Jia Liu

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Chemical graphitized r-GOs, as the thinnest and lightest material in the carbon family, exhibit high-efficiency electromagnetic interference (EMI) shielding at elevated temperature, attributed to the cooperation of dipole polarization and hopping conductivity. The r-GO composites show different temperature-dependent imaginary permittivities and EMI shielding performances with changing mass ratio.

Graphene-based nanostructures exhibit electronic properties that are not present in extended graphene. For example, quantum confinement in carbon nanotubes and armchair graphene nanoribbons leads to the opening of substantial electronic bandgaps that are directly linked to their structural boundary conditions. Nanostructures with zigzag edges are expected to host spin-polarized electronic edge states and can thus serve as key elements for graphene-based spintronics. The edge states of zigzag graphene nanoribbons (ZGNRs) are predicted to couple ferromagnetically along the edge and antiferromagnetically between the edges, but direct observation of spin-polarized edge states for zigzag edge topologies--including ZGNRs--has not yet been achieved owing to the limited precision of current top-down approaches. Here we describe the bottom-up synthesis of ZGNRs through surface-assisted polymerization and cyclodehydrogenation of specifically designed precursor monomers to yield atomically precise zigzag edges. Using scanning tunnelling spectroscopy we show the existence of edge-localized states with large energy splittings. We expect that the availability of ZGNRs will enable the characterization of their predicted spin-related properties, such as spin confinement and filtering, and will ultimately add the spin degree of freedom to graphene-based circuitry.

Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.

The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.

In the past decade, mesoporous silica nanoparticles (MSNs) with a large surface area and pore volume have attracted considerable attention for their application in drug delivery and biomedicine. In this review, we highlight the recent advances in silica-assisted drug delivery systems, including (1) MSN-based immediate/sustained drug delivery systems and (2) MSN-based controlled/targeted drug delivery systems. In addition, we summarize the biomedical applications of MSNs, including (1) MSN-based biotherapeutic agent delivery; (2) MSN-assisted bioimaging applications; and (3) MSNs as bioactive materials for tissue regeneration.This comprehensive review presents recent advances in mesoporous silica nanoparticles assisted drug delivery systems, including both immediate and sustained delivery systems as well as controlled release and targeted drug delivery systems. In addition to achieving therapeutic agent delivery, imaging applications and potential use of silica NPs in tissue regeneration are also discussed.

Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility. Moving to thick tissue blocks, we observed a molecularly defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells) and a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.

The precise control of the size, morphology, surface chemistry, and assembly process of each component is important to construction of integrated functional nanocomposites. We report here the fabrication of multifunctional microspheres which possess a core of nonporous silica-protected magnetite particles, transition layer of active gold nanoparticles, and an outer shell of ordered mesoporous silica with perpendicularly aligned pore channels. The well-designed microspheres have high magnetization (18.6 emu/g), large surface area (236 m(2)/g), highly open mesopores (approximately 2.2 nm), and stably confined but accessible Au nanoparticles and, as a result, show high performance in catalytic reduction of 4-nitrophenol (with conversion of 95% in 12 min), styrene epoxidation with high conversion (72%) and selectivity (80%), especially convenient magnetic separability, long life and good reusability. The unique nanostructure makes the microsphere to be a novel stable and approachable catalyst system for various catalytic industry processes.

We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic on tomato and Arabidopsis thaliana. The DC3000 genome (6.5 megabases) contains a circular chromosome and two plasmids, which collectively encode 5,763 ORFs. We identified 298 established and putative virulence genes, including several clusters of genes encoding 31 confirmed and 19 predicted type III secretion system effector proteins. Many of the virulence genes were members of paralogous families and also were proximal to mobile elements, which collectively comprise 7% of the DC3000 genome. The bacterium possesses a large repertoire of transporters for the acquisition of nutrients, particularly sugars, as well as genes implicated in attachment to plant surfaces. Over 12% of the genes are dedicated to regulation, which may reflect the need for rapid adaptation to the diverse environments encountered during epiphytic growth and pathogenesis. Comparative analyses confirmed a high degree of similarity with two sequenced pseudomonads, Pseudomonas putida and Pseudomonas aeruginosa, yet revealed 1,159 genes unique to DC3000, of which 811 lack a known function.

Deformation-tolerant devices are vital for the development of high-tech electronics of unconventional forms. In this study, a highly compressible supercapacitor has been fabricated by using newly developed polypyrrole-mediated graphene foam as electrode. The assembled supercapacitor performs based on the unique and robust foam electrodes achieves superb compression tolerance without significant variation of capacitances under long-term compressive loading and unloading processes. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), the pathogen of 2019 novel coronavirus disease (COVID-19), has posed a serious threat to global public health. The WHO has declared the outbreak of SARS-CoV-2 infection an international public health emergency. Lung lesions have been considered as the major damage caused by SARS-CoV-2 infection. However, liver injury has also been reported to occur during the course of the disease in severe cases. Similarly, previous studies have shown that liver damage was common in the patients infected by the other two highly pathogenic coronavirus - severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), and associated with the severity of diseases. In this review, the characteristics and mechanism of liver injury caused by SARS-CoV, MERS-CoV as well as SARS-CoV-2 infection were summarized, which may provide help for further studies on the liver injury of COVID-19.

<h2>Summary</h2> Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that <i>BAP1</i> loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function <i>SRSF2</i> mutations. Within D3-UM, <i>EIF1AX</i>- and <i>SRSF2</i>/<i>SF3B1</i>-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

The anti-hyperglycemic effect of metformin is believed to be caused by its direct action on signaling processes in hepatocytes, leading to lower hepatic gluconeogenesis. Recently, metformin was reported to alter the gut microbiota community in humans, suggesting that the hyperglycemia-lowering action of the drug could be the result of modulating the population of gut microbiota. However, the critical microbial signaling metabolites and the host targets associated with the metabolic benefits of metformin remained elusive. Here, we performed metagenomic and metabolomic analysis of samples from individuals with newly diagnosed type 2 diabetes (T2D) naively treated with metformin for 3 d, which revealed that Bacteroides fragilis was decreased and the bile acid glycoursodeoxycholic acid (GUDCA) was increased in the gut. These changes were accompanied by inhibition of intestinal farnesoid X receptor (FXR) signaling. We further found that high-fat-diet (HFD)-fed mice colonized with B. fragilis were predisposed to more severe glucose intolerance, and the metabolic benefits of metformin treatment on glucose intolerance were abrogated. GUDCA was further identified as an intestinal FXR antagonist that improved various metabolic endpoints in mice with established obesity. Thus, we conclude that metformin acts in part through a B. fragilis–GUDCA–intestinal FXR axis to improve metabolic dysfunction, including hyperglycemia. Metformin decreases the levels of Bacteroides fragilis while increasing the bile acid GUDCA to antagonize intestinal FXR and improves the metabolic health of humans and mice.

We present Habitat, a platform for research in embodied artificial intelligence (AI). Habitat enables training embodied agents (virtual robots) in highly efficient photorealistic 3D simulation. Specifically, Habitat consists of: (i) Habitat-Sim: a flexible, high-performance 3D simulator with configurable agents, sensors, and generic 3D dataset handling. Habitat-Sim is fast - when rendering a scene from Matterport3D, it achieves several thousand frames per second (fps) running single-threaded, and can reach over 10,000 fps multi-process on a single GPU. (ii) Habitat-API: a modular high-level library for end-toend development of embodied AI algorithms - defining tasks (e.g. navigation, instruction following, question answering), configuring, training, and benchmarking embodied agents. These large-scale engineering contributions enable us to answer scientific questions requiring experiments that were till now impracticable or `merely' impractical. Specifically, in the context of point-goal navigation: (1) we revisit the comparison between learning and SLAM approaches from two recent works [19, 16] and find evidence for the opposite conclusion - that learning outperforms SLAM if scaled to an order of magnitude more experience than previous investigations, and (2) we conduct the first cross-dataset generalization experiments {train, test} × {Matterport3D, Gibson} for multiple sensors {blind, RGB, RGBD, D} and find that only agents with depth (D) sensors generalize across datasets. We hope that our open-source platform and these findings will advance research in embodied AI.

Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. However, the existing research on circRNA-protein interactions is quite limited. Hence, in this review, we briefly summarize recent progress in the metabolism and functions of circRNAs and elaborately discuss the patterns of circRNA-protein interactions, including altering interactions between proteins, tethering or sequestering proteins, recruiting proteins to chromatin, forming circRNA-protein-mRNA ternary complexes and translocating or redistributing proteins. Many discoveries have revealed that circRNAs have unique expression signatures and play crucial roles in a variety of diseases, enabling them to potentially act as diagnostic biomarkers and therapeutic targets. This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs.

