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Abstract The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.

This study explores financial literacy (FL) and its influence on market participation among rural residents in China. Using the 2017 China Household Finance Survey, we find that rural residents have low FL and answer only 33% of basic and 20.8% of advanced questions on average. The findings indicate a substantial disparity in their FL skills. The ordinary least squares regression results reveal that advanced FL is statistically positively related to market participation. To mitigate endogeneity concerns, we adopt the instrument variable estimator within the generalized method of moment (IV-GMM). The IV-GMM results indicate that FL positively affects the market participation of Chinese rural households. The probability of market participation increases by over 7% with every unit increase in advanced FL scores. Additionally, the robustness tests confirm the positive correlation between advanced FL and market participation. Furthermore, the impact of FL on stock-market participation is more pronounced among rural residents in economically developed regions and those with greater financial assets.

Lychee juice was fermented with Lacticaseibacillus casei, Lactococcus lactis subsp. lactis, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Lactiplantibacillus plantarum, and Leuconostoc mesenteroides subsp. cremoris to study the effects of fermentation on the physicochemical properties, major active ingredient content, antioxidant capacity, and effects on defecation and small intestinal motility in mice. The results showed that fermentation with various probiotics decreased the pH of lychee juice while increasing total acid and soluble solids content. After fermentation, the total phenol and total flavonoid content, as well as the antioxidant capacity of lychee juice, decreased to varying degrees, while the polysaccharide content increased by 9.38 to 13.31 times. Specifically, lychee juice fermented with Lacticaseibacillus casei and Lactobacillus delbrueckii subsp. bulgaricus retained more active components and antioxidant activity. The experimental results in mice showed that the group of lychee juice fermented with Lacticaseibacillus casei shortened the time of first defecation by 47.39% compared to the model group. The quantity, weight and water content of red stool particles within 6 hours were significantly higher than those in the model group (P0.05). Therefore, lychee juice fermented with Lacticaseibacillus casei has a greater laxative effect, providing a theoretical basis for the further development of functional fermented lychee juice products.

BackgroundHeavy metal exposure may be associated with the risk of metabolic syndrome (MetS) and serum uric acid. The role of serum uric acid in the relationship between heavy metal exposure and MetS is currently unclear.ObjectiveTo evaluate the relationships of heavy metal exposure with MetS and serum uric acid, and to quantify the role of serum uric acid in the relationship.MethodsIn 2021, convenience sampling was used to select 571 local adults in Liuzhou, Guangxi. Demographic characteristics, lifestyle habits, and physiological and biochemical indicators were collected through questionnaire surveys and physical examinations. Fasting blood and mid-stream morning urine were also collected. The concentrations of 16 heavy metals in urine were measured using inductively coupled plasma mass spectrometry. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify heavy metals associated with MetS. Logistic regression and linear regression models were employed to evaluate the association between the selected heavy metals and MetS as well as serum uric acid. Bayesian kernel machine regression (BKMR) model was utilized to assess the impact of combined exposures to multiple metals on the risk of MetS and identify the main effect metals. Generalized structural equation model was used to evaluate potential mediating effect of serum uric acid on the relationship between heavy metal exposure and MetS.ResultsThe LASSO regression identified a total of 9 heavy metals that were associated with MetS. The logistic regression revealed a positive correlation between zinc and copper in urine and MetS (P trend

From the perspective of ecological control, harvesting behavior plays a crucial role in the ecosystem natural cycle. This paper proposes a diffusive predator-prey system with predator harvesting to explore the impact of harvesting on predatory ecological relationships. First, the existence and boundedness of system solutions were investigated and the non-existence and existence of non-constant steady states were obtained. Second, the conditions for Turing instability were given to further investigate the Turing patterns. Based on these conditions, the amplitude equations at the threshold of instability were established using weakly nonlinear analysis. Finally, the existence, direction, and stability of Hopf bifurcation were proven. Furthermore, numerical simulations were used to confirm the correctness of the theoretical analysis and show that harvesting has a strong influence on the dynamical behaviors of the predator-prey systems. In summary, the results of this study contribute to promoting the research and development of predatory ecosystems.

