Qing Liu

Post-transcriptional silencing of plant genes using anti-sense or co-suppression constructs usually results in only a modest proportion of silenced individuals. Recent work has demonstrated the potential for constructs encoding self-complementary 'hairpin' RNA (hpRNA) to efficiently silence genes. In this study we examine design rules for efficient gene silencing, in terms of both the proportion of independent transgenic plants showing silencing, and the degree of silencing. Using hpRNA constructs containing sense/anti-sense arms ranging from 98 to 853 nt gave efficient silencing in a wide range of plant species, and inclusion of an intron in these constructs had a consistently enhancing effect. Intron-containing constructs (ihpRNA) generally gave 90-100% of independent transgenic plants showing silencing. The degree of silencing with these constructs was much greater than that obtained using either co-suppression or anti-sense constructs. We have made a generic vector, pHANNIBAL, that allows a simple, single PCR product from a gene of interest to be easily converted into a highly effective ihpRNA silencing construct. We have also created a high-throughput vector, pHELLSGATE, that should facilitate the cloning of gene libraries or large numbers of defined genes, such as those in EST collections, using an in vitro recombinase system. This system may facilitate the large-scale determination and discovery of plant gene functions in the same way as RNAi is being used to examine gene function in Caenorhabditis elegans.

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.

We study the statistical properties of volatility---a measure of how much the market is likely to fluctuate. We estimate the volatility by the local average of the absolute price changes. We analyze (a) the S&P 500 stock index for the 13-year period Jan 1984 to Dec 1996 and (b) the market capitalizations of the largest 500 companies registered in the Trades and Quotes data base, documenting all trades for all the securities listed in the three major stock exchanges in the US for the 2-year period Jan 1994 to Dec 1995. For the S&P 500 index, the probability density function of the volatility can be fit with a log-normal form in the center. However, the asymptotic behavior is better described by a power-law distribution characterized by an exponent 1 + \mu \approx 4. For individual companies, we find a power law asymptotic behavior of the probability distribution of volatility with exponent 1 + \mu \approx 4, similar to the S&P 500 index. In addition, we find that the volatility distribution scales for a range of time intervals. Further, we study the correlation function of the volatility and find power law decay with long persistence for the S&P 500 index and the individual companies with a crossover at approximately 1.5 days. To quantify the power-law correlations, we apply power spectrum analysis and a recently-developed modified root-mean-square analysis, termed detrended fluctuation analysis (DFA). For the S&P 500 index, DFA estimates for the exponents characterizing the power law correlations are \alpha_1=0.66 for short time scales (within \approx 1.5 days) and \alpha_2=0.93 for longer time scales (up to a year). For individual companies, we find \alpha_1=0.60 and \alpha_2=0.74, respectively. The power spectrum gives consistent estimates of the two power-law exponents.

The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.

Spinal muscular atrophy (SMA) is an often fatal neuromuscular disease that has been directly linked to the protein product of the Survival of Motor Neurons (SMN) gene. The SMN protein is tightly associated with a novel protein, SIP1, and together they form a complex with several spliceosomal snRNP proteins. Here we show that the SMN-SIP1 complex is associated with spliceosomal snRNAs U1 and U5 in the cytoplasm of Xenopus oocytes. Antibodies directed against the SMN-SIP1 complex strongly interfere with the cytoplasmic assembly of the common (Sm) snRNP proteins with spliceosomal snRNAs and with the import of the snRNP complex into the nucleus. Thus, the SMN-SIP1 complex is directly involved in the biogenesis of spliceosomal snRNPs. Defects in spliceosomal snRNP biogenesis may, therefore, be the cause of SMA.

<h2>Abstract</h2> Spinal muscular atrophy (SMA), one of the most common fatal autosomal recessive diseases, is characterized by degeneration of motor neurons and muscular atrophy. The SMA disease gene, termed Survival of Motor Neurons (<i>SMN</i>), is deleted or mutated in over 98% of SMA patients. The function of the SMN protein is unknown. We found that SMN is tightly associated with a novel protein, SIP1, and together they form a specific complex with several spliceosomal snRNP proteins. SMN interacts directly with several of the snRNP Sm core proteins, including B, D1–3, and E. Interestingly, SIP1 has significant sequence similarity with Brr1, a yeast protein critical for snRNP biogenesis. These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA.

Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty-five of these patients with MHE were randomized to receive a synbiotic preparation (n = 20), fermentable fiber alone (n = 20), or placebo (n = 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non-urease-producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child-Turcotte-Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis. (HEPATOLOGY 2004;39:1441–1449.)

In this paper, we focus on tackling the problem of automatic accurate localization of detected objects in high-resolution remote sensing images. The two major problems for object localization in remote sensing images caused by the complex context information such images contain are achieving generalizability of the features used to describe objects and achieving accurate object locations. To address these challenges, we propose a new object localization framework, which can be divided into three processes: region proposal, classification, and accurate object localization process. First, a region proposal method is used to generate candidate regions with the aim of detecting all objects of interest within these images. Then, generic image features from a local image corresponding to each region proposal are extracted by a combination model of 2-D reduction convolutional neural networks (CNNs). Finally, to improve the location accuracy, we propose an unsupervised score-based bounding box regression (USB-BBR) algorithm, combined with a nonmaximum suppression algorithm to optimize the bounding boxes of regions that detected as objects. Experiments show that the dimension-reduction model performs better than the retrained and fine-tuned models and the detection precision of the combined CNN model is much higher than that of any single model. Also our proposed USB-BBR algorithm can more accurately locate objects within an image. Compared with traditional features extraction methods, such as elliptic Fourier transform-based histogram of oriented gradients and local binary pattern histogram Fourier, our proposed localization framework shows robustness when dealing with different complex backgrounds.

Water-soluble chitosan derivatives were prepared by graft copolymerization of maleic acid sodium onto hydroxypropyl chitosan and carboxymethyl chitosan sodium. Their scavenging activities against hydroxyl radical *OH were investigated by chemiluminescence technique. They exhibit IC(50) values ranging from 246 to 498 microg/mL, which should be attributed to their different contents of hydroxyl and amino groups and different substituting groups.

Nano-Sn/C composites are ideal anode materials for high energy and power density Li-ion batteries. However, because of the low melting point of Sn and the tendency of grain growth, especially during high temperature carbonization, it has been a significant challenge to create well-dispersed ultrasmall Sn nanoparticles within a carbon matrix. In this paper, we demonstrate an aerosol spray pyrolysis technique, as a facile and scalable method, to synthesize a nano-Sn/C composite with uniformly dispersed 10 nm nano-Sn within a spherical carbon matrix. The discharge capacity of nano-Sn/C composite sphere anodes maintains the initial capacity of 710 mAh/g after 130 cycles at 0.25 C. The nano-Sn/C composite sphere anodes can provide ∼600 mAh/g even at a high rate of 20 C. To the best of our knowledge, such high rate performance for Sn anodes has not been reported previously. The exceptional performance of the nano-Sn/C composite is attributed to the unique nano-Sn/C structure: (1) carbon matrix offers mechanical support to accommodate the stress associated with the large volume change of nano-Sn, thus alleviating pulverization; (2) the carbon matrix prevents Sn nanoparticle agglomeration upon prolonged cycling; and (3) carbon network provides continuous path for Li ions and electrons inside the nano-Sn/C composite spheres.

Tumor-associated macrophages (TAMs) are major components of tumor microenvironment that frequently associated with tumor metastasis in human cancers. Circulating tumor cell (CTC), originating from primary tumor sites, is considered to be the precursors of tumor metastasis. However, the regulatory mechanism of TAMs in CTC-mediated tumor metastasis still remains unclear. Immunohistochemical staining was used to detect the macrophages infiltration (CD68 and CD163), epithelial–mesenchymal transition (EMT) markers (E-cadherin and Vimentin) expression in serial sections of human colorectal cancer (CRC) specimens. Then, the correlations between macrophages infiltration and clinicopathologic features, mesenchymal CTC ratio, and patients’ prognosis were analyzed. A co-culture assay in vitro was used to evaluate the role of TAMs on CRC EMT, migration and invasion, and ELISA, luciferase reporter assay and CHIP were performed to uncover the underlying mechanism. Furthermore, an in vivo model was carried out to confirm the effect of TAMs on mesenchymal CTC-mediated metastasis. Clinically, CD163+ TAMs infiltrated in invasive front was associated with EMT, mesenchymal CTC ratio, and poor prognosis in patients with CRC. CRC–conditioned macrophages regulated EMT program to enhance CRC cells migration and invasion by secreting IL6. TAMs-derived IL6 activated the JAK2/STAT3 pathway, and activated STAT3 transcriptionally inhibited the tumor suppressor miR-506-3p in CRC cells. miR-506-3p, a key miRNA regulating FoxQ1, was downregulated in CRC cells, resulting in increased FoxQ1 expression, which in turn led to the production of CCL2 that promoted macrophage recruitment. Inhibition of CCL2 or IL6 broke this loop and reduced macrophage migration and mesenchymal CTC-mediated metastasis, respectively. Our data indicates that TAMs induce EMT program to enhance CRC migration, invasion, and CTC-mediated metastasis by regulating the JAK2/STAT3/miR-506-3p/FoxQ1 axis, which in turn leads to the production of CCL2 that promote macrophage recruitment, revealing a new cross-talk between immune cells and tumor cells in CRC microenvironment.