Late blight, caused by the oomycete pathogen Phytophthora infestans, is the most devastating potato disease in the world. Control of late blight in the United States and other developed countries relies extensively on fungicide application. We previously demonstrated that the wild diploid potato species Solanum bulbocastanum is highly resistant to all known races of P. infestans. Potato germplasm derived from S. bulbocastanum has shown durable and effective resistance in the field. Here we report the cloning of the major resistance gene RB in S. bulbocastanum by using a map-based approach in combination with a long-range (LR)-PCR strategy. A cluster of four resistance genes of the CC-NBS-LRR (coiled coil-nucleotide binding site-Leu-rich repeat) class was found within the genetically mapped RB region. Transgenic plants containing a LR-PCR product of one of these four genes displayed broad spectrum late blight resistance. The cloned RB gene provides a new resource for developing late blight-resistant potato varieties. Our results also demonstrate that LR-PCR is a valuable approach to isolate genes that cannot be maintained in the bacterial artificial chromosome system.

Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.

This paper presents a novel change detection approach for synthetic aperture radar images based on deep learning. The approach accomplishes the detection of the changed and unchanged areas by designing a deep neural network. The main guideline is to produce a change detection map directly from two images with the trained deep neural network. The method can omit the process of generating a difference image (DI) that shows difference degrees between multitemporal synthetic aperture radar images. Thus, it can avoid the effect of the DI on the change detection results. The learning algorithm for deep architectures includes unsupervised feature learning and supervised fine-tuning to complete classification. The unsupervised feature learning aims at learning the representation of the relationships between the two images. In addition, the supervised fine-tuning aims at learning the concepts of the changed and unchanged pixels. Experiments on real data sets and theoretical analysis indicate the advantages, feasibility, and potential of the proposed method. Moreover, based on the results achieved by various traditional algorithms, respectively, deep learning can further improve the detection performance.

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

Low-cost and highly efficient bifunctional electrocatalysts for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) are intensively investigated for overall water splitting. Herein, we combined experimental research with first-principles calculations based on density functional theory (DFT) to engineer the NiCo2S4@NiFe LDH heterostructure interface for enhancing overall water-splitting activity. The DFT calculations exhibit strong interaction and charge transfer between NiCo2S4 and NiFe LDH, which change the interfacial electronic structure and surface reactivity. The calculated chemisorption free energy of hydroxide (ΔEOH) is reduced from 1.56 eV for pure NiFe LDH to 1.03 eV for the heterostructures, indicating a dramatic improvement in OER performance, while the chemisorption free energy of hydrogen (ΔEH) maintains almost invariable. By the use of the facile hydrothermal method, NiCo2S4 nanotubes, NiFe LDH nanosheets, and NiCo2S4@NiFe LDH heterostructures are prepared on nickel foam, of which the corresponding experimental OER overpotentials are 306, 260, and 201 mV at 60 mA cm–2, respectively. These results are good agreement with the theoretical predictions. Meanwhile, the HER performance has little improvement, with an overpotential of about 200 mV at 10 mA cm–2. Due to the dramatic improvement in OER performance, there was an enhancement in the overall water-splitting activity of the NiCo2S4@NiFe LDH heterostructures, with a low voltage of 1.6 V.

Earth-abundant, noble-metal-free catalysts with outstanding electrochemical hydrogen evolution reaction catalytic activity in alkaline media play a key role in sustainable production of H2 fuel. Herein, the novel three-dimensional Ni(OH)2/MoS2 hybrid catalyst with synergistic effect has been synthesized by a facile approach for efficient alkaline hydrogen evolution reaction. Benefiting from abundant active interfaces, this hybrid catalyst shows high hydrogen evolution catalytic activity in 1 M KOH aqueous solution with an onset overpotential of 20 mV, an overpotential of 80 mV at 10 mA cm−2 and a Tafel slope of 60 mV dec−1. Further theoretical calculations offers a deeper insight of the synergistic effect of Ni(OH)2/MoS2 interface: Ni(OH)2 provides the active sites for hydroxyl adsorption, and MoS2 facilitates adsorption of hydrogen intermediates and H2 generation. This interfacial cooperation leads to a favorable hydrogen and hydroxyl species energetics and reduce the energy barrier of the initial water dissociation step, which is the rate-limiting step of MoS2 catalyst in alkaline media. The combination of experimental and theoretical investigations demonstrates that the sluggish alkaline hydrogen evolution process can be circumvented by rational catalysts interface engineering.

The kiwifruit (Actinidia chinensis) is an economically and nutritionally important fruit crop with remarkably high vitamin C content. Here we report the draft genome sequence of a heterozygous kiwifruit, assembled from ~140-fold next-generation sequencing data. The assembled genome has a total length of 616.1 Mb and contains 39,040 genes. Comparative genomic analysis reveals that the kiwifruit has undergone an ancient hexaploidization event (γ) shared by core eudicots and two more recent whole-genome duplication events. Both recent duplication events occurred after the divergence of kiwifruit from tomato and potato and have contributed to the neofunctionalization of genes involved in regulating important kiwifruit characteristics, such as fruit vitamin C, flavonoid and carotenoid metabolism. As the first sequenced species in the Ericales, the kiwifruit genome sequence provides a valuable resource not only for biological discovery and crop improvement but also for evolutionary and comparative genomics analysis, particularly in the asterid lineage.

Significant losses in harvested fruit can be directly attributable to decay fungi. Some of these pathogenic fungi are also the source of mycotoxins that are harmful to humans. Biological control of postharvest decay of fruits, vegetables and grains using antagonistic yeasts has been explored as one of several promising alternatives to chemical fungicides, the use of which is facing increasingly more stringent regulation. Yeast species have been isolated over the past two decades from a variety of sources, including fruit surfaces, the phyllosphere, soil and sea water, and their potential as postharvest biocontrol agents has been investigated. Several mechanisms have been proposed as responsible for their antagonistic activity, including competition for nutrients and space, parasitism of the pathogen, secretion of antifungal compounds, induction of host resistance, biofilm formation, and most recently, the involvement of reactive oxygen species (ROS) in defense response. It has been recognized that a biocontrol system is composed of a three-way interaction between the host (commodity), the pathogen and the yeast, all of which are affected by environmental factors. Efficacy and consistent performance in controlling postharvest diseases are the hurdles that must be overcome if the use of yeast biocontrol agents and other alternatives are to be widely used commercially. Therefore, attempts have been made to combine alternative treatments in order improve their overall performance. The current review provides a brief overview of the topic of the use of yeasts as postharvest biocontrol agents and includes information on the sources from which yeast antagonists have been isolated, their mode of action, and abiotic stress resistance in yeast as it relates to biocontrol performance. Areas in need of future research are also highlighted.

In this study, the effects of pyrolysis temperature and heating time on the yield and physicochemical and morphological properties of biochar obtained from straw and lignosulfonate were investigated. As pyrolysis temperature increased, pH, ash content, carbon stability, and total content of carbon increased while biochar yield, volatile matter, total content of hydrogen, oxygen, nitrogen and sulfur decreased. The data from scanning electron microscope image and nuclear magnetic resonance spectra indicated an increase in porosity and aromaticity of biochar produced at a high temperature. The results showed that feedstock types could also influence characteristics of the biochar with absence of significant effect on properties of biochar for heating time.

Graphite carbon nitride (g-C3 N4 ) is a promising candidate for photocatalytic hydrogen production, but only shows moderate activity owing to sluggish photocarrier transfer and insufficient light absorption. Herein, carbon quantum dots (CQDs) implanted in the surface plane of g-C3 N4 nanotubes were synthesized by thermal polymerization of freeze-dried urea and CQDs precursor. The CQD-implanted g-C3 N4 nanotubes (CCTs) could simultaneously facilitate photoelectron transport and suppress charge recombination through their specially coupled heterogeneous interface. The electronic structure and morphology were optimized in the CCTs, contributing to greater visible light absorption and a weakened barrier of the photocarrier transfer. As a result, the CCTs exhibited efficient photocatalytic performance under light irradiation with a high H2 production rate of 3538.3 μmol g-1 h-1 and a notable quantum yield of 10.94 % at 420 nm.

We quantitatively estimate properties of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions utilizing Bayesian statistics and a multi-parameter model-to-data comparison. The study is performed using a recently developed parametric initial condition model, TRENTO, which interpolates among a general class of particle production schemes, and a modern hybrid model which couples viscous hydrodynamics to a hadronic cascade. We calibrate the model to multiplicity, transverse momentum, and flow data and report constraints on the parametrized initial conditions and the temperature-dependent transport coefficients of the quark-gluon plasma. We show that initial entropy deposition is consistent with a saturation-based picture, extract a relation between the minimum value and slope of the temperature-dependent specific shear viscosity, and find a clear signal for a nonzero bulk viscosity.