Abstract Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors among oral cancers, and its treatment is based on radio-chemotherapy and surgery, which always produces more serious side effects and sequelae. Traditional medicine can compensate for the shortcomings of modern medical treatments and play a better therapeutic role. Currently, active ingredients derived from plants are attracting the attention of researchers and clinical professionals. We examined capsaicin (CAP), an active ingredient isolated from Capsicum annuum (family Solanaceae), and explored the effect of CAP combined with cisplatin (DDP) on epithelial-mesenchymal transition (EMT) and TSCC cells migration. Our results demonstrated that Transforming growth factor-β1(TGF-β1) induced EMT and promoted cell migration in TSCC cells. CAP combined with DDP inhibits non-TGF-β1-induced or TGF-β1-induced EMT and migration. Mechanistically, the inhibition of non-TGF-β1-induced EMT and migration by CAP combined with DDP was mediated by the AMPK/mTOR pathway, whereas TGF-β1-induced EMT and migration were regulated by the Claudin-1/PI3K/AKT/mTOR pathway. A nude lung metastasis mouse model was established for in vivo validation. These results support our hypothesis that the combination of CAP and DDP inhibits TSCC metastasis. These data set the stage for further studies aimed at validating CAP as an effective active ingredient for enhancing chemotherapy efficacy and reducing the dosage and toxicity of chemotherapeutic drugs, ultimately paving the way for translational research and clinical trials for TSCC eradication.

Abstract Background H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. Results Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. Conclusions Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract

Abstract Offloading some tasks from the local device to the remote cloud is one of the important methods to overcome the drawbacks of the medical mobile device, such as the limitation in the execution time and energy supply. The challenges of offloading task is how to meet multiple requirement while keeping energy-saving. We classify tasks in the medical mobile device into two kinds: the first is the task that hopes to be executed as soon as possible, those tasks always have a deadline; the second is the task that can be executed anytime and always has no deadlines. Past work always neglects the energy consumption when the medical mobile device is charged. To the best of our knowledge, this paper is the first paper that focuses on the energy efficiency of charging from a power grid to a medical device during work. By considering the energy consumption in different locations, the energy efficiency during working and energy transmission, the available energy of and the battery, we propose a scheduling method based on DQN. Simulations show that our proposed method can reduce the number of un-completed tasks, while having a minimum value in the average execution time and energy consumption.

Abstract Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival has not improved much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from anlotinib and eribulin combination. In this study, we investigated the combinational effect of anlotinib and eribulin on RLPS. In vitro experiments revealed that a low dose of anlotinib significantly enhances the cytotoxic effects of eribulin, leading to a remarkable suppression of RLPS cell proliferation, viability, colony formation, migration, and cell-cycle progression compared to individual drug treatments. At the organoid level, the combination treatment causes the spheroids in Matrigel to disintegrate earlier than the single-drug group. In vivo, RLPS patient-derived xenograft (PDX) models demonstrated that the combination of these two drugs can obviously exert a safe and effective anti-tumor effect. Through transcriptome analysis, we uncovered and validated that the synergistic effect mainly is induced by the endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo. Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.

Abstract Background At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear. Methods RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation. Results In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation. Conclusions The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS. Trial registration Not applicable.

Abstract Background A knowledge of gouty arthritis could help in the primary prevention of the disease development and lead to an early diagnosis if it occurs. This study investigated the knowledge, attitudes, and practices (KAP) toward gouty arthritis in the general population > 30 years old. Methods This web-based cross-sectional study was conducted among the general population > 30 years old between January and March 2023 in Chengdu, Sichuan. The questionnaire was designed by the investigators based on the available guidelines (Cronbach’s α = 0.846). A score above 70% indicated good knowledge, a positive attitude, and proactive practice. Multivariable and structural equation modeling (SEM) analyses were performed to analyze the factors influencing KAP. Results A total of 537 questionnaires were included. The knowledge, attitudes, and practices scores were 13.12 ± 6.41, 25.28 ± 3.97, and 45.25 ± 5.77, respectively. Female (OR = 0.47, 95%CI: 0.31–0.71, P 10,000 yuan (OR = 2.07, 95%CI: 1.12–3.81, P = 0.020) were independently associated with attitudes. Attitude (OR = 1.31, 95%CI: 1.23–1.40, P