The use of perfectly matched layers (PML) has recently been introduced by Berenger as a material absorbing boundary condition (ABC) for electromagnetic waves. In this paper, we will first prove that a fictitious elastodynamic material half-space exists that will absorb an incident wave for all angles and all frequencies. Moreover, the wave is attenuative in the second half-space. As a consequence, layers of such material could be designed at the edge of a computer simulation region to absorb outgoing waves. Since this is a material ABC, only one set of computer codes is needed to simulate an open region. Hence, it is easy to parallelize such codes on multiprocessor computers. For instance, it is easy to program massively parallel computers on the SIMD (single instruction multiple data) mode for such codes. We will show two- and three-dimensional computer simulations of the PML for the linearized equations of elastodynamics. Comparison with Liao’s ABC will be given.

FLT3 receptor tyrosine kinase is expressed on lymphoid and myeloid progenitors in the hematopoietic system. Activating mutations in FLT3 have been identified in approximately 30% of patients with acute myelogenous leukemia, making it one of the most common mutations observed in this disease. Frequently, the mutation is an in-frame internal tandem duplication (ITD) in the juxtamembrane region that results in constitutive activation of FLT3, and confers interleukin-3 (IL-3)–independent growth to Ba/F3 and 32D cells. FLT3-ITD mutants were cloned from primary human leukemia samples and assayed for transformation of primary hematopoietic cells using a murine bone marrow transplantation assay. FLT3-ITDs induced an oligoclonal myeloproliferative disorder in mice, characterized by splenomegaly and leukocytosis. The myeloproliferative phenotype, which was associated with extramedullary hematopoiesis in the spleen and liver, was confirmed by histopathologic and flow cytometric analysis. The disease latency of 40 to 60 days with FLT3-ITDs contrasted with wild-type FLT3 and enhanced green fluorescent protein (EGFP) controls, which did not develop hematologic disease (&amp;gt; 200 days). These results demonstrate that FLT3-ITD mutant proteins are sufficient to induce a myeloproliferative disorder, but are insufficient to recapitulate the AML phenotype observed in humans. Additional mutations that impair hematopoietic differentiation may be required for the development of FLT3-ITD–associated acute myeloid leukemias. This model system should be useful to assess the contribution of additional cooperating mutations and to evaluate specific FLT3 inhibitors in vivo.

A pseudospectral time-domain (PSTD) method is developed for solutions of Maxwell's equations. It uses the fast Fourier transform (FFT), instead of finite differences on conventional finite-difference–time-domain (FDTD) methods, to represent spatial derivatives. Because the Fourier transform has an infinite order of accuracy, only two cells per wavelength are required, compared to 8–16 cells per wavelength required by the FDTD method for the same accuracy. The wraparound effect, a major limitation caused by the periodicity assumed in the FFT, is removed by using Berenger's perfectly matched layers. The PSTD method is a factor of 4D–8D more efficient than the FDTD methods (D is the dimensionality). © 1997 John Wiley & Sons, Inc. Microwave Opt Technol Lett 15: 158–165, 1997.

Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under both physiological and pathological conditions. Although there is anatomical separation, emerging evidence has indicated the existence of bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), and brain. The cross-talk between gut microbiota and brain may have crucial impact during basic neurogenerative processes, in neurodegenerative disorders and tumors of CNS. In this review, we discuss the biological interplay between gut-brain axis, and further explore how this communication may be dysregulated in neurological diseases. Further, we highlight new insights in modification of gut microbiota composition, which may emerge as a promising therapeutic approach to treat CNS disorders.

This review summarizes the recent progress in methanation catalysts for SNG production, which will provide insights for future catalysts design.

AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs.

Abstract The Modern-Era Retrospective Analysis for Research and Applications (MERRA) is a state-of-the-art reanalysis that provides, in addition to atmospheric fields, global estimates of soil moisture, latent heat flux, snow, and runoff for 1979–present. This study introduces a supplemental and improved set of land surface hydrological fields (“MERRA-Land”) generated by rerunning a revised version of the land component of the MERRA system. Specifically, the MERRA-Land estimates benefit from corrections to the precipitation forcing with the Global Precipitation Climatology Project pentad product (version 2.1) and from revised parameter values in the rainfall interception model, changes that effectively correct for known limitations in the MERRA surface meteorological forcings. The skill (defined as the correlation coefficient of the anomaly time series) in land surface hydrological fields from MERRA and MERRA-Land is assessed here against observations and compared to the skill of the state-of-the-art ECMWF Re-Analysis-Interim (ERA-I). MERRA-Land and ERA-I root zone soil moisture skills (against in situ observations at 85 U.S. stations) are comparable and significantly greater than that of MERRA. Throughout the Northern Hemisphere, MERRA and MERRA-Land agree reasonably well with in situ snow depth measurements (from 583 stations) and with snow water equivalent from an independent analysis. Runoff skill (against naturalized stream flow observations from 18 U.S. basins) of MERRA and MERRA-Land is typically higher than that of ERA-I. With a few exceptions, the MERRA-Land data appear more accurate than the original MERRA estimates and are thus recommended for those interested in using MERRA output for land surface hydrological studies.

Abstract The realization of manganese oxide anode materials for lithium‐ion batteries is hindered by inferior cycle stability, rate capability, and high overpotential induced by the agglomeration of manganese metal grains, low conductivity of manganese oxide, and the high stress/strain in the crystalline manganese oxide structure during the repeated lithiation/delithiation process. To overcome these challenges, unique amorphous MnO x –C nanocomposite particles with interdispersed carbon are synthesized using aerosol spray pyrolysis. The carbon filled in the pores of amorphous MnO x blocks the penetration of liquid electrolyte to the inside of MnO x , thus reducing the formation of a solid electrolyte interphase and lowering the irreversible capacity. The high electronic and lithium‐ion conductivity of carbon also enhances the rate capability. Moreover, the interdispersed carbon functions as a barrier structure to prevent manganese grain agglomeration. The amorphous structure of MnO x brings additional benefits by reducing the stress/strain of the conversion reaction, thus lowering lithiation/delithiation overpotential. As the result, the amorphous MnO x ‐C particles demonstrated the best performance as an anode material for lithium‐ion batteries to date.

Intelligent Tutoring Systems (ITS) are computer programs that model learners’ psychological states to provide individualized instruction. They have been developed for diverse subject areas (e.g., algebra, medicine, law, reading) to help learners acquire domain-specific, cognitive and metacognitive knowledge. A meta-analysis was conducted on research that compared the outcomes from students learning from ITS to those learning from non-ITS learning environments. The meta-analysis examined how effect sizes varied with type of ITS, type of comparison treatment received by learners, type of learning outcome, whether knowledge to be learned was procedural or declarative, and other factors. After a search of major bibliographic databases, 107 effect sizes involving 14,321 participants were extracted and analyzed. The use of ITS was associated with greater achievement in comparison with teacher-led, large-group instruction (g .42), non-ITS computer-based instruction (g .57), and textbooks or workbooks (g .35). There was no significant difference between learning from ITS and learning from individualized human tutoring (g –.11) or small-group instruction (g .05). Significant, positive mean effect sizes were found regardless of whether the ITS was used as the principal means of instruction, a supplement to teacher-led instruction, an integral component of teacher-led instruction, or an aid to homework. Significant, positive effect sizes were found at all levels of education, in almost all subject domains evaluated, and whether or not the ITS provided feedback or modeled student misconceptions. The claim that ITS are relatively effective tools for learning is consistent with our analysis of potential publication bias.

To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.Systematic review and network meta-analysis.Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.PROSPERO CRD42017082553.

The human gut microbiome is comprised of densely colonizing microorganisms including bacteriophages, which are in dynamic interaction with each other and the mammalian host. To address how bacteriophages impact bacterial communities in the gut, we investigated the dynamic effects of phages on a model microbiome. Gnotobiotic mice were colonized with defined human gut commensal bacteria and subjected to predation by cognate lytic phages. We found that phage predation not only directly impacts susceptible bacteria but also leads to cascading effects on other bacterial species via interbacterial interactions. Metabolomic profiling revealed that shifts in the microbiome caused by phage predation have a direct consequence on the gut metabolome. Our work provides insight into the ecological importance of phages as modulators of bacterial colonization, and it additionally suggests the potential impact of gut phages on the mammalian host with implications for their therapeutic use to precisely modulate the microbiome.

DNA hybridization can finely regulate the intrinsic glucose oxidase like catalytic activity of AuNPs owing to the marked difference in adsorption of single- and double-stranded DNA on its surface. A sensing strategy for DNA and microRNA is presented; in a different approach, this DNA-regulated AuNP catalysis was coupled with AuNP-mediated seed growth, which was monitored in real time and at a single-nanoparticle level. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by 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.

Acetylation and Autophagy Autophagy allows cells to digest their own components when necessary to survive stressful conditions. Lin et al. (p. 477) and Yi et al. (p. 474) describe signaling mechanisms in mammalian cells and yeast, respectively, by which autophagy is regulated by protein acetylation. In mammalian cells deprived of serum, the acetyltransferase TIP60 was activated by phosphorylation by the protein kinase GSK3 (glycogen synthase kinase 3). TIP60's target appeared to be a protein kinase central to autophagy regulation, ULK1. This activating pathway was required for autophagy in the absence of serum, but was not needed for autophagy in cells deprived of glucose. In the yeast Saccharomyces cerevisiae starved of nitrogen, another acetylation mechanism was uncovered. Starvation led to activation of the histone acetyltransferase Esa1, which acetylated the protein Atg3, a key component of the autophagy machinery, thus increasing its interaction with another autophagy protein, Atg8.

In this paper, a novel image encryption method based on skew tent chaotic map and permutation–diffusion architecture is proposed. In the proposed method, the P-box is chosen as the same size of plain-image, which shuffles the positions of pixels totally. The keystream generated by skew tent chaotic map is related to the plain-image. Statistical analysis, information entropy analysis, and sensitivity analysis to plaintext and key on the proposed scheme are provided in this paper. It can be seen that this algorithm is efficient and reliable, with high potential to be adopted for network security and secure communications.

