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Abstract Social capital has long been recognized as a facilitator of socio-economic development. However, the role of social capital in enhancing resilience to multiple shocks in rural China remains insufficiently explored. This study focus on the resilience of households that have recently get rid of poverty and reside in underdeveloped rural areas of China. Unlike previous studies, the article incorporates multiple shocks, social capital, and households’ coping strategies into a research framework at the micro level. This study systematically analyses the multiple shocks experienced by households, their coping strategies, and further explores the mediating role of social capital. Utilizing two waves of a rural household panel survey data collected in six underdeveloped counties in 2015 and 2018 in China, we present four key findings. Currently, households primarily contend with drought, illness of family members, and the high costs of agricultural inputs as the main shocks. Their predominant coping strategy is reducing consumption. Importantly, social capital exhibits a mediating effect, accounting for 9.8% of the impact of multiple shocks on households’ coping strategies. Notably, natural disasters significantly diminish the informal functions of social capital. While social capital exerts a full mediating effect in non-agricultural households, this effect is not observed among others. This study contributes to a better understanding of the dynamics and specificities of social capital in vulnerable rural areas. Additionally, the findings provide policymakers with practical insights regarding differentiated and preemptive risk governance approaches.

Abstract To study the internal evolution characteristics of tar-rich coal under high-temperature pyrolysis and improve pyrolysis efficiency, three-dimensional reconstruction and analysis of tar-rich coal from northern Shaanxi after high-temperature pyrolysis were conducted using μCT technology. The evolutionary development of pore and fracture structure at different temperatures and the relationship between pore-fractures and permeability was studied and discussed. The results show that when tar-rich coal from 300 to 600 °C, it mainly undergoes two stages: in the first stage, the internal substance structure of the coal mainly undergoes thermal cracking, forming large fracture bands; in the second stage, the coal undergoes intense pyrolysis reactions, resulting in primarily circular or elliptical large pore structures within the coal, with a reduction in the number of fractures. Furthermore, a strong exponential relationship is exhibited between the porosity and permeability of tar-rich coal, and a predictive equation is provided. When the temperature exceeds 500 °C, the coupled effect of pores and fractures contributes more than 20% to permeability, and its impact cannot be ignored.

Abstract Background The impact of sodium intake on cardiovascular disease (CVD) health and mortality has been studied for decades, including the well-established association with blood pressure. However, non-linear patterns, dose–response associations, and sex differences in the relationship between sodium and potassium intakes and overall and cause-specific mortality remain to be elucidated and a comprehensive examination is lacking. Our study objective was to determine whether intake of sodium and potassium and the sodium–potassium ratio are associated with overall and cause-specific mortality in men and women. Methods We conducted a prospective analysis of 237,036 men and 179,068 women in the National Institutes of Health-AARP Diet and Health Study. Multivariable-adjusted Cox proportional hazard regression models were utilized to calculate hazard ratios. A systematic review and meta-analysis of cohort studies was also conducted. Results During 6,009,748 person-years of follow-up, there were 77,614 deaths, 49,297 among men and 28,317 among women. Adjusting for other risk factors, we found a significant positive association between higher sodium intake (≥ 2,000 mg/d) and increased overall and CVD mortality (overall mortality, fifth versus lowest quintile, men and women HRs = 1.06 and 1.10, Pnonlinearity

Objective: The aim of this study was to isolate and screen yeast with selenium enrichment function from marine samples, and its optimal fermentation conditions to enhance the selenium enrichment of the screened strain was investigated. Methods: A combination of selenium-tolerant and red selenium methods was used to screen the marine source microorganisms with high selenium enrichment capacity from mangroves in East Harbour National Nature Reserve, Hainan Province, and the strains were identified by morphological, physiological, biochemical and molecular biological approaches. The selenium content of the strain was quantified by 3,3'-diaminobenzidine hydrochloride, the optimal fermentation process to enhance the selenium enrichment of the screened strain was conducted by single-factor tests. Results: A safe strain of Lachancea fermentati HN-10 with selenium enrichment function was obtained from the marine source samples and its optimal fermentation process of 5% inoculum, initial pH6, fermentation temperature 22 ℃, fermentation speed 180 r/min, fermentation time 48 h and selenium addition 20 μg/mL was achieved. Under the optimal fermentation process, 4.52 g/L biomass density, a 1.57 mg/g selenium enrichment, and 35.43% selenium conversion was obtained. Conclusion: The L. fermentati HN-10 from marine source has potential application for the development of selenium-enriched food.

Abstract Background Clear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment. Methods Gathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis. Results Diverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial–mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation. Conclusions The tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation.

Abstract Background Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. Methods A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. Results (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC 1.02 mmol/L and LDL 1.25 mmol/L and LDL 1.10 mmol/L and LDL

Abstract Microglia are the resident immune cells in the brain that play a key role in driving neuroinflammation, a hallmark of neurodegenerative disorders. Inducible microglia-like cells have been developed as an in vitro platform for molecular and therapeutic hypothesis generation and testing. However, there has been no systematic assessment of similarity of these cells to primary human microglia along with their responsiveness to external cues expected of primary cells in the brain. In this study, we performed transcriptional characterization of commercially available human inducible pluripotent stem cell (iPSC)-derived microglia-like (iMGL) cells by bulk and single cell RNA sequencing to assess their similarity with primary human microglia. To evaluate their stimulation responsiveness, iMGL cells were treated with Liver X Receptor (LXR) pathway agonists and their transcriptional responses characterized by bulk and single cell RNA sequencing. Bulk transcriptome analyses demonstrate that iMGL cells have a similar overall expression profile to freshly isolated human primary microglia and express many key microglial transcription factors and functional and disease-associated genes. Notably, at the single-cell level, iMGL cells exhibit distinct transcriptional subpopulations, representing both homeostatic and activated states present in normal and diseased primary microglia. Treatment of iMGL cells with LXR pathway agonists induces robust transcriptional changes in lipid metabolism and cell cycle at the bulk level. At the single cell level, we observe heterogeneity in responses between cell subpopulations in homeostatic and activated states and deconvolute bulk expression changes into their corresponding single cell states. In summary, our results demonstrate that iMGL cells exhibit a complex transcriptional profile and responsiveness, reminiscent of in vivo microglia, and thus represent a promising model system for therapeutic development in neurodegeneration.

