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Ethnopharmacological Relevance: Buyang Huanwu Decoction (BYHWD), a traditional prescription known for its Supplementing Qi and Promoting Blood Circulation, has demonstrated noteworthy therapeutic roles in regulating macrophage polarization to atherosclerosis (AS). However, its underlying mechanisms remain unknown., Aim of the Study: The purpose of this paper was to decipher mechanism of BYHWD in regulating macrophage polarization to alleviate AS., Materials and Methods: A comprehensive virtual screening strategy, incorporating network pharmacology and batch molecular docking, combined with experimental validation techniques, was employed to systematically elucidate the underlying mechanism of BYHWD regulating macrophage polarization to alleviate AS., Results: Firstly, based on high-fat diet induced AS model in apolipoprotein E-deficient mice, it was found that BYHWD can significantly regulate macrophage polarization to alleviate AS. Then, the network pharmacological analysis revealed that the core targets of BYHWD regulating macrophage polarization to alleviate AS mainly involved TP53, AKT1 and BCL2. The mitochondrial function and metabolism were the main biological processes. Meanwhile, the main chemical components were identified as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E by batch molecular docking strategy. Further, the in vitro experiments demonstrated that BYHWD not only regulated macrophage polarization and alleviated macrophage foam formation but also modulated mitochondrial function and the expression of TP53, p-AKT, and BCL2 proteins. Finally, multivariate statistical analysis confirmed that the ameliorative effect of BYHWD on AS was closely related to mitochondrial function and macrophage polarization regulated by TP53, AKT1 and BCL2., Conclusions: BYHWD could activate key targets, including TP53, AKT1, and BCL2, to alleviate mitochondrial dysfunction and regulate macrophage polarization, thereby improving AS. The 10 active compounds of BYHWD, including 5-hydroxy-L-tryptophan zwitterion and Isoliquiritigenin, played an important role in regulating macrophages polarization to alleviate AS., Competing Interests: Declaration of Competing Interest ☒The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests, (Copyright © 2024. Published by Elsevier B.V.)

Microorganisms in the sediment play a pivotal role in the functioning and stability of seagrass ecosystems and their dynamics are influenced by the nutrient acquisition strategies of host plants. While the distinct impacts of microbial generalists and specialists on community dynamics are recognized, their distribution patterns and ecological roles within seagrass ecosystems remain largely unexplored. To address this issue, we conducted an analysis of community assembly processes and co-occurrence relationships of both microbial generalists and specialists within sediment profiles (0-100 cm) from seagrass habitats subjected to differing land use conditions. The results revealed that seagrasses in Yifeng Estuary experienced the large proportion of cultivated land and exhibited higher organic carbon content in the 0-20 cm surface sediment layer. Nitrogen-cycling bacteria were predominantly associated with seagrasses from Yifeng Estuary, whereas Vibrio spp. was more prevalent in seagrasses from Liusha Bay. Notably, seagrass Halophia beccarii (YHB) in Yifeng Estuary harbored higher niche breadths for both microbial generalist and specialist compared to Halodule uninervis (LHU) and Halophia ovalis (LHO) from Liusha Bay. Stochastic processes were pivotal in shaping seagrass sediment microbial communities, with a higher immigration rate observed in YHB, suggesting greater microbial turnover in this area. Additionally, YHB sediment presented lower drift and higher dispersal limitation among generalists compared to LHU and LHO, whereas the pattern was reversed among specialists. Specialists were found to play a crucial role in shaping microbial interactions within YHB sediment, with genera Halioglobus identified as keystone species in the network. The specialists were further found to significantly influence microbial β-diversity in seagrass sediment directly. Overall, our findings illustrated how microbial generalists and specialists were distributed in seagrass sediments in response to land use changes and provided new insights into the potential roles of microbial regulation in degraded seagrass ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The shift between photoautotrophic and phagotrophic strategies in mixoplankton significantly impacts the planktonic food webs and biogeochemical cycling. Considering the projected global warming, studying how temperature impacts this shift is crucial. Here, we combined the transcriptome of in-lab cultures (mixotrophic dinoflagellate Lepidodinium sp.) and the metatranscriptome dataset of the global ocean to investigate the mechanisms underlying the shift of trophic strategies and its relationship with increasing temperatures. Our results showed that phagocytosis-related pathways, including focal adhesion, regulation of actin cytoskeleton, and oxidative phosphorylation, were significantly stimulated in Lepidodinium sp. when cryptophyte prey were added. We further compared the expression profiles of photosynthesis and phagocytosis genes in Lepidodinium sp. in the global sunlit ocean. Our results indicated that Lepidodinium sp. became more phagotrophic with increasing temperatures when the ambient chlorophyll concentration was >0.3 mg.m -3 (~20.58% of the ocean surface) but became more photoautotrophic with increasing temperatures when the chlorophyll concentration was between 0.2 and 0.3 mg.m -3 (~11.47% of the ocean surface). Overall, we emphasized the crucial role of phagocytosis in phago-mixotrophy and suggested that the expression profile of phagocytosis genes can be a molecular marker to target the phagotrophic activity of mixoplankton in situ., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Neuston, situated at the air-sea interface, stands as a crucial frontier in the realm of the global warming. Despite its unique habitat, there remains a need to substantiate the composition, diel dynamic and biotic-abiotic interaction of neustonic zooplankton in the tropical seas. In this study, we present rare observational data on neustonic zooplankton (0-20 cm) in the oligotrophic tropical South China Sea (SCS) during the summer of 2022. A total of eighteen samples were collected and analyzed, revealing the presence of fourteen taxa from eight phyla. The most prevalent group was Cypridina, accounting for 33.7% of the total abundance, followed by copepods (29.0%) and jellyfish (10.9%). Within copepods, the genus Pontella exhibited the highest relative abundance (38.0%). Additionally, each neuston taxon displayed unique diel distribution patterns. Cypridina was the most abundant taxon during the night (40.4%), while it shifted to copepod dominance during the day (50.4%). Among copepods, genus Pontella and larvae were dominant groups at night (44.7%) and during the day (30.0%), respectively. Moreover, a multivariate biota-environment analysis demonstrated that temperature, pH, dissolved oxygen and Si(OH) 4 significantly impacted neuston composition. Notably, both jellyfish and sea snails showed a significant positive correlation with temperature, suggesting their potential dominance in the neuston community in response to future global warming in the oligotrophic tropical seas. This study lays a robust foundation for recognizing the neuston community in the oceanic SCS, and helps evaluate the long-term risks to neuston habitats under climate changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The oceanic-to-neritic species shift of microzooplanktonic tintinnids and their interaction with relevant abiotic variables are two crucial processes in the marine ecosystem. However, these processes remain poorly documented in China's marginal seas. In the summer of 2022, we investigated the community structure of pelagic tintinnids in surface waters from the South China Sea (SCS) to the Yellow Sea (YS), passing through the East China Sea (ECS). A number of 58 species from 23 genera were identified, with 36 and 22 species belonging to oceanic and neritic genera, respectively. The abundance proportion of oceanic and neritic genera exhibited a decreasing and increasing trend, respectively, from the SCS to YS. Furthermore, four distinctive tintinnid community groups were classified based on cluster analysis using tintinnid species and abundance data, and the position of southern Taiwan Strait was identified as the "Shift Point" for oceanic-to-neritic species dominance. The top two tintinnid species in each group showed distinct variations in body size. Additionally, multivariate biotic-abiotic statistical analyses revealed that temperature determined tintinnid species richness, while temperature, salinity, Si(OH) 4 , and Chl a determined tintinnid abundance. Our study provides a substantial foundation for recognizing the oceanic-to-neritic species shift of tintinnids in the China's marginal seas, and highlights the role of biotic-abiotic factors in driving biogeochemical fluxes and the potential response of microzooplankton to future climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plant growth-promoting rhizobacteria (PGPR) inoculation is a crucial strategy for maintaining the sustainability of agriculture and presents a promising solution for seagrass ecological restoration in the face of disturbances. However, the possible roles and functions of PGPRs in the seagrass rhizosphere remain unclear. Here, we isolated rhizosphere bacterial strains from both reef and coastal regions and screened two PGPR isolates regarding their in vivo functional traits. Subsequently, we conducted microcosm experiments to elucidate how PGPR inoculation affected seagrass photosynthesis and shape within each rhizosphere microbiome. Both screened PGPR strains, Raoultella terrigena NXT28 and Bacillus aryabhattai XT37, excelled at expressing a specific subset of plant-beneficial functions and increased the photosynthetic rates of the seagrass host. PGPR inoculation not only decreased the abundance of sulfur-cycling bacteria, it also improved the abundance of putative iron-cycling bacteria in the seagrass rhizosphere. Strain XT37 successfully colonized the seagrass rhizosphere and displayed a leading role in microbial network structure. As a nitrogen-fixing bacteria, NXT28 showed potential to change the microbial nitrogen cycle with denitrification in the rhizosphere and alter dissimilatory and assimilatory nitrate reduction in bulk sediment. These findings have implications for the development of eco-friendly strategies aimed at exploiting microbial communities to confer sulfide tolerance in coastal seagrass ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Microbial food webs (MFW) play an indispensable role in marine pelagic ecosystem, yet their composition and response to abiotic variables were poorly documented in the oligotrophic tropical Western Pacific. During winter of 2015, we conducted a survey to examine key components of MFW, including Synechococcus, Prochlorococcus, picoeukaryotes, heterotrophic prokaryotes (HP), heterotrophic/pigmented nanoflagellates and ciliates, across water column from surface to 2000 m. Each MFW component exhibited unique vertical distribution pattern, with abundance ratio varying over six and three orders of magnitude across Pico/Microplankton (1.6 ± 1.0 × 10 6 ) and Nano/Microplankton (3.2 ± 2.8 × 10 3 ), respectively. Furthermore, HP was main component for MFW in the bathypelagic (>1000 m) zone. Multivariate biota-environment analysis demonstrated that environmental variables, particularly temperature, significantly impacted MFW composition, suggesting that bottom-up control (resource availability) dominated the water column. Our study provides benchmark information for future environmental dynamics forcing on MFW in the oligotrophic tropical seas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Aims: NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation., Approach and Results: MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1 +/- ) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1 +/- mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization., Conclusions: In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Microeukaryotic diversity, community structure, and their regulating mechanisms remain largely unclear in chemosynthetic ecosystems. Here, using high-throughput sequencing data of 18S rRNA genes, we explored microeukaryotic communities from the Haima cold seep in the northern South China Sea. We compared three distinct habitats: active, less active, and non-seep regions, with vertical layers (0-25 cm) from sediment cores. The results showed that seep regions harbored more abundant and diverse parasitic microeukaryotes (e.g., Apicomplexa and Syndiniales) as indicator species, compared to nearby non-seep region. Microeukaryotic community heterogeneity was larger between habitats than within habitat, and greatly increased when considering molecular phylogeny, suggesting the local diversification in cold-seep sediments. Microeukaryotic α-diversity at cold seeps was positively increased by metazoan richness and dispersal rate of microeukaryotes, while its β-diversity was promoted by heterogeneous selection mainly from metazoan communities (as potential hosts). Their combined effects led to the significant higher γ-diversity (i.e., total diversity in a region) at cold seeps than non-seep regions, suggesting cold-seep sediment as a hotspot for microeukaryotic diversity. Our study highlights the importance of microeukaryotic parasitism in cold-seep sediment and has implications for the roles of cold seep in maintaining and promoting marine biodiversity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Structural docking between the adaptive immune receptors (AIRs), including T cell receptors (TCRs) and B cell receptors (BCRs), and their cognate antigens are one of the most fundamental processes in adaptive immunity. However, current methods for predicting AIR-antigen binding largely rely on sequence-derived features of AIRs, omitting the structure features that are essential for binding affinity. In this study, we present a deep learning framework, termed DeepAIR, for the accurate prediction of AIR-antigen binding by integrating both sequence and structure features of AIRs. DeepAIR achieves a Pearson's correlation of 0.813 in predicting the binding affinity of TCR, and a median area under the receiver-operating characteristic curve (AUC) of 0.904 and 0.942 in predicting the binding reactivity of TCR and BCR, respectively. Meanwhile, using TCR and BCR repertoire, DeepAIR correctly identifies every patient with nasopharyngeal carcinoma and inflammatory bowel disease in test data. Thus, DeepAIR improves the AIR-antigen binding prediction that facilitates the study of adaptive immunity.

