties were fabricated <italic>via</italic> self-assembly of functionalized boron nitride nanosheets and poly(vinyl alcohol).
DOI: 10.3389/fpls.2017.00295
2017
Cited 257 times
Exogenous Melatonin Confers Salt Stress Tolerance to Watermelon by Improving Photosynthesis and Redox Homeostasis
Melatonin, a pleiotropic signal molecule, has been shown to play important roles in the regulation of plant growth, development, and responses to environmental stresses. Since a few species have been investigated to unveil the effect of exogenous melatonin on salt stress, the underlying mechanism of melatonin-mediated salt stress tolerance in other plant species still remains largely unknown. In this study, the effects of melatonin on leaf photosynthesis and redox homeostasis in watermelon were examined under salt stress (300 mM NaCl) along with different doses of melatonin (50, 150, and 500 μM) pretreatment. NaCl stress inhibited photosynthesis and increased accumulation of reactive oxygen species and membrane damage in leaves of watermelon seedlings. However, pretreatment with melatonin on roots alleviated NaCl-induced decrease in photosynthetic rate and oxidative stress in a dose-dependent manner. The protection of photosynthesis by melatonin was closely associated with the inhibition of stomatal closure and improved light energy absorption and electron transport in photosystem II, while the reduction of oxidative stress by melatonin was attributed to the improved redox homeostasis coupled with the enhanced activities of antioxidant enzymes. This study unraveled crucial role of melatonin in salt stress mitigation and thus can be implicated in the management of salinity in watermelon cultivation.
DOI: 10.1021/ac302138c
2012
Cited 254 times
Highly Selective and Sensitive Fluorescent Paper Sensor for Nitroaromatic Explosive Detection
Rapid, sensitive, and selective detection of explosives such as 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenol (TNP), especially using a facile paper sensor, is in high demand for homeland security and public safety. Although many strategies have been successfully developed for the detection of TNT, it is not easy to differentiate the influence from TNP. Also, few methods were demonstrated for the selective detection of TNP. In this work, via a facile and versatile method, 8-hydroxyquinoline aluminum (Alq3)-based bluish green fluorescent composite nanospheres were successfully synthesized through self-assembly under vigorous stirring and ultrasonic treatment. These polymer-coated nanocomposites are not only water-stable but also highly luminescent. Based on the dramatic and selective fluorescence quenching of the nanocomposites via adding TNP into the aqueous solution, a sensitive and robust platform was developed for visual detection of TNP in the mixture of nitroaromatics including TNT, 2,4-dinitrotoluene (DNT), and nitrobenzene (NB). Meanwhile, the fluorescence intensity is proportional to the concentration of TNP in the range of 0.05–7.0 μg/mL with the 3σ limit of detection of 32.3 ng/mL. By handwriting or finger printing with TNP solution as ink on the filter paper soaked with the fluorescent nanocomposites, the bluish green fluorescence was instantly and dramatically quenched and the dark patterns were left on the paper. Therefore, a convenient and rapid paper sensor for TNP-selective detection was fabricated.
DOI: 10.1021/acsami.8b08832
2018
Cited 253 times
Degradable Carbon Dots with Broad-Spectrum Antibacterial Activity
The infection of bacteria and fungus is one of the most challenging global threats to human health. With the recent advancement in nanoscience and nanotechnology, much progress has been achieved in the development of antimicrobial nanomedicine; however, these nanomaterial-based antibacterial agents still suffer from potential biological toxicity, poor degradation, and various secondary pollution. Here, we demonstrate the fabrication of low-toxic and degradable carbon dots (CDs) from vitamin C by one-step electrochemical method. These newly generated CDs display a strong broad-spectrum antibacterial activity and antifungal activity even at low concentrations, as they destroy the bacterial walls during the diffusive entrance, perturb secondary structures of DNA/RNAs of bacteria and fungus, and inhibit important gene expressions to finally kill the bacteria and fungus. We also show that these well-characterized CDs can be completely degraded into CO2, CO and H2O under visible light in air (or at very mild temperature, about 37 °C).
