Identification of ferroptosis-associated genes and potential pharmacological targets in sepsis-induced myopathy.

Background: The role of Ferroptosis in the course of sepsis-induced myopathy is yet unclear. The objective of our work is to identify key genes connected with Ferroptosis in sepsis-induced myopathy and investigate possible pharmaceutical targets related to this process. This research aims to provide new insights into the management of sepsis-induced myopathy. Methods: We got the GSE13205 dataset from the Gene Expression Omnibus (GEO) and extracted Ferroptosis-associated genes from the FerrDb database. After conducting a functional annotation analysis of these genes, we created a protein-protein interaction network using Cytoscape software to identify important genes. Subsequently, we employed CMap to investigate prospective pharmaceuticals that could target these crucial genes. Results: A total of 61 genes that are expressed differently (DEGs) have been found concerning Ferroptosis. These genes are involved in a wide range of biological functions, including reacting to signals from outside the cell and the availability of nutrients, programmed cell death, controlling apoptosis, and responding to peptides, chemical stressors, and hormones. The KEGG pathway study revealed that these pathways are involved in Ferroptosis, autophagy, P53 signaling, PI3K-Akt signaling, mTOR signaling, HIF-1 signaling, endocrine resistance, and different tumorigenic processes. In addition, we created a network that shows the simultaneous expression of important genes and determined the top 10 medications that have the potential to treat sepsis-induced myopathy. Conclusion: The bioinformatics research undertaken sheds insight into the probable role of Ferroptosis-associated genes in sepsis-induced myopathy. The identified critical genes show potential as therapeutic targets for treating sepsis-induced myopathy, offering opportunities for the development of tailored medicines.

Self-efficacy as mediators of the association between dyadic coping and quality of life among spousal caregiver of patients with cervical cancer.

Objective: This study aims to explore the influence of dyadic coping (DC) on the quality of life (QoL) of spousal caregivers for patients with cervical cancer and to investigate the mediating role of self-efficacy in this relationship. Methods: A convenience sample of 206 spouses of cervical cancer patients from five hospitals in Jiangsu Province, China, was included in the study. The participants completed three instruments: the 12-item Short-Form Health Survey, the General Self-Efficacy Scale, and the Dyadic Coping Inventory. Structural Equation Modeling (SEM) was used to analyze the mediating effect of self-efficacy in the DC and QoL relationship. Results: The study found a positive correlation between self-efficacy and DC. Self-efficacy partially mediated the impact of DC on QoL, accounting for 16% of the total effect. Self-efficacy played a mediating role in facilitating the indirect positive effects of DC on QoL. Conclusions: Spousal caregivers of cervical cancer patients frequently experience a relatively low QoL. The results suggest that interventions aimed at enhancing DC among spousal caregivers should incorporate strategies to improve self-efficacy, given its mediating role in the positive relationship between DC and QoL.

Dirhodium-Catalyzed Enantioselective Synthesis of Difluoromethylated Cyclopropanes via Enyne Cycloisomerization.

(Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom-economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh2 (II)-catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.2 mol%), which can be easily transformed into highly functionalized difluoromethylated cyclopropanes with vicinal all-carbon quaternary stereocenters by ozonolysis. Mechanistic studies and the crystal structures of alkyne-dirhodium complexes reveal that the cooperative weak hydrogen bondings between the substrates and the dirhodium catalyst may play key roles in this reaction.).

PDGFß receptor-targeted delivery of truncated transforming growth factor ß receptor type II for improving the in vitro and in vivo anti-renal fibrosis activity via strong inactivation of TGF-ß1/Smad signaling pathway.