Controlling and monitoring extreme downside market risk are important for financial risk management and portfolio/investment diversification. In this paper, we introduce a new concept of Granger causality in risk and propose a class of kernel-based tests to detect extreme downside risk spillover between financial markets, where risk is measured by the left tail of the distribution or equivalently by the Value at Risk (VaR). The proposed tests have a convenient asymptotic standard normal distribution under the null hypothesis of no Granger causality in risk. They check a large number of lags and thus can detect risk spillover that occurs with a time lag or that has weak spillover at each lag but carries over a very long distributional lag. Usually, tests using a large number of lags may have low power against alternatives of practical importance, due to the loss of a large number of degrees of freedom. Such power loss is fortunately alleviated for our tests because our kernel approach naturally discounts higher order lags, which is consistent with the stylized fact that today’s financial markets are often more influenced by the recent events than the remote past events. A simulation study shows that the proposed tests have reasonable size and power against a variety of empirically plausible alternatives in finite samples, including the spillover from the dynamics in mean, variance, skewness and kurtosis respectively. In particular, nonuniform weighting delivers better power than uniform weighting and a Granger-type regression procedure. The proposed tests are useful in investigating large comovements between financial markets such as financial contagions. An application to the Eurodollar and Japanese Yen highlights the merits of our approach.

A fluorescent sensor QB, based on quinoline with DPA as receptor, is designed as a ratiometric sensor for Zn(2+) and CHEF (chelation enhanced fluorescence) sensor for Cd(2+). Moreover, another ratiometric signal output for Cd(2+) can be observed when the bound Zn(2+) in the QB-Zn(2+) complex is displaced by Cd(2+). These results demonstrate that QB can act not only as a ratiometirc sensor for Zn(2+) but also as a dual-mode Cd(2+)-selective sensor via the CHEF mechanism and ratiometric displacement.

As one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace. This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.

In urban logistics, the last-mile delivery from the warehouse to the consumer’s home has become more and more challenging with the continuous growth of E-commerce. It requires elaborate planning and scheduling to minimize the global traveling cost, but often results in unattended delivery as most consumers are away from home. In this paper, we propose an effective large-scale mobile crowd-tasking model in which a large pool of citizen workers are used to perform the last-mile delivery. To efficiently solve the model, we formulate it as a network min-cost flow problem and propose various pruning techniques that can dramatically reduce the network size. Comprehensive experiments were conducted with Singapore and Beijing datasets. The results show that our solution can support real-time delivery optimization in the large-scale mobile crowd-sourcing problem.

Molecular chemistry offers a unique toolkit to draw inspiration for the design of artificial metamolecules. For a long time, optical circular dichroism has been exclusively the terrain of natural chiral molecules, which exhibit optical activity mainly in the UV spectral range, thus greatly hindering their significance for a broad range of applications. Here we demonstrate that circular dichroism can be generated with artificial plasmonic chiral nanostructures composed of the minimum number of spherical gold nanoparticles required for three-dimensional (3D) chirality. We utilize a rigid addressable DNA origami template to precisely organize four nominally identical gold nanoparticles into a three-dimensional asymmetric tetramer. Because of the chiral structural symmetry and the strong plasmonic resonant coupling between the gold nanoparticles, the 3D plasmonic assemblies undergo different interactions with left and right circularly polarized light, leading to pronounced circular dichroism. Our experimental results agree well with theoretical predictions. The simplicity of our structure geometry and, most importantly, the concept of resorting on biology to produce artificial photonic functionalities open a new pathway to designing smart artificial plasmonic nanostructures for large-scale production of optically active metamaterials.

Two-dimensional (2D), layered transition metal dichalcogenides (TMDCs) can grow in two different growth directions, that is, horizontal and vertical. In the horizontal growth, 2D TMDC layers grow in planar direction with their basal planes parallel to growth substrates. In the vertical growth, 2D TMDC layers grow standing upright on growth substrates exposing their edge sites rather than their basal planes. The two distinct morphologies present unique materials properties suitable for specific applications, such as horizontal TMDCs for optoelectronics and vertical TMDCs for electrochemical reactions. Precise control of the growth orientation is essential for realizing the true potential of these 2D materials for large-scale, practical applications. In this Letter, we investigate the transition of vertical-to-horizontal growth directions in 2D molybdenum (or tungsten) disulfide and study the underlying growth mechanisms and parameters that dictate such transition. We reveal that the thickness of metal seed layers plays a critical role in determining their growth directions. With thick (>∼ 3 nm) seed layers, the vertical growth is dominant, while the horizontal growth occurs with thinner seed layers. This finding enables the synthesis of novel 2D TMDC heterostructures with anisotropic layer orientations and transport properties. The present study paves a way for developing a new class of 2D TMDCs with unconventional materials properties.

A Hall-Petch slope (k) that is highly changeable with texture, as extensively reported in Mg alloys, is ultimately related to the variation of deformation modes. In this paper, the influence of different (0002) distributions on k for twinning and slip was systematically studied using an AZ31 rolled plate ([0002]//ND) and extruded rod ([0002]⊥ED together with a random distribution around the ED). The ND and ED refer to the normal direction of the plate and extrusion direction of the rod, respectively. A high dependency of k on the (0002) distribution is found, namely, a much lower k for {101¯2} twinning in the plate (219 MPa μm1/2) than that in the rod (435 MPa μm1/2), but a much higher k for slip in the plate (437 MPa μm1/2) than that in the rod (235 MPa μm1/2). Compound use of the difference in Schmid factor (ΔSF) and geometric compatibility factor (m′) quantitatively explains this orientation effect on k. ΔSF relates to the extra stress needed for the activation of slip/twinning in a neighboring grain, and m′ reflects the efficiency of the stress concentration at the onset of slip/twinning in an adjacent grain. The lower m′ for twinning in the rod versus the plate primarily accounts for the higher k for twinning in the rod. A much larger inclination of basal poles away from the ideal texture exists in the plate than in the rod, which induces a higher activity of basal slip during tension. The resultant high fraction of slip transfer from basal slip in one grain to prismatic slip in the neighboring grain largely amplifies ΔSF and reduces m′, both of which yield a higher k for slip in the plate than in the rod. The relationship between the crystallographic orientation and m′ was also calculated for different types of deformation transfer, and the main factor that determines m′ was revealed.

Abstract Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms 1–3 . Here we report the 409-megabase genome sequence of the blue-petal water lily ( Nymphaea colorata ). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata . The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.

An active absorption device is proposed based on vanadium dioxide metamaterials. By controlling the conductivity of vanadium dioxide, resonant absorbers are designed to work at wide range of terahertz frequencies. Numerical results show that a broadband terahertz absorber with nearly 100% absorptance can be achieved, and its normalized bandwidth of 90% absorptance is 60% under normal incidence for both transverse-electric and transverse-magnetic polarizations when the conductivity of vanadium dioxide is equal to 2000 Ω-1cm-1. Absorptance at peak frequencies can be continuously tuned from 30% to 100% by changing the conductivity from 10 Ω-1cm-1 to 2000 Ω-1cm-1. Absorptance spectra analysis shows a clear independence of polarization and incident angle. The presented results may have tunable spectral applications in sensor, detector, and thermophotovoltaic device working at terahertz frequency bands.

Currently, large-scale farmland degradation resulted from the overuse of chemical fertilizers has become a major issue in China. Meanwhile, a large sum of straw nutrient resources have been lost from the farmland due to the straw removal from fields, which in return aggravated the degradation in farmland quality and long-term productive capacity of soil resources. Whether current straw management practices represent rational utilization and how straw can be used more efficiently have become the most important but least studied problems for China's green agricultural development. Based on the China's Official Statistics, we first collected a large number of data on the annual crop yields, crop sown areas and chemical fertilizer consumption of different crop types in 31 China's mainland provinces from 1998 to 2014. Straw yields and straw nutrient resources were calculated to assess the potential contribution of straw resources to chemical fertilizers. Our estimation demonstrates that straw returning to farmlands could counterbalance all of the K2O, the majority of the P2O5, and a portion of the N in chemical fertilizers. Promoting the return of straw to field has a great potential to reduce the use of chemical fertilizer, air pollutant emission and environmental burden. Thus, we propose that the Chinese government should adjust the policies to take promoting straws returned to field as priority, instead of greatly encouraging straw removal from field. Innovative straw decomposing technologies and returning practices are also needed to assure China's green agricultural development and reduce environmental pollution in the future.

Enhanced anti-ferroelectric properties and high recoverable energy densities from 2.5–2.9 J cm⁻³ were achieved in 0.1 wt% Mn-doped AgNbO₃ ceramics over 20–180 °C.

Fabricating hierarchical core-shell nanostructures is currently the subject of intensive research in the electrochemical field owing to the hopes it raises for making efficient electrodes for high-performance supercapacitors. Here, we develop a simple and cost-effective approach to prepare CuO@MnO2 core-shell nanostructures without any surfactants and report their applications as electrodes for supercapacitors. An asymmetric supercapacitor with CuO@MnO2 core-shell nanostructure as the positive electrode and activated microwave exfoliated graphite oxide (MEGO) as the negative electrode yields an energy density of 22.1 Wh kg−1 and a maximum power density of 85.6 kW kg−1; the device shows a long-term cycling stability which retains 101.5% of its initial capacitance even after 10000 cycles. Such a facile strategy to fabricate the hierarchical CuO@MnO2 core-shell nanostructure with significantly improved functionalities opens up a novel avenue to design electrode materials on demand for high-performance supercapacitor applications.