Accurately predicting the antigen-binding specificity of adaptive immune receptors (AIRs), such as T-cell receptors (TCRs) and B-cell receptors (BCRs), is essential for discovering new immune therapies. However, the diversity of AIR chain sequences limits the accuracy of current prediction methods. This study introduces SC-AIR-BERT, a pre-trained model that learns comprehensive sequence representations of paired AIR chains to improve binding specificity prediction. SC-AIR-BERT first learns the 'language' of AIR sequences through self-supervised pre-training on a large cohort of paired AIR chains from multiple single-cell resources. The model is then fine-tuned with a multilayer perceptron head for binding specificity prediction, employing the K-mer strategy to enhance sequence representation learning. Extensive experiments demonstrate the superior AUC performance of SC-AIR-BERT compared with current methods for TCR- and BCR-binding specificity prediction., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hypoxia and ocean warming are two mounting global environmental threats influencing marine ecosystems. However, the interactive effects of rising temperature and depleted dissolved oxygen (DO) on marine protists remains unknown. Here, we conducted a series of laboratory experiments on four protozoa with distinct cell sizes to investigate the combined effects of temperature (19, 22, 25, 28, and 31 °C) and oxygen availability (hypoxia, 2 mg DO L -1 and normoxia, 7 mg DO L -1 ) on their physiological performances (i.e., growth, ingestion, and respiration rates). The hypoxia-induced inhibition in three physiological rates increased with the biovolume of the protists. As the larger surface area to volume (SA/V) quotients of smaller protists facilitate higher capabilities of oxygen absorption and utilization, the smaller protists suffered less inhibitions induced by hypoxia. Moreover, the hypoxia-induced inhibition in physiological rates was exacerbated by increasing temperature, which can be verified by the reductions in the temperature sensitivities (represented by the activation energy, E). These results suggest that hypoxia could lead to a shift of protistan community with enhanced domination of small protists, and warming could exacerbate such a trend. We further examined our laboratory results in the Pearl River Estuary, where extensive bottom hypoxia often occurs in summer. We found the mean protist biovolume in hypoxic waters was significantly lower than that at normal stations. Also, the mean protist biovolume decreased with declining DO concentration and rising temperature, indicating the interactive effect of temperature and oxygen availability. Collectively, we suggest that hypoxia could cause a higher proportion of small-sized cells in the marine protistan community, and the projected ocean warming could intensify the tendency, which could undermine the capacity of oceanic carbon sequestration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Prime editing is a revolutionary gene-editing method that is capable of introducing insertions, deletions and base substitutions into the genome. However, the editing efficiency of Prime Editor (PE) is limited by the DNA repair process. Here, we show that overexpression of the flap structure-specific endonuclease 1 (FEN1) and the DNA ligase 1 (LIG1) increases the efficiency of prime editing, which is similar to the dominant negative mutL homolog 1 (MLH1dn). In addition, MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing. Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE., Competing Interests: A patent application on the method of overexpressing FEN1 or LIG1 for genome editing is pending in State Intellectual Property Office of China., (© 2023 The Authors.)