DOI: 10.1016/j.nanoen.2019.01.044
2019
Cited 253 times
Scalable, eco-friendly and ultrafast solar steam generators based on one-step melamine-derived carbon sponges toward water purification
Solar steam generation can be a practical and sustainable technology for wastewater purification and seawater desalination. However, both the inefficient utilization of solar energy and high complicity/cost of current solar steam generators hinder the scalable application of this technique. Herein, we demonstrate a facile, scalable and low-cost approach to produce highly-efficient solar steam generator via a one-step calcination of commercial melamine sponges (MS) in air. The in-air calcinated MS (AMS) with thermal insulator achieves an ultrafast solar evaporation rate (1.98 kg m−2 h−1) and a high photothermal efficiency (~92%) under one sun illumination (1 kW m−2), superior to most reported values. This high solar evaporation rate is attributed to the effective heat localization and adequate water supply in AMS, caused by the low bulk thermal conductivity, high porosity and hydrophilicity of AMS, as well as the set-up of a thermal insulator. The AMS is found to be highly efficient and stable, and it can be used to purify various types of waste water, including river water, seawater, and strong acid/alkaline water. Performance analysis of a large-scale prototype device based on the AMS design for field tests promises significant opportunities for highly-efficient, reusable, portable and low-cost water purification systems.
DOI: 10.1016/j.jgg.2016.07.003
2016
Cited 250 times
Rapid improvement of grain weight via highly efficient CRISPR/Cas9-mediated multiplex genome editing in rice
Currently, international development requires innovative solutions to address imminent challenges like climate change, unsustainable food system, food waste, energy crisis, and environmental degradation. All the same, addressing these concerns with conventional technologies is time-consuming, causes harmful environmental impacts, and is not cost-effective. Thus, biotechnological tools become imperative for enhancing food and energy resilience through eco-friendly bio-based products by valorisation of plant and food waste to meet the goals of circular bioeconomy in conjunction with Sustainable Developmental Goals (SDGs). Genome editing can be accomplished using a revolutionary DNA modification tool, CRISPR-Cas9, through its uncomplicated guided mechanism, with great efficiency in various organisms targeting different traits. This review's main objective is to examine how the CRISPR-Cas system, which has positive features, could improve the bioeconomy by reducing food loss and waste with all-inclusive food supply chain both at on-farm and off-farm level; utilising food loss and waste by genome edited microorganisms through food valorisation; efficient microbial conversion of low-cost substrates as biofuel; valorisation of agro-industrial wastes; mitigating greenhouse gas emissions through forestry plantation crops; and protecting the ecosystem and environment. Finally, the ethical implications and regulatory issues that are related to CRISPR-Cas edited products in the international markets have also been taken into consideration.
DOI: 10.1039/c5nr07380d
2016
Cited 249 times
Facet-dependent solar ammonia synthesis of BiOCl nanosheets via a proton-assisted electron transfer pathway
The distinct structures of oxygen vacancies on different BiOCl facets strongly affect their solar N<sub>2</sub> fixation <italic>via</italic> a proton-assisted electron transfer pathway.
DOI: 10.1109/iccv.2019.00655
2019
Cited 247 times
SoftTriple Loss: Deep Metric Learning Without Triplet Sampling
Distance metric learning (DML) is to learn the embeddings where examples from the same class are closer than examples from different classes. It can be cast as an optimization problem with triplet constraints. Due to the vast number of triplet constraints, a sampling strategy is essential for DML. With the tremendous success of deep learning in classifications, it has been applied for DML. When learning embeddings with deep neural networks (DNNs), only a mini-batch of data is available at each iteration. The set of triplet constraints has to be sampled within the mini-batch. Since a mini-batch cannot capture the neighbors in the original set well, it makes the learned embeddings sub-optimal. On the contrary, optimizing SoftMax loss, which is a classification loss, with DNN shows a superior performance in certain DML tasks. It inspires us to investigate the formulation of SoftMax. Our analysis shows that SoftMax loss is equivalent to a smoothed triplet loss where each class has a single center. In real-world data, one class can contain several local clusters rather than a single one, e.g., birds of different poses. Therefore, we propose the SoftTriple loss to extend the SoftMax loss with multiple centers for each class. Compared with conventional deep metric learning algorithms, optimizing SoftTriple loss can learn the embeddings without the sampling phase by mildly increasing the size of the last fully connected layer. Experiments on the benchmark fine-grained data sets demonstrate the effectiveness of the proposed loss function.
