Scalable batch-correction approach for integrating large-scale single-cell transcriptomes.

Integration of accumulative large-scale single-cell transcriptomes requires scalable batch-correction approaches. Here we propose Fugue, a simple and efficient batch-correction method that is scalable for integrating super large-scale single-cell transcriptomes from diverse sources. The core idea of the method is to encode batch information as trainable parameters and add it to single-cell expression profile; subsequently, a contrastive learning approach is used to learn feature representation of the additive expression profile. We demonstrate the scalability of Fugue by integrating all single cells obtained from the Human Cell Atlas. We benchmark Fugue against current state-of-the-art methods and show that Fugue consistently achieves improved performance in terms of data alignment and clustering preservation. Our study will facilitate the integration of single-cell transcriptomes at increasingly large scale.

A universal approach for integrating super large-scale single-cell transcriptomes by exploring gene rankings.

Advancement in single-cell RNA sequencing leads to exponential accumulation of single-cell expression data. However, there is still lack of tools that could integrate these unlimited accumulations of single-cell expression data. Here, we presented a universal approach iSEEEK for integrating super large-scale single-cell expression via exploring expression rankings of top-expressing genes. We developed iSEEEK with 11.9 million single cells. We demonstrated the efficiency of iSEEEK with canonical single-cell downstream tasks on five heterogenous datasets encompassing human and mouse samples. iSEEEK achieved good clustering performance benchmarked against well-annotated cell labels. In addition, iSEEEK could transfer its knowledge learned from large-scale expression data on new dataset that was not involved in its development. iSEEEK enables identification of gene-gene interaction networks that are characteristic of specific cell types. Our study presents a simple and yet effective method to integrate super large-scale single-cell transcriptomes and would facilitate translational single-cell research from bench to bedside.

Aggregation-Induced Emission Phosphorescence Featured Au-Ag Coordination Polymer with a Diphosphine N-Heterocyclic Carbene Ligand for Highly Sensitive Detection of Cr(VI).

Luminescent materials with aggregation-induced emission (AIE) characteristics have been recognized as highly selective and sensitive probes for the detection of toxic metal ions in recent years. In this paper, a Au-Ag cluster-based coordination polymer [Au3Ag3(L)2(CN)6(H2O)2]n [1, L = 1,3-bis((diphenylphosphanyl)methyl)-4,5-dihydro-imidazolylidene] was prepared by in situ generation of the diphosphine N-heterocyclic carbene (PCNHCP)-type ligand L in the presence of the corresponding metal salts. Compound 1 exhibited 530 nm phosphorescence under 380 nm excitation with a QY of 6.30% and a lifetime (τ) of 7.14 µs in the solid state. 1 showed good AIE behavior in the mixture of MeOH/H2O while the best aggregation state (fwater = 90%, QY = 6.79%, τ = 6.70 µs) exhibited selective and sensitive emission quenching toward Cr(VI) ions. Ultralow detection limits of 9.7 ppb (w/w) for Cr2O72- and 17.9 ppb (w/w) for CrO42- were achieved.

One-Dimensional Heterobimetallic Au/Ag Coordination Polymer Showing a Selective, Reversible, and Visible Vapor-Chromic Photoluminescent Response toward Methanol.

A heterobimetallic coordination polymer [Au4(dppmt)4(AgCl)2]n (1) incorporating an in situ generated P-S ligand (dppmtH) was synthesized from the solvothermal reaction of Au(tht)Cl, AgCl, and dpppyatc in CH3CN/CH2Cl2 (dppmtH = (diphenylphosphino)methanethiol, tht = tetrahydrothiophene, dpppyatc = N,N-bis((diphenylphosphaneyl)methyl)-N-(pyridin-2-yl)-amino-thiocarbamide). The structure of 1 contains a one-dimensional helical Au-Au chain in which the unique [Au4Ag2S2] cluster units are connected by [Au2(dppmt)2] dimers. Upon excitation at 343 nm, 1 exhibited cyan (495 nm) phosphorescent emission at quantum yield (QY) = 22.3% and τ = 0.78 µs (λex = 375 nm). Coordination polymer 1 exhibited a rapid, selective, reversible, and visible vapor-chromic response on exposure to methanol (MeOH) vapor with its emission shifting to a more intense green (530 nm, λex = 388 nm) with QY = 46.8% and τ = 1.24 µs (λex = 375 nm). A polymethylmethacrylate film containing 1 served as a reversible chemical sensor for the sensitive detection of MeOH in air.

Salmonellosis outbreak archive in China: data collection and assembly.

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.

Influence of chronic diseases on the occurrence of depression: A 13-year follow-up study from the Survey of Health, Ageing and Retirement in Europe.