Marine sediments are important methane reservoirs. Methane efflux from the seabed is significantly restricted by anaerobic methanotrophic (ANME) archaea through a process known as anaerobic oxidation of methane (AOM). Different clades of ANME archaea occupy distinct niches in methane seeps, but their underlying molecular mechanisms still need to be fully understood. To provide genetic explanations for the niche partitioning of ANME archaea, we applied comparative genomic analysis to ANME archaeal genomes retrieved from global methane seeps. Our results showed that ANME-2 archaea are more prevalent than ANME-1 archaea in shallow sediments because they carry genes that encode a significantly higher number of outer membrane multiheme c -type cytochromes and flagellar proteins. These features make ANME-2 archaea perform direct interspecies electron transfer better and benefit more from electron acceptors in AOM. Besides, ANME-2 archaea carry genes that encode extra peroxidase compared to ANME-1 archaea, which may lead to ANME-2 archaea better tolerating oxygen toxicity. In contrast, ANME-1 archaea are more competitive in deep layers than ANME-2 archaea because they carry extra genes ( mtb and mtt ) for methylotrophic methanogenesis and a significantly higher number of frh and mvh genes for hydrogenotrophic methanogenesis. Additionally, ANME-1 archaea carry exclusive genes ( sqr , TST , and mddA ) involved in sulfide detoxification compared to ANME-2 archaea, leading to stronger sulfide tolerance. Overall, this study reveals the genomic mechanisms shaping the niche partitioning among ANME archaea in global methane seeps. IMPORTANCE Anaerobic methanotrophic (ANME) archaea are important methanotrophs in marine sediment, controlling the flux of biologically generated methane, which plays an essential role in the marine carbon cycle and climate change. So far, no strain of this lineage has been isolated in pure culture, which makes metagenomics one of the fundamental approaches to reveal their metabolic potential. Although the niche partitioning of ANME archaea was frequently reported in different studies, whether this pattern was consistent in global methane seeps had yet to be verified, and little was known about the genetic mechanisms underlying it. Here, we reviewed and analyzed the community structure of ANME archaea in global methane seeps and indicated that the niche partitioning of ANME archaea was statistically supported. Our comparative genomic analysis indicated that the capabilities of interspecies electron transfer, methanogenesis, and the resistance of oxygen and hydrogen sulfide could be critical in defining the distribution of ANME archaea in methane seep sediment.

Cold seeps are biological oases of the deep sea fueled by methane, sulfates, nitrates, and other inorganic sources of energy. Chemolithoautotrophic bacteria and archaea dominate seep sediment, and their diversity and biogeochemical functions are well established. Fungi are likewise diverse, metabolically versatile, and known for their ability to capture and oxidize methane. Still, no study has ever explored the functional role of the mycobiota in the cold seep biome. To assess the complex role of fungi and fill in the gaps, we performed network analysis on 147 samples to disentangle fungal-prokaryotic interactions (fungal 18S and prokaryotic 16S) in the Haima cold seep region. We demonstrated that fungi are central species with high connectivity at the epicenter of prokaryotic networks, reduce their random-attack vulnerability by 60%, and enhance information transfer efficiency by 15%. We then scavenged a global metagenomic and metatranscriptomic data set from 10 cold seep regions for fungal genes of interest (hydrophobins, cytochrome P450s, and ligninolytic family of enzymes); this is the first study to report active transcription of 2,500+ fungal genes in the cold seep sediment. The genera Fusarium and Moniliella were of notable importance and directly correlated with high methane abundance in the sulfate-methane transition zone (SMTZ), likely due to their ability to degrade and solubilize methane and oils. Overall, our results highlight the essential yet overlooked contribution of fungi to cold seep biological networks and the role of fungi in regulating cold seep biogeochemistry. IMPORTANCE The challenges we face when analyzing eukaryotic metagenomic and metatranscriptomic data sets have hindered our understanding of cold seep fungi and microbial eukaryotes. This fact does not make the mycobiota any less critical in mediating cold seep biogeochemistry. On the contrary, many fungal genera can oxidize and solubilize methane, produce methane, and play a unique role in nutrient recycling via saprotrophic enzymatic activity. In this study, we used network analysis to uncover key fungal-prokaryotic interactions that can mediate methane biogeochemistry and metagenomics and metatranscriptomics to report that fungi are transcriptionally active in the cold seep sediment. With concerns over rising methane levels and cold seeps being a pivotal source of global methane input, our holistic understanding of methane biogeochemistry with all domains of life is essential. We ultimately encourage scientists to utilize state-of-the-art tools and multifaceted approaches to uncover the role of microeukaryotic organisms in understudied systems.

Background: Many deep-sea invertebrates largely depend on chemoautotrophic symbionts for energy and nutrition, and some of them have reduced functional digestive tracts. By contrast, deep-sea mussels have a complete digestive system although symbionts in their gills play vital roles in nutrient supply. This digestive system remains functional and can utilise available resources, but the roles and associations among gut microbiomes in these mussels remain unknown. Specifically, how the gut microbiome reacts to environmental change is unclear., Results: The meta-pathway analysis showed the nutritional and metabolic roles of the deep-sea mussel gut microbiome. Comparative analyses of the gut microbiomes of original and transplanted mussels subjected to environmental change revealed shifts in bacterial communities. Gammaproteobacteria were enriched, whereas Bacteroidetes were slightly depleted. The functional response for the shifted communities was attributed to the acquisition of carbon sources and adjusting the utilisation of ammonia and sulphide. Self-protection was observed after transplantation., Conclusion: This study provides the first metagenomic insights into the community structure and function of the gut microbiome in deep-sea chemosymbiotic mussels and their critical mechanisms for adapting to changing environments and meeting of essential nutrient demand., (© 2023. The Author(s).)