DOI: 10.1016/j.memsci.2016.03.050
2016
Cited 244 times
Simultaneous enhancement of mechanical properties and CO2 selectivity of ZIF-8 mixed matrix membranes: Interfacial toughening effect of ionic liquid
Fine-tuning of interfacial adhesion between fillers and polymer matrices is crucial to the separation performance of mixed matrix membranes (MMMs) and their mechanical properties. Direct incorporation of metal-organic framework (MOF) particles in polymers often leads to insufficient adhesion and non-selective interfacial voids. Herein, we present a novel strategy to develop toughened MOF-polymer interface by confining a room temperature ionic liquid (IL) [bmim][Tf2N] into ZIF-8 cages. The diffusion of the IL out of the IL-incorporated ZIF-8 ([email protected]) was restrained by a water-washing process, confirmed by energy-dispersive X-ray spectra. Scanning electron microscopy images and differential scanning calorimetry measurements verified the interfacial toughening between the polymer and the [email protected] filler. As a result, the mechanical properties and gas separation performance of [email protected]/Pebax membranes were significantly improved at the same time. The maximum tensile strength and elongation at break of [email protected]/Pebax membranes, obtained at a loading of 15 wt%, were 20% and 280% higher than those of pure Pebax membrane, respectively. Moreover, [email protected]/Pebax membranes showed improved molecular sieving properties compared to ZIF-8/Pebax membranes, due to a stiffer interphase between the filler and the polymer and a reduction in the effective aperture size of ZIF-8. The MMM with 15 wt% [email protected] has a substantial improvement in both CO2 permeability (increased by 45%) and selectivity (increased by 74% for CO2/N2 and 92% for CO2/CH4) over pure Pebax membrane. The presented strategy of fabricating [email protected]/polymer membranes with desired interfacial structures can be conveniently expanded to a wide range of material combinations.
DOI: 10.1002/chem.201102606
2012
Cited 238 times
New Insight into Daylight Photocatalysis of AgBr@Ag: Synergistic Effect between Semiconductor Photocatalysis and Plasmonic Photocatalysis
Noble metal nanoparticles (NPs) are often used as electron scavengers in conventional semiconductor photocatalysis to suppress electron-hole (e(-)-h(+) ) recombination and promote interfacial charge transfer, and thus enhance photocatalytic activity of semiconductors. In this contribution, it is demonstrated that noble metal NPs such as Ag NPs function as visible-light harvesting and electron-generating centers during the daylight photocatalysis of AgBr@Ag. Novel Ag plasmonic photocatalysis could cooperate with the conventional AgBr semiconductor photocatalysis to enhance the overall daylight activity of AgBr@Ag greatly because of an interesting synergistic effect. After a systematic investigation of the daylight photocatalysis mechanism of AgBr@Ag, the synergistic effect was attributed to surface plasmon resonance induced local electric field enhancement on Ag, which can accelerate the generation of e(-)-h(+) pairs in AgBr, so that more electrons are produced in the conduction band of AgBr under daylight irradiation. This study provides new insight into the photocatalytic mechanism of noble metal/semiconductor systems as well as the design and fabrication of novel plasmonic photocatalysts.
DOI: 10.1016/j.biortech.2013.12.074
2014
Cited 234 times
Conversion efficiency and oil quality of low-lipid high-protein and high-lipid low-protein microalgae via hydrothermal liquefaction
Hydrothermal liquefaction (HTL) is a promising technology for converting algae into biocrude oil. Here, HTL of a low-lipid high-protein microalgae (Nannochloropsis sp.) and a high-lipid low-protein microalgae (Chlorella sp.) was studied. An orthogonal design was applied to investigate the effects of reaction temperature (220-300°C), retention time (30-90 min), and total solid content (TS, 15-25%wt) of the feedstock. The highest biocrude yield for Nannochloropsis sp. was 55% at 260°C, 60 min and 25%wt, and for Chlorella sp. was 82.9% at 220°C, 90 min and 25%wt. The maximum higher heating values (HHV) of biocrude oil from both algae were ∼ 37 MJ/kg. GC-MS revealed a various distribution of chemical compounds in biocrude. In particular, the highest hydrocarbons content was 29.8% and 17.9% for Nannochloropsis and Chlorella sp., respectively. This study suggests that algae composition greatly influences oil yield and quality, but may not be in similar effects.