Abstract The regulation of PD‐L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD‐L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD‐L1 expression and protein stability, and the deubiquitinase ubiquitin‐specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD‐L1. Importantly, a combination of EZH2 inhibitors with anti‐PD‐1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD‐L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2‐USP22‐PD‐L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor‐based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.

Breast cancer is the most common malignant tumor in women, posing a serious threat to women’s health. HER2 has been identified as a key oncogene and prognostic factor in breast cancer. Recent studies have reported inconsistencies in ER, PR, and/or HER2 expression between primary breast tumors and metastatic lesions. Rarely is it reported that all three biomarkers experience conversion. In this report, we present the case of a female patient with relapsed and metastatic breast cancer, whose histology transformed from initially triple-negative to Luminal-B type (HER2 positive) (i.e., ER, PR, and HER2 positive). She underwent systematic chemotherapy, targeted therapy, and cranial radiotherapy, which was followed by maintenance treatment with targeted and endocrine therapy. Currently, she has been in nearly complete remission (nCR) for more than 12 months. For recurrent and metastatic breast cancer, it is necessary to perform the second biopsy for metastases, which would contribute to precision treatment and prognosis improvement.

The encapsulation of sodium sulfobutylether-β-cyclodextrin (SBE-β-CD) is influenced not only by the degree of substitution (DS) but also by the presence of strong-bonded water (SBW). Guests compete with SBW for positions within the cavity of SBE-β-CD. However, the correlation between DS and SBW was not clear. This study revealed a positive correlation between DS and SBW utilizing Karl Fischer titration. The mechanism may be attributed to molecular polarizability. To explore the impact of SBW inside SBE-β-CD with different DS on encapsulation, density functional theory was employed. Throughout the release process, an increase in enthalpy is unfavorable, while an increase in entropy favors spontaneous reaction occurrence. For SBE-β-CD (DS = 2, 3), enthalpy increase is the primary factor, leading to the retention of SBW within the cavities and consequently hindering guest entry. In contrast, for SBE-β-CD (DS = 4, 7), the situation differs. For SBE10-β-CD, the influence of SBW is minimal. This study aims to elucidate the relationship between DS and SBW, as well as the effect of SBW inside SBE-β-CD with different DS on encapsulation. It is crucial for a comprehensive understanding of the factors affecting the encapsulation of SBE-β-CD, thereby promoting quality control and functional development of SBE-β-CD.

BackgroundCOVID-19 screening is an effective nonpharmaceutical intervention for identifying infected individuals and interrupting viral transmission. However, questions have been raised regarding its effectiveness in controlling the spread of novel variants and its high socioeconomic costs. Therefore, the optimization of COVID-19 screening strategies has attracted great attention. ObjectiveThis review aims to summarize the evidence and provide a reference basis for the optimization of screening strategies for the prevention and control of COVID-19. MethodsWe applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. We conducted a scoping review of the present publications on the optimization of COVID-19 screening strategies. We searched the PubMed, Web of Science, and Elsevier ScienceDirect databases for publications up to December 31, 2022. English publications related to screening and testing strategies for COVID-19 were included. A data-charting form, jointly developed by 2 reviewers, was used for data extraction according to the optimization directions of the screening strategies. ResultsA total of 2770 unique publications were retrieved from the database search, and 95 abstracts were retained for full-text review. There were 62 studies included in the final review. We summarized the results in 4 major aspects: the screening population (people at various risk conditions such as different regions and occupations; 12/62, 19%), the timing of screening (when the target population is tested before travel or during an outbreak; 12/62, 19%), the frequency of screening (appropriate frequencies for outbreak prevention, outbreak response, or community transmission control; 6/62, 10%), and the screening and detection procedure (the choice of individual or pooled detection and optimization of the pooling approach; 35/62, 56%). ConclusionsThis review reveals gaps in the optimization of COVID-19 screening strategies and suggests that a number of factors such as prevalence, screening accuracy, effective allocation of resources, and feasibility of strategies should be carefully considered in the development of future screening strategies.

The imbalance of follicular helper T (Tfh) cell subset is closely related to the occurrence of inflammatory bowel disease (IBD). Ginsenoside Rg1 (G-Rg1), the main component of ginseng, has excellent immunomodulatory and anti-inflammatory effects. Here, mice colitis was induced by dextran sulfate sodium and treated with G-Rg1 (200 mg/kg/day) for 14 days. Results showed that G-Rg1 can significantly alleviate symptoms of colitis in mice, regulate the balance of Tfh cell subsets, promote the secretion of IL-4 and IL-10, and inhibit the expression of IFN-γ, IL-17A, and IL-21. Molecular docking analysis revealed that G-Rg1 has excellent binding activity with target genes of the TLR/MyD88 signaling pathway, and and can reduce the expression levels of proteins such as TLR2, MyD88, IRAK4, TRAF6, and TAK1. These findings suggest that G-Rg1 can effectively regulate the balance of Tfh cell subsets, and its potential mechanism is related to the inhibition of the TLR/MyD88 signaling pathway.