(Cell 173, 371–385.e1–e9; April 5, 2018) It has come to our attention that we made two errors in preparation of this manuscript. First, in the STAR Methods, under the subheading of “Hypermutators and Immune Infiltrates” within the “Quantification and Statistical Analysis” section, we inadvertently referred to Figures S7A–S7C for data corresponding to sample stratification by hypermutator status alone in the last sentence. It should have referred to Figure S6A–S6C. Second, the lists of highly frequent missense mutations for COAD (colon adenocarcinoma) and READ (rectum adenocarcinoma) displayed in Figure S7 were incorrect because when we ordered the mutations in the initial analysis, we mistakenly combined the two cancer types COAD and READ for analysis, despite the fact that they were listed as two separate cancer types in the x-axis of the figure. After re-ordering the mutations by frequency for COAD and READ independently, information on highly frequent missense mutations for each of these cancer types is different and updated now in the revised Figure S7. These errors don’t change the major conclusions of the paper and have been corrected online. We apologize for any confusion they may have caused.Figure S7On-Label/Off-Label Calculations for Druggable Mutations in Cancer (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Comprehensive Characterization of Cancer Driver Genes and MutationsBailey et al.CellApril 05, 2018In BriefA comprehensive analysis of oncogenic driver genes and mutations in >9,000 tumors across 33 cancer types highlights the prevalence of clinically actionable cancer driver events in TCGA tumor samples. Full-Text PDF Open Access

How do category-selective regions arise in human extrastriate cortex? Visually presented words provide an ideal test of the role of experience: Although individuals have extensive experience with visual words, our species has only been reading for a few thousand years, a period not thought to be long enough for natural selection to produce a genetically specified mechanism dedicated to visual word recognition per se. Using relatively high-resolution functional magnetic resonance imaging (1.4 x 1.4 x 2-mm voxels), we identified a small region of extrastriate cortex in most participants that responds selectively to both visually presented words and consonant strings, compared with line drawings, digit strings, and Chinese characters. Critically, we show that this pattern of selectivity is dependent on experience with specific orthographies: The same region responds more strongly to Hebrew words in Hebrew readers than in nonreaders of Hebrew. These results indicate that extensive experience with a given visual category can produce strong selectivity for that category in discrete cortical regions.

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target.We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo.LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Covalent organic frameworks (COFs) are excellent platforms with tailored functionalities in photocatalysis. There are still challenges in increasing the photochemical performance of COFs. Therefore, we designed and prepared a series of COFs for photocatalytic hydrogen generation. Varying different ratios of β-ketoenamine to imine moieties in the linkages could differ the ordered structure, visible light harvesting, and bandgap. Overall, β-ketoenamine-linked COFs exhibited much better photocatalytic activity than those COFs having both β-ketoenamine and imine moieties on account of a nonquenched excited state and more favorable HOMO level in the photoinduced oxidation reaction from the former. Specifically, after in situ growth of β-ketoenamine-linked COFs onto NH2–Ti3C2Tx MXene via covalent connection, the heterohybrid showed an obvious improvement in photocatalytic H2 evolution because of strong covalent coupling, electrical conductivity, and efficient charge transfer. This integrated linkage evolution and covalent hybridization approach advances the development of COF-based photocatalysts.

(Immunity 48, 812–830.e1–e14; April 17, 2018) In the originally published version of this article, the authors neglected to include Younes Mokrab and Aaron M. Newman as co-authors and misspelled the names of authors Charles S. Rabkin and Ilya Shmulevich. The author names have been corrected here and online. In addition, the concluding sentence of the subsection “Immune Signature Compilation” in the Method Details in the original published article was deemed unclear because it did not specify differences among the gene set scoring methods. The concluding sentences now reads “Gene sets from Bindea et al., Senbabaoglu et al., and the MSigDB C7 collection were scored using single-sample gene set enrichment (ssGSEA) analysis (Barbie et al., 2009), as implemented in the GSVA R package (Hänzelmann et al., 2013). All other signatures were scored using methods found in the associated citations.” The Immune Landscape of CancerThorsson et al.ImmunityApril 5, 2018In BriefThorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy. Full-Text PDF Open Access

Background and Purpose— Interleukin-4 (IL-4) is a unique cytokine that may contribute to brain repair by regulating microglia/macrophage functions. Thus, we examined the effect of IL-4 on long-term recovery and microglia/macrophage polarization in 2 well-established stroke models. Methods— Transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion was induced in wild-type and IL-4 knockout C57/BL6 mice. In a separate cohort of wild-type animals, IL-4 (60 ng/d for 7 days) or vehicle was infused into the cerebroventricle after transient middle cerebral artery occlusion. Behavioral outcomes were assessed by the Rotarod, corner, foot fault, and Morris water maze tests. Neuronal tissue loss was verified by 2 independent neuron markers. Markers of classically activated (M1) and alternatively activated (M2) microglia were assessed by real-time polymerase chain reaction, immunofluorescence, and flow cytometry. Results— Loss of IL-4 exacerbated sensorimotor deficits and impaired cognitive functions ≤21 days post injury. In contrast to the delayed deterioration of neurological functions, IL-4 deficiency increased neuronal tissue loss only in the acute phase (5 days) after stroke and had no impact on neuronal tissue loss 14 or 21 days post injury. Loss of IL-4 promoted expression of M1 microglia/macrophage markers and impaired expression of M2 markers at 5 and 14 days post injury. Administration of IL-4 into the ischemic brain also enhanced long-term functional recovery. Conclusions— The cytokine IL-4 improves long-term neurological outcomes after stroke, perhaps through M2 phenotype induction in microglia/macrophages. These results are the first to suggest that immunomodulation with IL-4 is a promising approach to promote long-term functional recovery after stroke.

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.

Serious concerns on privacy protection in social networks have been raised in recent years; however, research in this area is still in its infancy. The problem is challenging due to the diversity and complexity of graph data, on which an adversary can use many types of background knowledge to conduct an attack. One popular type of attacks as studied by pioneer work [2] is the use of embedding subgraphs. We follow this line of work and identify two realistic targets of attacks, namely, NodeInfo and LinkInfo. Our investigations show that k-isomorphism, or anonymization by forming k pairwise isomorphic subgraphs, is both sufficient and necessary for the protection. The problem is shown to be NP-hard. We devise a number of techniques to enhance the anonymization efficiency while retaining the data utility. A compound vertex ID mechanism is also introduced for privacy preservation over multiple data releases. The satisfactory performance on a number of real datasets, including HEP-Th, EUemail and LiveJournal, illustrates that the high symmetry of social networks is very helpful in mitigating the difficulty of the problem.

Advanced MaterialsVolume 21, Issue 13 p. 1377-1382 Communication Synthesis of Core/Shell Colloidal Magnetic Zeolite Microspheres for the Immobilization of Trypsin Yonghui Deng, Yonghui Deng Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorChunhui Deng, Chunhui Deng Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorDawei Qi, Dawei Qi Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorChong Liu, Chong Liu Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorJia Liu, Jia Liu Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorXiangmin Zhang, Xiangmin Zhang Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorDongyuan Zhao, Corresponding Author Dongyuan Zhao [email protected] Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China).Search for more papers by this author Yonghui Deng, Yonghui Deng Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorChunhui Deng, Chunhui Deng Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorDawei Qi, Dawei Qi Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorChong Liu, Chong Liu Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorJia Liu, Jia Liu Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorXiangmin Zhang, Xiangmin Zhang Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Search for more papers by this authorDongyuan Zhao, Corresponding Author Dongyuan Zhao [email protected] Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China)Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and Advanced Materials Laboratory Fudan University, Shanghai 200433 (PR China).Search for more papers by this author First published: 30 March 2009 https://doi.org/10.1002/adma.200801766Citations: 270AboutPDF 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 onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Magnetic zeolite microspheres are synthesized by combining sol-gel synthesis and vapor-phase transport. The microspheres, which have magnetite cores and crystalline zeolite shells (see figure), exhibit super-paramagnetism and a high adsorption capacity for trypsin. Trypsin-adsorbed microspheres digest proteins very efficiently (in only 15 s) in the presence of microwave radiation. Supporting Information 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. Filename Description adma_200801766_sm_suppdata.pdf868.2 KB suppdata Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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fMRI studies have reported three regions in human ventral visual cortex that respond selectively to faces: the occipital face area (OFA), the fusiform face area (FFA), and a face-selective region in the superior temporal sulcus (fSTS). Here, we asked whether these areas respond to two first-order aspects of the face argued to be important for face perception, face parts (eyes, nose, and mouth), and the T-shaped spatial configuration of these parts. Specifically, we measured the magnitude of response in these areas to stimuli that (i) either contained real face parts, or did not, and (ii) either had veridical face configurations, or did not. The OFA and the fSTS were sensitive only to the presence of real face parts, not to the correct configuration of those parts, whereas the FFA was sensitive to both face parts and face configuration. Further, only in the FFA was the response to configuration and part information correlated across voxels, suggesting that the FFA contains a unified representation that includes both kinds of information. In combination with prior results from fMRI, TMS, MEG, and patient studies, our data illuminate the functional division of labor in the OFA, FFA, and fSTS.