RNA interference (RNAi)—using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein—is very useful in dissecting genetic function and holds significant promise as a molecular therapeutic. A major obstacle in achieving gene silencing with RNAi technology is the systemic delivery of therapeutic oligonucleotides. Here we demonstrate an engineered gold nanoshell (NS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly-l-lysine peptide (PLL) epilayer covalently attached to the NS surface (NS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotides, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. Controlled release of the captured therapeutic oligonucleotides in each case is accomplished by continuous wave NIR laser irradiation at 800 nm, near the resonance wavelength of the nanoshell. Fluorescently tagged oligonucleotides were used to monitor the time-dependent release process and light-triggered endosomal release. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and gene silencing mediated by the NS-PLL carrying GFP gene-specific single-stranded DNA antisense oligonucleotide (AON-GFP), or a double-stranded siRNA (siRNA-GFP), in vitro. Light-triggered delivery resulted in ∼47% and ∼49% downregulation of the targeted GFP expression by AON-GFP and siRNA-GFP, respectively. Cytotoxicity induced by both the NS-PLL delivery vector and by laser irradiation is minimal, as demonstrated by a XTT cell proliferation assay.

Imbalanced data is one type of datasets that are frequently found in real-world applications, e.g., fraud detection and cancer diagnosis. For this type of datasets, improving the accuracy to identify their minority class is a critically important issue. Feature selection is one method to address this issue. An effective feature selection method can choose a subset of features that favor in the accurate determination of the minority class. A decision tree is a classifier that can be built up by using different splitting criteria. Its advantage is the ease of detecting which feature is used as a splitting node. Thus, it is possible to use a decision tree splitting criterion as a feature selection method. In this paper, an embedded feature selection method using our proposed weighted Gini index (WGI) is proposed. Its comparison results with Chi2, F-statistic and Gini index feature selection methods show that F-statistic and Chi2 reach the best performance when only a few features are selected. As the number of selected features increases, our proposed method has the highest probability of achieving the best performance. The area under a receiver operating characteristic curve (ROC AUC) and F-measure are used as evaluation criteria. Experimental results with two datasets show that ROC AUC performance can be high, even if only a few features are selected and used, and only changes slightly as more and more features are selected. However, the performance of Fmeasure achieves excellent performance only if 20% or more of features are chosen. The results are helpful for practitioners to select a proper feature selection method when facing a practical problem.

Abstract Sodium‐ion batteries (SIBs) show promising application in large‐scale energy storage as future alternatives to lithium‐ion batteries. Carbonaceous materials are attractive anode candidates for SIBs due to low cost, abundance, and high safety. In general, doping heteroatoms such as N, B, O, S, and P in carbon‐based materials gives rise to high electronic mobility, good sodium mobility, and enhanced capacity, showing a great potential in sodium storage. This review summarizes the recent progress in the design, synthesis, and electrochemical properties of heteroatom‐doped carbon anodes, including one‐element doped carbons and several‐elements codoped carbons, aiming to help the readers comprehensively learn how to fabricate heteroatom‐doped carbons and use them in SIBs. Additionally, the advantages, mechanism, critical issues, and possible solutions of heteroatom‐doped carbons are discussed and the future research trends are proposed. This will provide a deep insight into the development of SIBs anode materials.

Background The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. Methods Patients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. Results Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001). Conclusion NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.

This paper contributes to the literature by identifying the causal effect of firm investment on exporting behavior. The identification hinges on regional variations in the 2004 value-added tax pilot reform in China, which generated positive investment shocks. The instrumental variable estimation results show that firm investment significantly and substantially increases the likelihood of exporting, and this effect is largely due to the positive effect of firm investment on firm productivity. Finally, the paper documents some heterogeneity of the effect across industries with different degrees of competition and financial constraints.

The efficient delivery of a therapeutic gene into target tissues has remained a major obstacle in realizing a viable gene-based medicine. Herein, we introduce a facile and universal strategy to construct a DNA nanostructure-based codelivery system containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (doxorubicin, DOX) for combined therapy of multidrug resistant tumor (MCF-7R). This novel codelivery system, which is structurally similar to a kite, is rationally designed to contain multiple functional groups for the targeted delivery and controlled release of the therapeutic cargoes. The self-assembled DNA nanokite achieves efficient gene delivery and exhibits effective inhibition of tumor growth in vitro and in vivo without apparent systemic toxicity. These structurally and chemically well-defined codelivery nanovectors provide a new platform for the development of gene therapeutics for not only cancer but also a wide range of diseases.

N 6-methyladenosine (m6A), the most abundant internal modification on mRNAs in eukaryotes, play roles in adipogenesis. However, the underlying mechanism remains largely unclear. Here, we show that m6A plays a critical role in regulating macroautophagy/autophagy and adipogenesis through targeting Atg5 and Atg7. Mechanistically, knockdown of FTO, a well-known m6A demethylase, decreased the expression of ATG5 and ATG7, leading to attenuation of autophagosome formation, thereby inhibiting autophagy and adipogenesis. We proved that FTO directly targeted Atg5 and Atg7 transcripts and mediated their expression in an m6A-dependent manner. Further study identified that Atg5 and Atg7 were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis. Furthermore, we generated an adipose-selective fto knockout mouse and find that FTO deficiency decreased white fat mass and impairs ATG5- and ATG7-dependent autophagy in vivo. Together, these findings unveil the functional importance of the m6A methylation machinery in autophagy and adipogenesis regulation, which expands our understanding of such interplay that is essential for development of therapeutic strategies in the prevention and treatment of obesity.Abbreviations 3-MA: 3-methyladenine; ACTB: actin, beta; ATG: autophagy-related; Baf A1: bafilomycin A1; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; CEBPB: CCAAT/enhancer binding protein (C/EBP), beta; FABP4: fatty acid binding protein 4, adipocyte; FTO: fat mass and obesity associated; HFD: high-fat diet; LC-MS/MS: liquid chromatography-tandem mass spectrometry; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; m6A: N6-methyladenosine; MEFs: mouse embryo fibroblasts; MeRIP-qPCR: methylated RNA immunoprecipitation-qPCR; PPARG: peroxisome proliferator activated receptor gamma; RIP: RNA-immunoprecipitation; SAT: subcutaneous adipose tissue; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; ULK1: unc-51 like kinase 1; VAT: visceral adipose tissue; WAT: white adipose tissue; YTHDF: YTH N6-methyladenosine RNA binding protein

Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN-PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b+/CD163+ TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN-PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN-PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential.

Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE's utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations.

The tensile and compressive properties of AZ31 plates were dramatically enhanced by pre-rolling with small thickness reduction along the transverse direction. The yield asymmetry was also greatly improved. This is attributed to the subdivision of grains by introducing extension twin boundaries. Moreover, the introduction of twin boundaries had less impact on the slope of the stage III strain hardening curve, while it slightly prolonged the stage III curve in compression. The deformation mechanism of the materials containing twin lamellae was also discussed.

Tea is widely consumed all over the world. Generally, tea is divided into six categories: White, green, yellow, oolong, black, and dark teas, based on the fermentation degree. Tea contains abundant phytochemicals, such as polyphenols, pigments, polysaccharides, alkaloids, free amino acids, and saponins. However, the bioavailability of tea phytochemicals is relatively low. Thus, some novel technologies like nanotechnology have been developed to improve the bioavailability of tea bioactive components and consequently enhance the bioactivity. So far, many studies have demonstrated that tea shows various health functions, such as antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, anti-obesity, and hepato-protective effects. Moreover, it is also considered that drinking tea is safe to humans, since reports about the severe adverse effects of tea consumption are rare. In order to provide a better understanding of tea and its health potential, this review summarizes and discusses recent literature on the bioactive components, bioavailability, health functions, and safety issues of tea, with special attention paid to the related molecular mechanisms of tea health functions.

The gut microbiota can significantly affect the function of the intestinal barrier. Some intestinal probiotics (such as Lactobacillus, Bifidobacteria, a few Escherichia coli strains, and a new generation of probiotics including Bacteroides thetaiotaomicron and Akkermansia muciniphila) can maintain intestinal epithelial homeostasis and promote health. This review first summarizes probiotics' regulation of the intestinal epithelium via their surface compounds. Surface layer proteins, flagella, pili and capsular polysaccharides constitute microbial-associated molecular patterns and specifically bind to pattern recognition receptors, which can regulate signaling pathways to produce cytokines or inhibit apoptosis, thereby attenuating inflammation and enhancing the function of the gut epithelium. The review also explains the effects of metabolites (such as secreted proteins, organic acids, indole, extracellular vesicles and bacteriocins) of probiotics on host receptors and the mechanisms by which these metabolites regulate gut epithelial barrier function. Previous reviews summarized the role of the surface macromolecules or metabolites of gut microbes (including both probiotics and pathogens) in human health. However, these reviews were mostly focused on the interactions between these substances and the intestinal mucosal immune system. In the current review, we only focused on probiotics and discussed the molecular interaction between these bacteria and the gut epithelial barrier.

Abstract The purpose of this study was to compare the performance of logistic regression, artificial neural networks (ANNs) and decision tree models for predicting diabetes or prediabetes using common risk factors. Participants came from two communities in Guangzhou, China; 735 patients confirmed to have diabetes or prediabetes and 752 normal controls were recruited. A standard questionnaire was administered to obtain information on demographic characteristics, family diabetes history, anthropometric measurements and lifestyle risk factors. Then we developed three predictive models using 12 input variables and one output variable from the questionnaire information; we evaluated the three models in terms of their accuracy, sensitivity and specificity. The logistic regression model achieved a classification accuracy of 76.13% with a sensitivity of 79.59% and a specificity of 72.74%. The ANN model reached a classification accuracy of 73.23% with a sensitivity of 82.18% and a specificity of 64.49%; and the decision tree (C5.0) achieved a classification accuracy of 77.87% with a sensitivity of 80.68% and specificity of 75.13%. The decision tree model (C5.0) had the best classification accuracy, followed by the logistic regression model, and the ANN gave the lowest accuracy.