Abstract Background The short physical performance battery (SPPB) is an easy-to-use tool for fall risk prediction, but its predictive value for falls and fall-induced injuries among community dwellers has not been examined through a large-sample longitudinal study. Methods We analyzed five-round follow-up data (2, 3, 4, 5, 7 years) of the China Health and Retirement Longitudinal Study (CHARLS) (2011–2018). Data concerning falls and fall-induced injuries during multi-round follow-ups were collected through participant self-report. The Cochran-Armitage trend test examined trends in fall incidence rate across SPPB performance levels. Multivariable logistic regression and negative binomial regression models examined associations between SPPB performance and subsequent fall and fall-induced injury. The goodness-of-fit and area under the receiver operating curve (AUC) were used together to quantify the value of the SPPB in predicting fall and fall-induced injury among community-dwelling older adults. Results The CHARLS study included 9279, 6153, 4142, 4148, and 3583 eligible adults aged 60 years and older in the five included follow-up time periods. SPPB performance was associated with fall and fall-induced injury in two and three of the five follow-up time periods, respectively (P

ABSTRACTLignocellulolytic enzymes play an important role in various industrial applications as well as the sustainable valorisation of lignocellulosic materials. Enzyme production using lignocellulosic fungi has shown great advantages such as high enzyme diversity, high production efficiency, and the availability of solid waste as raw materials. Agricultural waste, an abundant and non-food competitive feedstock, can be used to produce fungal lignocellulolytic enzymes. Pretreatment helps break down the complex structure of the raw material, thereby significantly improving product yield but also requiring more energy consumption. Multiple fermentation technologies, including submerged fermentation, solid-state fermentation, and co-culture, can be used for producing lignocellulolytic enzymes. Process optimisation may promote the yield and productivity of such enzymes without additional investment. Genetic engineering is also useful for enhancing enzyme production to meet industrial requirements. This review summarises the research progress in the fungal production of lignocellulolytic enzymes from various agricultural wastes via advanced fermentation strategies. It aims to provide technical references for the scale-up production of fungal lignocellulolytic enzymes.

A cellulose-based triboelectric nanogenerator (TENG) with fiber–wave–arch structure was prepared through a multi-fluid electrospinning process for air filtration and wind sensing. The TENG is composed of a cellulose nanocrystals (CNC)/zein membrane and a cyanoethyl cellulose (CEC)/polyvinylidene fluoride (PVDF) membrane. The results show that the addition of CEC improves the output performance and filterability of TENG. At the same time, the reduced diameter and high roughness of CEC/PVDF nanofibers improve the output performance of the TENG. The TENG with a 6 wt% CEC/PVDF solution concentration has the highest output performance with a short-circuit current of 3.30 μA and an open-circuit voltage of 10.01 V. The particle filtration of 12 wt% CEC/PVDF TENG is the best, showing an efficiency of 98.84% and a pressure drop of 50 Pa. The TENG also has a good formaldehyde filtration capability with an efficiency of 92% at 0.25 mg/m3. The TENG shows great potential in self-powered sensor applications.

Probiotics are safe, inexpensive, and effective feed additives, and Clostridium butyricum (CB) has been reported to regulate bone health in addition to having conventional probiotic effects. The bone health of laying hens is closely related to their production performance. Here, we investigated the effects of CB supplementation on the bone health and performance of laying hens. We added CB to the feed of green-shell laying hens, Luhua laying hens, and Hy-line Brown laying hens and examined changes in body weight, feed intake, egg production performance, and egg quality to determine the impact of CB on production performance. The impact of CB on the bones of laying hens was determined by analyzing the bone index, bone bending strength, bone calcium and phosphorus content, and bone mineral density. The study found that CB had little effect on the body weight and feed intake of laying hens. Feed additions of 108 and 109 CFU/kg CB can significantly increase the tibia index and bone mineral density of four-week-old green-shell laying hens. Feed additions of 107 and 108 CFU/kg CB can significantly increase the average egg weight, eggshell weight, and tibia index of 26-week-old Luhua laying hens, but 107 CFU/kg CB will reduce the egg production rate. Adding 108 CFU/kg CB to feed can significantly increase the average egg weight, eggshell weight, and tibia bending strength of 40-week-old Hy-line Brown laying hens. In summary, adding 108 CFU/kg CB is beneficial to the bone and production health of laying hens.

Abstract Background By evaluating equity and effectiveness, this study provides evidence-based knowledge for scientific decision-making and the optimization of magnetic resonance imaging (MRI) configuration and utilization at the provincial level. Methods Using data from 2017, we applied a Gini coefficient to analyze the equity of MRI services in 11 sample cities in Henan province. An agglomeration degree was then applied to measure equity from the perspective of population and geography, and a data envelopment analysis was used to evaluate MRI efficiency. Results The overall Gini coefficient of MRI allocation by population in the 11 sample cities is 0.117; however, equity varies considerably among the sample cities. The sample’s comprehensive efficiency is only 0.732, indicating the overall ineffectiveness of provincial MRI utilization. The pure technical and scale efficiencies of four sample cities are below 1, indicating lower MRI effectiveness than the rest. Conclusions Although the overall equity of configuration at the provincial level is relatively good, equity varies at the municipal level. Our results demonstrate a low MRI utilization efficiency; accordingly, policymakers should dynamically adjust the policy based on equity and efficiency.

Abstract Background Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear. Methods This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD. Results A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD. Conclusion This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG.

A case of Wolf's isotopic response is reported. A 68-year-old-female presented with vesicles and bullae on the scars of the left chest and the back for 2 months. Dermatological examination revealed five vesicles and bullae of various sizes on the edge of a 10 cm×5 cm scar, with a deep central ulcer sized 5 cm×5 cm, under the left armpit. Ulcer was with little discharge and dark crusts. The vesicles were with clear fluid and negative for Nikolsky's sign. Two bullae were seen on a 3 cm×2 cm hypertrophic scar at T2 to T4 of the left anterior chest. One hypertrophic scar with a bulla sized 1.5 cm and another one with 1 cm erosion and pustular secretion were on the left back. Patient had no mucosal involvement. Histology of skin lesion showed subepidermal blister and perivascular infiltrates of a few lymphohistiocytes, neutrophils and plasma cells in the superficial dermis. Direct immunofluorescence showed linear deposition of C3 in the basement membrane zone. The diagnosis was isotopic response: bullous pemphigoid secondary to herpes zoster. After the treatment with oral prednisone acetate, the blisters resolved in 2 weeks. No recurrence was observed during 15-months follow-up. The follow-up is still ongoing.

Abstract Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899).