DOI: 10.1016/j.apcatb.2018.01.018
2018
Cited 234 times
Visible light driven selective oxidation of amines to imines with BiOCl: Does oxygen vacancy concentration matter?
The relationship between oxygen vacancy (OV) concentration of semiconductors and their photocatalytic performances is far from clarified. In this study, by tuning the OV concentration of BiOCl (001) surface via a novel H2O2 treatment coupled infrared irradiation method, we demonstrate that OV concentration of BiOCl (001) surface strongly determine its surface atomic and electronic structures to modulate the photocatalytic pathways. Being of shorter BiBi and BiO bond lengths as well as more electrons being less localized, BiOCl (001) surface with higher OV concentration favored molecular oxygen activation to generate O22− via a two-electron transfer pathway, while the generated O22− could prevent the over oxidation of amines and thus achieve high selectivity in the oxidation of amines to imines. Similar phenomena were also observed for other semiconductor photocatalysts such as TiO2 and Nb2O5, suggesting the generality of oxygen vacancy concentration mediated selectivity enhancement. These findings shed light on the relationship between the oxygen vacancy concentration and the surface structure of semiconductor photocatalysts and offer a novel pathway to realize photocatalytic selective oxidation of amines to imines.
DOI: 10.1002/adma.201906910
2020
Cited 230 times
Sulfur Loading and Speciation Control the Hydrophobicity, Electron Transfer, Reactivity, and Selectivity of Sulfidized Nanoscale Zerovalent Iron
Sulfidized nanoscale zerovalent iron (SNZVI) is a promising material for groundwater remediation. However, the relationships between sulfur content and speciation and the properties of SNZVI materials are unknown, preventing rational design. Here, the effects of sulfur on the crystalline structure, hydrophobicity, sulfur speciation, corrosion potential, and electron transfer resistance are determined. Sulfur incorporation extended the nano-Fe0 BCC lattice parameter, reduced the Fe local vacancies, and lowered the resistance to electron transfer. Impacts of the main sulfur species (FeS and FeS2 ) on hydrophobicity (water contact angles) are consistent with density functional theory calculations for these FeSx phases. These properties well explain the reactivity and selectivity of SNZVI during the reductive dechlorination of trichloroethylene (TCE), a hydrophobic groundwater contaminant. Controlling the amount and speciation of sulfur in the SNZVI made it highly reactive (up to 0.41 L m-2 d-1 ) and selective for TCE degradation over water (up to 240 moles TCE per mole H2 O), with an electron efficiency of up to 70%, and these values are 54-fold, 98-fold, and 160-fold higher than for NZVI, respectively. These findings can guide the rational design of robust SNZVI with properties tailored for specific application scenarios.
DOI: 10.1109/icra.2018.8461224
2018
Cited 230 times
Robust and Precise Vehicle Localization Based on Multi-Sensor Fusion in Diverse City Scenes
We present a robust and precise localization system that achieves centimeter-level localization accuracy in disparate city scenes. Our system adaptively uses information from complementary sensors such as GNSS, LiDAR, and IMU to achieve high localization accuracy and resilience in challenging scenes, such as urban downtown, highways, and tunnels. Rather than relying only on LiDAR intensity or 3D geometry, we make innovative use of LiDAR intensity and altitude cues to significantly improve localization system accuracy and robustness. Our GNSS RTK module utilizes the help of the multi-sensor fusion framework and achieves a better ambiguity resolution success rate. An error-state Kalman filter is applied to fuse the localization measurements from different sources with novel uncertainty estimation. We validate, in detail, the effectiveness of our approaches, achieving 5-10cm RMS accuracy and outperforming previous state-of-the-art systems. Importantly, our system, while deployed in a large autonomous driving fleet, made our vehicles fully autonomous in crowded city streets despite road construction that occurred from time to time. A dataset including more than 60 km real traffic driving in various urban roads is used to comprehensively test our system.