The causal association between chronic diseases and depression remains unclear. This study aimed to explore the effects of types and number of chronic diseases on the risk of depression using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). A self-admitted questionnaire was used to obtain data on 14 predefined chronic diseases and the European-Depression Scale (EURO-D) was used to assess depression. Among the 16,080 baseline depression-free participants aged 50+, 31.29% (5032) developed depression over 13 years. Multivariate Cox regression models showed that individuals with any chronic diseases were at higher risk of new onset depression compared to disease-free participants. The risk of new onset depression increased with an increasing number of diseases among both younger (50-64) and older (65+) adults. Individuals with heart attack, stroke, diabetes, chronic lung disease, and arthritis were at increased risk of depression across age groups. However, some age-specific associations were observed, with cancer increasing depression risk among younger- and peptic ulcer, Parkinson's disease and cataracts increasing depression risk among older adults. These findings highlight the importance of managing chronic diseases, especially among those with more than two diseases, to prevent the development of depression among middle-aged and older adults.

Infant food production environments: A potential reservoir for vancomycin-resistant enterococci non-nosocomial infections.

Enterococcus has been considered one of the most important nosocomial pathogens for human infections, and the hospital environment is an important reservoir for vancomycin-resistant enterococci (VRE) that leads to antimicrobial therapeutic failure. However, infant foods and their production environments could pose risks for the immature population, while this question remains unaddressed. This study conducted an extensive and thorough Enterococcus isolation, VRE risk assessment of the Chinese infant food production chains and additional online-marketing infant foods, including powdered infant formula (PIF) and infant complementary food (ICF). To investigate the prevalence of Enterococcus along infant food chains and commodities, a total of 482 strains of Enterococcus, including E. faecium (n = 363), E. faecalis (n = 84), E. casseliflavus (n = 13), E. mundtii (n = 12), E. gallinarum (n = 4), E. hirae (n = 4), and E. durans (n = 2) were recovered from 459 samples collected from infant food production chains (71/254) and food commodities (67/205). A decreasing trend for Enterococcus detection rate was found in the PIF production chain (PIF-PC), particularly during the preparation of the PIF base powder (From 100 % in raw milk to 8.70 % in end products), while an increasing trend was observed in the ICF production chain (ICF-PC) mainly during the initial processing of farm crops and the further processing of the product (20 % at farm crops increasing to 76.92 % at end products). The result indicated that the PIF-PC process effectively reduced Enterococcus contamination, while the ICF-PC showed the opposite trend. Importantly, eleven VRE isolates were recovered from the infant food production chain, including seven E. casseliflavus isolates carrying vanC2/C3 and four E. gallinarum isolates carrying vanC1. Ten VRE isolates were from food production environments. Collectively, our study demonstrated that infant food production environments represent potential reservoirs for VRE non-nosocomial infections in vulnerable populations.

A Cross-Sectional Study of Companion Animal-Derived Multidrug-Resistant Escherichia coli in Hangzhou, China.

Antimicrobial resistance poses a challenge to global public health, and companion animals could serve as the reservoir for antimicrobial-resistant bacteria. However, the prevalence of antimicrobial-resistant bacteria, especially multidrug-resistant (MDR) bacteria, and the associated risk factors from companion animals are partially understood. Here, we aim to investigate the prevalence of MDR Escherichia coli, as an indicator bacterium, in pet cats and dogs in Hangzhou, China, and evaluate the factors affecting the prevalence of MDR E. coli. The proportion of pets carrying MDR E. coli was 35.77% (49/137), i.e., 40.96% (34/83) for dogs and 27.28% (15/54) for cats. Isolates resistant to trimethoprim-sulfamethoxazole (49.40% and 44.44%), amoxicillin-clavulanic acid (42.17% and 38.89%), and nalidixic acid (40.96% and 35.19%) were the most prevalent in dogs and cats. Interestingly, comparable prevalence of MDR E. coli was observed in pet dogs and cats regardless of the health condition and the history of antibiotic use. Genetic diversity analysis indicates a total of 86 sequencing types (23 clonal complexes), with ST12 being the most dominant. Further genomic investigation of a carbapenem-resistant E. coli ST410 isolate reveals abundant antimicrobial-resistance genes and a plasmid-borne carbapenemase gene (NDM-5) flanked by insertion sequences of IS91 and IS31, suggesting the plasmid and insertion sequences may be involved in carbapenem-resistance dissemination. These data show that companion animal-derived MDR bacteria could threaten public health, and further regulation and supervision of antimicrobial use in pet clinics should be established in China. IMPORTANCE MDR Escherichia coli are considered a global threat because of the decreasing options for antimicrobial therapy. Companion animals could be a reservoir of MDR E. coli, and the numbers of pets and households owning pets in China are booming. However, the prevalence and risk factors of MDR E. coli carriage in Chinese pets were rarely studied. Here, we investigated the prevalence of MDR E. coli in pets in Hangzhou, one of the leading cities with the most established pet market in China, and explored the factors that affected the prevalence. Our findings showed high prevalences of MDR E. coli in pet dogs and cats regardless of their health condition and the history of antibiotic use, suggesting their potential role of public health risk. A call-to-action for improved regulation of antimicrobial use in companion animal is needed in China.