The structural and compositional evolution of precipitates in Al-Mg-Si-Cu alloys were systematically investigated by atomic resolution high-angle annular dark-field scanning transmission electron microscopy and atom probe tomography. In under-aged alloys, most of precipitates have a disordered structure, with a substructure of β″ (LDC) and Cu sub-unit cluster or C unit cell. After aging to peak strength, disordered precipitates including β″, QP1 and QP2 phases are formed. The disordered QP1 and QP2 phases, which contain the unit cells of Q′ and C phases, respectively, are the precursor phases of Q′ phase in these alloys. The β″ phase can transform into the disordered QP1 phase by incorporating Cu atoms, forming Cu sub-unit clusters and QP lattice. When the alloy is over-aged, the ordering and transformation of QP1 to Q′ occurs by the formation of Cu sub-unit clusters, the ordering of QP lattice, and the ordering of QC lattice. In contrast, the transformation of the disordered QP2 phase are rather sluggish. After sufficient aging, Q′, C and disordered QP2 transform into the Q phase. During the evolution of the precipitates in these alloys, a continuous incorporation of Mg, Si and Cu atoms and release of Al atoms occur. These findings provide new insights in understanding precipitation in Al-Mg-Si-Cu alloys.

We demonstrate a highly sensitive label-free Mach–Zehnder interferometer (MZI) biosensor based on silicon nitride slot waveguide. Unlike the conventional MZI sensors, the sensing arm of the sensor consists of a slot waveguide while the reference arm consists of a strip waveguide. Thanks to the slot waveguide's property to provide high optical intensity in a subwavelength-size low refractive index region (slot region), which allows high light–analyte interaction, higher sensitivity can be obtained as compared to conventional waveguides using the slot waveguide as sensing region. The bulk refractive index sensitivity of the slot waveguide MZI sensor was found to be 1864π/RIU (refractive index unit) with 7 mm long slot waveguide sensing arm, which shows higher sensitivity compared to the conventional MZI device based on silicon nitride. The biosensing capability of the developed slot waveguide MZI was investigated using biotin–streptavidin binding as a model system. The sensitivity of the system was demonstrated down to 18.9 fM or 1 pg/ml of streptavidin solution and to the best of our knowledge, it is the best reported experimental value for the limit of detection of a MZI sensor. Furthermore, we investigated the specific detection and quantification of the methylation of DAPK (Death-associated protein kinase) gene, which is a widely used biomarker for human cancers. We have shown that methylation sequences of DAPK gene of various methylation densities (100%, 50%, and 0% of methylation sites) can be quantified and discriminated even at a concentration as low as 1 fmol/μl or 1 nM.

Enhancement and manipulation of light absorption in graphene is a significant issue for applications of graphene-based optoelectronic devices. In order to achieve this purpose in the visible region, we demonstrate a design of a graphene optical absorber inspired by metal-dielectric-metal metamaterial for perfect absorption of electromagnetic waves. The optical absorbance ratios of single and three atomic layer graphene are enhanced up to 37.5% and 64.8%, respectively. The graphene absorber shows polarization-dependence and tolerates a wide range of incident angles. Furthermore, the peak position and bandwidth of graphene absorption spectra are tunable in a wide wavelength range through a specific structural configuration. These results imply that graphene in combination with plasmonic perfect absorbers have a promising potential for developing advanced nanophotonic devices.

Microplastics (MPs) have become a major global issue; their release from various products affects the aquatic environment, especially marine ecosystems. As a primary source of MPs, personal care and cosmetics products (PCCPs) containing MPs contribute to this environmental risk. We visited several supermarket chains in Beijing, China to identify PCCPs containing MPs. Overall, 7.1% of facial cleansers contained MPs, with an average weight of 25.04 ± 10.69 mg MP/g and average size of 313 ± 130 μm; whereas, 2.2% of shower gel products contained an average weight of 17.80 ± 7.50 mg MPs/g with an average size of 422 ± 185 μm. The majority of MPs were made of polyethylene, based on Raman and Fourier transform-infrared spectra analyses, while only a few were made of walnut shells and carbon particles. Finally, estimated 39 tons MPs were released into the environment based on PCCPs use in China based on available data.

Prevention of postsurgery infection and promotion of biointegration are the key factors to achieve long-term success in orthopedic implants. Localized delivery of antibiotics and bioactive molecules by the implant surface serves as a promising approach toward these goals. However, previously reported methods for surface functionalization of the titanium alloy implants to load bioactive ingredients suffer from time-consuming complex processes and lack of long-term stability. Here, we present the design and characterization of an adhesive, osteoconductive, and antimicrobial hydrogel coating for Ti implants. To form this multifunctional hydrogel, a photo-cross-linkable gelatin-based hydrogel was modified with catechol motifs to enhance adhesion to Ti surfaces and thus promote coating stability. To induce antimicrobial and osteoconductive properties, a short cationic antimicrobial peptide (AMP) and synthetic silicate nanoparticles (SNs) were introduced into the hydrogel formulation. The controlled release of AMP loaded in the hydrogel demonstrated excellent antimicrobial activity to prevent biofilm formation. Moreover, the addition of SNs to the hydrogel formulation enhanced osteogenesis when cultured with human mesenchymal stem cells, suggesting the potential to promote new bone formation in the surrounding tissues. Considering the unique features of our implant hydrogel coating, including high adhesion, antimicrobial capability, and the ability to induce osteogenesis, it is believed that our design provides a useful alternative method for bone implant surface modification and functionalization.

We demonstrate that a broadband terahertz absorber with near-unity absorption can be realized using a net-shaped periodically sinusoidally-patterned graphene sheet, placed on a dielectric spacer supported on a metallic reflecting plate. Because of the gradient width modulation of the unit graphene sheet, continuous plasmon resonances can be excited, and therefore broadband terahertz absorption can be achieved. The results show that the absorber's normalized bandwidth of 90% terahertz absorbance is over 65% under normal incidence for both TE and TM polarizations when the graphene chemical potential is set as 0.7 eV. And the broadband absorption is insensitive to the incident angles and the polarizations. The peak absorbance remains more than 70% over a wide range of the incident angles up to 60° for both polarizations. Furthermore, this absorber also has the advantage of flexible tunability via electrostatic doping of graphene sheet, which peak absorbance can be continuously tuned from 14% to 100% by controlling the chemical potential from 0 eV to 0.8 eV. The design scheme is scalable to develop various graphene-based tunable broadband absorbers at other terahertz, infrared, and visible frequencies, which may have promising applications in sensing, detecting, and optoelectronic devices.

Abstract The Soil Moisture Active Passive (SMAP) mission Level-4 Surface and Root-Zone Soil Moisture (L4_SM) data product is generated by assimilating SMAP L-band brightness temperature observations into the NASA Catchment land surface model. The L4_SM product is available from 31 March 2015 to present (within 3 days from real time) and provides 3-hourly, global, 9-km resolution estimates of surface (0–5 cm) and root-zone (0–100 cm) soil moisture and land surface conditions. This study presents an overview of the L4_SM algorithm, validation approach, and product assessment versus in situ measurements. Core validation sites provide spatially averaged surface (root zone) soil moisture measurements for 43 (17) “reference pixels” at 9- and 36-km gridcell scales located in 17 (7) distinct watersheds. Sparse networks provide point-scale measurements of surface (root zone) soil moisture at 406 (311) locations. Core validation site results indicate that the L4_SM product meets its soil moisture accuracy requirement, specified as an unbiased RMSE (ubRMSE, or standard deviation of the error) of 0.04 m3 m−3 or better. The ubRMSE for L4_SM surface (root zone) soil moisture is 0.038 m3 m−3 (0.030 m3 m−3) at the 9-km scale and 0.035 m3 m−3 (0.026 m3 m−3) at the 36-km scale. The L4_SM estimates improve (significantly at the 5% level for surface soil moisture) over model-only estimates, which do not benefit from the assimilation of SMAP brightness temperature observations and have a 9-km surface (root zone) ubRMSE of 0.042 m3 m−3 (0.032 m3 m−3). Time series correlations exhibit similar relative performance. The sparse network results corroborate these findings over a greater variety of climate and land cover conditions.

Abstract Metasurfaces enable the design of optical elements by engineering the wavefront of light at the subwavelength scale. Due to their ultrathin and compact characteristics, metasurfaces possess great potential to integrate multiple functions in optoelectronic systems for optical device miniaturisation. However, current research based on multiplexing in the 2D plane has not fully utilised the capabilities of metasurfaces for multi-tasking applications. Here, we demonstrate a 3D-integrated metasurface device by stacking a hologram metasurface on a monolithic Fabry–Pérot cavity-based colour filter microarray to simultaneously achieve low-crosstalk, polarisation-independent, high-efficiency, full-colour holography, and microprint. The dual functions of the device outline a novel scheme for data recording, security encryption, colour displays, and information processing. Our 3D integration concept can be extended to achieve multi-tasking flat optical systems by including a variety of functional metasurface layers, such as polarizers, metalenses, and others.

Introducing local structural heterogeneity can be a feasible way to achieve a high and thermally stable piezoelectric response in lead-free piezoelectrics.

<h2>Summary</h2> Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health. How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear. Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage. Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host. We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload. This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.