Abstract The International Agency for Research on Cancer reported that some chemicals in hair dyes are probably carcinogenic to those exposed to them occupationally. Biological mechanisms through which hair dye use may be related to human metabolism and cancer risk are not well-established. We conducted the first serum metabolomic examination comparing hair dye users and nonusers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Metabolite assays were conducted using ultrahigh performance liquid chromatography-tandem mass spectrometry. The association between metabolite levels and hair dye use was estimated using linear regression, adjusting for age, body mass index, smoking, and multiple comparisons. Among the 1,401 detected metabolites, 11 compounds differed significantly between the two groups, including four amino acids and three xenobiotics. Redox-related glutathione metabolism was heavily represented, with L-cysteinylglycine disulfide showing the strongest association with hair dye (effect size (β) = − 0.263; FDR adjusted p-value = 0.0311), along with cysteineglutathione disulfide (β = − 0.685; FDR adjusted p-value = 0.0312). 5alpha-Androstan-3alpha,17beta-diol disulfate was reduced in hair dye users (β = − 0.492; FDR adjusted p-value = 0.077). Several compounds related to antioxidation/ROS and other pathways differed significantly between hair dye users and nonusers, including metabolites previously associated with prostate cancer. Our findings suggest possible biological mechanisms through which the use of hair dye could be associated with human metabolism and cancer risk.

Abstract Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan–Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan–Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells’ expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4+ T cells, B cells, CD8+ T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.

Abstract Background The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads rapidly and insidiously. Coronavirus disease 2019 (COVID-19) screening is an important means of blocking community transmission in China, but the costs associated with testing are high. Quarantine capacity and medical resources are also threatened. Therefore, we aimed to evaluate different screening strategies to balance outbreak control and consumption of resources. Methods A community network of 2000 people, considering the heterogeneities of household size and age structure, was generated to reflect real contact networks, and a stochastic individual-based dynamic model was used to simulate SARS-CoV-2 transmission and assess different whole-area nucleic acid screening strategies. We designed a total of 87 screening strategies with different sampling methods, frequencies of screening, and timings of screening. The performance of these strategies was comprehensively evaluated by comparing the cumulative infection rates, the number of tests, and the quarantine capacity and consumption of medical resource, which were expressed as medians (95% uncertainty intervals, 95% UIs). Results To implement COVID-19 nucleic acid testing for all people (Full Screening), if the screening frequency was four times/week, the cumulative infection rate could be reduced to 13% (95% UI: 1%, 51%), the miss rate decreased to 2% (95% UI: 0%, 22%), and the quarantine and medical resource consumption was lower than higher-frequency Full Screening or sampling screening. When the frequency of Full Screening increased from five to seven times/week (which resulted in a 2581 increase in the number of tests per positive case), the cumulative infection rate was only reduced by 2%. Screening all people weekly by splitting them equally into seven batches could reduce infection rates by 73% compared to once per week, which was similar to Full Screening four times/week. Full Screening had the highest number of tests per positive case, while the miss rate, number of tests per positive case, and hotel quarantine resource consumption in Household-based Sampling Screening scenarios were lower than Random Sampling Screening. The cumulative infection rate of Household-based Sampling Screening or Random Sampling Screening seven times/week was similar to that of Full Screening four times/week. Conclusions If hotel quarantine, hospital and shelter hospital capacity are seriously insufficient, to stop the spread of the virus as early as possible, high-frequency Full Screening would be necessary, but intermediate testing frequency may be more cost-effective in non-extreme situations. Screening in batches is recommended if the testing capacity is low. Household-based Sampling Screening is potentially a promising strategy to implement. Graphical Abstract

Abstract Background Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood. Materials and methods In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology. Results In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN. Conclusion ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer.

Assessing drivers’ mental workload is crucial for reducing road accidents. This study examined drivers’ mental workload in a simulated auditory-based dual-task driving scenario, with driving tasks as the main task, and auditory-based N-back tasks as the secondary task. A total of three levels of mental workload (i.e., low, medium, high) were manipulated by varying the difficulty levels of the secondary task (i.e., no presence of secondary task, 1-back, 2-back). Multimodal measures, including a set of subjective measures, physiological measures, and behavioral performance measures, were collected during the experiment. The results showed that an increase in task difficulty led to increased subjective ratings of mental workload and a decrease in task performance for the secondary N-back tasks. Significant differences were observed across the different levels of mental workload in multimodal physiological measures, such as delta waves in EEG signals, fixation distance in eye movement signals, time- and frequency-domain measures in ECG signals, and skin conductance in EDA signals. In addition, four driving performance measures related to vehicle velocity and the deviation of pedal input and vehicle position also showed sensitivity to the changes in drivers’ mental workload. The findings from this study can contribute to a comprehensive understanding of effective measures for mental workload assessment in driving scenarios and to the development of smart driving systems for the accurate recognition of drivers’ mental states.

The balance between memory Th17 cells (mTh17) and memory Treg cells (mTreg) plays a key role in the pathogenesis of ulcerative colitis (UC), and TIGIT signaling is involved in the differentiation of mTh17/mTreg cells. Astragalus polysaccharide (APS) has good immunomodulatory and anti-inflammatory effects. Here, the regulatory effects and potential mechanisms of APS on mTh17/mTreg cells in UC are explored. A UC model was induced with dextran sulfate sodium (DSS) and treated simultaneously with APS (200 mg/kg/day) for 10 days. After APS treatment, the mice showed a significant increase in colonic length and a significant decrease in colonic weight, colonic weight index and colonic weight/colonic length, and more intact mucosa and lighter inflammatory cell infiltration. Notably, APS significantly down-regulated the percentages of Th17 (CD4+CCR6+), cmTh17 (CD4+CCR7+CCR6+) and emTh17 (CD4+CCR7−CCR6+) cells and significantly up-regulated the percentages of cmTreg (CD4+CCR7+Foxp3+) and emTreg (CD4+CCR7−Foxp3+) cells in the mesenteric lymph nodes of the colitis mice. Importantly, APS reversed the expression changes in the TIGIT molecule on mTh17/mTreg cells in the colitis mice with fewer CD4+CCR6+TIGIT+, CD4+CCR7−CCR6+TIGIT+ and CD4+CCR7−CCR6+TIGIT+ cells and more CD4+Foxp3+TIGIT+, CD4+CCR7−Foxp3+TIGIT+ and CD4+CCR7−Foxp3+TIGIT+ cells. Meanwhile, APS significantly inhibited the protein expression of the TIGIT ligands CD155, CD113 and CD112 and downstream proteins PI3K and AKT in the colon tissues of the colitis mice. In conclusion, APS effectively alleviated DSS-induced UC in mice by regulating the balance between mTh17/mTreg cells, which was mainly achieved through regulation of the TIGIT/CD155 signaling pathway.