Spatial omics technologies generate wealthy but highly complex datasets. Here we present Spatial Omics DataBase (SODB), a web-based platform providing both rich data resources and a suite of interactive data analytical modules. SODB currently maintains >2,400 experiments from >25 spatial omics technologies, which are freely accessible as a unified data format compatible with various computational packages. SODB also provides multiple interactive data analytical modules, especially a unique module, Spatial Omics View (SOView). We conduct comprehensive statistical analyses and illustrate the utility of both basic and advanced analytical modules using multiple spatial omics datasets. We demonstrate SOView utility with brain spatial transcriptomics data and recover known anatomical structures. We further delineate functional tissue domains with associated marker genes that were obscured when analyzed using previous methods. We finally show how SODB may efficiently facilitate computational method development. The SODB website is https://gene.ai.tencent.com/SpatialOmics/ . The command-line package is available at https://pysodb.readthedocs.io/en/latest/ ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Underlying medical conditions, such as cancer, kidney disease and heart failure, are associated with a higher risk for severe COVID-19. Accurate classification of COVID-19 patients with underlying medical conditions is critical for personalized treatment decision and prognosis estimation. In this study, we propose an interpretable artificial intelligence model termed VDJMiner to mine the underlying medical conditions and predict the prognosis of COVID-19 patients according to their immune repertoires. In a cohort of more than 1400 COVID-19 patients, VDJMiner accurately identifies multiple underlying medical conditions, including cancers, chronic kidney disease, autoimmune disease, diabetes, congestive heart failure, coronary artery disease, asthma and chronic obstructive pulmonary disease, with an average area under the receiver operating characteristic curve (AUC) of 0.961. Meanwhile, in this same cohort, VDJMiner achieves an AUC of 0.922 in predicting severe COVID-19. Moreover, VDJMiner achieves an accuracy of 0.857 in predicting the response of COVID-19 patients to tocilizumab treatment on the leave-one-out test. Additionally, VDJMiner interpretively mines and scores V(D)J gene segments of the T-cell receptors that are associated with the disease. The identified associations between single-cell V(D)J gene segments and COVID-19 are highly consistent with previous studies. The source code of VDJMiner is publicly accessible at https://github.com/TencentAILabHealthcare/VDJMiner. The web server of VDJMiner is available at https://gene.ai.tencent.com/VDJMiner/., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Nutrient pollution in the coastal environment has been accelerated by progressively intensifying aquaculture activities. Excessive nutrients can lead to coastal eutrophication with serious economic and ecological consequences. In this study, we studied coastal planktonic microbial community over a year to understand the aquaculture impact on coastal water quality and function. We observed increased total inorganic nitrogen concentrations in active fish farms to favor the diverse Alpha- and Gammaproteobacteria. Bacterial community alpha diversity in fish farms was positively correlated with total inorganic nitrogen, and active fish farming co-influenced the bacterial structural composition and regional beta diversity. By analyzing the nitrogen cycle-related functional compositions and pathways using PICRUSt2 prediction on inferred genomes, we identified the contribution of over 600 bacterial species to four major pathways. Enhanced nitrogen load in active fish farms was positively correlated with elevated dissimilatory nitrate reduction and denitrification pathway abundances. Fallowed fish farms were characterized by a predicted high abundance of nirA and narB genes contributing to assimilatory nitrate reduction pathway due to the prevalence of Cyanobacteria. Overall, these results suggested active operation and short hiatus in coastal aquaculture practices could rapidly impact planktonic bacterial communities and further influence nitrogen cycling and associated processes. These findings will improve the understanding of the responses and interactions between microbiome and aquaculture activities. In a world of increasing aquaculture demands, this work has important implications for sustainable water resource management and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lo, Xu, Lee, Lau, Qiu, Liu, Qian and Cheng.)

Renal fibrosis (RF) is the common pathway for a variety of chronic kidney diseases that progress to end-stage renal disease. Chitosan oligosaccharide (COS) has been identified as possessing many health functions. However, it is not clear whether COS can prevent RF. The purpose of this paper was to explore the action and mechanism of COS in alleviating RF. First, an acute unilateral ureteral obstruction operation (UUO) in male BALB/c mice was performed to induce RF, and COS or fosinopril (positive control drug) were administered for 7 consecutive days. Data from our experiments indicated that COS treatment can significantly alleviate kidney injury and decrease the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) in the UUO mouse model. More importantly, our results show that COS can reduce collagen deposition and decrease the expression of fibrosis proteins, such as collagen IV, fibronectin, collagen I, α-smooth muscle actin (α-SMA) and E-cadherin, ameliorating experimental renal fibrosis in vivo. In addition, we also found that COS suppressed oxidative stress and inflammation in RF model mice. Further studies indicated that the mechanism by which COS alleviates renal fibrosis is closely related to the regulation of the TGF-β1/Smad pathway. COS has a therapeutic effect on ameliorating renal fibrosis similar to that of the positive control drug fosinopril. Taken together, COS can alleviate renal fibrosis induced by UUO by reducing oxidative stress damage and regulating the TGF-β1/Smad pathway., (© 2022. The Author(s).)

Optical metasurfaces are researched more and more intensively for the possible realization of lightweight and compact optical devices with novel functionalities. In this paper, a new beam-steering system based on double metasurface lenses (metalenses) is proposed and developed. The proposed system is lightweight, small volume, low cost, and easy to integrate. The exact close-form forward and numerical inverse solutions are derived respectively using the generalized Snell's law of refraction. Given the orientations of the double metalenses, the pointing position can be accurately determined. If the desired pointing position is given, the required metalenses' orientations can be obtained by applied global optimization algorithms to solve nonlinear equations related to the inverse problem. The relationships of the scan region and blind zone with the system parameters are derived. The method to eliminate the blind zone is given. Comparison with double Risley-prism systems is also conducted. This work provides a new approach to control light beams., (© 2022. The Author(s).)

Phytoplankton diversity and community compositions vary across spaces and are fundamentally affected by several deterministic (e.g., environmental selection) and stochastic (e.g., ecological drift) processes. How this suite of different processes regulates the biogeography of phytoplankton remains to be comprehensively explored. Using high-throughput sequencing data and null model analysis, we revealed the ecological processes shaping the latitudinal community structure of three major phytoplankton groups (i.e., diatoms, Synechococcus , and haptophytes) across the Pacific Ocean (70°N, 170°W to 35°S, 170°W). At the basin scale, heterogeneous selection (selection under heterogeneous environmental conditions) dominated the assembly processes of all phytoplankton groups; however, its relative importance varied greatly at the climatic zonal scale, explaining the distinct latitudinal α- and β-diversity among phytoplankton groups. Assembly processes in Synechococcus and haptophyte communities were mainly controlled by physical and nutrient factors, respectively. High temperature drove Synechococcus communities to be more deterministic with higher diversity, while haptophyte communities were less environmentally selected at low latitudes due to their wide niche breadth and mixotrophic lifestyle. Diatom communities were overwhelmingly dominated by the selection process but with low correlation of measured environmental factors to their community compositions. This could be attributed to the high growth rate of diatoms, as indicated by their lower site occupation frequency than predicted in the neutral community model. Our study showed that heterogeneous selection is the main force that shaped the biogeography of three key phytoplankton groups in the Pacific Ocean, with a latitudinal variation of relative importance due to the distinct traits among phytoplankton. IMPORTANCE Phytoplankton are diverse and abundant as primary producers in the ocean, with diversity and community compositions varying spatially. How fundamental processes (e.g., selection, dispersal, and drift) regulate their global biogeography remains to be comprehensively explored. In this study, we disentangled the ecological processes of three key phytoplankton groups (i.e., diatoms, Synechococcus , and haptophytes) along the same latitudinal gradients in the Pacific Ocean. Heterogeneous selection, by promoting species richness and reducing similarity between communities, was the dominant process shaping the communities of each phytoplankton group at the basin scale. However, its relative importance varied greatly among different phytoplankton groups in different climate zones, explaining the uneven latitudinal α- and β-diversity. We also highlight the importance of identifying key factors mediating the relative importance of assembly processes in phytoplankton communities, which will enhance our understanding of their biogeography in the ocean and future patterns under climate changes.