The bottom-up approach to synthesize graphene nanoribbons strives not only to introduce a band gap into the electronic structure of graphene, but also to accurately tune its value by designing both width and edge structure of the ribbons with atomic precision.We report the synthesis of an armchair graphene nanoribbon with a width of 9 carbon atoms on Au(111) through surfaceassisted aryl-aryl coupling and subsequent cyclodehydrogenation of a properly chosen molecular precursor.By combining high-resolution atomic force microscopy, scanning tunneling microscopy and Raman spectroscopy, we demonstrate that the atomic structure of the fabricated ribbons is exactly as designed.Angle-resolved photoemission spectroscopy and Fouriertransformed scanning tunneling spectroscopy reveal an electronic band gap of 1.4 eV and effective masses of ≈0.1 m e for both electrons and holes, constituting a substantial improvement over previous efforts towards the development of transistor applications.We use ab initio calculations to gain insight into the dependence of the Raman spectra on excitation wavelength, as well as to rationalize the symmetry-dependent contribution of the ribbons' electronic states to the tunneling current.We propose a simple rule for the visibility of frontier electronic bands of armchair graphene nanoribbons in scanning tunneling spectroscopy.

Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury.This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs.A literature search was carried out regarding our topic with the keywords of "atherosclerosis" or "Nrf2/HO-1" or "vascular endothelial cells" or "oxidative stress" or "Herbal medicine" or "natural products" or "natural extracts" or "natural compounds" or "traditional Chinese medicines" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed.These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies.Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

Complex symmetrical CuS nanostructures were synthesized in large scale by a simple wet chemical method at low temperature. As a semiconductor material with superstructure, CuS was well characterized and firstly introduced into PVDF to form nanocomposites. The substantial enhancement of wave absorption (−102 dB at 7.7 GHz) was observed by addition of CuS with a low filler loading (5 wt%). The mechanism for the enhanced wave absorbing properties was explained in detail.

The effects of preharvest chitosan spray (PCS) or/and postharvest chitosan coating (PCC) treatments on the quality and physiological response of table grape fruit stored at 20 or 0 °C was evaluated, respectively. PCS/PCC treatment showed the best control effect on decay. PCC or PCS/PCC treatment significantly decreased the weight loss of fruit stored at 20 °C. Additionally, all chitosan treatments inhibited the increase in rate of soluble solid content to titratable acid in fruit, stored at 20 °C, while enhancing the rate at 0 °C and affecting the content of total phenolic compounds in the fruit. Furthermore, the activities of superoxide dismutase decreased in all chitosan treatments and PCS or/and PCC treatments also changed the activities of polyphenol oxidase, peroxidase and phenylalanine ammonia-lyase. The results indicated the beneficial effect of chitosan by preharvest spray and/or postharvest coating on fruit quality and resistance to fruit decay.

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

High invasion and metastasis are the primary factors causing poor prognosis of patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying these biological behaviors have not been completely elucidated. In this study, we investigate the molecular mechanism by which hypoxia promotes HCC invasion and metastasis through inducing epithelial-mesenchymal transition (EMT).The expression of EMT markers was analyzed by immunohistochemistry. Effect of hypoxia on induction of EMT and ability of cell migration and invasion were performed. Luciferase reporter system was used for evaluation of Snail regulation by hypoxia-inducible factor -1α (HIF-1α).We found that overexpression of HIF-1α was observed in HCC liver tissues and was related to poor prognosis of HCC patients. HIF-1α expression profile was correlated with the expression levels of SNAI1, E-cadherin, N-cadherin and Vimentin. Hypoxia was able to induce EMT and enhance ability of invasion and migration in HCC cells. The same phenomena were also observed in CoCl2-treated cells. The shRNA-mediated HIF-1α suppression abrogated CoCl2-induced EMT and reduced ability of migration and invasion in HCC cells. Luciferase assay showed that HIF-1α transcriptional regulated the expression of SNAI1 based on two hypoxia response elements (HREs) in SNAI1 promoter.We demonstrated that hypoxia-stabilized HIF1α promoted EMT through increasing SNAI1 transcription in HCC cells. This data provided a potential therapeutic target for HCC treatment.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper motor neurons comprising the corticospinal tract and lower motor neurons arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining motor neurons in ALS patients and animal models of the disease.

Multi-spatial-resolution change detection is a newly proposed issue and it is of great significance in remote sensing, environmental and land use monitoring, etc. Though multi-spatial-resolution image-pair are two kinds of representations of the same reality, they are often incommensurable superficially due to their different modalities and properties. In this paper, we present a novel multi-spatial-resolution change detection framework, which incorporates deep-architecture-based unsupervised feature learning and mapping-based feature change analysis. Firstly, we transform multi-resolution image-pair into the same pixel-resolution through co-registration, followed by details recovery, which is designed to remedy the spatial details lost in the registration. Secondly, the denoising autoencoder is stacked to learn local and high-level representation/feature from the local neighborhood of the given pixel, in an unsupervised fashion. Thirdly, motivated by the fact that multi-resolution image-pair share the same reality in the unchanged regions, we try to explore the inner relationships between them by building a mapping neural network. And it can be used to learn a mapping function based on the most-unlikely-changed feature-pairs, which are selected from all the feature-pairs via a coarse initial change map generated in advance. The learned mapping function can bridge the different representations and highlight changes. Finally, we can build a robust and contractive change map through feature similarity analysis, and the change detection result is obtained through the segmentation of the final change map. Experiments are carried out on four real datasets, and the results confirmed the effectiveness and superiority of the proposed method.

The extensive computational burden limits the usage of CNNs in mobile devices for dense estimation tasks. In this paper, we present a lightweight network to address this problem, namely LEDNet, which employs an asymmetric encoder-decoder architecture for the task of real-time semantic segmentation. More specifically, the encoder adopts a ResNet as backbone network, where two new operations, channel split and shuffle, are utilized in each residual block to greatly reduce computation cost while maintaining higher segmentation accuracy. On the other hand, an attention pyramid network (APN) is employed in the decoder to further lighten the entire network complexity. Our model has less than 1M parameters, and is able to run at over 71 FPS in a single GTX 1080Ti GPU. The comprehensive experiments demonstrate that our approach achieves state-of-the-art results in terms of speed and accuracy trade-off on CityScapes dataset.

Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently.The purpose of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through targeting FADD.Our results show that FADD participates in H2O2-induced necrosis by influencing the formation of RIPK1 and RIPK3 complexes in H9c2 cells. We further demonstrate that miR-103/107 target FADD directly. Knockdown of miR-103/107 antagonizes necrosis in the cellular model and also myocardial infarction in a mouse ischemia/reperfusion model. The miR-103/107-FADD pathway does not participate in tumor necrosis factor-α-induced necrosis. In exploring the molecular mechanism by which miR-103/107 are regulated, we show that long noncoding RNA H19 directly binds to miR-103/107 and regulates FADD expression and necrosis.Our results reveal a novel myocardial necrosis regulation model, which is composed of H19, miR-103/107, and FADD. Modulation of their levels may provide a new approach for preventing myocardial necrosis.

Nanoneedle-like ZnO demonstrates the enhanced dielectric properties and multi-region microwave absorption at elevated temperature, which mainly arises from the dipole and interfacial polarizations, indicating a promising structural absorber.

<h2>Summary</h2> The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on "chromatin-state" to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.

Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). We discuss the engineering advances that facilitated their development and highlight several achievements in genome engineering that were made possible by these tools. We also consider artificial transcription factors, illustrating how this technology can complement targeted nucleases for synthetic biology and gene therapy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.

Single crystalline perovskites exhibit high optical absorption, long carrier lifetime, large carrier mobility, low trap-state-density and high defect tolerance. Unfortunately, all single crystalline perovskites attained so far are limited to bulk single crystals and small area wafers. As such, it is impossible to design highly demanded flexible single-crystalline electronics and wearable devices including displays, touch sensing devices, transistors, etc. Herein we report a method of induced peripheral crystallization to prepare large area flexible single-crystalline membrane (SCM) of phenylethylamine lead iodide (C6H5C2H4NH3)2PbI4 with area exceeding 2500 mm2 and thinness as little as 0.6 μm. The ultrathin flexible SCM exhibits ultralow defect density, superior uniformity and long-term stability. Using the superior ultrathin membrane, a series of flexible photosensors were designed and fabricated to exhibit very high external quantum efficiency of 26530%, responsivity of 98.17 A W-1 and detectivity as much as 1.62 × 1015 cm Hz1/2 W-1 (Jones).