An integrated nationwide genomics study reveals transmission modes of typhoid fever in China.

IMPORTANCE: Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.

Generative pretraining from large-scale transcriptomes for single-cell deciphering.

Exponential accumulation of single-cell transcriptomes poses great challenge for efficient assimilation. Here, we present an approach entitled generative pretraining from transcriptomes (tGPT) for learning feature representation of transcriptomes. tGPT is conceptually simple in that it autoregressive models the ranking of a gene in the context of its preceding neighbors. We developed tGPT with 22.3 million single-cell transcriptomes and used four single-cell datasets to evalutate its performance on single-cell analysis tasks. In addition, we examine its applications on bulk tissues. The single-cell clusters and cell lineage trajectories derived from tGPT are highly aligned with known cell labels and states. The feature patterns of tumor bulk tissues learned by tGPT are associated with a wide range of genomic alteration events, prognosis, and treatment outcome of immunotherapy. tGPT represents a new analytical paradigm for integrating and deciphering massive amounts of transcriptome data and it will facilitate the interpretation and clinical translation of single-cell transcriptomes.

Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer.

INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) is over-activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3 was attributed to either up-regulated phosphorylation by several tyrosine-kinases or down-regulated activity of phosphatases. Although several factors have been identified to phosphorylate STAT3, it remains unclear how STAT3 is dephosphorylated by PTPMeg2. The aim of this study was to determine the role of PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast cancers. METHODS: Immunoprecipitation assays were used to study the interaction of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231 (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo. Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated STAT3. RESULTS: PTPMeg2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine phosphorylation of STAT3 while depletion of PTPMeg2 increased its phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with suppression of STAT3 transcriptional activity and reduced tumor growth in vitro and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated in breast cancer tissues (P = 0.004). CONCLUSIONS: PTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development.

Prevalence and Genomic Investigation of Multidrug-Resistant Salmonella Isolates from Companion Animals in Hangzhou, China.

Salmonella is a group of bacteria that constitutes the leading cause of diarrheal diseases, posing a great disease burden worldwide. There are numerous pathways for zoonotic Salmonella transmission to humans; however, the role of companion animals in spreading these bacteria is largely underestimated in China. We aimed to investigate the prevalence of Salmonella in pet dogs and cats in Hangzhou, China, and characterize the antimicrobial resistance profile and genetic features of these pet-derived pathogens. In total, 137 fecal samples of pets were collected from an animal hospital in Hangzhou in 2018. The prevalence of Salmonella was 5.8% (8/137) in pets, with 9.3% (5/54) of cats and 3.6% (3/83) of dogs being Salmonella positive. By whole-genome sequencing (WGS), in silico serotyping, and multilocus sequence typing (MLST), 26 pet-derived Salmonella isolates were identified as Salmonella Dublin (ST10, n = 22) and Salmonella Typhimurium (ST19, n = 4). All of the isolates were identified as being multidrug-resistant (MDR), by conducting antimicrobial susceptibility testing under both aerobic and anaerobic conditions. The antibiotics of the most prevalent resistance were streptomycin (100%), cotrimoxazole (100%), tetracycline (96.20%), and ceftriaxone (92.30%). Versatile antimicrobial-resistant genes were identified, including floR (phenicol-resistant gene), blaCTX-M-15, and blaCTX-M-55 (extended-spectrum beta-lactamase genes). A total of 11 incompatible (Inc) plasmids were identified, with IncA/C2, IncFII(S), and IncX1 being the most predominant among Salmonella Dublin, and IncFIB(S), IncFII(S), IncI1, and IncQ1 being the most prevailing among Salmonella Typhimurium. Our study applied WGS to characterize pet-derived Salmonella in China, showing the presence of MDR Salmonella in pet dogs and cats with a high diversity of ARGs and plasmids. These data indicate a necessity for the regular surveillance of pet-derived pathogens to mitigate zoonotic diseases.

Work-Related Stress and Occurrence of Cardiovascular Disease: A 13-Year Prospective Study.

OBJECTIVE: The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD). METHODS: A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association. RESULTS: High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk. CONCLUSIONS: Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD.