Truncated transforming growth factor ß receptor type II (tTßRII), serving as a trap for binding excessive transforming growth factor ß1 (TGF-ß1) by means of competing with wild-type TßRII, is a promising strategy for the treatment of kidney fibrosis. Platelet-derived growth factor ß receptor (PDGFßR) is highly expressed in interstitial myofibroblasts in kidney fibrosis. This study identified the interaction between a novel tTßRII variant Z-tTßRII (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of tTßRII) and TGF-ß1. Moreover, Z-tTßRII highly targeted to TGF-ß1-activated NIH3T3 cells and UUO-induced fibrotic kidney, but less to normal cells, tissues, and organs. Furthermore, Z-tTßRII significantly inhibited cell proliferation and migration, and reduced fibrosis markers expression and phosphorylation level of Smad2/3 in activated NIH3T3 cells. Meanwhile, Z-tTßRII markedly alleviated the kidney histopathology and fibrotic responses, and inhibited the TGF-ß1/Smad signaling pathway in UUO mice. Besides, Z-tTßRII showed good safety performance in the treatment of UUO mice. In conclusion, these results demonstrated that Z-tTßRII may be a potential candidate for a targeting therapy on renal fibrosis due to the high potential of fibrotic kidney-targeting and strong anti-renal fibrosis activity.

Development and validation of a nomogram for predicting persistent inflammation, immunosuppression, and catabolism syndrome in trauma patients.

Background: Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS) is a significant contributor to adverse long-term outcomes in severe trauma patients. Objective: The objective of this study was to establish and validate a PIICS predictive model in severe trauma patients, providing a practical tool for early clinical prediction. Patients and methods: Adult severe trauma patients with an Injury Severity Score (ISS) of ≥16, admitted between October 2020 and December 2022, were randomly divided into a training set and a validation set in a 7:3 ratio. Patients were classified into PIICS and non-PIICS groups based on diagnostic criteria. LASSO regression was used to select appropriate variables for constructing the prognostic model. A logistic regression model was developed and presented in the form of a nomogram. The performance of the model was evaluated using calibration and ROC curves. Results: A total of 215 patients were included, consisting of 155 males (72.1%) and 60 females (27.9%), with a median age of 51 years (range: 38-59). NRS2002, ISS, APACHE II, and SOFA scores were selected using LASSO regression to construct the prognostic model. The AUC of the ROC analysis for the predictive model in the validation set was 0.84 (95% CI 0.72-0.95). The Hosmer-Lemeshow test in the validation set yielded a χ2 value of 14.74, with a value of p of 0.098. Conclusion: An accurate and easily implementable PIICS risk prediction model was established. It can enhance risk stratification during hospitalization for severe trauma patients, providing a novel approach for prognostic prediction.

Seminal Plasma ExLncRNA Pairs: Updating Perspectives in the Search for Testicular Spermatozoa Retrieval Biomarkers in Nonobstructive Azoospermia Patients with mTESE by WGCNA.

PURPOSE: This study aims to find candidates for testicular spermatozoa retrieval biomarkers among the seminal plasma exLncRNA pairs. MATERIALS AND METHODS: A set of exLncRNA pairs with the best potential biomarkers was selected and validated in 96 NOA samples. Weighted correlation network analysis (WGCNA) and Least Absolute Shrinkage and Selection Operator were used to identify possible biomarkers for these pairs (LASSO). These pairs' potential biomarkers were identified using receiver operating curves. Confusion matrices and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), FP, false-negative rates (FNR), and F1 scores are calculated. Through F1 scores, we selected the best threshold value. RESULTS: The relative differential expression of each pair in testicular spermatozoa retrieval (+) and testicular spermatozoa retrieval (-) men were validated. The six pairs displayed the best biomarker potential. Among them, CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair showed the most significant potential and stability for detecting testicular spermatozoa retrieval in the selected and validated cohort. CONCLUSION: CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair have the potential to become new molecular biomarkers that could help to select clinical strategies for microdissection testicular sperm extraction.

Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3.