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

Why do some people recognize faces easily and others frequently make mistakes in recognizing faces? Classic behavioral work has shown that faces are processed in a distinctive holistic manner that is unlike the processing of objects. In the study reported here, we investigated whether individual differences in holistic face processing have a significant influence on face recognition. We found that the magnitude of face-specific recognition accuracy correlated with the extent to which participants processed faces holistically, as indexed by the composite-face effect and the whole-part effect. This association is due to face-specific processing in particular, not to a more general aspect of cognitive processing, such as general intelligence or global attention. This finding provides constraints on computational models of face recognition and may elucidate mechanisms underlying cognitive disorders, such as prosopagnosia and autism, that are associated with deficits in face recognition.

Three dimensional (3D) hierarchical network configurations are composed of NiCo2S4 nanotube @Ni-Mn layered double hydroxide (LDH) arrays in situ grown on graphene sponge. The 3D graphene sponge with robust hierarchical porosity suitable for as a basal growth has been obtained from a colloidal dispersion of graphene oxide using a simple directional freeze-drying technique. The high conductive NiCo2S4 nanotube arrays grown on 3D graphene shows excellent pseudocapacity and good conductive support for high-performance Ni-Mn LDH. The 3D NiCo2S4@Ni-Mn LDH/GS shows a high specific capacitance (Csp) 1740 mF cm(-2) at 1 mA cm(-2), even at 10 mA cm(-2), 1267.9 mF cm(-2) maintained. This high-performance composite electrode proposes a new and feasible general pathway as 3D electrode configuration for energy storage devices.

Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients and chemotherapy resistance is the major obstacle to effective cancer therapy. Increasing evidence suggests that mesenchymal stem cells (MSCs) make important contributions to development of drug resistance. However, the underlying mechanism remains elusive. In this study, we discovered that abundant MSCs in tumor tissues predicted a poor prognosis in GC patients. MSCs promoted stemness and chemoresistance in GC cells through fatty acid oxidation (FAO) in vitro and in vivo. Mechanically, transforming growth factor β1 (TGF-β1) secretion by MSCs activated SMAD2/3 through TGF-β receptors and induced long non-coding RNA (lncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p. Moreover, pharmacologic inhibition of FAO with etomoxir (ETX) attenuated MSC-induced FOLFOX regiment resistance in vivo. These results suggest that FAO plays an important role in MSC-mediated stemness and chemotherapy resistance in GC and FAO inhibitors in combination with chemotherapeutic drugs present as a promising strategy to overcome chemoresistance.

Abstract Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still &gt;70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.

All that glitters is gold: highly phosphorescent gold(III) complexes with extended π-conjugated cyclometalating ligands exhibit rich photophysical and photochemical properties. They act as efficient photocatalysts/photosensitizers for oxidative functionalizations of secondary and tertiary benzylic amines and homogeneous hydrogen production from a water/acetonitrile mixture.

In this paper, a redox and enzyme dual-stimuli responsive delivery system (MSN-SS-HA) based on mesoporous silica nanoparticles (MSN) for targeted drug delivery has been developed, in which hyaluronic acid (HA) was conjugated on the surface of silica by cleavable disulfide (SS) bonds. HA possesses many attractive features, including acting as a targeting ligand and simultaneously a capping agent to achieve targeted and controlled drug release, prolonging the blood circulation time, and increasing the physiological stability and biocompatibility of MSN. The anticancer drug doxorubicin (DOX) was chosen as a model drug. In vitro drug release profiles showed that the release of DOX was markedly restricted in pH 7.4 and pH 5.0 phosphate buffer solution (PBS), while it was significantly accelerated upon the addition of glutathione (GSH)/hyaluronidases (HAase). In addition, the release was further accelerated in the presence of both GSH and HAase. Confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) showed that MSN-SS-HA exhibited a higher cellular uptake via cluster of differentiation antigen-44 (CD44) receptor-mediated endocytosis compared with thiol (SH)-functionalized MSN (MSN-SH) in CD44 receptor over-expressed in human HCT-116 cells. The DOX-loaded MSN-SS-HA was more cytotoxic against HCT-116 cells than NIH-3T3 (CD44 receptor-negative) cells due to the enhanced cellular uptake of MSN-SS-HA. This paper describes the development of an effective method for using a single substance as multi-functional material for MSN to simultaneously regulate drug release and achieve targeted delivery.

Gold clusters loaded on various supports have been widely used in the fields of energy and biology. However, the poor photostability of Au clusters on support interfaces under prolonged illumination usually results in loss of catalytic performance. Covalent organic frameworks (COFs) with periodic and ultrasmall pore structures are ideal supports for dispersing and stabilizing Au clusters, although it is difficult to encapsulate Au clusters in the ultrasmall pores. In this study, a two-dimensional (2D) COF modified with thiol chains in its pores was prepared. With −SH groups as nucleation sites, Au nanoclusters (NCs) could grow in situ within the COF. The ultrasmall pores of the COF and the strong S−Au binding energy combine to improve the dispersibility of Au NCs under prolonged light illumination. Interestingly, Au–S–COF bridging as observed in this artificial Z-scheme photocatalytic system is deemed to be an ideal means to increase charge-separation efficiency.

In this paper, we develop a facile UV-derived in-situ dual-reaction to prepare a flexible poly(ethylene oxide) (PEO)-based solid polymer electrolyte (SPE), which is applied for ambient-temperature all-solid-state lithium battery. By modifying the amorphous domain of PEO through cross-linking with tetraglyme (TEGDME) and introducing a rigid linear oligomer of tetraethylene glycol dimethacrylate (TEGDMA) into the matrix, a SPE is obtained with high ionic conductivity (2.7 × 10−4 S cm−1 at 24 °C) and enhanced mechanical strength. The as-prepared SPE shows superior electrochemical properties with decent lithium transference number of 0.56, wide electrochemical stability window above 5 V vs. Li+/Li and low interfacial resistance. By means of galvanostatic cycling studies in Li//Li symmetrical and LiFePO4//Li cells, we further demonstrate that the SPE exhibits excellent cycling performance with minimization of lithium dendrite formation.

Dental decay is one of the most prevalent chronic diseases worldwide. A variety of factors, including microbial, genetic, immunological, behavioral and environmental, interact to contribute to dental caries onset and development. Previous studies focused on the microbial basis for dental caries have identified species associated with both dental health and disease. The purpose of the current study was to improve our knowledge of the microbial species involved in dental caries and health by performing a comprehensive 16S rDNA profiling of the dental plaque microbiome of both caries-free and caries-active subjects. Analysis of over 50,000 nearly full-length 16S rDNA clones allowed the identification of 1,372 operational taxonomic units (OTUs) in the dental plaque microbiome. Approximately half of the OTUs were common to both caries-free and caries-active microbiomes and present at similar abundance. The majority of differences in OTU's reflected very low abundance phylotypes. This survey allowed us to define the population structure of the dental plaque microbiome and to identify the microbial signatures associated with dental health and disease. The deep profiling of dental plaque allowed the identification of 87 phylotypes that are over-represented in either caries-free or caries-active subjects. Among these signatures, those associated with dental health outnumbered those associated with dental caries by nearly two-fold. A comparison of this data to other published studies indicate significant heterogeneity in study outcomes and suggest that novel approaches may be required to further define the signatures of dental caries onset and progression.

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases.

Hierarchical deep neural networks are currently popular learning models for imitating the hierarchical architecture of human brain. Single-layer feature extractors are the bricks to build deep networks. Sparse feature learning models are popular models that can learn useful representations. But most of those models need a user-defined constant to control the sparsity of representations. In this paper, we propose a multiobjective sparse feature learning model based on the autoencoder. The parameters of the model are learnt by optimizing two objectives, reconstruction error and the sparsity of hidden units simultaneously to find a reasonable compromise between them automatically. We design a multiobjective induced learning procedure for this model based on a multiobjective evolutionary algorithm. In the experiments, we demonstrate that the learning procedure is effective, and the proposed multiobjective model can learn useful sparse features.