DOI: 10.1039/c3nr03597b
2013
Cited 228 times
Self-doping and surface plasmon modification induced visible light photocatalysis of BiOCl
In this study we demonstrate that self-doping and surface plasmon resonance could endow a wide-band-gap ternary semiconductor BiOCl with remarkable visible light driven photocatalytic activity on the degradation of organic pollutants and photocurrent generation properties. The self-doped BiOCl with plasmonic silver modification was synthesized by a facile one-pot nonaqueous approach and systematically characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, UV-visible diffuse reflectance spectra, electron spin resonance, and X-ray photoelectron spectroscopy. The photocurrent enhancement was found to be intimately dependent on the irradiation wavelength and matched well with the intensity of the absorption of the Ag nanoparticles. Reactive species trapping experiments and electron spin resonance spectroscopy with 5,5-dimethyl-1-pyrroline-N-oxide spin-trapping adducts confirmed that more oxidative species could be generated from the photogenerated electrons due to the plasmon-excitation of the metallic Ag in the self-doped BiOCl with plasmonic silver modification, which is responsible for the great enhancement of photocatalytic activity and photocurrent. Surface photovoltage spectroscopy and time-resolved photoluminescence spectroscopy results revealed the transfer of plasmon-band-induced electrons from Ag nanoparticles into BiOCl and the acceleration effect of surface plasmon resonance-induced intense oscillating electric fields on this electron transfer. This study would not only provide direct evidence of plasmonic photocatalysis, but also shed light on the design of highly efficient metal-semiconductor composite photocatalysts.
DOI: 10.1021/acs.est.8b07322
2019
Cited 220 times
Oxygen Vacancies Promoted the Selective Photocatalytic Removal of NO with Blue TiO<sub>2</sub> via Simultaneous Molecular Oxygen Activation and Photogenerated Hole Annihilation
Semiconductor photocatalytic technology has great potential for the removal of dilute gaseous NO in indoor and outdoor atmospheres but suffers from unsatisfactory NO-removal selectivity due to undesirable NO2 byproduct generation. In this study, we demonstrate that the 99% selectivity of photocatalytic NO oxidation toward nitrate can be achieved over blue TiO2 bearing oxygen vacancies (OVs) under visible-light irradiation. First-principles density functional theory calculation and experimental results suggested that the OVs of blue TiO2 with localized electrons could facilitate the molecular oxygen activation through single-electron pathways to generate ·O2- and simultaneously promote the photogenerated hole annihilation. The generated ·O2- directly converted NO to nitrate, while the hole annihilation inhibited the side-reaction between holes and NO to avoid toxic NO2 byproduct formation, resulting in the highly selective removal of NO. This study reveals the dual functions of OVs in defective photocatalysts and also provides fundamental guidance for the selective purification of NO with photocatalytic technology.
DOI: 10.1103/physrevx.9.041040
2019
Cited 220 times
Topological Electronic Structure and Its Temperature Evolution in Antiferromagnetic Topological Insulator <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi>MnBi</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub><mml:msub><mml:mrow><mml:mi>Te</mml:mi></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>
Topological quantum materials coupled with magnetism can provide a platform for realizing rich exotic physical phenomena, including quantum anomalous Hall effect, axion electrodynamics and Majorana fermions. However, these unusual effects typically require extreme experimental conditions such as ultralow temperature or sophisticate material growth and fabrication. Recently, new intrinsic magnetic topological insulators were proposed in MnBi2Te4-family compounds - on which rich topological effects could be realized under much relaxed experimental conditions. However, despite the exciting progresses, the detailed electronic structures observed in this family of compounds remain controversial up to date. Here, combining the use of synchrotron and laser light sources, we carried out comprehensive and high resolution angle-resolved photoemission spectroscopy studies on MnBi2Te4, and clearly identified its topological electronic structures including the characteristic gapless topological surface states. In addition, the temperature evolution of the energy bands clearly reveals their interplay with the magnetic phase transition by showing interesting differences for the bulk and surface states, respectively. The identification of the detailed electronic structures of MnBi2Te4 will not only help understand its exotic properties, but also pave the way for the design and realization of novel phenomena and applications.
