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The importance of metabolism-related alterations in the development of gastric cancer (GC) is increasingly recognized. The present study aimed to identify metabolism-related genes to facilitate prognosis of GC patients.Gene expression datasets and clinical information of GC patients were downloaded from TCGA and GEO databases. We scored the enrichment of human metabolism-related pathways (n = 86) in GC samples by GSV, constructed prognostic risk models using LASSO algorithm and multivariate Cox regression analysis, combined with clinical information to construct a nomogram, and finally cis score algorithm to analyze the abundance of immune-related cells in different subtypes. We used Weka software to screen for prognosis-related marker genes and finally validated the expression of the selected genes in clinical cancer patient tissues.We identified that two GC metabolism-related signatures were strongly associated with OS and the levels of immune cell infiltration. Moreover, a survival prediction model for GC was established based on six GC metabolism-related genes. Time-dependent ROC analysis showed good stability of the risk prediction scoring model. The model was successfully validated in an independent ACRG cohort, and the expression trends of key genes were also verified in the GC tissues of patients. DLX1, LTBP2, FGFR1 and MMP2 were highly expressed in the cluster with poorer prognosis while SLC13A2 and SLCO1B3 were highly expressed in the cluster with better prognosis.We identified a risk predictive score model based on six metabolism-related genes related to survival, which may serve as prognostic indicators and potential therapeutic targets for GC.

The air-cooled battery thermal management system (BTMS) is a safe and cost-effective system to control the operating temperature of battery energy storage systems (BESSs) within a desirable range. Different from the design of the air supply flow field of most BESSs in previous studies, this study proposes a novel combined the cooling air duct and the battery pack calculation method to enhance the heat dissipation of the battery. Using computational fluid dynamics (CFD) models, potential problems with numerical calculations of cooling air duct and battery packs alone and coupled simulations of the two are investigated. The important factor influencing the uniformity of air supply is identified, and creative measures for improvement are proposed. The results in this paper indicate that the uniformity of the outlet air supply does not indicate that the temperature uniformity performance of the matrix battery meets the requirements due to the variation of the sub air duct outlet pressure, and the coupling simulation of the cooling air duct and the battery pack is an essential process for BESSs. With the improvements proposed in this paper, the standard deviation coefficient of velocity is reduced from 60.3% to 12.6%. Furthermore, the innovative improvement of placing the partition at the connecting duct can regulates the battery temperature between 298.58 K and 311.73 K and ensures a maximum temperature difference of only 4.22 K for a single battery. Ultimately, the power consumption of the cooling system can be reduced by 6.9%. The results of the paper provide a guide for uniform heat dissipation in BESSs.

Uridine, a pyrimidine nucleoside, plays a crucial role in the synthesis of metabolites. According to recent research, higher plasma uridine levels are associated with a lower risk of atrial fibrillation (AF). However, the casual inference between uridine and AF is still unknown. In this study, we used the Mendelian randomization (MR) approach to elucidate possible causality. Three genetic variants associated with uridine were identified from the Metabolomics GWAS server (7,824 participants); summary-level datasets associated with AF were acquired from a genome-wide association study (GWAS) meta-analysis containing 1,030,836 European participants (60,620 AF cases). We duplicated the MR analyses using datasets from AF HRC studies and the FinnGen consortium and conducted a meta-analysis to combine the main results. The incidence of AF was incidentally associated with a one standard deviation increase in genetically determined plasma uridine [odds ratio (OR), 0.27; 95% confidence interval (CI), 0.16, 0.47; p = 2.39 ⋅ 10− 6)]. In the meta-analysis that combined the various datasets, the association remained consistent (OR, 0.27; 95% CI, 0.17, 0.42; p = 1.34 ⋅ 10− 8). In conclusion, genetic liability for higher plasma uridine levels is associated with a reduction in the risk of AF. Raising plasma uridine levels might provide new opportunities for AF prophylaxis.