Abstract Vallisneria spinulosa Yan (V.spinulosa Yan) with good ability of water purification is often used for ecological restoration of polluted water bodies. However, it is difficult to survive in turbid water bodies due to the low lighting condition. This study explored the feasibility of introducing artificial underwater light source into water bodies with high turbidity to strengthen the water restoration by V.spinulosa Yan. Addition of underwater light source promoted the clonal reproduction ability of V.spinulosa Yan, thus enhancing the removal loads of total nitrogen (TN), total phosphorus (TP), and nitrate nitrogen ( $${\mathrm{NO}}^{-}_{3}{\mbox{-}}{\mathrm{N}}$$ NO 3 − - N ) by 1.60–3.43 × 10−2, 1.49–3.49 × 10−3, and 0.80–2.06 × 10−2 g m−2 d−1, respectively. Underwater light source significantly reduced the abundance of microbial community on V.spinulosa Yan leaves, as well as most nitrifying bacteria (Nitrosomonadaceae) and denitrifying bacteria (Nitrospira, Comamonadaceae, and Rhodocyclaceae) in the system. But the attachment of some Cyanophyta (Chloroplast and Cyanobacteria) and Photosynthetic bacteria (Rhodobacter) onto the leaves and the growth of Methyloligellaceae in water and sediments were promoted. Nitrogen and phosphorus removal by the growth system of V.spinulosa Yan without underwater light source mainly depended on the biological processes by functional bacteria, while the absorption and co-assimilation effect of V.spinulosa Yan with underwater light source.

Abstract Background Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer’s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. Methods This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman’s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. Results The participants’ mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P

Abstract For patients presenting with prostate imaging reporting and data system (PI-RADS) 3/4 findings on magnetic resonance imaging (MRI) examinations, the standard recommendation typically involves undergoing a biopsy for pathological assessment to ascertain the nature of the lesion. This course of action, though essential for accurate diagnosis, invariably amplifies the psychological distress experienced by patients and introduces a host of potential complications associated with the biopsy procedure. However, [18F]DCFPyL PET/CT imaging emerges as a promising alternative, demonstrating considerable diagnostic efficacy in discerning benign prostate lesions from malignant ones. This study aims to explore the diagnostic value of [18F]DCFPyL PET/CT imaging for prostate cancer in patients with PI-RADS 3/4 lesions, assisting in clinical decision-making to avoid unnecessary biopsies. 30 patients diagnosed with PI-RADS 3/4 lesions through mpMRI underwent [18F]DCFPyL PET/CT imaging, with final biopsy pathology results as the “reference standard”. Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, evaluating the diagnostic efficacy of molecular imaging PSMA (miPSMA) visual analysis and semi-quantitative analysis in [18F]DCFPyL PET/CT imaging. Lesions were assigned miPSMA scores according to the prostate cancer molecular imaging standardized evaluation criteria. Among the 30 patients, 13 were pathologically confirmed to have prostate cancer. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis in [18F]DCFPyL PET/CT imaging for diagnosing PI-RADS 3/4 lesions were 61.5%, 88.2%, 80.0%, 75.0%, and 76.5%, respectively. Using SUVmax 4.17 as the optimal threshold, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis were 92.3%, 88.2%, 85.7%, 93.8%, and 90.0%, respectively. The area under the ROC curve (AUC) for semi-quantitative analysis was 0.94, significantly higher than visual analysis at 0.80. [18F]DCFPyL PET/CT imaging accurately diagnosed benign lesions in 15 (50%) of the PI-RADS 3/4 patients. For patients with PI-RADS 4 lesions, the positive predictive value of [18F]DCFPyL PET/CT imaging reached 100%. [18F]DCFPyL PET/CT imaging provides potential preoperative prediction of lesion nature in mpMRI PI-RADS 3/4 patients, which may aid in treatment decision-making and reducing unnecessary biopsies.

Abstract Background Tyrosine phosphorylation of intracellular proteins is a post‐translational modification that plays a regulatory role in signal transduction during cellular events. Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases (PTPs) contributed their role as a convergent node to mediate cross‐talk between signaling pathways. In the context of cancer, PTP‐mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy. This is achieved by the promotion of constitutive activation of growth‐stimulatory signaling pathways or modulation of the immune‐suppressive tumor microenvironment. Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors, reversing drug resistance that was responsible for clinical failures during cancer therapy. Areas covered This review aimed to elaborate recent insights that supported the involvement of PTP‐mediated pathways in the development of resistance to targeted therapy and immune‐checkpoint therapy. Expert opinion This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long‐term tumor regression. Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced‐stage tumors.