DOI: 10.1016/j.jmst.2020.04.005
2020
Cited 219 times
Self-assembling anchored film basing on two tetrazole derivatives for application to protect copper in sulfuric acid environment
Two tetrazole compounds (BTA, BTTA) self-assembled on copper substrate and their inhibition effect toward copper corrosion in 0.5 M H2SO4 was evaluated through atomic force microscopy (AFM), scanning electron microscopy (SEM), weight loss measurement along with electrochemical techniques including electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. Results indicate that BTTA can provide superior inhibition performance to BTA, and the highest inhibition efficiency values of 96.3% (BTA) and 99.8% (BTTA) were achieved respectively at 2 mM. Both tetrazole inhibitor films follow Langmuir model concerning both physical and chemical adsorption, which can be verified by X-ray photoelectronic spectroscopy (XPS) analysis. Besides, the negative value of adsorption free energy infers a spontaneous adsorption process of these tetrazole compounds on Cu surface. Molecular dynamics (MD) simulation reveals stronger multiple anchor adsorption of BTTA molecules than BTA because of the existence of S atom.
DOI: 10.1111/j.1747-4949.2011.00584.x
2011
Cited 218 times
The China National Stroke Registry for Patients with Acute Cerebrovascular Events: Design, Rationale, and Baseline Patient Characteristics
Background As a leading cause of severe disability and death, stroke places an enormous burden on the health care system in China. There are limited data on the pattern of current medical practice and quality of care delivery for stroke patients at the national level. Aim The nation-wide prospective registry, China National Stroke Registry, will be considered with regard to its design, progress, geographic coverage, and hospital and patient characteristics. Methods Between September 2007 and August 2008, the China National Stroke Registry recruited consecutive patients with diagnoses of acute cerebrovascular events from 132 hospitals that cover all 27 provinces and four municipalities (including Hong Kong region) in China. Clinical data were collected prospectively using paper-based registry forms. Patients were followed for clinical and functional outcomes through phone interviews at three, six, 12, 18, and 24 months after disease onset. Results These patients ( n = 21 902) were 63·8 years of age on average, and 39% were females. Ischaemic stroke was predominant (66·4%), and the other subtypes were intracerebral haemorrhage (23·4%), subarachnoid haemorrhage (3·4%), and transient ischaemic attack (6·2%). Conclusions The China National Stroke Registry is a large-scale nationwide registry in China. Rich data collected from this prospective registry may provide the opportunity to evaluate the quality of care for stroke patients in China.
DOI: 10.1016/j.apcatb.2017.05.049
2017
Cited 217 times
Carbon dots enhance the stability of CdS for visible-light-driven overall water splitting
Cadmium sulfide (CdS) has long time been one of the most promising inorganic photocatalysts for hydrogen production driven by visible light. However, the photocorrosion of CdS is the most serious problem which constrains its development. Here, we report the design and fabrication of a carbon dots-cadmium sulfide (CDs-CdS) nanocomposite, showing significant photocatalytic water splitting properties with impressive stability without requirement for any sacrificial agents or cocatalysts. The highest hydrogen production rate was obtained for about 2.55 μmol h−1, with an oxygen evolution rate for about 0.52 μmol h−1, when the concentration of CDs in the sample is 0.03 gCDs/gcatalyst. Even the produced H2 and O2 are not equal to the stoichiometric ratio of 2:1 (H2:O2), the CDs-CdS nanocomposite shows greater stability (8-time repetitive catalytic experiments) than the CdS catalysts reported up to now (without sacrificial agents or cocatalysts). It is also inspiring that when we increased the concentration of CDs in the catalysts, the produced H2 and O2 were gradually adjusted to meet the stoichiometric ratio of 2:1 in spite of low hydrogen production rate (0.13 μmol h−1).