Background. The association involving cuprotosis, molecular subtype, and specific immune cell groups in the tumor microenvironment has been focused on by more recent studies. In lung adenocarcinoma (LUAD), the potential functions of cuprotosis remain elusive. Methods. The cuprotosis regulations and tumor immune profile of 567 LUAD patients and the correlation between the cuprotosis patterns and the immune landscape were comprehensively evaluated. The cuprotosisScore was calculated using principal component analysis (PCA). The prognostic significance of the cuprotosisScore was evaluated by Cox regression statistics analysis. Results. Five cuprotosisClusters (named mc1, 2, 3, 4, 5)—characterized by differences in expression of immunomodulatory genes, mRNA, or lncRNA expression, and prognosis were identified. We established cuprotosisScore to quantify the cuprotosis pattern of individual LUAD patients. As is shown in further analyses, the cuprotosisScore was a relatively potential independent prognostic factor of LUAD involved in mc1. Finally, the prognostic value of the cuprotosisScore and its association with tumor immune microenvironment (iTME) of LUAD in five cuprotosisClusters were verified. Conclusions. We demonstrated the correlation between cuprotosis modification, the molecular subtype, and tumor immune landscape in LUAD. The cuprotosisCluster with high cuprotosisScore and high tumor mutation burden (TMB) was identified with a good prognosis and immune functions. The comprehensive evaluation of cuprotosis patterns in individual LUAD patients enhances the understanding of iTME and gives a new insight toward improved immune treatment strategies for LUAD patients.

All files and processed data for Coronavirus paper

The pathogenesis of COVID-19 emerges as complex, with multiple factors leading to injury of different organs. Several studies on underlying cellular processes have produced contradictory claims, e.g. on SARS-CoV-2 cell entry or innate immune responses. However, clarity in these matters is imperative for therapy development. We therefore performed a meta-study with a diverse set of transcriptomes under infections with SARS-CoV-2, SARS-CoV and MERS-CoV, including data from different cells and COVID-19 patients. Using these data, we investigated viral entry routes and innate immune responses. First, our analyses support the existence of cell entry mechanisms for SARS and SARS-CoV-2 other than the ACE2 route with evidence of inefficient infection of cells without expression of ACE2; expression of TMPRSS2/TPMRSS4 is unnecessary for efficient SARS-CoV-2 infection with evidence of efficient infection of A549 cells transduced with a vector expressing human ACE2. Second, we find that innate immune responses in terms of interferons and interferon simulated genes are strong in relevant cells, for example Calu3 cells, but vary markedly with cell type, virus dose, and virus type.

Shen-qi-Yi-zhu decoction (SQYZD) is an empirical prescription with antigastric cancer (GC) property created by Xu Jing-fan, a National Chinese Medical Master. However, its underlying mechanisms are still unclear. Based on network pharmacology and experimental verification, this study puts forward a systematic method to clarify the anti-GC mechanism of SQYZD. The active ingredients of SQYZD and their potential targets were acquired from the TCMSP database. The target genes related to GC gathered from GeneCards, DisGeNET, OMIM, TTD, and DrugBank databases were imported to establish protein-protein interaction (PPI) networks in GeneMANIA. Cytoscape was used to establish the drug-ingredients-targets-disease network. The hub target genes collected from the SQYZD and GC were parsed via GO and KEGG analysis. Our findings from network pharmacology were successfully validated using an in vitro HGC27 cell model experiment. In a word, this study proves that the combination of network pharmacology and in vitro experiments is effective in clarifying the potential molecular mechanism of traditional Chinese medicine (TCM).

We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol−1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.