SUMMARY Applications running on leadership platforms are more and more bottlenecked by storage input/output (I/O). In an effort to combat the increasing disparity between I/O throughput and compute capability, we created Adaptable IO System (ADIOS) in 2005. Focusing on putting users first with a service oriented architecture, we combined cutting edge research into new I/O techniques with a design effort to create near optimal I/O methods. As a result, ADIOS provides the highest level of synchronous I/O performance for a number of mission critical applications at various Department of Energy Leadership Computing Facilities. Meanwhile ADIOS is leading the push for next generation techniques including staging and data processing pipelines. In this paper, we describe the startling observations we have made in the last half decade of I/O research and development, and elaborate the lessons we have learned along this journey. We also detail some of the challenges that remain as we look toward the coming Exascale era. Copyright © 2013 John Wiley &amp; Sons, Ltd.

Emerging evidence has suggested a potential impact of gut microbiota on the pathophysiology of heart failure (HF). However, it is still unknown whether HF is associated with dysbiosis in gut microbiota. We investigated the composition of gut microbiota in patients with HF to elucidate whether gut microbial dysbiosis is associated with HF. We performed 16S ribosomal RNA gene sequencing of fecal samples obtained from 12 HF patients and 12 age-matched healthy control (HC) subjects, and analyzed the differences in gut microbiota. We further compared the composition of gut microbiota of 12 HF patients younger than 60 years of age with that of 10 HF patients 60 years of age or older. The composition of gut microbial communities of HF patients was distinct from that of HC subjects in both unweighted and weighted UniFrac analyses. Eubacterium rectale and Dorea longicatena were less abundant in the gut microbiota of HF patients than in that of HC subjects. Compared to younger HF patients, older HF patients had diminished proportions of Bacteroidetes and larger quantities of Proteobacteria. The genus Faecalibacterium was depleted, while Lactobacillus was enriched in the gut microbiota of older HF patients. These results suggest that patients with HF harbor significantly altered gut microbiota, which varies further according to age. New concept of heart-gut axis has a great potential for breakthroughs in the development of novel diagnostic and therapeutic approach for HF.

Abstract The N6-methyladenosine (m6A) modification influences various mRNA metabolic events and tumorigenesis, however, its functions in nonsense-mediated mRNA decay (NMD) and whether NMD detects induced carcinogenesis pathways remain undefined. Here, we showed that the m6A methyltransferase METTL3 sustained its oncogenic role by modulating NMD of splicing factors and alternative splicing isoform switches in glioblastoma (GBM). Methylated RNA immunoprecipitation-seq (MeRIP-seq) analyses showed that m6A modification peaks were enriched at metabolic pathway–related transcripts in glioma stem cells (GSC) compared with neural progenitor cells. In addition, the clinical aggressiveness of malignant gliomas was associated with elevated expression of METTL3. Furthermore, silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of GSCs. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of serine- and arginine-rich splicing factors (SRSF), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. Reduced expression of SRSFs led to larger changes in alternative splicing isoform switches. Importantly, the phenotypes mediated by METTL3 deficiency could be rescued by downregulating BCL-X or NCOR2 isoforms. Overall, these results establish a novel function of m6A in modulating NMD and uncover the mechanism by which METTL3 promotes GBM tumor growth and progression. Significance: These findings establish the oncogenic role of m6A writer METTL3 in glioblastoma stem cells.

We report a simple and rapid method for fabricating a surface-enhanced Raman scattering (SERS) substrate, which offers good flexibility, excellent optical transparency, and high SERS activity. Specifically, the SERS substrate (AuNPs/PMMA film) was obtained through self-assembly of gold nanoparticles (AuNPs) on newborn poly(methyl methacrylate) (PMMA) template. The UV-vis spectroscopy analysis and scanning electron microscopy observation revealed that the gold nanoparticles were closely assembled on the flexible and transparent PMMA template. The fabricated AuNPs/PMMA film SERS substrate allowed detection of model molecule, malachite green isothiocyanate, at a concentration as low as 0.1 nM, and exhibited good reproducibility in the SERS measurement. The Raman enhancement factor (EF) of the AuNPs/PMMA film was found to be as high as (2.4 ± 0.3) × 10(7). In addition, measure of residual malachite green on fish surface was carried out, and the result indicated that the AuNPs/PMMA film had great potential in the in situ ultrasensitive detection of analyte on irregular objects.

Summary Plant laccase ( LAC ) enzymes belong to the blue copper oxidase family and polymerize monolignols into lignin. Recent studies have established the involvement of micro RNA s in this process; however, physiological functions and regulation of plant laccases remain poorly understood. Here, we show that a laccase gene, LAC 4 , regulated by a micro RNA , miR397b, controls both lignin biosynthesis and seed yield in Arabidopsis. In transgenic plants, overexpression of miR397b ( OX miR397b) reduced lignin deposition. The secondary wall thickness of vessels and the fibres was reduced in the OX miR397b line, and both syringyl and guaiacyl subunits are decreased, leading to weakening of vascular tissues. In contrast, overexpression of miR397b‐resistant laccase m RNA results in an opposite phenotype. Plants overexpressing miR397b develop more than two inflorescence shoots and have an increased silique number and silique length, resulting in higher seed numbers. In addition, enlarged seeds and more seeds are formed in these miR397b overexpression plants. The study suggests that miR397‐mediated development via regulating laccase genes might be a common mechanism in flowering plants and that the modulation of laccase by miR397 may be potential for engineering plant biomass production with less lignin.

Nitrogen-doped carbon quantum dots (N-CQDs) prepared <italic>via</italic> a one-step hydrothermal reaction exhibited highly selective and sensitive detection of Hg²⁺ and I⁻ through fluorescence quenching and recovery processes, respectively.

A novel and ultrasensitive label-free electrochemical immunosensor was fabricated for quantitative detection of carcino-embryonic antigen (CEA). The nitrogen-doped graphene quantum dots (N-GQDs) supported PtPd bimetallic nanoparticles (PtPd/N-GQDs) were synthesized by a simple and green hydrothermal procedure. Subsequently, PtPd/N-GQDs functionalized Au nanoparticles (PtPd/[email protected]) were prepared successfully via a self-assembly approach. Because of the synergetic effect present in PtPd/[email protected], this novel nanocomposites has shown excellent electrocatalytic activity towards hydrogen peroxide (H2O2) reduction. Featuring good biocompatibility, excellent conductivity and large surface area, PtPd/[email protected] was applied as transducing materials to efficiently conjugate capture antibodies and amplify electrochemical signal. Under the optimal conditions, the proposed immunosensor was used for the detection of CEA with wide dynamic range in the range from 5 fg/mL to 50 ng/mL with a low detection limit of 2 fg/mL (S/N=3). Furthermore, this label-free immunosensor possesses high sensitivity, special selectivity and long-term stability, which shows promising application in bioassay analysis.

Transition metal dichalcogenides (TMDCs) are a promising class of two-dimensional (2D) materials for use in applications such as 2D electronics, optoelectronics, and catalysis. Due to the van der Waals (vdW) bonding between layers, vdW heterostructures can be constructed between two different species of TMDCs. Most studies employ exfoliation or co-vapor growth schemes, which are limited by the small size and uneven distribution of heterostructures on the growth substrate. In this work we demonstrate a one-step synthesis procedure for large-area vdW heterostructures between horizontal TMDCs MoS2 and WS2. The synthesis procedure is scalable and provides patterning ability, which is critical for electronic applications in integrated circuits. We demonstrate rectification characteristics of large-area MoS2/WS2 stacks. In addition, hydrogen evolution reaction performance was measured in these horizontal MoS2 and WS2 thin films, which indicate that, in addition to the catalytically active sulfur edge sites, defect sites may serve as catalyst sites.

The immuno-inflammatory activation triggered by various stresses play an important role in pathophysiology of depression. The immune responses display differential pathological characters in different stresses. However, comparative data and analysis on behavioural, inflammatory and neurochemical changes in different stress-induced depression is limited. To imitate different stressful situations, in this study, mice were subjected to a single injection of LPS (0.5 mg/kg, i.p.) and UCMS (4 week period), respectively. LPS-stressed mice showed more immobility time in FST and TST, as well as more time in periphery in OFT than UCMS-stressed mice. Further, LPS-stressed mice showed robuster expression and release of TNF-α, IL-1β and IL-6 in serum and depression-related brain areas (prefrontal cortex, hippocampus and striatum) as compared to UCMS-stressed mice. The ELISA results showed that IDO expression was significantly increased following LPS and UCMS stresses, but more increased IDO expression was observed in prefrontal cortex and hippocampus of LPS-stressed mice. The decrease of 5-HT and BDNF was detected only in hippocampus of LPS-stressed mice, but in overall all the brain areas assessed in UCMS-stressed mice as compared to control. The data indicate that LPS induced more severe depressive-like behaviours and robuster immune activation than UCMS. Our study strongly imply that hippocampus is relatively more vulnerable to acute inflammatory challenge in depression, while chronic psychological stress is more likely to cause the multidimensional symptoms of clinical depression. Our findings provide more insight into pathophysiology in various stress-induced depression and also implicate a potential suitability of different stress models.

Transformations involving Pd(I) and Pd(III) have received growing attention over the past few years, providing various methodologies for the construction of numerous carbocyclic and heterocyclic ring systems. Compared with Pd(0)/(II)/(IV) chemistry, Pd(I)/(III)-mediated reactions are generally conducted through a single electron transfer process, leading to so-called palladium radical involved reactions. This review gives an up-to-date overview of catalytic methodologies involving palladium radical intermediates, which are sorted into two categories: (i) Pd(I) involved reactions and (ii) Pd(III) involved reactions. For most of these transformations, plausible mechanisms are demonstrated in detail. Clarification of these issues is the key point for understanding the palladium radical involved reactions and developing new high-performance methodologies.