DOI: 10.1109/cvpr.2018.00761
2018
Cited 217 times
DoubleFusion: Real-Time Capture of Human Performances with Inner Body Shapes from a Single Depth Sensor
We propose DoubleFusion, a new real-time system that combines volumetric dynamic reconstruction with data-driven template fitting to simultaneously reconstruct detailed geometry, non-rigid motion and the inner human body shape from a single depth camera. One of the key contributions of this method is a double layer representation consisting of a complete parametric body shape inside, and a gradually fused outer surface layer. A pre-defined node graph on the body surface parameterizes the non-rigid deformations near the body, and a free-form dynamically changing graph parameterizes the outer surface layer far from the body, which allows more general reconstruction. We further propose a joint motion tracking method based on the double layer representation to enable robust and fast motion tracking performance. Moreover, the inner body shape is optimized online and forced to fit inside the outer surface layer. Overall, our method enables increasingly denoised, detailed and complete surface reconstructions, fast motion tracking performance and plausible inner body shape reconstruction in real-time. In particular, experiments show improved fast motion tracking and loop closure performance on more challenging scenarios.
DOI: 10.1016/s1473-3099(15)00177-2
2015
Cited 215 times
Emerging tick-borne infections in mainland China: an increasing public health threat
Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.
DOI: 10.1103/physrevlett.127.180502
2021
Cited 215 times
Phase-Programmable Gaussian Boson Sampling Using Stimulated Squeezed Light
We report phase-programmable Gaussian boson sampling (GBS) which produces up to 113 photon detection events out of a 144-mode photonic circuit. A new high-brightness and scalable quantum light source is developed, exploring the idea of stimulated emission of squeezed photons, which has simultaneously near-unity purity and efficiency. This GBS is programmable by tuning the phase of the input squeezed states. The obtained samples are efficiently validated by inferring from computationally friendly subsystems, which rules out hypotheses including distinguishable photons and thermal states. We show that our GBS experiment passes a nonclassicality test based on inequality constraints, and we reveal nontrivial genuine high-order correlations in the GBS samples, which are evidence of robustness against possible classical simulation schemes. This photonic quantum computer, Jiuzhang 2.0, yields a Hilbert space dimension up to ∼10^{43}, and a sampling rate ∼10^{24} faster than using brute-force simulation on classical supercomputers.
DOI: 10.1038/ncomms4044
2014
Cited 214 times
Hydrochromic molecular switches for water-jet rewritable paper
The days of rewritable paper are coming, printers of the future will use water-jet paper. Although several kinds of rewritable paper have been reported, practical usage of them is rare. Herein, a new rewritable paper for ink-free printing is proposed and demonstrated successfully by using water as the sole trigger to switch hydrochromic dyes on solid media. Water-jet prints with various colours are achieved with a commercial desktop printer based on these hydrochromic rewritable papers. The prints can be erased and rewritten dozens of times with no significant loss in colour quality. This rewritable paper is promising in that it can serve an eco-friendly information display to meet the increasing global needs for environmental protection.
DOI: 10.1111/pbi.12669
2017
Cited 214 times
Generation of targeted mutant rice using a <scp>CRISPR</scp>‐Cpf1 system
Summary CRISPR ‐Cpf1 is a newly identified CRISPR ‐Cas system, and Cpf1 was recently engineered as a molecular tool for targeted genome editing in mammalian cells. To test whether the engineered CRISPR ‐Cpf1 system could induce the production of rice mutants, we selected two genome targets in the Os PDS and Os BEL genes. Our results show that both targets could be efficiently mutated in transgenic rice plants using CRISPR ‐Cpf1. We found that pre‐cr RNA s with a full‐length direct repeat sequence exhibited considerably increased efficiencies compared with mature cr RNA s. In addition, the specificity and transmission of the mutation were investigated, and the behaviours of cr RNA ‐Cpf1‐induced plant targeted genome mutagenesis were assessed. Taken together, our results indicate that CRISPR ‐Cpf1 expression via stable transformation can efficiently generate specific and heritable targeted mutations in rice and thereby constitutes a novel and important approach to specific and precise plant genome editing.