The stamping process produces thin-walled structures that, in general, have uniform wall thickness and no enclosed cavity. However, it is difficult to satisfy the above geometric requirements with the current density-based topology optimization method, since configuring the related geometric constraints is challenging. In order to solve this problem, a topology optimization method for stamping structures based on a directional density field is proposed. Specifically, the directional density field is developed to enable the adding and removing of materials only along the stamping direction, so as to avoid internal voids and concave features. The geometric control for uniform wall thickness is realized by tuning the truncation threshold of the Heaviside projection that processes the directional density field into the 0–1 binary field. At the same time, a calibrated filter radius of the truncation thresholds will facilitate the drawing angle control of the stamping ribs. The effectiveness of the established method has been verified by a number of numerical case studies. Results show that the proposed method can perform topology optimization for stamping structures with tunable uniform thickness and drawing angle control of the ribs. No internal voids or undercuts appear in the results. The results also disclose that a constant truncation threshold increment does not guarantee uniform wall thickness, and varying the threshold increments through surface offset and polynomial fitting is necessary.

Autoimmune diseases are heterogeneous disorders believed to stem from the immune system’s inability to distinguish between auto- and foreign- antigens. B lymphocytes serve a crucial role in humoral immunity as they generate antibodies and present antigens. Dysregulation of B cell function induce the onset of autoimmune disorders by generating autoantibodies and pro-inflammatory cytokines, resulting in an imbalance in immune regulation. New research in immunometabolism shows that cellular metabolism plays an essential role in controlling B lymphocytes immune reactions by providing the energy and substrates for B lymphocytes activation, differentiation, and function. However, dysregulated immunometabolism lead to autoimmune diseases by disrupting self-tolerance mechanisms. This review summarizes the latest research on metabolic reprogramming of B lymphocytes in autoimmune diseases, identifying crucial pathways and regulatory factors. Moreover, we consider the potential of metabolic interventions as a promising therapeutic strategy. Understanding the metabolic mechanisms of B cells brings us closer to developing novel therapies for autoimmune disorders.

Screening programmes are important for early diagnosis and treatment of colorectal cancer (CRC) but they are not equally efficient in all locations. Depending on which hospital people belong to, they often are not willing to follow up even after a positive result, resulting in a lower-than-expected overall detection rate. Improved allocation of health resources would increase the program’s efficiency and assist hospital accessibility. A target population exceeding 70,000 people and 18 local hospitals were included in the investigation of an optimization plan based on a locationallocation model. We calculated the hospital service areas and the accessibility for people in communities to CRC-screening hospitals using the Huff Model and the Two-Step Floating Catchment Area (2SFCA) approach. We found that only 28.2% of the residents with initially a positive screening result had chosen followup with colonoscopy and significant geographical differences in spatial accessibility to healthcare services indeed exist. The lowest accessibility was found in the Southeast, including the Zhangjiang, Jichang and Laogang communities with the best accessibility mainly distributed near the city centre of Lujiazui; the latter also had relatively a high level of what is called “ineffective screening” as it represents wasteful resource allocation. It is recommended that Hudong Hospital should be chosen instead of Punan Hospital as the optimization, which can improve the service population of each hospital and the populations served per colonoscope. Based on our results, changes in hospital configuration in colorectal cancer screening programme are needed to achieve adequate population coverage and equitable facility accessibility. Planning of medical services should be based on the spatial distribution trends of the population served.

Graphical Abstract

ABSTRACT: Antibiotic treatment failure is increasingly encountered for the emergence of pandrug-resistant isolates, including the prototypical broad-host-range Salmonella enterica serovar (S.) Typhimurium, which mainly transmitted to humans through poultry products. In this study we explored the therapeutic potential of a Salmonella phage composition containing a virulent phage and a nonproductive phage that does not produce progeny phage against chicks infected with a pandrug-resistant S. Typhimurium strain of avian origin. After approximately 107 CFU of S. Typhimurium strain ST149 were administrated to chicks by intraperitoneal injection, the phage combination (∼108 PFU) was gavaged at 8-h, 32-h, and 54-h postinfection. At d 10 postinfection, phage treatment completely protected chicks from Salmonella-induced death compared to 91.7% survival in the Salmonella challenge group. In addition, phage treatment also greatly reduced the bacterial load in various organs, with Salmonella colonization levels decreasing more significantly in spleen and bursa than in liver and cecal contents, possibly due to higher phage titers in these immune organs. However, phages could not alleviate the decreased body weight gain and the enlargement of spleen and bursa of infected chicks. Further examination of the bacterial flora in the cecal contents of chicks found that S. Typhimurium infection caused a remarkable decrease in abundance of Clostridia vadin BB60 group and Mollicutes RF39 (the dominant genus in chicks), making Lactobacillus the dominate genus. Although phage treatment partially restored the decline of Clostridia vadin BB60 group and Mollicutes RF39 and increased abundance of Lactobacillus caused by S. Typhimurium infection, Fournierella that may aggravate intestinal inflammation became the major genus, followed by increased Escherichia-Shigella as the second dominate bacterial genus. These results suggested that successive phage treatment modulated the structural composition and abundance of bacterial communities, but failed to normalize the intestinal microbiome disrupted by S. Typhimurium infection. Phages need to be combined with other means to control the spread of S. Typhimurium in poultry.