Porous hard carbons are synthesized via carbonizing lotus stems with naturally hierarchical structures. The hard carbon carbonized at 1400 °C (LS1400) delivers a total capacity 350 mAh g−1 in the current density of 100 mA g−1 and a plateau capacity of 250 mAh g−1. Even cycled at 100 mA g−1 after 450 cycles, the capacity still retains 94%. Further investigation shows that the sodium storage of LS carbons involves Na+ adsorption in the defect sites, Na+ insertion and Na metal deposition in the closed pores. However, the Na metal deposition in closed pores mainly contribute to the plateau capacity, leading to the excellent sodium storage performance of LS1400 with a large closed pore ratio of 66%. The results show that the intrinsic structure of natural biomass can inspire us to design hard carbon with large closed pore ratio as excellent anode for sodium ion batteries.

Glioma is one of the most common malignant tumor of the central nervous system and is characterized by extensive infiltrative growth, neovascularization, and resistance to various combined therapies. In addition to heterogenous population of tumor cells, the glioma stem cells (GSCs) and other nontumor cells present in the glioma microenvironment serve as critical regulators of tumor progression and recurrence. In this review, we discuss the role of several resident or peripheral factors with distinct tumor-promoting features and their dynamic interactions in the development of glioma. Localized antitumor factors could be silenced or even converted to suppressive phenotypes, due to stemness-related cell reprograming and immunosuppressive mediators in glioma-derived microenvironment. Therefore, we also summarize the latest knowledge on GSCs and key microenvironment components, and discuss the emerging immunotherapeutic strategies to cure this disease.

Diets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency (Tlr5KO).Mice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters.Inulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis.These results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD.

Abstract Hydrogel‐based wearable electronic devices have received increasing attention. However, the construction of underwater strain sensors remains a significant challenge because of the swelling of hydrogels in an aquatic environment. This work presents the fabrication of an anti‐swellable hydrogel composed of polyvinyl alcohol (PVA), a copolymer of [2‐(methacryloyloxy) ethyl]dimethyl‐(3‐sulfopropyl) ammonium hydroxide (SBMA) and 2‐hydroxyethyl methacrylate. Interestingly, facile switch of the SBMA moiety from neutral to positively charged status at a low pH value leads to reduced osmotic pressure of the hydrogel for electrostatic repulsion‐driven elimination of water molecules and anti‐swelling. The resulting anti‐swellable hydrogel exhibits high toughness (518 kJ m −3 ) and compressive modulus (8.12 Mpa), ionic conductivity (up to 4.58 S m −1 ), and anti‐swelling behavior (equilibrium swelling ratio of 9% in water for 30 days). An underwater strain sensor based on this anti‐swellable hydrogel is further developed to monitor the movements of underwater sports. High sensitivity is achieved to identify multidirectional motions, including raising the head, swinging the arm, bending the elbow, knee and finger. Therefore, this study offers a facile strategy to generate hydrogel‐based sensors that can be adopted in an underwater environment as well as expands the potential applications of wearable electronic devices.

Tea is among the most consumed drink worldwide, and its strong antioxidant activity is considered as the main contributor to several health benefits, such as cardiovascular protection and anticancer effect. In this study, the antioxidant activities of 30 tea infusions, which were obtained by the mimic of drinking tea of the public, from green, black, oolong, white, yellow and dark teas, were evaluated using ferric-reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays, ranging from 504.80 ± 17.44 to 4647.47 ± 57.87 µmol Fe2+/g dry weight (DW) and 166.29 ± 24.48 to 2532.41 ± 50.18 µmol Trolox/g DW, respectively. Moreover, their total phenolic contents (TPC) were detected by Folin-Ciocalteu assay and were in the range of 24.77 ± 2.02 to 252.65 ± 4.74 mg gallic acid equivalent (GAE)/g DW. Generally, Dianqing Tea, Lushan Yunwu Tea, and Xihu Longjing Tea showed the strongest antioxidant activities among 30 teas. Furthermore, the phenolic compounds in tea infusions were identified and quantified, with catechins most commonly detected, especially in green tea infusions, which were main contributors to their antioxidant activities. Besides tea polyphenols, considerable content of caffeine also presented in 30 tea infusions.

Tumor microenvironment (TME) is a complex environment containing tumor cells, tumor-associated macrophages (TAMs), interstitial cells, and non-cellular components. Epithelial-mesenchymal transition (EMT), as a major actor in cancer tumorigenicity and metastasis, was involved in the interaction between TAMs and tumor cells. However, the potential mechanisms of EMT and how EMT-programmed tumor cells affect M2-like TAMs still need further exploration.An integrated analysis of nine CRC miRNA expression datasets was performed. Functional assays, including the EdU, clone formation, wound healing, and transwell assays, were used to determine the anticancer role of miR-195-5p in human CRC progression. Furthermore, RNA immunoprecipitation, RNA decay, and dual-luciferase reporter assays were used to determine the mechanism of miR-195-p CRC progression. Then co-culture, migration, and ELISA assays were applied to determine the role of miR-195-5p in macrophage recruitment and alternative polarization. Xenograft mouse models were used to determine the role of miR-195-5p in CRC tumorigenicity and TAM polarization in vivo.An integrated analysis confirmed that miR-195-5p was significantly downregulated in CRC tissues, and patients with a low level of miR-195-5p had significantly shortened overall survival as revealed by the TCGA-COAD dataset. Altered miR-195-5p in colon cancer cells led to distinct changes of proliferation, migration, invasion, and EMT. Mechanistically, miR-195-5p regulated NOTCH2 expression in a post-transcriptional manner by directly binding to 3'-UTR of the Notch2 mRNA. Subsequently, miR-195-5p/NOTCH2 suppressed GATA3-mediated IL-4 secretion in CRC cells and ultimately inhibited M2-like TAM polarization.miR-195-5p may play a vital role in regulating NOTCH2-mediated tumor cell EMT, thereby affecting IL-4-related M2-like TAM polarization in CRC.

Background Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Patients and methods Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population). Results After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval [CI] 67.7–79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8–69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9–87.7) than in the CCRT alone group (73.1%, 95% CI 67.2–79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% [39/238] versus 9.7% [23/238], p = 0.029). Conclusion IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.

A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31hiEmcnhi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.

The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC.Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months.The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy.The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group.In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.ClinicalTrials.gov Identifier: NCT02111460.

Objective We aimed to systematically identify the possible risk factors responsible for severe cases. Methods We searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients’ disease. We analyzed the potential associations between clinical characteristics and severe cases. Results We identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34–2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33–1.71), obesity (OR = 1.89, 95% CI: 1.44–2.46), history of smoking (OR = 1.40, 95% CI:1.06–1.85), hypertension (OR = 2.42, 95% CI: 2.03–2.88), diabetes (OR = 2.40, 95% CI: 1.98–2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22–3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63–5.41), cerebrovascular disease ( OR = 2.47, 95% CI: 1.54–3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89–4.38), malignancy (OR = 2.60, 95% CI: 2.00–3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06–2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99–78.41), shock (OR = 21.50, 95% CI: 10.49–44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34–18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions. Conclusion Patients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.

Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function.

Formamidinium lead halide (FAPbX3) has attracted greater attention and is more prominent recently in photovoltaic devices due to its broad absorption and higher thermal stability in comparison to more popular methylammonium lead halide MAPbX3. Herein, a simple and highly reproducible room temperature synthesis of device grade high quality formamidinium lead bromide CH(NH2)2PbBr3 (FAPbBr3) colloidal nanocrystals (NC) having high photoluminescence quantum efficiency (PLQE) of 55-65% is reported. In addition, we demonstrate high brightness perovskite light emitting device (Pe-LED) with these FAPbBr3 perovskite NC thin film using 2,2',2″-(1,3,5-Benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) commonly known as TPBi and 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-methylpyrimidine (B3PYMPM) as electron transport layers (ETL). The Pe-LED device with B3PYMPM as ETL has bright electroluminescence of up to 2714 cd/m2, while the Pe-LED device with TPBi as ETL has higher peak luminous efficiency of 6.4 cd/A and peak luminous power efficiency of 5.7 lm/W. To our knowledge this is the first report on high brightness light emitting device based on CH(NH2)2PbBr3 widely known as FAPbBr3 nanocrystals in literature.

Background Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer. Methods In this phase 2, single-arm, prospective study, we recruited patients aged 18–70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov, number NCT02867956. Findings Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6–71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2–78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded. Interpretation The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted. Funding None.

Calcium oxide (CaO) and sodium carbonate (Na2CO3) are potential activators for ground granulated blast furnace slag, but they result in slow strength development, especially at the early age. To overcome this issue and explore the application of CaO/Na2CO3 compound activators in alkali-activated slag (AAS) systems, this paper investigated the mechanical and hydration properties of CaO/Na2CO3-activated slag binders by measuring the compressive strength, pH value of pore solution and non-evaporable water content up to 28 days. The hydration products and microstructure of hardened pastes were analyzed by X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy techniques. It was found that the ratio of CaO to Na2CO3 played a vital role in the performance of the AAS binders. The combination of 2.5% CaO and 5% Na2CO3 significantly increased the quantities of hydration products and thus resulted in a much denser microstructure and higher compressive strength. This increment was attributed to the generation of sodium hydrate and low crystalline calcium carbonate by the reaction of CaO with Na2CO3, which was beneficial for the formation of hydration products. XRD and TGA results showed that the main hydration products were calcium silicate hydrate gels and hydrotalcite-like phases for all samples except the one with only Na2CO3. In addition, low crystalline calcium carbonate was detected in the samples with both CaO and Na2CO3.

Abstract Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.