A photoluminescent thermometer made from a thermoresponsive tetranuclear gold complex and phosphor N630.

Reaction of [(3-bdppmapy)(AuCl)2] with NaHmba (3-bdppmapy = N,N'-bis-(diphenylphosphanylmethyl-3-aminopytidine, H2mba = 2-mercaptobenzoic acid) resulted in a new tetranuclear Au/P/S complex [(3-bdppmapy)2(AuHmba)3(AuCl)] (1). Upon excitation at 370 nm, 1 exhibited solid state, room temperature, green fluorescent emission (QY = 4.7%, τ = 2.58 ns) which was significantly enanced at lower temperatures due to strengthening of the Au-Au interaction. Different ratios of 1 with phosphor N630 in PMMA were used to make thermochromic photoluminescent films and fibres that could be fabricated into an optical thermometer sensitive over temperature ranges 80-300 K and 300-370 K.

Prediction of Two Molecular Subtypes of Gastric Cancer Based on Immune Signature.

Gastric cancer is the fifth most common type of human cancer and the third leading cause of cancer-related death. The purpose of this study is to investigate the immune infiltration signatures of gastric cancer and their relation to prognosis. We identified two distinct subtypes of gastric cancer (C1/C2) characterized by different immune infiltration signatures. C1 is featured by immune resting, epithelial-mesenchymal transition, and angiogenesis pathways, while C2 is featured by enrichment of the MYC target, oxidative phosphorylation, and E2F target pathways. The C2 subtype has a better prognosis than the C1 subtype (HR = 0.61, 95% CI: 0.44-0.85; log-rank test, p = 0.0029). The association of C1/C2 with prognosis remained statistically significant (HR = 0.62, 95% CI: 0.44-0.87; p = 0.006) after controlling for age, gender, and stage. The prognosis prediction of C1/C2 was verified in four independent cohorts (including an internal cohort). In summary, our study is helpful for better understanding of the association between immune infiltration and the prognosis of gastric cancer.

Transcriptomic Analysis Identified Two Subtypes of Brain Tumor Characterized by Distinct Immune Infiltration and Prognosis.

BACKGROUND: Brain tumor ranks as the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from receiving therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction. METHODS: We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods, including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses, were employed. RESULTS: We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound-healing, and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 - 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 - 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation, and co-deletion of 1p and 19q. This finding was validated in six datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6). CONCLUSIONS: We identified two distinctive subtypes of brain tumor with different immune infiltration signatures, which might be helpful as an independent prognosticator for brain tumor.

Miscell: An efficient self-supervised learning approach for dissecting single-cell transcriptome.

We developed Miscell, a self-supervised learning approach with deep neural network as latent feature encoder for mining information from single-cell transcriptomes. We demonstrated the capability of Miscell with canonical single-cell analysis tasks including delineation of single-cell clusters and identification of cluster-specific marker genes. We evaluated Miscell along with three state-of-the-art methods on three heterogeneous datasets. Miscell achieved at least comparable or better performance than the other methods by significant margin on a variety of clustering metrics such as adjusted rand index, normalized mutual information, and V-measure score. Miscell can identify cell-type specific markers by quantifying the influence of genes on cell clusters via deep learning approach.

Eradication of Helicobacter Pylori Infections and GERD: A systematic review and meta-analysis.

BACKGROUND/AIMS: This study evaluates the association between the eradication of Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: Relevant studies were identified by conducting literature search in PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. The prevalence rates of gastroesophageal reflux, heartburn, epigastric pain, and nausea were extracted from the identified research articles and were used in meta-analysis of relative risks (RR) to achieve an overall effect size of the relationship between H. pylori eradication and GERD. RESULTS: A total of 19 randomized controlled trials were included in this meta-analysis. The prevalence of gastroesophageal reflux was significantly higher in patients with H. pylori eradication compared with patients without it (RR: 1.54, 95% CI: 1.06-2.24; p=0.02). A subgroup analysis did not identify any significant difference in GERD prevalence in studies conducted outside China (RR: 1.62, 95% CI: 0.98-2.68) or in China (RR: 1.30, 95% CI: 0.76-2.22). There were no significant differences in heartburn (RR: 1.03, 95% CI: 0.88-1.20), epigastric pain (RR: 0.98, 95% CI: 0.13-7.56), or nausea (RR: 0.44, 95% CI: 0.07-2.72) risk between patients with and without H. pylori eradication. CONCLUSION: Eradication of H. pylori infection is found to be associated with GERD, although regional differences may exist in the prevalence. Well-designed studies especially those with stratification of patients' basic conditions are needed to seek refined evidence of the association between H. pylori eradication and the GERD.