Abstract Background To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes. Methods The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture. Results Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839–29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804–36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183–42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018–0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029). Conclusions Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.

Objective: The amylase-producing strain screened on the surface of Yunnan Malong C3F-2016 tobacco leaves were used as the starting strain to mutagenically select high amylase-producing strain and to study the enzymatic properties before and after mutagenesis. Methods: The amylase-producing strain were selected by ARTP technique and the amylase activity was determined by the 3,5-dinitrosalicylic acid (DNS) method before and after mutagenesis, and the effects of different temperatures, pH, metal ions and UV light on the amylase activity were investigated. Results: A mutant strain Bacillus koreensis FS-103 was selected by mutagenesis with improved enzyme activity and stable transmission, and its amylase activity reached 9050 U/mL, which was 90% higher than that of the starting strain. The optimum action temperature of amylase produced by the high-yielding mutant strain FS-103 was 60 ℃ and the optimum action pH5.5, with good stability between 40 and 50 ℃ and pH5~6, Ca2+ and Mg2+ had a promoting effect on amylase activity, and the effect of UV irradiation on amylase activity was weakened. Conclusion: This method of mutagenic selection of amylase-producing strain was feasible and lays the theoretical foundation for the research and development of enzyme preparations by this type of strain.

Abstract Background Abnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships. Methods We examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9–11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%). Results Overall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07–2.14; P-values

Quantitative metal grade inversion based on hyperspectral data is an effective approach to achieve the real-time in situ determination of ore body grades and has the advantages of low cost compared with traditional chemical analysis methods. However, the redundant nature of hyperspectral data and the parameter-limiting nature of machine learning algorithms reduce the modeling accuracy and precision, resulting in severe limitations on the application of hyperspectral techniques for the grade inversion of Deerni copper ore bodies. In this paper, we first obtained visible-NIR hyperspectral data for 190 ore samples using a spectrometer and determined the copper content of the sample set using chemical analysis; then, we processed the raw hyperspectral data using three dimensionality reduction algorithms and optimized a BP neural network based on an evolutionary algorithm. Finally, a Deerni copper grade inversion model was established using the hyperspectral data before and after dimensionality reduction, and the inversion accuracy and precision was compared and analyzed with that obtained by the BP neural network, the random forest and the variable hidden layer nodes models. The combination of the LLE dimensionality reduction algorithm and the optimized BP neural network algorithm achieves the highest modeling precision, with an R2 of 0.950.

Abstract Background The continuous mutation of severe acute respiratory syndrome coronavirus 2 has made the coronavirus disease 2019 (COVID-19) pandemic complicated to predict and posed a severe challenge to the Beijing 2022 Winter Olympics and Winter Paralympics held in February and March 2022. Methods During the preparations for the Beijing 2022 Winter Olympics, we established a dynamic model with pulse detection and isolation effect to evaluate the effect of epidemic prevention and control measures such as entry policies, contact reduction, nucleic acid testing, tracking, isolation, and health monitoring in a closed-loop management environment, by simulating the transmission dynamics in assumed scenarios. We also compared the importance of each parameter in the combination of intervention measures through sensitivity analysis. Results At the assumed baseline levels, the peak of the epidemic reached on the 57th day. During the simulation period (100 days), 13,382 people infected COVID-19. The mean and peak values of hospitalized cases were 2650 and 6746, respectively. The simulation and sensitivity analysis showed that: (1) the most important measures to stop COVID-19 transmission during the event were daily nucleic acid testing, reducing contact among people, and daily health monitoring, with cumulative infections at 0.04%, 0.14%, and 14.92% of baseline levels, respectively (2) strictly implementing the entry policy and reducing the number of cases entering the closed-loop system could delay the peak of the epidemic by 9 days and provide time for medical resources to be mobilized; (3) the risk of environmental transmission was low. Conclusions Comprehensive measures under certain scenarios such as reducing contact, nucleic acid testing, health monitoring, and timely tracking and isolation could effectively prevent virus transmission. Our research results provided an important reference for formulating prevention and control measures during the Winter Olympics, and no epidemic spread in the closed-loop during the games indirectly proved the rationality of our research results. Graphical Abstract

Influenza virus, with a global distribution, diverse animal host range and multiple virus subtypes, has caused several pandemics. To better prepare for the emergence of new subtypes and the possible threat of the next pandemic, the global status of animal influenza must be defined and documented. We created a global database of animal influenza events by searching scientific databases and the primary literature on animal influenza-related events up to and including 2016. The temporal, spatial and host distribution of animal influenza and the diversity of influenza subtypes in different regions were analyzed. A total of 70,472 records and 4712 events of animal influenza throughout the world were identified. Events involving subtypes H5N2, H7N7 and H7N9 were relatively constant, with a slow upward trend during the past decade. Asia was the region with the most clusters of events. Poultry was the main host reported in Asia and Africa, and wild birds in Europe and North America. We found that wild birds carried a very rich array of virus subtypes, a warning for the possible generation of reassortment viruses with pandemic potential. Influenza virus subtype diversity - a risk for virus reassortment - was greatest in Asia, North America and Europe. Our database provides a comprehensive overview of the historical and current status of animal influenza events throughout the world. Influenza surveillance needs to be strengthened in some countries and regions to prevent the emergence of new subtypes. Importantly, improvement of the global influenza surveillance system and structures to enable sharing of surveillance data is very much needed to prepare for the next pandemic.