Coronavirus Disease 2019 (COVID-19) is an ongoing global health emergency that has caused tremendous stress and loss of life worldwide. The viral spike glycoprotein is a critical molecule mediating transmission of SARS-CoV-2 by interacting with human ACE2. However, through the course of the pandemics, there has not been a thorough analysis of the spike protein mutations, and on how these mutants influence the transmission of SARS-CoV-2. Besides, cases of SARS-CoV-2 infection among pets and wild animals have been reported, so the susceptibility of these animals requires great attention to investigate, as they may also link to the renewed question of a possible intermediate host for SARS-CoV-2 before it was transmitted to humans. With over 226,000 SARS-CoV-2 sequences obtained, we found 1573 missense mutations in the spike gene, and 226 of them were within the receptor-binding domain (RBD) region that directly interacts with human ACE2. Modeling the interactions between SARS-CoV-2 spike mutants and ACE2 molecules showed that most of the 74 missense mutations in the RBD region of the interaction interface had little impact on spike binding to ACE2, whereas several within the spike RBD increased the binding affinity toward human ACE2 thus making the virus likely more contagious. On the other hand, modeling the interactions between animal ACE2 molecules and SARS-CoV-2 spike revealed that many pets and wild animals' ACE2 had a variable binding ability. Particularly, ACE2 of bamboo rat had stronger binding to SARS-CoV-2 spike protein, whereas that of mole, vole, Mus pahari, palm civet, and pangolin had a weaker binding compared to human ACE2. Our results provide structural insights into the impact on interactions of the SARS-CoV-2 spike mutants to human ACE2, and shed light on SARS-CoV-2 transmission in pets and wild animals, and possible clues to the intermediate host(s) for SARS-CoV-2.

BACKGROUND: Traditional Chinese medicine (TCM) is increasingly extensively being applied as a complementary and alternative therapy for gastric cancer (GC); however, there is a lack of large-scale evidence-based deep learning for the guidance of its clinical prescription. METHODS: The combinational search terms of “Gastric cancer and/or gastric malignancy” and “Traditional Chinese Medicine” were used to retrieve clinical study-based herbal prescriptions from public database over the past 3 decades [1990–2020]. Association rules mining (ARM) was used to analyze the prescription patterns of the herbs extracted from the eligible studies. Deep machine learning and computational prediction were conducted to explore candidate prescriptions with general applicability for GC. The action mechanism of the preferred prescription was investigated through network pharmacology, and further validated via in vivo and in vitro experiments. RESULTS: A total of 194 clinical study-based herbal prescriptions with good efficacy for GC were collected. TCM with focus on invigorating the Spleen and tonifying the vital-Qi is a promising adjuvant therapy for GC. The preferred prescription is composed of Atractylodis Macrocephalae Rhizoma, Astragali Radix, Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Herba Hedyotidis Diffusae, Crataegi Fructus, and so on. We screened 74 bioactive compounds and 2,128 predictive targets of the preferred prescription from public databases. Eventually, 135 GC-related genes were identified as the targets of the preferred prescription. The compound-target network revealed that the crucial substances in the preferred prescription are quercetin, kaempferol, baicalein, and nobiletin. Experimentally, the preferred prescription was validated to modulate GC cell survival and inhibit tumor progression mainly via the hTERT/MDM2-p53 signaling pathway in vivo and in vitro. CONCLUSIONS: TCM aimed at invigorating the Spleen and tonifying the vital-Qi is a promising adjuvant therapy for GC, which offers a guidance for worldwide use of TCM in the treatment of GC.

A Cu2O/g-C3N4/WS2 triple-layer photocathode was fabricated by using a layer-by-layer assembly method for photoelectrochemical hydrogen evolution. Cu2O was electrodeposited on the FTO as the active layer for light harvesting. The chemically inert g-C3N4 can protect the unstable Cu2O layer and form a p-n junction with Cu2O to increase the light-to-electricity conversion efficiency. Mixed-phase WS2 nanosheets were obtained through a lithium insertion method and used as an effective hydrogen evolution catalyst for photocurrent-to-hydrogen conversion. This photocathode is effective for photoelectrochemical hydrogen evolution, and a photocurrent of −9.5 mA cm−2 at −0.55 V versus RHE (pH 6.0) can be obtained under visible light (λ≥420 nm, 100 mW cm−2).