AIMS: To identify N-acetyltransferase 10 (NAT10) and its downstream signaling pathways in myocytes and skeletal muscle, and to investigate its role in inflammation-induced muscle atrophy. MATERIALS AND METHODS: Cecal ligation and puncture models were used to induce sepsis in C57BL/6 mice, which were treated with either a NAT10 inhibitor or a control agent. The therapeutic effect of NAT10 inhibitor was investigated by evaluating the mass, morphology, and molecular characteristics of mouse skeletal muscle. C2C12 cells were stimulated with LPS, and the expression of the NAT10 gene, downstream protein content, and atrophy phenotype were analyzed using a NAT10 inhibitor, to further explore the atrophic effect of NAT10 on C2C12 differentiated myotubes. RESULTS: Gene set enrichment analysis revealed that NAT10 expression was elevated in the Lateral femoris muscle of patients with ICUAW. In vitro and in vivo experiments showed that sepsis or LPS induced the upregulation of NAT10 expression in skeletal muscles and C2C12 myotubes. Skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with atrophic response in sepsis models. Remodelin ameliorated the LPS-induced skeletal muscle weight loss, as well as muscular atrophy, and improved survival. Remodelin reversed the atrophy program that was induced by inflammation through the downregulation of the ROS/NLRP3 pathway, along with the inhibition of the expression of MuRF1 and Atrogin-1. CONCLUSION: NAT10 is closely related to skeletal muscle atrophy during sepsis. Remodelin improves the survival rate of mice by improving the systemic inflammatory response and skeletal muscle atrophy by downregulating the ROS/NLRP3 signaling pathway.

Enantioselective Synthesis of Biscyclopropanes Using Alkynes as Dicarbene Equivalents.

Chiral biscyclopropanes are an important skeleton in many bioactive molecules. However, there are few routes to synthesize these molecules with high stereoselectivity due to the nature of multiple stereocenters. Herein, we report the first example of Rh2 (II)-catalyzed enantioselective synthesis of bicyclopropanes with alkynes as dicarbene equivalents. The bicyclopropanes with 4-5 vicinal stereocenters and 2-3 all-carbon quaternary centers were constructed in excellent stereoselectivity. This protocol features high efficiency and excellent functional group tolerance. Moreover, the protocol was also extended to the cascaded cyclopropanation/cyclopropenation with excellent stereoselectivities. In these processes, both sp-carbons of alkyne were converted into stereogenic sp3 -carbons. Experimental and density functional theory (DFT) calculations revealed that the cooperative weak hydrogen bonds between the substrates and the dirhodium catalyst may play key roles in this reaction.

The Comprehensive Analysis of N6-Methyadenosine Writer METTL3 and METTL14 in Gastric Cancer.

Methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) were two core components of the N6-methyadenosine (m6A) methyltransferase complex (MTC) and played a basic role in maintaining an appropriate m6A level of target genes. In gastric cancer (GC), previous researches on the expression and role of METTL3 and METTL14 were not consistent, and their specific function and mechanism have remained elusive. In this study, the expression of METTL3 and METTL14 was evaluated based on the TCGA database, 9 paired GEO datasets, and our 33 GC patient samples, and METTL3 was highly expressed and acted as a poor prognostic factor, whereas METTL14 showed no significant difference. Moreover, GO and GSEA analyses were performed, and the results pointed out that METTL3 and METTL14 were jointly involved in multiple biological processes, while they could also take part in different oncogenic pathways independently. And BCLAF1 was predicted and identified as a novel shared target of METTL3 and METTL14 in GC. In total, we conducted a comprehensive analysis of METTL3 and METTL14 in GC including their expression, function, and role, which could provide a novel insight into the research of m6A modification in GC.

Inhibition of DDX3X alleviates persistent inflammation, immune suppression and catabolism syndrome in a septic mice model.