Ever since its emergence in 2019, COVID-19 has rapidly disseminated worldwide, engendering a pervasive pandemic that has profoundly impacted healthcare systems and the socio-economic milieu. A plethora of studies has been conducted targeting its pathogenic virus, SARS-CoV-2, to find ways to combat COVID-19. The ubiquitin-proteasome system (UPS) is widely recognized as a crucial mechanism that regulates human biological activities by maintaining protein homeostasis. Within the UPS, the ubiquitination and deubiquitination, two reversible modifications, of substrate proteins have been extensively studied and implicated in the pathogenesis of SARS-CoV-2. The regulation of E3 ubiquitin ligases and DUBs(Deubiquitinating enzymes), which are key enzymes involved in the two modification processes, determines the fate of substrate proteins. Proteins associated with the pathogenesis of SARS-CoV-2 may be retained, degraded, or even activated, thus affecting the ultimate outcome of the confrontation between SARS-CoV-2 and the host. In other words, the clash between SARS-CoV-2 and the host can be viewed as a battle for dominance over E3 ubiquitin ligases and DUBs, from the standpoint of ubiquitin modification regulation. This review primarily aims to clarify the mechanisms by which the virus utilizes host E3 ubiquitin ligases and DUBs, along with its own viral proteins that have similar enzyme activities, to facilitate invasion, replication, escape, and inflammation. We believe that gaining a better understanding of the role of E3 ubiquitin ligases and DUBs in COVID-19 can offer novel and valuable insights for developing antiviral therapies.

Summary: The nuclear factor κB (NF-κB) pathway plays essential roles in innate and adaptive immunity, but little is known how NF-κB signaling is compartmentalized and spatiotemporally activated in the cytoplasm. Here, we show that the lipogenesis signal cascade Scap-SREBP1-S1P/S2P orchestrates the homeostasis and spatiotemporal activation of NF-κB. SREBP cleavage-activating protein (Scap) and sterol regulatory element-binding protein 1 (SREBP1) form a super complex with inhibitors of NF-κB α (IκBα) to associate NF-κB close to the endoplasmic reticulum (ER). Upon lipopolysaccharide (LPS) stimulation, Scap transports the complex to the Golgi apparatus, where SREBP1 is cleaved by site-1 protease (S1P)/S2P, liberating IκBα for IκB kinase (Ikk)-mediated phosphorylation and subsequent activation of NF-κB. Loss of Scap or inhibition of S1P or S2P diminishes, while SREBP1 deficiency augments, LPS-induced NF-κB activation and subsequent inflammatory responses. Our results reveal the Scap-SREBP1 complex as an additional cytoplasmic checkpoint for NF-κB homeostasis and unveil the Golgi apparatus as the optimal cellular platform for NF-κB activation, providing insights into the crosstalk between lipogenesis signaling and immunity.

Avian colibacillosis, caused by avian Escherichia coli (E. coli), has historically been one of the most prevalent infectious diseases in large-scale poultry production, causing growth delays and mortality in chickens, resulting in huge economic losses. In recent years, the widespread use of antibiotics has led to the emergence of multidrug resistance in E. coli as a significant global problem and long-term challenge. Resistant E. coli can be transmitted to humans through animal products or the environment, which presents significant public health concerns and food safety issues. In this study, we analyzed the features of 135 E. coli strains obtained from a white feather broiler farm in Shandong, China, including antimicrobial susceptibility tests, detection of class 1 integrons, drug resistance genes, virulence genes, and phylogenetic subgroups. It is particularly worrying that all 135 E. coli strains were resistant to at least five antibiotic agents, and 100% of them were multidrug-resistant (MDR). Notably, the resistance genes of blaTEM, blaCTX-M, qnrS, aaC4, tetA, and tetB exhibited a high prevalence of carriage among the tested resistance genes. However, mcr-2~mcr-9 were not detected, while the prevalence of mcr-1 was found to be 2.96%. The most common virulence genes detected were EAST1 (14.07%, encoding enterotoxins) and fyuA (14.81%, encoding biofilm formation). Phylogenetic subgroup analysis revealed that E. coli belonging to groups B2 and D, which are commonly associated with high virulence, constituted 2.22% and 11.11%, respectively. The positive rate of class 1 integrons was 31.1%. Whole-genome sequencing (WGS) and animal experiments were performed on a unique isolated strain called 21EC78 with an extremely strong membrane-forming capacity. The WGS results showed that 21EC78 carried 11 drug resistance genes and 16 virulence genes. Animal experiments showed that intraperitoneal injection with 2 × 105 CFU could cause the death of one-day-old SPF chickens in 3 days. However, the mortality of Luhua chickens was comparatively lower than that of SPF chickens. This study reports the isolation of multidrug-resistant E. coli strains in poultry, which may pose a potential threat to human health via the food chain. Furthermore, the findings of this study enhance our comprehension of the frequency and characteristics of multidrug-resistant E. coli in poultry farms, emphasizing the urgent need for improved and effective continuous surveillance to control its dissemination.

Salmonella enterica subsp. enterica serovar Gallinarum biovar pullorum (Salmonella pullorum) is an avian-specific pathogen that has caused considerable economic losses to the poultry industry. High endemicity, poor implementation of hygiene measures, and lack of effective vaccines hinder the prevention and control of this disease in intensively maintained poultry flocks. In recent years, the incidence of arthritis in chicks caused by Salmonella pullorum infection has increased. In this study, four Salmonella pullorum strains were identified from the livers, spleens, and joint fluids of Qingjiaoma chicken breeders with arthritis clinical signs, and an arthritis model of chicks was successfully established using SP206-2. Whole genome sequencing of the SP206-2 strain showed that the genome was 4,730,579 bp, 52.16% GC content, and contained 5007 genes, including 4729 protein-coding regions. The genomic analysis of four arthritis-causing isolates and three diarrhea-causing isolates showed that the genome of arthritis-causing isolates was subject to nonsynonymous mutations, shift mutations, and gene copy deletions. An SNP phylogenetic tree analysis showed that arthritis-causing isolates are located in a different evolutionary branch from diarrhea-causing isolates. Further differential genes analysis showed that the genome of arthritis-causing isolates had missense mutations in genes related to substance metabolism and substance transport, as a result of adaptive evolution.