Mesoscale eddies are ubiquitous oceanographic features that influence the metabolism and community structure of Synechococcus. However, the metabolic adaptations of this genus to eddy-associated environmental changes have rarely been studied. We recovered two high-quality Synechococcus metagenome-assembled genomes (MAGs) from eddies in the South China Sea and compared their metabolic variations using metatranscriptomic samples obtained at the same time. The two MAGs (syn-bin1 and syn-bin2) are affiliated with marine Synechococcus subclusters 5.2 (S5.2) and 5.3 (S5.3), respectively. The former exhibited a higher abundance at the surface layer, whereas the latter was more abundant in the deep euphotic layer. Further analysis indicated that syn-bin1 had a strong ability to utilize organic nutrients, which could help it to thrive in the nutrient-deprived surface water. By contrast, syn-bin2 had the genetic potential to perform chromatic acclimation, which could allow it to capture green or blue light at different depths. Additionally, transcriptomic analysis showed that syn-bin2 upregulated genes involved in the synthesis of C4 acids, photosystem II proteins, and HCO 3 - transporters in the deep euphotic layer, which might contribute to its predominance in low-light environments. Overall, this study expands our understanding of oceanic S5.2 and S5.3 Synechococcus by revealing their metabolic adaptations to mesoscale eddies., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Background: The dose-response relationship between patient engagement and long-term intervention effects in mobile health (mHealth) interventions are understudied. Studies exploring long-term and potentially changing relationships between patient engagement and health outcomes in mHealth interventions are needed., Objective: This study aims to examine dose-response relationships between patient engagement and 3 psychosocial outcomes in an mHealth intervention, Run4Love, using repeated measurements of outcomes at baseline and 3, 6, and 9 months., Methods: This study is a secondary analysis using longitudinal data from the Run4Love trial, a randomized controlled trial with 300 people living with HIV and elevated depressive symptoms to examine the effects of a 3-month mHealth intervention on reducing depressive symptoms and improving quality of life (QOL). We examined the relationships between patient engagement and depressive symptoms, QOL, and perceived stress in the intervention group (N=150) using 4-time-point outcome measurements. Patient engagement was assessed using the completion rate of course assignments and frequency of items completed. Cluster analysis was used to categorize patients into high- and low-engagement groups. Generalized linear mixed effects models were conducted to investigate the dose-response relationships between patient engagement and outcomes., Results: The cluster analysis identified 2 clusters that were distinctively different from each other. The first cluster comprised 72 participants with good compliance to the intervention, completing an average of 74% (53/72) of intervention items (IQR 0.22). The second cluster comprised 78 participants with low compliance to the intervention, completing an average of 15% (11/72) of intervention items (IQR 0.23). Results of the generalized linear mixed effects models showed that, compared with the low-engagement group, the high-engagement group had a significant reduction in more depressive symptoms (β=-1.93; P=.008) and perceived stress (β=-1.72; P<.001) and an improved QOL (β=2.41; P=.01) over 9 months. From baseline to 3, 6, and 9 months, the differences in depressive symptoms between the 2 engagement groups were 0.8, 1.6, 2.3, and 3.7 points, respectively, indicating widening between-group differences over time. Similarly, between-group differences in QOL and perceived stress increased over time (group differences in QOL: 0.9, 1.9, 4.7, and 5.1 points, respectively; group differences in the Perceived Stress Scale: 0.9, 1.4, 2.3, and 3.0 points, respectively)., Conclusions: This study revealed a positive long-term dose-response relationship between patient engagement and 3 psychosocial outcomes among people living with HIV and elevated depressive symptoms in an mHealth intervention over 9 months using 4 time-point repeat measurement data. The high- and low-engagement groups showed significant and widening differences in depressive symptoms, QOL, and perceived stress at the 3-, 6-, and 9-month follow-ups. Future mHealth interventions should improve patient engagement to achieve long-term and sustained intervention effects., Trial Registration: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://www.chictr.org.cn/showproj.aspx?proj=21019., (©Yiran Li, Yan Guo, Y Alicia Hong, Yu Zeng, Aliza Monroe-Wise, Chengbo Zeng, Mengting Zhu, Hanxi Zhang, Jiaying Qiao, Zhimeng Xu, Weiping Cai, Linghua Li, Cong Liu. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 04.01.2022.)

An angle estimation algorithm for tracking indoor moving targets with WiFi is proposed. First, phase calibration and static path elimination are proposed and performed on the collected channel state information signals from different antennas. Then, the angle of arrival information is obtained with the joint estimation algorithm of the angle of arrival (AOA) and time of flight (TOF). To deal with the multipath effects, we adopt the DBscan spatiotemporal clustering algorithm with adaptive parameters. In addition, the time-continuous angle of arrival information is obtained by interpolating and supplementing points to extract the dynamic signal paths better. Finally, the least-squares method is used for linear fitting to obtain the final angle information of a moving target. Experiments are conducted with the tracking data set presented with Tsinghua's Widar 2.0. The results show that the average angle estimation error with the proposed algorithm is smaller than Widar2.0. The average angle error is about 7.18° in the classroom environment, 3.62° in the corridor environment, and 12.16° in the office environment; they are smaller than the errors of the existing system.

Effects of nutrient-imbalanced diet on the growth and fitness of zooplankton were widely reported as key issues to aquatic ecology. However, little is known about the molecular mechanisms driving the physiological changes of zooplankton under nutrient stress.In this study, we investigated the physiological fitness and transcriptomic response of Daphnia magna when exposed to nitrogen (N)-limited or phosphorus (P)-limited algal diet ( Chlamydomonas reinhardtii ) compared to regular algae (N and P saturated). D. magna showed higher ingestion rates and overexpression of genes encoding digestive enzymes when fed with either N-limited or P-limited algae, reflecting the compensatory feeding. Under P-limitation, both growth rate and reproduction rate of D. magna were greatly reduced, which could be attributed to the downregulated genes within the pathways of cell cycle and DNA replication. Growth rate of D. magna under N-limitation was similar to normal group, which could be explained by the high methylation level (by degradation of methionine) supporting the body development.Phenotypic changes of D. magna under nutrient stress were explained by gene and pathway regulations from transcriptome data. Generally, D. magna invested more on growth under N-limitation but kept maintenance (e.g., cell structure and defense to external stress) in priority under P-limitation. Post-translational modifications (e.g., methylation and protein folding) were important for D. magna to deal with nutrient constrains.This study reveals the fundamental mechanisms of zooplankton in dealing with elemental imbalanced diet and sheds light on the transfer of energy and nutrient in aquatic ecosystems., Competing Interests: All authors declare no conflict of interest., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Counting the number of people and estimating their walking speeds are essential in crowd control and flow. In this work, we propose a system that uses prevalent Wi-Fi signals to identify the number of people entering and leaving a room through a door. It selects the best subcarrier of Wi-Fi signals and applies the Hampel filter to remove outlier information first. Then, it employs a double threshold method to determine the start and end times of entering or leaving. Afterward, it compares the detected signals with the precollected database using the dynamic time-warping algorithm and determines the number of people. It uses a variance threshold method to identify the states of entering or leaving. It also employs a nonlinear fitting approach to calculate the walking speeds. The experiments show that, in a large empty laboratory, the accuracy rates in determining the number of people are 100% for one person, 81% for two persons, and 95% for three persons. In a small office, the accuracy rates for detecting the number of people are 98% for one or two persons, 82% for three persons, 93% for four, and 75% for five persons. For the walking speed estimation, the accuracy rate for a speed error of less than 0.2410 m/s is 75% for a single person.