The advanced treatment of industrial wastewater often calls upon the use of highly-efficient treatment methods to remove hazardous pollutants prior to the effluent discharge. Adsorption can be used towards removing micro-pollutants. Congo Red dye is widely used in the paper and textile industry, and residual quantities are present in the process effluents. Adsorbing metal oxide nanoparticles have abundant pores of appropriate size, a large specific surface area, and can efficiently remove organic pollutants from waste water. FexCo3-xO4 nanoparticle adsorbents were synthesized. Their magnetic properties facilitate their recovery. Experiments were conducted for different Congo Red concentrations and FexCo3-xO4 nanoparticles dosage. The maximum Congo Red adsorption capacity of FexCo3-xO4 nanoparticles at equilibrium was 128.6 mg/g. The adsorption yield of Congo Red decreased from 86.12% to 79.53% when the initial concentration of Congo Red increased from 10 mg/L to 30 mg/L, Adsorption results were modeled to define essential parameters such as the adsorption mechanisms and kinetics. A pseudo-first-order kinetic model fitted the results. The equilibrium adsorption data were moreover fitted by isotherm models, with both the Langmuir and Freundlich equations shown appropriate. The re-use of the nanoparticle adsorbent was moreover investigated for 5 successive adsorption cycles, without loss of adsorption capacity. A case study for the adsorption of Congo Red on the FexCo3-xO4 nanoparticles demonstrates that the required mass of adsorbent can be calculated for any amount of Congo Red to be removed. It was demonstrated that the fairly cheap and environmentally friendly FexCo3-xO4 nanoparticles have a strong adsorption and removal ability for dyes and are easy to recycle.

Designing low-cost and highly efficient bifunctional electrocatalysts for compatible integration with the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for overall water splitting is critical but challenging<bold>.</bold>

Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥ 65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1) models. We found that circulating TMAO increased with age both in humans and mice. Next, we observed that a TMAO treatment for 16 weeks induced vascular aging in SAMR1 mice and accelerated the process in SAMP8 mice, as measured by an upregulation of senescence markers including senescence-associated β-galactosidase (SA-β-gal), p53, and p21, vascular dysfunction and remodeling. In vitro, we demonstrated that prolonged TMAO treatment induced senescence in human umbilical vein endothelial cells (HUVECs), characterized by reduced cell proliferation, increased expressions of senescence markers, stagnate G0/G1, and impaired cell migration. Furthermore, TMAO suppressed sirtuin 1 (SIRT1) expression and increased oxidative stress both in vivo and in vitro and then activated the p53/p21/Rb pathway resulting in increased p53, acetylation of p53, p21, and decreased CDK2, cyclinE1, and phosphorylation of Rb. In summary, these data suggest that elevated circulating TMAO during the aging process may deteriorate EC senescence and vascular aging, which is probably associated with repression of SIRT1 expression and increased oxidative stress, and, thus, the activation of the p53/p21/Rb pathway.

Abstract The reaction kinetics of alkaline hydrogen evolution reactions (HER) is a trade‐off between adsorption and desorption for intermediate species (H 2 O, OH, and H ads ). However, due to the complicated correlation between the intermediates adsorption energy and electronic states, targeted regulating the adsorption energy at the atomic level is not comprehensive. Herein, nonmetals (B, N, O, and F) are used to modulate the adsorption energy and electronic structure of Ni 3 S 4 , and propose that H 2 O and OH adsorption energy are correlate directly with d‐band center (ε d ) of transition metal Ni, and H ads adsorption energy has a linear dependence on p‐band center (ε p ) of nonmetal S. Direct experimental evidence is offered that in all nonmetals doping samples, Tafel slope and exchange current density can be improved regularly with the ε d and ε p , and F‐Ni 3 S 4 shows the optimum activity with tiny overpotential 29 and 92 mV for harvesting current density 10 and 100 mA cm −2 , respectively. Furthermore, the micro‐kinetics analysis and density functional theory calculations verify that F‐doping can efficiently reduce the energy barrier of the Volmer step, eventually accelerating the HER kinetics. This work provides atomic‐level insight into the structure‐properties relationship, and opens an avenue for kinetic‐oriented design of alkaline HER and beyond.

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has antiinflammatory and anticancer effects. The present study investigated the protective effects of PLG in rotenone-induced PD cell and mouse models. We found that PLG administration (2 and 4 mg/kg) for 4 wk attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra induced by oral administration of rotenone (10 mg/kg) for 6 wk. PLG improved cell viability and enhanced mitochondrial function in primary neurons and SK-N-SH cells. These protective effects were exerted via inhibition of apoptosis and induction of autophagy through enhancement of BCL2 phosphorylation at Ser70. These results demonstrate that PLG exerts therapeutic effects in a rotenone-induced PD models by restoring the balance between apoptosis and autophagy.6-OHDA, 6-hydroxydopamine; ACTB, actin, beta; BafA1, bafilomycin A1; BAK1, BCL2-antagonist/killer 1; BAX, BCL2-associated X protein; BCL2, B cell leukemia/lymphoma2; BECN1, Beclin 1, autophagy related; CoQ10, coenzyme Q10; COX4I1/COX IV, cytochrome c oxidase subunit 4I1; CsA, cyclosporine A; ED50, 50% effective dose; FITC, fluorescein isothiocyanate; GFP, green fluorescent protein; HPLC, high-performance liquid chromatography; JC-1, tetraethylbenz-imidazolylcarbocyanine iodide; LC3, microtubule-associated protein 1 light chain3; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LDH, lactate dehydrogenase; l-dopa, 3, 4-dihydroxyphenyl-l-alanine; MAPK8/JNK1, mitogen-activated protein kinase 8; MMP, mitochondrial membrane potential; mPTP, mitochondrial permeability transition pore; mRFP, monomeric red fluorescent protein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NFE2L2/NRF2, nuclear factor, erythroid derived 2, like 2; PD, Parkinson disease; PLG, piperlongumine; pNA, p-nitroanilide; PI, propidium iodide; PtdIns3K, phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol-3-phosphate; PTX, paclitaxel; Rap, rapamycin; SQSTM1/p62, sequestosome 1; TH, tyrosine hydroxylase; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; WIPI2, WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1, zinc finger, FYVE domain containing 1.

(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell CarcinomaRicketts et al.Cell ReportsApril 5, 2018In BriefRicketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Full-Text PDF Open Access

Byzantine-robust federated learning aims to enable a service provider to learn an accurate global model when a bounded number of clients are malicious. The key idea of existing Byzantine-robust federated learning methods is that the service provider performs statistical analysis among the clients' local model updates and removes suspicious ones, before aggregating them to update the global model. However, malicious clients can still corrupt the global models in these methods via sending carefully crafted local model updates to the service provider. The fundamental reason is that there is no root of trust in existing federated learning methods. In this work, we bridge the gap via proposing FLTrust, a new federated learning method in which the service provider itself bootstraps trust. In particular, the service provider itself collects a clean small training dataset (called root dataset) for the learning task and the service provider maintains a model (called server model) based on it to bootstrap trust. In each iteration, the service provider first assigns a trust score to each local model update from the clients, where a local model update has a lower trust score if its direction deviates more from the direction of the server model update. Then, the service provider normalizes the magnitudes of the local model updates such that they lie in the same hyper-sphere as the server model update in the vector space. Our normalization limits the impact of malicious local model updates with large magnitudes. Finally, the service provider computes the average of the normalized local model updates weighted by their trust scores as a global model update, which is used to update the global model. Our extensive evaluations on six datasets from different domains show that our FLTrust is secure against both existing attacks and strong adaptive attacks.

Environmentally compatible energy management is one of the biggest challenges of the 21st century. Low-temperature conversion of chemical to electrical energy is of particular importance to minimize the impact to the environment while sustaining the consumptive economy. In this review, we shed light on one of the most versatile energy-conversion technologies: heterogeneous catalysts. We establish the integrity of structural tailoring in heterogeneous catalysts at different scales in the context of an emerging paradigm in materials science: catalytic nanoarchitectonics. Fundamental backgrounds of energy-conversion catalysis are first provided together with a perspective through state-of-the-art energy-conversion catalysis including catalytic exhaust remediation, fuel-cell electrocatalysis and photosynthesis of solar fuels. Finally, the future evolution of catalytic nanoarchitectonics is overviewed: possible combinations of heterogeneous catalysts, organic molecules and even enzymes to realize reaction-selective, highly efficient and long-life energy conversion technologies which will meet the challenge we face.

Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/β-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding.

Urban spatiotemporal flow prediction is of great importance to traffic management, land use, public safety. This prediction task is affected by several complex and dynamic factors, such as patterns of human activities, weather, events, and holidays. Datasets evaluated the flow come from various sources in different domains, e.g. mobile phone data, taxi trajectories data, metro/bus swiping data, bike-sharing data. To summarize these methodologies of urban flow prediction, in this paper, we first introduced four main factors affecting urban flow. Second, in order to further analyze urban flow, we partitioned the preparation process of multi-source spatiotemporal data related with urban flow into three groups. Third, we chose the spatiotemporal dynamic data as a case study for the urban flow prediction task. Fourth, we analyzed and compared some representative flow prediction methods in detail, classifying them into five categories: statistics-based, traditional machine learning-based, deep learning-based, reinforcement learning-based, and transfer learning-based methods. Finally, we showed open challenges of urban flow prediction and discussed many recent research works on urban flow prediction. This paper will facilitate researchers to find suitable methods and public datasets for addressing urban spatiotemporal flow forecast problems.