There are two main types of root systems in flowering plants, namely taproot systems of dicots and fibrous root systems found in monocots. Despite this fundamental split, our current knowledge of cellular and molecular mechanism driving root development is mainly based on studies of the dicot model Arabidopsis. However, the world major crops are monocots and little is known about the transcriptional programs underlying cell-type specification in this clade. Here, we report the transcriptomes of more than 20 000 single cells derived from root tips of two agronomically important rice cultivars. Using combined computational and experimental analyses we were able to robustly identify most of the major cell types and define novel cell-type-specific marker genes for both cultivars. Importantly, we found divergent cell types associated with specific regulatory programs, including phytohormone biosynthesis, signaling, and response, which were well conserved between the two rice cultivars. In addition, we detected substantial differences between the cell-type transcript profiles of Arabidopsis and rice. These species-specific features emphasize the importance of analyzing tissues across diverse model species, including rice. Taken together, our study provides insight into the transcriptomic landscape of major cell types of rice root tip at single-cell resolution and opens new avenues to study cell-type specification, function, and evolution in plants.

Heavy metals refer to metals with a density above 5 × 103 kg m-3, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). Even a trace amount of heavy metals is detrimental to human health. With the increasing significance of detection of heavy metals, the use of the electrochemical detection technique combined with microfluidics is a promising strategy and has thus attracted wide attention from academia and is the subject of this review. First, this review introduces the basics of electrochemical detection and microfluidics. Second, this review presents and evaluates a variety of electrochemical microfluidics technologies for heavy metal ions detection that are user friendly, portable, inexpensive, and easy to manufacture compared to traditional methods. The categorization is based on different detected ions in the order of Pb, Cd, As, Hg, Mn, and Zn. Finally, the author summarizes the development of detection technology in recent years and puts forward a perspective for the future prospects.

Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD600), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.

This review summaries the characterization techniques for Pt single-atom catalysts and focuses on FT-EXAFS spectroscopy to study the coordination environment of Pt–M for atomically dispersed Pt catalysts on diverse supports.

Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer.This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety.Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%).Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Selective conversion of levulinic acid/ester to γ-valerolactone or 1,4-pentanediol was achieved over copper-based catalysts with tunable acidic and basic sites.

DNA quantification is important for biomedical research, but the routinely used techniques rely on nucleic acid amplification which have inherent issues like cross-contamination risk and quantification bias. Here, we report a CRISPR-Cas12a-based molecular diagnostic technique for amplification-free and absolute quantification of DNA at the single-molecule level. To achieve this, we first screened out the optimal reaction parameters for high-efficient Cas12a assay, yielding over 50-fold improvement in sensitivity compared with the reported Cas12a assays. We further leveraged the microdroplet-enabled confinement effect to perform an ultralocalized droplet Cas12a assay, obtaining excellent specificity and single-molecule sensitivity. Moreover, we demonstrated its versatility and quantification capability by direct counting of diverse virus’s DNAs (African swine fever virus, Epstein–Barr virus, and Hepatitis B virus) from clinical serum samples with a wide range of viral titers. Given the flexible programmability of crRNA, we envision this amplification-free technique as a versatile and quantitative platform for molecular diagnosis.

Abstract Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.

With the rapid development of lithium‐ion batteries (LIBs), safety problems are the great obstacles that restrict large‐scale applications of LIBs, especially for the high‐energy‐density electric vehicle industry. Developing component materials (e.g., cathode, anode, electrolyte, and separator) with high thermal stability and intrinsic safety is the ultimate solution to improve the safety of LIBs. Separators are crucial components that do not directly participate in electrochemical reactions during charging/discharging processes, but play a vital role in determining the electrochemical performance and safety of LIBs. In this review, the recent advances on traditional separators modified with ceramic materials and multifunctional separators ranging from the prevention of the thermal runaway to the flame retardant are summarized. The component–structure–performance relationship of separators and their effect on the comprehensive performance of LIBs are discussed in detail. Furthermore, the research challenges and future directions toward the advancement in separators for high‐safety LIBs are also proposed.

Advanced Functional MaterialsVolume 29, Issue 43 1905423 Full Paper Atomic Pd on Graphdiyne/Graphene Heterostructure as Efficient Catalyst for Aromatic Nitroreduction Jiaqiang Li, Jiaqiang Li Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorLixiang Zhong, Lixiang Zhong School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 SingaporeSearch for more papers by this authorLianming Tong, Corresponding Author Lianming Tong tonglm@pku.edu.cn Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorYue Yu, Yue Yu Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorQing Liu, Qing Liu Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorShuchen Zhang, Shuchen Zhang Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorChen Yin, Chen Yin Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorLiang Qiao, Liang Qiao School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 Singapore College of Science, Changchun University, Changchun, 130022 P. R. ChinaSearch for more papers by this authorShuzhou Li, Corresponding Author Shuzhou Li LISZ@ntu.edu.sg School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 SingaporeE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorRui Si, Corresponding Author Rui Si sirui@sinap.ac.cn Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai, 201204 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorJin Zhang, Corresponding Author Jin Zhang jinzhang@pku.edu.cn orcid.org/0000-0003-3731-8859 Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this author Jiaqiang Li, Jiaqiang Li Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorLixiang Zhong, Lixiang Zhong School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 SingaporeSearch for more papers by this authorLianming Tong, Corresponding Author Lianming Tong tonglm@pku.edu.cn Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorYue Yu, Yue Yu Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorQing Liu, Qing Liu Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorShuchen Zhang, Shuchen Zhang Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorChen Yin, Chen Yin Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaSearch for more papers by this authorLiang Qiao, Liang Qiao School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 Singapore College of Science, Changchun University, Changchun, 130022 P. R. ChinaSearch for more papers by this authorShuzhou Li, Corresponding Author Shuzhou Li LISZ@ntu.edu.sg School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 SingaporeE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorRui Si, Corresponding Author Rui Si sirui@sinap.ac.cn Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai, 201204 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this authorJin Zhang, Corresponding Author Jin Zhang jinzhang@pku.edu.cn orcid.org/0000-0003-3731-8859 Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 P. R. ChinaE-mail: LISZ@ntu.edu.sg, jinzhang@pku.edu.cn, sirui@sinap.ac.cn, tonglm@pku.edu.cnSearch for more papers by this author First published: 16 August 2019 https://doi.org/10.1002/adfm.201905423Citations: 82Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract With the maximum atom-utilization efficiency, single atom catalysts (SACs) have attracted great research interest in catalysis science recently. To address the following key challenges for the further development of SACs: i) how to stabilize and avoid the aggregation of SACs, ii) how to enhance the specific surface area and conductivity of supports, and iii) how to achieve scalable mass production with low cost, a SAC consisting of single Pd atoms anchored on well-designed graphdiyne/graphene (GDY/G) heterostructure (Pd1/GDY/G) is synthesized. Pd1/GDY/G exhibits high catalytic performance, as demonstrated by the reduction reaction of 4-nitrophenol. Furthermore, density functional theory calculation indicates that graphene in the GDY/G heterostructure plays a key role in the enhancement of catalytic efficiency owing to the electron transfer process, deriving from the gap between the Fermi level of graphene and the conduction band minimum of GDY. The GDY/G heterostructure is a promising support for the preparation of extremely efficient and stable SACs, which can be used in a broad range of future industrial reactions. 5 Conflict of Interest The authors declare no conflict of interest. Citing Literature Supporting Information Filename Description adfm201905423-sup-0001-S1.pdf9.8 MB Supplementary adfm201905423-sup-0001-S1.mp45 MB Supplementary 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. Volume29, Issue43October 24, 20191905423 RelatedInformation

This study studied the change of functionalities in the biochar formed in pyrolysis of poplar wood in a wide range of temperature. The in situ Diffuse Reflectance Infrared Fourier transform spectroscopy characterization indicated that aldehydes and ketones functionalities formation initiated at 100 °C, dominated at 300 to 500 °C. Carboxyl group was less stable than carbonyls. Cellulose crystal in poplar decomposed slightly at 300 °C and significantly at 350 °C. The temperature from 250 to 350 °C significantly affected biochar yields, while the drastic fusion of the ring structures in biochar occurred from 550 to 650 °C, making biochar more aliphatic while less more aromatic. High pyrolysis temperature also created more defective structures in the biochar and favored the absorption of the CO2 generated during the pyrolysis. The results provide the reference information for understanding the structural configuration and evolution of the functionalities during in pyrolysis of poplar biomass.

Abstract The NASA Soil Moisture Active Passive (SMAP) mission Level‐4 Soil Moisture (L.4_SM) product provides global, 3‐hourly, 9‐km resolution estimates of surface (0–5 cm) and root zone (0–100 cm) soil moisture with a mean latency of ~2.5 days. The underlying L4_SM algorithm assimilates SMAP radiometer brightness temperature (Tb) observations into the NASA Catchment land surface model using a spatially distributed ensemble Kalman filter. In Version 4 of the L4_SM modeling system the upward recharge of surface soil moisture from below under nonequilibrium conditions was reduced, resulting in less bias and improved dynamic range of L4_SM surface soil moisture compared to earlier versions. This change and additional technical modifications to the system reduce the mean and standard deviation of the observation‐minus‐forecast Tb residuals and overall soil moisture analysis increments while maintaining the skill of the L4_SM soil moisture estimates versus independent in situ measurements; the average, bias‐adjusted root‐mean‐square error in Version 4 is 0.039 m 3 /m 3 for surface and 0.026 m 3 /m 3 for root zone soil moisture. Moreover, the coverage of assimilated SMAP observations in Version 4 is near global owing to the use of additional satellite Tb records for algorithm calibration. L4_SM soil moisture uncertainty estimates are biased low (by 0.01–0.02 m 3 /m 3 ) against actual errors (computed versus in situ measurements). L4_SM runoff estimates, an additional product of the L4_SM algorithm, are biased low (by 35 mm/year) against streamflow measurements. Compared to Version 3, bias in Version 4 is reduced by 46% for surface soil moisture uncertainty estimates and by 33% for runoff estimates.