Ischemic heart disease (IHD) is defined as a syndrome of ischemic cardiomyopathy. Myogenesis and angiogenesis in the ischemic myocardium are important for cardiomyocyte (CM) survival, improving cardiac function and decreasing the progression of heart failure after IHD. Cellular senescence is a state of permanent irreversible cell cycle arrest caused by stress that results in a decline in cellular functions, such as proliferation, migration, homing, and differentiation. In addition, senescent cells produce the senescence-associated secretory phenotype (SASP), which affects the tissue microenvironment and surrounding cells by secreting proinflammatory cytokines, chemokines, growth factors, and extracellular matrix degradation proteins. The accumulation of cardiovascular-related senescent cells, including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), CMs and progenitor cells, is an important risk factor of cardiovascular diseases, such as vascular aging, atherosclerotic plaque formation, myocardial infarction (MI) and ventricular remodeling. This review summarizes the processes of angiogenesis, myogenesis and cellular senescence after IHD. In addition, this review focuses on the relationship between cellular senescence and cardiovascular disease and the mechanism of cellular senescence. Finally, we discuss a potential therapeutic strategy for MI targeting senescent cells., Competing Interests: Conflicts of Interest The authors declare that they have no competing interests, and all authors can confirm the accuracy of this statement., (copyright: © 2021 Yan et al.)

Background: Nutrient stoichiometry of phytoplankton frequently changes with aquatic ambient nutrient concentrations, which is mainly influenced by anthropogenic water treatment and the ecosystem dynamics. Consequently, the stoichiometry of phytoplankton can markedly alter the metabolism and growth of zooplankton. However, the effects of nutrient-imbalanced prey on the interplay between zooplankton and their gut microbiota remain unknown. Using metatranscriptome, a 16 s rRNA amplicon-based neutral community model (NCM) and experimental validation, we investigated the interactions between Daphnia magna and its gut microbiota in a nutrient-imbalanced algal diet., Results: Our results showed that in nutrient-depleted water, the nutrient-enriched zooplankton gut stimulated the accumulation of microbial polyphosphate in fecal pellets under phosphorus limitation and the microbial assimilation of ammonia under nitrogen limitation. Compared with the nutrient replete group, both N and P limitation markedly promoted the gene expression of the gut microbiome for organic matter degradation but repressed that for anaerobic metabolisms. In the nutrient limited diet, the gut microbial community exhibited a higher fit to NCM (R 2  = 0.624 and 0.781, for N- and P-limitation, respectively) when compared with the Control group (R 2  = 0.542), suggesting increased ambient-gut exchange process favored by compensatory feeding. Further, an additional axenic grazing experiment revealed that the growth of D. magna can still benefit from gut microbiota under a nutrient-imbalanced diet., Conclusions: Together, these results demonstrated that under a nutrient-imbalanced diet, the microbes not only benefit themselves by absorbing excess nutrients inside the zooplankton gut but also help zooplankton to survive during nutrient limitation.

The emergence of the new coronavirus (nCoV-19) has impacted human health on a global scale, while the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under the current adverse situation, we employ virtual screening tools in searching for drugs and natural products which have been already deposited in DrugBank in an attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Additionally, we have built an interactive online platform (https://shennongproject.ai/) for browsing these results with the visual display of a small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory work, it may serve not only as the assessment tool for the new drug discovery but also an educational web site for the public.

Despite a strong evidence on the negative association between HIV-related stigma and quality of life (QoL), few studies have examined the indirect effects of this relationship. This study aimed to examine the association between HIV-related stigma and QoL and the indirect effects of positive coping and perceived stress in people living with HIV and depressive symptoms (PLWHD). This study used baseline date from a randomized controlled trial. Structural equation model was used to examine the association between HIV-related stigma and QoL as well as the indirect effects of positive coping and perceived stress. Perceived and internalized stigma had negative direct ( β  = -0.14, p  < 0.05) effect on QoL. Moreover, perceived and internalized stigma had indirect effects on QoL through decreased positive coping and increased perceived stress ( β  = -0.23, p  < 0.001). Multilevel interventions to reduce perceived and internalized stigma and perceived stress as well as programs to enhance positive coping may improve QoL of PLWHD. Integrated interventions that both enhance positive coping and reduce perceived stress and stigma are potentially more effective in improving QoL than programs that focus on only one aspect of stigma reduction among PLWHD.

Background: People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population., Objective: The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China., Methods: We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants' hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants' progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument., Results: Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=-5.77, 95% CI -7.82 to -3.71; P<.001; standard effect size d=0.66). The mean changes in CES-D score from baseline to the 6- and 9-month follow-ups between the two groups remained statistically significant. No adverse events were reported., Conclusions: The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention., Trial Registration: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF)., (©Yan Guo, Y Alicia Hong, Weiping Cai, Linghua Li, Yuantao Hao, Jiaying Qiao, Zhimeng Xu, Hanxi Zhang, Chengbo Zeng, Cong Liu, Yiran Li, Mengting Zhu, Yu Zeng, Frank J Penedo. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.02.2020.)

Few studies have examined the relationship between inconsistent condom use and sexual partnership characteristics among people living with HIV (PLWH). The current study focused on such association and its gender differences. The study was conducted in a large hospital in South China in 2013. A total of 320 dyads (PLWH indexes and their sexual partners) were recruited from an outpatient clinic using convenience sampling. The proportion of inconsistent condom use in the last six months among female indexes was higher than that among male indexes (52.4% vs. 43.6%). Of sexual partnership characteristics, HIV seropositive status was a risk factor for inconsistent condom use for both male and female indexes (aOR = 2.32, 95%CI = 1.15∼4.66, aOR = 3.09, 95%CI = 1.10∼8.67, respectively). For male indexes, lower educational level was also a risk factor (aOR = 2.39, 95%CI = 1.23∼4.67); while having had emotionally intimate relationships was a protective factor (aOR = 0.40, 95%CI = 0.21∼0.77). For female indexes, receiving material support was a risk factor (aOR = 10.17, 95%CI = 2.13∼48.61) and receiving health-related advice was a protective factor (aOR = 0.11, 95%CI = 0.02∼0.55). Future HIV interventions for PLWH need to be gender-sensitive and include their sexual partners.

Background: People living with HIV and depression have high rates of suicide. Studies of mobile health (mHealth) interventions have shown feasibility, acceptability, and efficacy in improving mental health in people living with HIV and depression. However, few studies have examined the mechanisms and effects of mHealth interventions on suicide., Objective: This study was designed to examine the mechanisms and effects of a WeChat-based intervention, Run4Love, on suicide among people living with HIV and depression in China, while considering perceived stress and depressive symptoms as mediators., Methods: A sample of 300 People living with HIV and depression was recruited from the outpatient clinic of a large HIV or AIDS treatment hospital and was randomized to the Run4Love group or a control group. Data were collected at baseline, 3-, 6-, and 9-month follow-ups. Path analysis modeling, with longitudinal data, was used in data analyses., Results: The Run4Love mHealth intervention had a direct effect on reducing suicide rate at the 6-month follow-up (beta=-.18, P=.02) and indirect effect through reducing perceived stress and depressive symptoms at the 3-month follow-up (beta=-.09, P=.001). A partial mediating effect between perceived stress and depressive symptoms accounted for 33% (-0.09/-0.27) of the total effect., Conclusions: Through path analyses, we understood the mechanisms and effects of an mHealth intervention on suicide prevention. The findings underscored the importance of stress reduction and depression treatment in such a program. We call for more effective suicide prevention, especially mHealth interventions targeting the vulnerable population of people living with HIV and depression., Trial Registration: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showprojen.aspx?proj=21019., (©Yiran Li, Yan Guo, Y Alicia Hong, Mengting Zhu, Chengbo Zeng, Jiaying Qiao, Zhimeng Xu, Hanxi Zhang, Yu Zeng, Weiping Cai, Linghua Li, Cong Liu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.11.2019.)