OBJECTIVE: DDX3X is involved in various pathological processes such as infection, immunity and cell death. This study aimed to investigate the effect of RK-33, a specific inhibitor of DDX3X, on the progression of sepsis to persistent inflammation, immune suppression and catabolism syndrome(PICS). METHODS: The septic mice model was established using caecal ligation and perforation (CLP). The mice were randomly divided into four groups: sham group, sham + RK-33 group (20 mg/kg, intraperitoneal injection, once a day), CLP group and CLP + RK-33 group (20 mg/kg, intraperitoneal injection, once a day). The number of inflammatory cells in the peripheral blood, spleen and bone marrow was calculated, and inflammatory cytokines were detected using an enzyme-linked immunosorbent assay. The septic mice's body weight and skeletal muscle mass were measured, and skeletal muscle tissues were examined using eosin staining. Western blotting was performed to detect the expression levels of MuRF1, atrogin1 and NLRP3 in the skeletal muscle of septic mice. Additionally, reactive oxidative species, superoxide dismutase and malondialdehyde were measured using commercial kits. RESULTS: RK-33 reduced inflammatory cell counts and cytokine levels in CLP mice, ameliorated the decline in CD4 and CD8 T cells and prevented the loss of body weight and skeletal muscle mass in septic mice. Additionally, RX-33 reduced oxidative stress in the skeletal muscle of septic mice. CONCLUSION: In the established sepsis mouse model, RK-33 alleviated inflammation and oxidative stress, ameliorated CLP-induced immunosuppression and skeletal muscle atrophy and improved survival. These findings suggest that RK-33 could be a novel potential therapeutic agent for preventing the progression of sepsis to PICS.

Network Pharmacology Analysis and Experimental Verification on Antiangiogenesis Mechanism of Hedyotis diffusa Willd in Liver Cancer.

Purpose: Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the therapy of cancer. However, the potential mechanisms of its antiangiogenic effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against liver cancer angiogenesis (LCA) and used a mouse orthotopic liver cancer model for experimental verification accordingly. Methods: The effective components, primary active compounds, and possible targets in the therapy of LCA were predicted using network pharmacology and bioinformatics. In vivo testing of the pharmacodynamic foundation of HDW in the treatment of LCA was performed. Hepa1-6 cells were implanted in C57BL/6 mice to establish an orthotopic liver cancer model to evaluate the antitumor and antiangiogenesis effects of the drug. Furthermore, protein levels were evaluated by western blotting, immunofluorescence, and immunohistochemistry. Results: We firstly confirmed the therapeutic effect of HDW on LCA and subsequently screened 7 active compounds from HDW according to their pharmacokinetic properties. Network analysis and enrichment analysis indicated that these compounds exhibit antiangiogenic effect by acting on multiple targets and thereby regulating multiple pathways mainly involved in Akt1, IL-6, IL-1ß, IL-17, hypoxia inducible factor-1α (HIF-1α), and tumor necrosis factor-α (TNF-α). Importantly, we preliminarily verified the results of the network pharmacology analysis in vivo. Conclusion: Collectively, our work initially explored the therapeutic mechanism of HDW on tumor angiogenesis, which lays an experimental reference for further exploring its pharmacological action and its clinical application.

Circular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h.

PURPOSE: To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood. METHODS: Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)-520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2'-Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively. Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo. RESULTS: Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h. Furthermore, CDC42 was a functional target of miR-520h in regulating GC cell behaviors. CONCLUSION: Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.

Identification of Novel Imatinib-Resistant Genes in Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are common ICC precursor sarcomas, which are considered to be a potential malignant mesenchymal tumor driven by specific KIT or PDGFRA signals in the gastrointestinal tract. The standard treatment for GIST without metastasis is surgical resection. GIST with metastasis is usually treated with tyrosine kinase inhibitors (TKIs) only but cannot be cured. The TKI imatinib is the main drug of GIST drug therapy. In adjuvant therapy, the duration of imatinib adjuvant therapy is 3 years. It has been proved that imatinib can improve the overall survival time (OS). However, many GIST patients develop drug resistance due to the long-term use of imatinib. We were forced to look for new strategies to treat GIST. The purpose of the current academic work is to study the drug-resistant genes of imatinib and their potential mechanisms. A total of 897 differentially expressed genes (DEGs) were found between imatinib-sensitive cell line GIST882 and imatinib-resistant cell line GIST430 by RNA sequencing (RNA-seq). After analyzing the DEGs, 10 top genes were selected (NDN, FABP4, COL4A1, COLEC11, MEG3, EPHA3, EDN3, LMO3, RGS4, and CRISP2). These genes were analyzed by RT-PCR, and it was confirmed that the expression trend of FABP4, COL4A1, and RGS4 in different imatinib-resistant cell lines was in accord with the GEO database. It is suggested that these genes may play a potential role in the clinical diagnosis and treatment of imatinib resistance in GIST.