Abstract Solid‐state lithium metal batteries are regarded to be the ultimate choice for future energy storage systems due to their high theoretical energy density and safety. However, the practical applications of solid‐state batteries are hindered by severe interfacial issues, such as high interfacial resistance, inferior electro‐/chemical compatibility, as well as poor stability. Moreover, lithium dendrite growth and mechanical degradation caused by interfacial stress during repeated cycling induce the failure of a working solid‐state battery. Therefore, understanding the failure mechanism of a solid‐state lithium battery is imperative and significant to construct a better interface for a safe solid‐state lithium battery. In this review, the current fundamental understanding of the impact of the lithium/solid‐state electrolyte interface on the solid‐state ionics and interfacial chemistry are introduced first. The failure mechanisms underlying electrical, chemical, electrochemical, and mechanical aspects of solid‐state lithium batteries are summarized. The emerging perspectives regarding future research directions are also included. This sheds fresh light on the rational construction of high‐efficiency solid‐state lithium batteries.

The earliest microwave absorbing materials (MAMs) are fabricated in the early 20th century for military purpose to inhibit radar detection. Currently, the application of MAMs has been existing in every part of human's life to prevent radiation and interference. The microwave absorbant and microwave absorbing coatings classified by composition including alloys, metal oxides, conductive polymers, carbon materials, ceramic materials both in traditional and innovative forms are introduced in this work. Considering the harsh and complex application environment, MAMs with high temperature resistance and infrared-compatible stealth performance are involved. Metamaterials, showing excellent electromagnetic properties which are far beyond that of the materials can achieve, including perfect absorber, digitally coded control metamaterials, bionic structural materials, and adjustable smart metamaterials, are also introduced specifically in this work. In addition, to investigate electromagnetic response of absorbant, the first-principles calculations works are overviewed. The electromagnetic properties, loss mechanisms, structure, fabrication method, regulation approaches, designing principles, current applications, and future prospects of MAMs are involved in this work. This work gives a comprehensively overview over the MAMs for their theoretical and experimental advances in recent years including the military radar (frequency range of 2–18 GHz) stealth materials, relevant infrared compatible (infrared-visible, infrared-radar, infrared-laser) stealth materials, and other stealth materials with multifrequency adaptability.

The mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating cell growth, proliferation, and life span. mTOR signaling is a central regulator of autophagy by modulating multiple aspects of the autophagy process, such as initiation, process, and termination through controlling the activity of the unc51-like kinase 1 (ULK1) complex and vacuolar protein sorting 34 (VPS34) complex, and the intracellular distribution of TFEB/TFE3 and proto-lysosome tubule reformation. Parkinson's disease (PD) is a serious, common neurodegenerative disease characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and the accumulation of Lewy bodies. An increasing amount of evidence indicates that mTOR and autophagy are critical for the pathogenesis of PD. In this review, we will summarize recent advances regarding the roles of mTOR and autophagy in PD pathogenesis and treatment. Further characterizing the dysregulation of mTOR pathway and the clinical translation of mTOR modulators in PD may offer exciting new avenues for future drug development.

We present Habitat, a platform for research in embodied artificial intelligence (AI). Habitat enables training embodied agents (virtual robots) in highly efficient photorealistic 3D simulation. Specifically, Habitat consists of: (i) Habitat-Sim: a flexible, high-performance 3D simulator with configurable agents, sensors, and generic 3D dataset handling. Habitat-Sim is fast -- when rendering a scene from Matterport3D, it achieves several thousand frames per second (fps) running single-threaded, and can reach over 10,000 fps multi-process on a single GPU. (ii) Habitat-API: a modular high-level library for end-to-end development of embodied AI algorithms -- defining tasks (e.g., navigation, instruction following, question answering), configuring, training, and benchmarking embodied agents. These large-scale engineering contributions enable us to answer scientific questions requiring experiments that were till now impracticable or 'merely' impractical. Specifically, in the context of point-goal navigation: (1) we revisit the comparison between learning and SLAM approaches from two recent works and find evidence for the opposite conclusion -- that learning outperforms SLAM if scaled to an order of magnitude more experience than previous investigations, and (2) we conduct the first cross-dataset generalization experiments {train, test} x {Matterport3D, Gibson} for multiple sensors {blind, RGB, RGBD, D} and find that only agents with depth (D) sensors generalize across datasets. We hope that our open-source platform and these findings will advance research in embodied AI.

High-throughput amplicon sequencing spanning conserved portions of microbial genomes (16s rRNA and ITS) was used in the present study to describe the endophytic microbiota associated with three apple varieties, "Royal Gala," "Golden Delicious," and "Honey Crisp," and two rootstocks, M.9 and M.M.111. The objectives were to (1) determine if the microbiota differs in different rootstocks and apple varieties and (2) determine if specific rootstock-scion combinations influence the microbiota composition of either component.Results indicated that Ascomycota (47.8%), Zygomycota (31.1%), and Basidiomycota (11.6%) were the dominant fungal phyla across all samples. The majority of bacterial sequences were assigned to Proteobacteria (58.4%), Firmicutes (23.8%), Actinobacteria (7.7%), Bacteroidetes (2%), and Fusobacteria (0.4%). Rootstocks appeared to influence the microbiota of associated grafted scion, but the effect was not statistically significant. Pedigree also had an impact on the composition of the endophytic microbiota, where closely-related cultivars had a microbial community that was more similar to each other than it was to a scion cultivar that was more distantly-related by pedigree. The more vigorous rootstock (M.M.111) was observed to possess a greater number of growth-promoting bacterial taxa, relative to the dwarfing rootstock (M.9).The mechanism by which an apple genotype, either rootstock or scion, has a determinant effect on the composition of a microbial community is not known. The similarity of the microbiota in samples with a similar pedigree suggests the possibility of some level of co-evolution or selection as proposed by the "holobiont" concept in which metaorganisms have co-evolved. Clearly, however, the present information is only suggestive, and a more comprehensive analysis is needed.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD is complicated and remains obscure, but growing evidence suggests the involvement of mitochondrial and lysosomal dysfunction. Mitophagy, the process of removing damaged mitochondria, is compromised in PD patients and models, and was found to be associated with accelerated neurodegeneration. Several PD-related proteins are known to participate in the regulation of mitophagy, including PINK1 and Parkin. In addition, mutations in several PD-related genes are known to cause mitochondrial defects and neurotoxicity by disturbing mitophagy, indicating that mitophagy is a critical component of PD pathogenesis. Therefore, it is crucial to understand how these genes are involved in mitochondrial quality control or mitophagy regulation in the study of PD pathogenesis and the development of novel treatment strategies. In this review, we will discuss the critical roles of mitophagy in PD pathogenesis, highlighting the potential therapeutic implications of mitophagy regulation.

Structural identification of natural products by tandem mass spectrometry requires laborious spectral analysis. Herein, we report a targeted post-acquisition data processing strategy, key ion filtering (KIF), to analyze untargeted mass spectral data. This strategy includes four steps: (1) untargeted data acquisition by ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry (UHPLC/orbitrap-MS); (2) construction of a key ion database according to diagnostic MS/MS fragmentations and conservative substructures of natural compounds; (3) high-resolution key ion filtering of the acquired data to recognize substructures; and (4) structural identification of target compounds by analyzing their MS/MS spectra. The herbal medicine Huang-Qin (Scutellaria baicalensis Georgi) was used to illustrate this strategy. Its extract was separated within 20 min on a C18 column (1.8 μm, 2.1×150 mm) eluted with acetonitrile, methanol, and water containing 0.1% formic acid. The compounds were detected in the (-)-ESI mode, and their MS/MS spectra were recorded in the untargeted manner. Key ions were then filtered from the LC/MS data to recognize flavones, flavanones, O-/C-glycosides, and phenylethanoid glycosides. Finally, a total of 132 compounds were identified from Huang-Qin, and 59 of them were reported for the first time. This study provides an efficient data processing strategy to rapidly profile the chemical constituents of complicated herbal extracts.

Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its application, and provide insights as to when, what and how different strategies should be taken. In addition, we highlight future perspectives of DCEO biotechnology for the successful establishment of biorefineries.