Abstract Background The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and β-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and β-hCG levels on early reproductive outcomes 12 days after embryo transfer. Methods A total of 1521 patients with β-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women’s Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and β-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and β-hCG concentrations. Results Notable distinctions were observed in the serum E2 and β-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and β-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and β-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and β-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. Conclusions Serum E2 and β-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study’s findings suggest that the combination of early E2 and β-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs.

Abstract Background A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. Methods A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. Results In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR

Abstract Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.

Abstract Innate lymphoid cell precursors (ILCPs) develop into distinct subsets of innate lymphoid cells (ILCs) with specific functions. The epigenetic program underlying the differentiation of ILCPs into ILC subsets remains poorly understood. Here, we reveal the genome-wide distribution and dynamics of the DNA methylation and hydroxymethylation in ILC subsets and their respective precursors. Additionally, we find that the DNA hydroxymethyltransferase TET1 suppresses ILC1 but not ILC2 or ILC3 differentiation. TET1 deficiency promotes ILC1 differentiation by inhibiting TGF-β signaling. Throughout ILCP differentiation at postnatal stage, gut microbiota contributes to the downregulation of TET1 level. Microbiota decreases the level of cholic acid in the gut, impairs TET1 expression and suppresses DNA hydroxymethylation, ultimately resulting in an expansion of ILC1s. In adult mice, TET1 suppresses the hyperactivation of ILC1s to maintain intestinal homeostasis. Our findings provide insights into the microbiota-mediated epigenetic programming of ILCs, which links microbiota-DNA methylation crosstalk to ILC differentiation.

Abstract Background To explore the relationship between occupational stress, burnout and depressive symptoms among railroad workers in Fuzhou, and to analyze the interaction of burnout and occupational stress on depressive symptoms. Methods In this study, 861 railway employees of Fuzhou railway bureau were randomly selected from January to April, 2022. Occupational stress inventory revised edition (OSI-R), China job burnout inventory (CMBI) and Symptom Checklist-90 (SCL-90) were used to investigate the occupational stress, job burnout and depressive symptoms of railway workers. Interactions associated with depressive symptoms were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). Results Occupational stress, job burnout and depressive symptoms accounted for 50.58%, 93.47%, and 11.19% of the study population, respectively. There were intergroup differences between age, marriage status, and length of service (P

Abstract The weak cosmic censorship conjecture is a hypothesis about the nature of event horizons and singularities during the formation of black holes. It posits that singularities are always enveloped by the event horizons of black holes, thereby preventing naked singularities from affecting the causal structure of spacetime. In this paper, we study the effect of rotating short haired black holes on the weak cosmic censorship conjecture. Discussion of whether the event horizons of a rotating short haired black hole is disrupted by studying incident neutral test particles and scalar fields. In the context of short haired black holes, when incident neutral test particles are considered for extreme and near extreme cases, our research results indicate that neutral test particles can destroy the event horizons of short haired black holes, violating the weak cosmic censorship conjecture. In the case of scalar field incidence in short haired black holes, for extreme situations, when the incident wave modes fall within the range of $$\frac{1}{2\kappa M+\frac{\beta }{M\kappa }}

Abstract Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice. We proposed a simplified definition for assessing MetS risk in youths aged 6–17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89–0.92) and 0.79 (0.78–0.81) when using the IDF or NCEP definition as the gold standard, respectively. The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Abstract Background Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology. Methods The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshr cre+ Stat3 f/f ) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshr cre+ Stat3 f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function. Results We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshr cre+ Stat3 f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function. Conclusion IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.