N6-methyladenosine RNA modification and its interaction with regulatory non-coding RNAs in colorectal cancer.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers.

Digestive system cancers are common cancers with high cancer deaths worldwide. They have become a major threat to public health and economic burden. As one of the most universal RNA modifications in eukaryotes, the N6-methyladenosine (m6A) modification is involved in the occurrence, development, prognosis, and treatment response of various cancers, including digestive system cancers. M6A demethylases shape the m6A landscape dynamically, playing important roles in cancers. In addition, accumulating evidence reveal that many environmental toxicants are the established risk factors for digestive system cancers and associated with m6A modification. In this review, we summarize the multiple functions of M6A demethylases (fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and AlkB homolog 3 (ALKBH3)) in digestive system cancers, which are aberrantly expressed and affect cancer progression. We also discuss the potential roles of m6A demethylases in the assessment of environmental exposure, the signature for prevention and diagnosis of digestive system cancers.

An Enhanced Insect Pest Counter Based on Saliency Map and Improved Non-Maximum Suppression.

Accurately counting the number of insect pests from digital images captured on yellow sticky traps remains a challenge in the field of insect pest monitoring. In this study, we develop a new approach to counting the number of insect pests using a saliency map and improved non-maximum suppression. Specifically, as the background of a yellow sticky trap is simple and the insect pest object is small, we exploit a saliency map to construct a region proposal generator including saliency map building, activation region formation, background-foreground classifier, and tune-up boxes involved in region proposal generation. For each region proposal, a convolutional neural network (CNN) model is used to classify it as a specific insect pest class, resulting in detection bounding boxes. By considering the relationship between detection bounding boxes, we thus develop an improved non-maximum suppression to sophisticatedly handle the redundant detection bounding boxes and obtain the insect pest number through counting the handled detection bounding boxes, each of which covers one insect pest. As this insect pest counter may miscount insect pests that are close to each other, we further integrate the widely used Faster R-CNN with the mentioned insect pest counter to construct a dual-path network. Extensive experimental simulations show that the two proposed insect pest counters achieve significant improvement in terms of F1 score against the state-of-the-art object detectors as well as insect pest detection methods.

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model.

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which usually results in extended recovery periods and multiple complications. Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has been demonstrated to have anti-inflammatory, antibacterial, and antioxidant activities. The aim of this study was to investigate whether the administration of alpinetin could attenuate PICS in a septic mouse model. Mice were randomly divided into four groups: the (1) sham-operated group, (2) sham+alpinetin (1 mg/kg intravenously infused for once per day after sham operation), (3) cecal ligation and puncture (CLP), and (4) CLP+alpinetin (50 mg/kg intravenously infused for once per day after CLP). Eight days after sham operation or CLP surgery, mice were euthanized for subsequent examination. Alpinetin significantly improved the survival of septic mice. Also, it attenuated the CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome. The level of plasma proinflammatory cytokines and apoptosis of T lymphocytes were obviously decreased by alpinetin as well. Moreover, oxidative stress in the organs was compelling lower in the alpinetin-treated CLP mice. In this clinically relevant model of sepsis, alpinetin ameliorates CLP-induced organ dysfunction and improves the likelihood of survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis. These findings suggested that alpinetin could be a potential novel therapeutic approach to prevent sepsis-induced PICS.

Gibberellin inhibition of taproot formation by modulation of DELLA-NAC complex activity in turnip (Brassica rapa var. rapa).