Background: Although several studies have investigated the effects of mobile health (mHealth) interventions on depression among people living with HIV, few studies have explored mediators of mHealth-based interventions to improve mental health in people living with HIV. Identifying influential mediators may enhance and refine effective components of mHealth interventions to improve mental health of people living with HIV., Objective: This study aimed to examine mediating factors of the effects of a mHealth intervention, Run4Love, designed to reduce depression among people living with HIV using 4 time-point measurement data., Methods: This study used data from a randomized controlled trial of a mHealth intervention among people living with HIV with elevated depressive symptoms in Guangzhou, China. A total of 300 patients were assigned to receive either the mHealth intervention (n=150) or a waitlist control group (n=150) through computer-generated block randomization. Depressive symptoms, coping, and HIV-related stigma were measured at baseline, 3-, 6-, and 9-month follow-ups. The latent growth curve model was used to examine the effects of the intervention on depressive symptoms via potential mediators. Mediating effects were estimated using bias-corrected 95% bootstrapped CIs (BCIs) with resampling of 5000., Results: Enhanced positive coping and reduced HIV-related stigma served as effective treatment mediators in the mHealth intervention. Specially, there was a significant indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of positive coping (beta=-2.86; 95% BCI -4.78 to -0.94). The indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of HIV-related stigma was also statistically significant (beta=-1.71; 95% BCI -3.03 to -0.40). These findings indicated that enhancement of positive coping and reduction of HIV-related stigma were important mediating factors of the mHealth intervention in reducing depression among people living with HIV., Conclusions: This study revealed the underlying mediators of a mHealth intervention to reduce depression among people living with HIV using latent growth curve model and 4 time-point longitudinal measurement data. The study results underscored the importance of improving positive coping skills and mitigating HIV-related stigma in mHealth interventions to reduce depression among people living with HIV., (©Mengting Zhu, Weiping Cai, Linghua Li, Yan Guo, Aliza Monroe-Wise, Yiran Li, Chengbo Zeng, Jiaying Qiao, Zhimeng Xu, Hanxi Zhang, Yu Zeng, Cong Liu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 15.11.2019.)

Background: The prognostic value of tumor deposit (TD) in gastric cancer is controversial. This study aims to investigate the prognostic value of TD., Methods: The consecutive patients diagnosed with gastric cancer from October 2007 to October 2012 were selected. The patients were divided by whether they suffered TD into two groups. The basic data were comparable between the two groups after propensity score matching (PSM), then survival analysis [overall survival (OS) and cancer-specific survival (CSS)] was applied in two groups. After that, all the patients were divided by pN staging and survival analysis were applied in each subgroup. At last, all patients were divided into TD group, pN1 stage group, pN2 stage group, pN3a, and pN3b stage group, OS and CSS were compared between them. Multivariable competing risk analyses tested association of TD with OS and CSS, before and after PSM., Results: Eight hundred and three patients were concluded. After PSM, 137 patients with TD and 274 patients without TD were selected, the 5-year OS and CSS rates of patients with TD were significantly worse than patients without TD (OS: 19.7% vs. 42.0%, P<0.001; CSS: 22.6% vs. 45.6%, P<0.001). In all patients' survival analysis, the 5-year OS and CSS rates of TD group were comparable with pN3a group (OS: 19.7% vs. 25.3%, P=0.221, CSS: 22.6% vs. 30.1%, P=0.092) and pN3b group (OS: 19.7% vs. 19.6% P=0.349, CSS: 22.6% vs. 23.5%, P=0.452). Meanwhile, on multivariable cox regression analyses, the presence of TD significantly reduces the OS and CSS of patients in gastric cancer., Conclusions: TD has a marked impact on the prognosis of gastric cancer. Even patients with TD had the same prognosis with pN3 stage., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Unemployment is associated with depression in people living with HIV (PLWH). However, few studies have examined the effects of unemployment on PLWH with different levels of depression. The current study explores the plausible differential effects of unemployment on the different percentiles of depression in PLWH employing a quantile regression (QR) approach, based on a recent survey of 411 PLWH in China. Among participants, 47.7% had elevated depressive symptoms, and 23.8% were unemployed. The effects of unemployment on depression were statistically significant with a trend of initial increase followed by a decline at the quantile levels of 0.51-0.90 of depression. The maximum effect of unemployment status on depression was statistically significant at the 70th and 75th percentiles of depression (coefficient = 7.0, p  < .01). Tailored strategies and interventions should be implemented to address the differential needs of PLWH with various levels of depressive symptoms.

Insufficient nutrients supply will greatly affect the function of cardiac myocytes. The adaptive responses of cardiac myocytes to nutritional stress are not fully known. Ginsenoside Rg1 is one of the most pharmacologically active components in Panax Ginseng and possesses protective effects on cardiomyocyte. Here, we investigate the effects of ginsenoside Rg1 on H9c2 cells which were subjected to nutritional stress. Nutritional stress-induced by glucose deprivation strongly induced cell death and this response was inhibited by ginsenoside Rg1. Importantly, glucose deprivation decreased intracellular ATP levels and mitochondrial membrane potential. Ginsenoside Rg1 rescued ATP levels and mitochondrial membrane potential in nutrient-starved cells. For molecular mechanisms, ginsenoside Rg1 increased the expressions of PTEN-induced kinase 1 (PINK1) and p-AMPK in glucose deprivation treated H9c2 cells. Reducing the expression of aldolase in H9c2 cells inhibited ginsenoside Rg1's actions on PINK1 and p-AMPK. Further, the nutritional stress mice were used to verify the mechanisms obtained in vitro. Ginsenoside Rg1 increased the expressions of aldolase, p-AMPK, and PINK1 in starved mice heart. Taken together, our results reveal that ginsenoside Rg1 limits nutritional stress-induced H9c2 cells injury by regulating the aldolase /AMP-activated protein kinase/PINK1 pathway., (© 2019 Wiley Periodicals, Inc.)

Although Cas9 nucleases are remarkably diverse in microorganisms, the range of genomic sequences targetable by a CRISPR/Cas9 system is restricted by the requirement of a short protospacer adjacent motif (PAM) at the target site. Here, we generate a group of chimeric Cas9 (cCas9) variants by replacing the key region in the PAM interaction (PI) domain of Staphylococcus aureus Cas9 (SaCas9) with the corresponding region in a panel of SaCas9 orthologs. By using a functional assay at target sites with different nucleotide recombinations at PAM position 3-6, we identify several cCas9 variants with expanded recognition capability at NNVRRN, NNVACT, NNVATG, NNVATT, NNVGCT, NNVGTG, and NNVGTT PAM sequences. In summary, we provide a panel of cCas9 variants accessible up to 1/4 of all the possible genomic targets in mammalian cells.