DOI: 10.1039/c9ta08740k
2019
Cited 213 times
Low-temperature synthesis of small-sized high-entropy oxides for water oxidation
A novel low temperature strategy was developed for preparing high entropy oxide, which is conducive to solve the bottlenecks encountered by traditional methods and broaden their application areas.
DOI: 10.1002/adma.202005423
2020
Cited 213 times
Defect‐Rich Adhesive Molybdenum Disulfide/rGO Vertical Heterostructures with Enhanced Nanozyme Activity for Smart Bacterial Killing Application
Abstract Nanomaterials with intrinsic enzyme‐like activities, namely “nanozymes,” are showing increasing potential as a new type of broad‐spectrum antibiotics. However, their feasibility is still far from satisfactory, due to their low catalytic activity, poor bacterial capturing capacity, and complicated material design. Herein, a facile synthesis of a defect‐rich adhesive molybdenum disulfide (MoS 2 )/rGO vertical heterostructure (VHS) through a one‐step microwave‐assisted hydrothermal method is reported. This simple, convenient but effective method for rapid material synthesis enables extremely uniform and well‐dispersed MoS 2 /rGO VHS with abundant S and Mo vacancies and rough surface, for a performance approaching the requirements of practical application. It is demonstrated experimentally and theoretically that the as‐prepared MoS 2 /rGO VHS possesses defect and irradiation dual‐enhanced triple enzyme‐like activities (oxidase, peroxidase, and catalase) for promoting free‐radical generation, owing to much more active edge sites exposure. Meanwhile, the VHS‐achieved rough surface exhibits excellent capacity for bacterial capture, with elevated reactive oxygen species (ROS) destruction through local topological interactions. As a result, optimized efficacy against drug‐resistant Gram‐negative and Gram‐positive bacteria can be explored by such defect‐rich adhesive nanozymes, demonstrating a simple but powerful way to engineered nanozymes for alternative antibiotics.
DOI: 10.1021/acs.nanolett.6b05177
2017
Cited 212 times
Carbon Quantum Dots/TiO<sub><i>x</i></sub> Electron Transport Layer Boosts Efficiency of Planar Heterojunction Perovskite Solar Cells to 19%
In planar n-i-p heterojunction perovskite solar cells, the electron transport layer (ETL) plays important roles in charge extraction and determine the morphology of the perovskite film. Here, we report a solution-processed carbon quantum dots (CQDs)/TiO2 composite that has negligible absorption in the visible spectral range, a very attractive feature for perovskite solar cells. Using this novel CQDs/TiO2 ETL in conjunction with a planar n-i-p heterojunction, we achieved an unprecedented efficiency of ∼19% under standard illumination test conditions. It was found that a CQDs/TiO2 combination increases both the open circuit voltage and short-circuits current density as compared to using TiO2 alone. Various advanced spectroscopic characterizations including ultrafast spectroscopy, ultraviolet photoelectron spectroscopy, and electronic impedance spectroscopy elucidate that the CQDs increases the electronic coupling between the CH3NH3PbI3–xClx and TiO2 ETL interface as well as energy levers that contribute to electron extraction.
DOI: 10.1093/eurheartj/ehx261
2017
Cited 211 times
IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult
Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult.Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon β-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1β, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced β1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis.Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.
DOI: 10.1038/nature16936
2016
Cited 207 times
Structure- and function-based design of Plasmodium-selective proteasome inhibitors
The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome, resulting in toxicity that precludes their use as therapeutic agents. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, here we use a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We design inhibitors based on amino-acid preferences specific to the parasite proteasome, and find that they preferentially inhibit the β2-subunit. We determine the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy and single-particle analysis, to a resolution of 3.6 Å. These data reveal the unusually open P. falciparum β2 active site and provide valuable information about active-site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin family anti-malarials, we observe growth inhibition synergism with low doses of this β2-selective inhibitor in artemisinin-sensitive and -resistant parasites. Finally, we demonstrate that a parasite-selective inhibitor could be used to attenuate parasite growth in vivo without appreciable toxicity to the host. Thus, the Plasmodium proteasome is a chemically tractable target that could be exploited by next-generation anti-malarial agents.