The current study focuses on understanding the factors (subjective norms (SNs), personal attitude, and perceived behaviour control (PBC)) that influence consumer purchase intention regarding organic food from the theory of planned behaviour and health consciousness as an additional factor in Tanzania and Kenya. It further explains the role of knowledge as a moderating variable in organic food purchase intention. A total of 331 responses from Tanzania and 350 responses from Kenya were obtained. Confirmatory factor analysis was applied for validation, and results were analysed using structural equation modeling. SNs, personal attitudes, and health consciousness were found to be significant predictors of organic purchase intention in both countries. Furthermore, findings show that knowledge positively moderates the relationship among SNs, personal attitude, health consciousness, and organic food purchase intention. However, PBC was found to be a weak influencer on consumer purchase intention in Kenya, and no knowledge interaction between PBC and consumer purchase intention in Tanzania was found. The current study theoretically contributes to the literature by introducing the moderating role of knowledge in the relationship. The results show that knowledge interaction increases the effects of the majority of predictors after being introduced in the relationship. Finally, this study provides an understanding of consumers’ perspective regarding their intention to purchase organic foods, which will help stakeholders, such as marketers, retailers, and producers, to achieve marketing strategies for the development of these products.

In this study, an magnetically separable iron sulfide (greigite, Fe3S4) was synthesized by solvothermal method and employed for effective removal of Cr(VI). The Cr(VI) removal process followed a pseudo-first-order kinetic model that was highly dependent on the initial Fe3S4:Cr(VI) molar ratio. The total Cr(VI) removal was involved in surface adsorption/reduction and solution reduction/precipitation processes via electrostatic attraction, electron transfer and co-precipitation mechanisms. The apparent Cr(VI) removal rate constants decreased from 0.061 to 0.017 min−1 with solution pH increased from 3.5 to 10.0, which resulted from the higher reducibility and surface electropositivity of Fe3S4 at low pH. The 1,10-phenanthrolin inhibitory experiment revealed that the Cr(VI) reduction process was mainly mediated by ferrous ions rather than sulfides. By means of analyses on the iron and sulfur species, the efficient Cr(VI) removal with Fe3S4 was ascribed to the surface Fe(III)/Fe(II) cycles induced by the sulfide ions. As for the reusability of Fe3S4, the Cr(VI) removal efficiency after 3 cycles was decreased to ca. 50% under the same conditions, which may be caused by the generation of Cr (oxide)hydroxyl and sulfide. These findings provide new insights into the concerned chromate transfer mechanisms mediated by magnetic iron sulfides, and have great prospects in construction of highly efficient systems for the Cr(VI) removal.

Thousands of different nanoparticles (NPs) involve in our daily life with various origins from food, cosmetics, drugs, etc. It is believed that decreasing the size of materials up to nanometer levels can facilitate their unfavorable absorption since they can pass the natural barriers of live tissues and organs even they can go across the relatively impermeable membranes. The interaction of these NPs with the biological environment disturbs the natural functions of cells and its components and cause health issues. In the lack of the detailed and comprehensive standard protocols about the toxicity of NPs materials, their control, and effects, this review study focuses on the current research literature about the related factors in toxicity of NPs such as size, concentration, etc. with an emphasis on metal and metal oxide nanoparticles. The goal of the study is to highlight their potential hazard and the advancement of green non-cytotoxic nanomaterials with safe threshold dose levels to resolve the toxicity issues. This study supports the NPs design along with minimizing the adverse effects of nanoparticles especially those used in biological treatments.

Abstract Driven by the persisting poor understanding of the sluggish kinetics of the hydrogen evolution reaction (HER) on Pt in alkaline media, a direct correlation of the interfacial water structure and activity is still yet to be established. Herein, using Pt and Pt–Ni nanoparticles we first demonstrate a strong dependence of the proton donor structure on the HER activity and pH. The structure of the first layer changes from the proton acceptors to the donors with increasing pH. In the base, the reactivity of the interfacial water varied its structure, and the activation energies of water dissociation increased in the sequence: the dangling O−H bonds &lt; the trihedrally coordinated water &lt; the tetrahedrally coordinated water. Moreover, optimizing the adsorption of H and OH intermediates can re‐orientate the interfacial water molecules with their H atoms pointing towards the electrode surface, thereby enhancing the kinetics of HER. Our results clarified the dynamic role of the water structure at the electrode–electrolyte interface during HER and the design of highly efficient HER catalysts.

The direct Z-scheme heterojunction has been recently emerging as an appealing architecture for photocatalysts design. Its efficiency depends on the interfacial and structural features of the photocatalysts. Herein, the two-dimensional ZnIn2S4 nanosheets are grown on the surface of CdS hollow cubes to construct the CdS@ZnIn2S4 hierarchical hollow photocatalysts with chemically bonded interface. The visualized measurements based on spatial-resolved surface photovoltage spectroscopy, combined with other spectroscopic and simulation investigations, clearly disclose that the CdS@ZnIn2S4 hollow cubes constitute a highly efficient direct Z-scheme system. This accounts for the stoichiometric generation of H2 and H2O2 from pure water observed for the CdS@ZnIn2S4 sulfide-only photocatalysts under visible light irradiation with an apparent quantum efficiency of 1.63 % at 400 nm. The present work demonstrates an effective protocol to achieve comprehensive insights into the charge transfer route at semiconductor heterojunction, and offers a viable way for constructing efficient sulfide-only photocatalysts for driving water splitting reaction.

Esophageal squamous cell cancer (ESCC) is a high incidence and mortality disease worldwide. However, specificity and sensitivity of its diagnostic and prognostic biomarkers are still unsatisfactory. Recently, circular RNAs (circRNAs) as biomarkers have been studied extensively while the expression profile and clinical significance of circRNAs in ESCC have rarely been studied. We performed circular RNA microarray in 3 pairs of ESCC frozen tumor and non-tumor tissues to identify ESCC-related circRNAs and found 1045 up-regulated and 1032 down-regulated circRNAs among which 6 circRNAs (hsa_circ_0062459, hsa_circ_0076535, hsa_circ_0072215, hsa_circ_0042261, hsa_circ_0001946, and hsa_circ_0043603) displayed consistency with microarray results by qRT-PCR. 3 circRNAs (hsa_circ_0062459, hsa_circ_0001946, and hsa_circ_0043603) were also detected in plasma and 2 of them except hsa_circ_0062459 could be used as diagnostic biomarkers and found in exosome of cell-conditioned culture conditioned media. The AUC, sensitivity and specificity of hsa_circ_0001946 were 0.894, 92, 80%, of hsa_circ_0043603 were 0.836, 64, 92% while a signature combining them were 0.928, 84 and 98%. Hsa_circ_0001946 was confirmed to predict the recurrence, overall survival (OS) and disease-free survival (DFS) in frozen and FFPE tissues, while its overexpression decreased cell proliferation, migration, and invasion.

Abstract Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene ( AGPG ) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG . Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.

Depending on the requirements of specific applications, implanted materials including metals, ceramics, and polymers have been used in various disciplines of medicine. Titanium and its alloys as implant materials play a critical role in the orthopedic and dental procedures. However, they still require the utilization of surface modification technologies to not only achieve the robust osteointegration but also to increase the antibacterial properties, which can avoid the implant-related infections. This article aims to provide a summary of the latest advances in surface modification techniques, of titanium and its alloys, specifically in biomedical applications. These surface techniques include plasma spray, physical vapor deposition, sol-gel, micro-arc oxidation, etc. Moreover, the microstructure evolution is comprehensively discussed, which is followed by enhanced mechanical properties, osseointegration, antibacterial properties, and clinical outcomes. Future researches should focus on the combination of multiple methods or improving the structure and composition of the composite coating to further enhance the coating performance.

Atherosclerosis, a chronic multifactorial disease, is closely related to the development of cardiovascular diseases and is one of the predominant causes of death worldwide. Normal vascular endothelial cells play an important role in maintaining vascular homeostasis and inhibiting atherosclerosis by regulating vascular tension, preventing thrombosis and regulating inflammation. Currently, accumulating evidence has revealed that endothelial cell apoptosis is the first step of atherosclerosis. Excess apoptosis of endothelial cells induced by risk factors for atherosclerosis is a preliminary event in atherosclerosis development and might be a target for preventing and treating atherosclerosis. Interestingly, accumulating evidence shows that natural medicines have great potential to treat atherosclerosis by inhibiting endothelial cell apoptosis. Therefore, this paper reviewed current studies on the inhibitory effect of natural medicines on endothelial cell apoptosis and summarized the risk factors that may induce endothelial cell apoptosis, including oxidized low-density lipoprotein (ox-LDL), reactive oxygen species (ROS), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), homocysteine (Hcy) and lipopolysaccharide (LPS). We expect this review to highlight the importance of natural medicines, including extracts and monomers, in the treatment of atherosclerosis by inhibiting endothelial cell apoptosis and provide a foundation for the development of potential antiatherosclerotic drugs from natural medicines.