Background: Most people living with HIV (PLWH) reside in middle- and low-income countries with limited access to health services. Thus, cost-effective interventions that can reach a large number of PLWH are urgently needed., Objective: The objective of our study was to assess the feasibility and acceptability of an mHealth intervention among PLWH in China., Methods: Based on previous formative research, we designed an mHealth intervention program that included sending weekly reminders to participants via text messages (short message service, SMS) and articles on HIV self-management three times a week via a popular social media app WeChat. A total of 62 PLWH recruited from an HIV outpatient clinic were randomly assigned to intervention or control group. The intervention lasted for 3 months, and all participants were assessed for their medication adherence, presence of depression, quality of life (QoL), and CD4 (cluster of differentiation 4) counts. Upon completing the intervention, we interviewed 31 participants to further assess the feasibility and acceptability of the study., Results: At baseline, the intervention and control groups did not differ in terms of demographic characteristics or any of the major outcome measures. About 85% (53/62) of the participants completed the intervention, and they provided valuable feedback on the design and content of the intervention. Participants preferred WeChat as the platform for receiving information and interactive communication for ease of access. Furthermore, they made specific recommendations about building trust, interactive features, and personalized feedback. In the follow-up assessment, the intervention and control groups did not differ in terms of major outcome measures., Conclusions: This pilot study represents one of the first efforts to develop a text messaging (SMS)- and WeChat-based intervention that focused on improving the medication adherence and QoL of PLWH in China. Our data indicates that an mHealth intervention is feasible and acceptable to this population. The data collected through this pilot study will inform the future designs and implementations of mHealth interventions in this vulnerable population. We recommend more innovative mHealth interventions with rigorous designs for the PLWH in middle- and low-income countries., Trial Registration: Chinese Clinical Trial Registry ChiCTR1800017987; http://www.chictr.org.cn/showprojen.aspx?proj=30448 (Archived by WebCite at http://www.webcitation.org/71zC7Pdzs)., Registered Report Ientifier: RR1-10.2196/., (©Yan Guo, Zhimeng Xu, Jiaying Qiao, Y Alicia Hong, Hanxi Zhang, Chengbo Zeng, Weiping Cai, Linghua Li, Cong Liu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.09.2018.)

Marine microbial eukaryotes are ubiquitous, comprised of phylogenetically diverse groups and play key roles in microbial food webs and global biogeochemical cycling. However, their vertical distribution in the deep sea has received little attention. In this study, we investigated the composition and diversity of the eukaryotes of both 0.2-3 μm and >3 μm size fractions from the surface to the hadal zone (8727 m) of the Mariana Trench using Illumina MiSeq sequencing for the 18S rDNA. The microbial eukaryotic community structure differed substantially across size fractions and depths. Operational taxonomic unit (OTU) richness in the >3 μm fraction was higher than that in the 0.2-3 μm fraction at the same depth. For the 0.2-3 μm fraction, sequences of Retaria (Rhizaria) were most abundant in the surface water (53.5%). Chrysophyceae (Stramenopiles) sequences dominated mostly in the samples from water depths below 1795 m. For the >3 μm fraction, sequences of Dinophyceae (Alveolata) were most abundant in surface waters (49.3%) and remained a significant proportion of total sequences at greater depths (9.8%, on average). Retaria sequences were abundant in samples of depths ≥1000 m. Amoebozoa and Apusozoa sequences were enriched in the hadal sample, comprising 38 and 20.4% of total sequences, respectively. Fungi (Opisthokonta) sequences were most abundant at 1759 m in both size fractions. Strong positive associations were found between Syndiniales (mainly MALV-I and MALV-II) and Retaria while negative associations were shown between MALV-II and Fungi in a co-occurrence analysis. This study compared the community structure of microbial eukaryotes in different zones in the deep sea and identified a distinct hadal community in the larger size fraction, suggesting the uniqueness of the eukaryotes in the biosphere in the Mariana Trench.

Background: People living with HIV (PLWH) suffer from high rates of mental illness; but targeted effective interventions are limited, especially in developing countries. High penetration of smartphone usage and widespread acceptance of social media applications provide an unprecedented opportunity for mobile-based health interventions (mHealth interventions) in resource-limited settings like China. The current report describes the design and sample characteristics of the Run4Love randomized controlled trial (RCT) aimed at improving mental health in PLWH in China., Methods: A total of 300 PLWH with elevated depressive symptoms were recruited and randomized into either the intervention or control group. Participants in the intervention group received an adapted cognitive-behavioral stress management (CBSM) course delivered by the enhanced WeChat platform (for 3 months) and were motivated to engage in physical activities. Progress of the participants was automatically tracked and monitored with timely feedback and rewards. The control group received a brochure on nutrition for PLWH in addition to standard care. The outcome assessments are conducted at baseline, 3, 6, and 9 months using tablets. The primary outcome is depressive symptoms measured by the scale of the Center for Epidemiology Studies Depression (CES-D). Secondary outcomes include quality of life, chronic stress measured with biomarker of hair cortisol, and other measures of stress and depression, self-efficacy, coping, HIV-related stigma, physical activity, and patient satisfaction. Mixed effects model with repeated measures (MMRM) will be used to analyze the intervention effects., Discussion: The Run4Love study is among the first efforts to develop and evaluate a multicomponent and integrated mHealth intervention to improve the mental health and quality of life of PLWH. Once proven effective, Run4Love could be scaled up and potentially integrated into the routine case management of PLWH and adapted to other populations with chronic diseases., Trial Registration: Chinese Clinical Trial Registry - ChiCTR-IPR-17012606 , registered on 07 September 2017.

Aim: To investigate the effects of emodin on the treatment of non-alcoholic fatty liver in rats induced by liquid fructose-feeding in rats and the possible underlying mechanisms., Methods: Sprague-Dawley rats were divided into the control, fructose-feeding group, and three fructose-feeding groups treated with 40, 80 and 160 mg/kg emodin, respectively. After 4 weeks of feeding, liquid consumption, food intake, bodyweight, liver index, serum triglyceride (TG), glucose and aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), liver TG contents and histology features were examined. The hepatic expression of lipogenic and fatty acid oxidation key enzymes, and an upstream transcriptional factor, sterol regulatory element-binding protein 1c (SREBP1c) were determined. Glucose regulated protein 78 (GRP78), a liver endoplasmic reticulum stress (ERS) marker and the unfolded protein response (UPR) related proteins were also measured., Results: Emodin reduced bodyweight, liver index, serum TG levels of fructose-feeding rats with no significant difference in serum glucose, AST and ALT levels. Emodin improved hepatic steatosis by inhibiting SREBP1c activation and its target genes, and enhancing carnitine palmitoyltransferase 1 expression in fructose-feeding rats. Emodin resolved hepatic ERS and the UPR induced by liquid fructose in rats., Conclusion: Emodin is capable of improving the lipid accumulation through the ERS-SREBP1c pathway in fructose-induced non-alcoholic fatty liver disease., (© 2015 The Japan Society of Hepatology.)

Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochondrial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechanism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet- and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catalpol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and increased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameliorate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events., (© The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.)

Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin-induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mitochondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice daily for 4 weeks. Body weight (BW), fasting blood glucose (FBG) level, and glucose disposal (IPGTT) were measured during or after the treatment. The results showed a dose-dependent reduction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total cholesterol and triglyceride levels in the diabetic mice. In addition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol (200 mg/kg) rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) α was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol, resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal muscle of HFD/STZ-induced diabetic mice., (© The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.)