Turnip is a member of the Brassica rapa species and is characterized by a swollen taproot that develops from the hypocotyl and part of the root. Gibberellins (GAs) are plant growth regulators involved in promoting cell elongation and play important roles in many aspects of plant growth and development. Interestingly, exogenous application of GA3 was found to significantly inhibit taproot formation in turnip. Moreover, endogenous GA contents decreased during the early developmental stages of taproot formation, suggesting that GA plays a negative role in taproot formation. We examined the anatomical structure of the taproot and found that lignification of the xylem cell wall was enhanced after treatment with GA3. Yeast two-hybrid assays suggested the occurrence of protein interactions between DELLAs and NACs in turnip. We also found that the expression of NAC-targeted genes involved in lignification of the secondary cell wall was significantly upregulated upon GA3 treatment. Taken together, these results supported the hypothesis that GA induced DELLA proteins degradation to release NAC proteins and induced xylem lignification, therefore inhibiting taproot formation, providing new insight into the molecular mechanism underlying turnip taproot formation.

Lessons Learned Comparing Immune System Alterations of Bacterial Sepsis and SARS-CoV-2 Sepsis.

Background: Bacterial sepsis has been used as a prototype to understand the pathogenesis of severe coronavirus disease 2019 (COVID-19). In addition, some management programs for critically ill COVID-19 patients are also based on experience with bacterial sepsis. However, some differences may exist between these two types of sepsis. Methods: This retrospective study investigated whether there are differences in the immune system status of these two types of sepsis. A total of 64 bacterial sepsis patients and 43 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sepsis were included in this study. Demographic data were obtained from medical records. Laboratory results within 24 h after the diagnosis of sepsis were provided by the clinical laboratory. Results: The results of blood routine (neutrophil, lymphocyte, and monocyte counts), infection biomarkers (C-reactive protein, ferritin, and procalcitonin levels), lymphocyte subset counts (total T lymphocyte, CD4+ T cell, CD8+ T cell, B cell, and NK cell counts), and lymphocyte subset functions (the proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4+, CD8+ T cells, and NK cells) were similar in bacterial sepsis patients and SARS-CoV-2 sepsis patients. Cytokine storm was milder, and immunoglobulin and complement protein levels were higher in SARS-CoV-2 sepsis patients. Conclusions: There are both similarities and differences in the immune system status of bacterial sepsis and SARS-CoV-2 sepsis. Our findings do not support blocking the cytokine storm or supplementing immunoglobulins in SARS-CoV-2 sepsis, at least in the early stages of the disease. Treatments for overactivation of the complement system and lymphocyte depletion may be worth exploring further.

Development and validation of a metabolic gene signature for predicting overall survival in patients with colon cancer.

The reprogramming of cellular metabolism is a hallmark of tumorigenesis. However, the prognostic value of metabolism-related genes in colon cancer remains unclear. This study aimed to identify a metabolic gene signature to categorize colon cancer patients into high- and low-risk groups and predict prognosis. Samples from the Gene Expression Omnibus database were used as the training cohort, while samples from The Cancer Genome Atlas database were used as the validation cohort. A metabolic gene signature was established to investigate a robust risk stratification for colon cancer. Subsequently, a prognostic nomogram was established combining the metabolism-related risk score and clinicopathological characteristics of patients. A total of 351 differentially expressed metabolism-related genes were identified in colon cancer. After univariate analysis and least absolute shrinkage and selection operator-penalized regression analysis, an eight-gene metabolic signature (MTR, NANS, HADH, IMPA2, AGPAT1, GGT5, CYP2J2, and ASL) was identified to classify patients into high- and low-risk groups. High-risk patients had significantly shorter overall survival than low-risk patients in both the training and validation cohorts. A high-risk score was positively correlated with proximal colon cancer (P = 0.012), BRAF mutation (P = 0.049), and advanced stage (P = 0.027). We established a prognostic nomogram based on metabolism-related gene risk score and clinicopathologic factors. The areas under the curve and calibration curves indicated that the established nomogram showed a good accuracy of prediction. We have established a novel metabolic gene signature that could predict overall survival in colon cancer patients and serve as a biomarker for colon cancer.