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of a parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, caused the apparent permeability coefficient of ranitidine to decrease to 4.62 × 10−5, 4.5 × 10−5, 3.61 × 10−5 and 1.08 × 10−5 in Caco-2 cells, respectively. The same results were obtained from an oral pharmacokinetic study in rats. Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability.

Indoor fire is a sudden and frequent disaster that severely threatens the safety of indoor people worldwide. Indoor fire emergency evacuation is crucial to reducing losses involving various objects and complex relations. However, traditional studies only rely on numerical simulation, which cannot provide adequate support for decision-making in indoor fire scenarios. The knowledge graph is a knowledge base that can fully utilize massive heterogeneous data to form a sound knowledge system; however, it has not been effectively applied in the fire emergency domain. This study is a preliminary attempt to construct a knowledge graph for indoor fire emergency evacuation. We constructed the indoor fire domain ontology and proposed a four-tuple knowledge representation model. A knowledge graph was constructed with 1852 nodes and 2364 relations from 25 indoor fire events. The proposed method was tested for the case study of Henan Pingdingshan ‘5.25’ Fire Accident in China. Results show that the proposed knowledge representation model and the corresponding knowledge graph can represent complicated indoor fire events and support indoor fire emergency evacuation.

The radiated seismic energy is an important index for the intensity assessment of microseismic (MS) events and the early warning of dynamic disasters. However, the energy of MS signals is significantly attenuated due to the heterogeneity and viscous damping of rock media. Therefore, the study on attenuation characteristics of MS signals in underground engineering has practical significance for the accurately estimation of radiated seismic energy. Based on a pendulum impact test facility and MS monitoring system, an in situ investigation was carried out to explore attenuation characteristics at a deep tunnel. The results show that the seismic energy and peak particle velocity (PPV) attenuation are exponentially related to the propagation distance. The attenuation coefficient of energy is larger than that of PPV. With the increase in the input impact-energy, the seismic energy attenuation coefficient decreases as a power function. An empirical relationship between energy attenuation coefficient and wave impedance of rock mass was established in this scenario. Moreover, the time-frequency characteristics and energy distribution laws of impact-induced signals were investigated by the continuous wavelet transform (CWT) and wavelet packet analyses, respectively. The dominant frequency of signals decreases gradually as the propagation distance increases. Based on the energy attenuation characteristics, a new method was proposed to calculate the released source energy of MS events in the field. This study can provide an insight into energy attenuation characteristics of seismic waves and references for attenuation correction in seismic energy calculation.

Dysregulation of metabolism plays an important role in the onset and progression of multiple pathogenic diseases, including viral hepatitis. However, a model to predict viral hepatitis risk by metabolic pathways is still lacking. Thus, we developed two risk assessment models for viral hepatitis based on metabolic pathways identified through univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The first model is designed to assess the progression of the disease by evaluating changes in the Child–Pugh class, hepatic decompensation, and the development of hepatocellular carcinoma. The second model is focused on determining the prognosis of the illness, taking into account the patient’s cancer status. Our models were further validated by Kaplan–Meier plots of survival curves. In addition, we investigated the contribution of immune cells in metabolic processes and identified three distinct subsets of immune cells—CD8+ T cells, macrophages, and NK cells—that have significantly affected metabolic pathways. Specifically, our findings suggest that resting or inactive macrophages and NK cells contribute to maintaining metabolic homeostasis, particularly with regard to lipid and α-amino acid metabolism, thereby potentially reducing the risk of viral hepatitis progression. Moreover, maintaining metabolic homeostasis ensures a balance between killer-proliferative and exhausted CD8+ T cells, which helps in mitigating CD8+ T cell-mediated liver damage while preserving energy reserves. In conclusion, our study offers a useful tool for early disease detection in viral hepatitis patients through metabolic pathway analysis and sheds light on the immunological understanding of the disease through the examination of immune cell metabolic disorders.

With the increasing incidence and mortality of chronic kidney disease (CKD), targeted therapies for CKD have been explored constantly. The important role of gut microbiota on CKD has been emphasized increasingly, it is necessary to analyze the metabolic mechanism of CKD patients from the perspective of gut microbiota. In this study, bioinformatics was used to analyze the changes of gut microbiota between CKD and healthy control (HC) groups using 315 samples from NCBI database. Diversity analysis showed significant changes in evenness compared to the HC group. PCoA analysis revealed significant differences between the two groups at phylum level. In addition, the F/B ratio was higher in CKD group than in HC group, suggesting the disorder of gut microbiota, imbalance of energy absorption and the occurrence of metabolic syndrome in CKD group. The study found that compared with HC group, the abundance of bacteria associated with impaired kidney was increased in CKD group, such as Ralstonia and Porphyromonas, which were negatively associated with eGFR. PICRUSt2 was used to predict related functions and found that different pathways between the two groups were mainly related to metabolism, involving the metabolism of exogenous and endogenous substances, as well as Glycerophospholipid metabolism, which provided evidence for exploring the relationship between gut microbiota and lipid metabolism. Therefore, in subsequent studies, special attention should be paid to these bacteria and metabolic pathway, and animal experiments and metabolomics studies should be conducted explore the association between bacterial community and CKD, as well as the therapeutic effects of these microbial populations on CKD.

Dendrite growth of lithium (Li) metal anode severely hinders its practical application, while the situation becomes more serious at low temperatures due to the sluggish kinetics of Li-ion diffusion. This perspective is intended to clearly understand the energy chemistry of low-temperature Li metal batteries (LMBs). The low-temperature chemistries between LMBs and traditional Li-ion batteries are firstly compared to figure out the features of the low-temperature LMBs. Li deposition behaviors at low temperatures are then discussed concerning the variation in Li-ion diffusion behaviors and solid electrolyte interphase (SEI) features. Subsequently, the strategies to enhance the diffusion kinetics of Li ions and suppress dendrite growth including designing electrolytes and electrode/electrolyte interfaces are analyzed. Finally, conclusions and outlooks are drawn to shed lights on the future design of high-performance low-temperature LMBs.

Abstract Background Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. Methods In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. Results Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. Conclusions This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.