Tailwater-based hydroponic vegetable is a promising strategy for domestic wastewater recycling. However, the effect of residual antibiotics on the hydroponic vegetable system and the relation between hydroponic culture parameters and the residual water quality are still unclear. Here, the typical antibiotic Levofloxacin (LVFX) was employed, and the effect of LVFX (5 mg/L) on the residual water quality, plant growth and microbial community of water spinach hydroponic culture system were investigated under different hydraulic residence times (HRT). Obvious toxic effects on water spinach were observed, and the highest removal rate of LVFX (about 6 %) and TN (25.67±1.43 %) was observed when HRT was 7 days. Hydroponic culture increased the microbial abundance, diversity, and microbial community stability. To optimize the hydroponic culture, actual sewage plant tailwater spiked with 20 μg/L LVFX, along with three common planting substrates (sponge, ceramsite, and activated carbon) were used for the hydroponic culture of lettuce (seasonal reasons). The inhibition effect of LVFX on the removal of NO3--N and TN was observed even as the LVFX concentration decreased significantly (from 14.62 ± 0.44 μg/L to 0.65 ± 0.07 μg/L). The best growth situation of lettuce and removal rates of NH4+-N, NO3--N, TN, especially LVFX (up to 95.65 ± 0.54 %) were observed in the activated carbon treated group. The overall results indicate the negative effect of residual antibiotics on the hydroponic vegetable systems, and adding activated carbon as substrate is an effective strategy for supporting plant growth and controlling discharged risk.

Breast cancer is the most common malignancy in women worldwide, and major challenges in its treatment include drug resistance and metastasis. Three-dimensional cell culture systems have received widespread attention in drug discovery studies but existing models have limitations, that warrant the development of a simple and repeatable three-dimensional culture model for high-throughput screening. In this study, we designed a simple, reproducible, and highly efficient microencapsulated device to co-culture MCF-7 cells and HUVECs in microcapsules to establish an in vitro vascularized micro-tumor model for chemotherapeutic drug screening. First, to construct a three-dimensional micro-tumor model, cell encapsulation devices were created using three different sizes of flat-mouthed needles. Immunohistochemistry and immunofluorescence assays were conducted to determine vascular lumen formation. Cell proliferation was detected using the Cell Counting Kit-8 assay. Finally, to observe the drug reactions between the models, anticancer drugs (doxorubicin or paclitaxel) were added 12 h after the two-dimensional cultured cells were plated or 7 days after cell growth in the core-shell microcapsules. Vascularized micro-tumors were obtained after 14 days of three-dimensional culture. The proliferation rate in the three-dimensional cultured cells was slower than that of two-dimensional cultured cells. Three-dimensional cultured cells were more resistant to anticancer drugs than two-dimensional cultured cells. This novel sample encapsulation device formed core-shell microcapsules and can be used to successfully construct 3D vascularized micro-tumors in vitro . The three-dimensional culture model may provide a platform for drug screening and is valuable for studying tumor development and angiogenesis.

This research reports a case of histological transformation from non-small cell lung cancer (NSCLC) to transformed small cell lung cancer (T-SCLC) in a patient undergoing EGFR-tyrosine kinase inhibitors (TKIs). The aggressive characteristics of the tumor diverged significantly from those commonly associated with lung adenocarcinomas, leading to further histological analysis. The subsequent histological examination confirmed the transformation to SCLC, consistent with established mechanisms of acquired resistance in NSCLC. Given the limited therapeutic options, the patient was administered a serplulimab-based immunochemotherapy regimen, achieving a progression-free survival (PFS) of 6 months post-transformation. The study underscores the potential of PD-1 inhibitors, particularly serplulimab, in the treatment landscape for T-SCLC and highlights the need for future comprehensive research.

BackgroundHypertension management apps (HMAs) can be effective in controlling blood pressure, but their actual impact is often suboptimal. Establishing a user satisfaction evaluation indicator system for HMAs can assist app developers in enhancing app design and functionality, while also helping users identify apps that best meet their needs. This approach aims to improve the overall effectiveness of app usage. ObjectiveThis study aims to systematically collect data on HMAs and their user reviews in the United States and China. It analyzes app usage patterns and functional characteristics, identifies factors influencing user satisfaction from existing research, and develops a satisfaction evaluation indicator system to provide more accurate recommendations for improving user satisfaction. MethodsWe conducted a descriptive statistical analysis to assess the development status of HMAs in both countries and applied the task-technology fit model to evaluate whether the app functionalities align with business needs. We separately summarized the factors influencing user satisfaction in both countries from previous research, utilized the analytic hierarchy process to develop an evaluation indicator system for HMA user satisfaction, and calculated satisfaction levels. Based on these findings, we propose improvements to enhance app functionality and user satisfaction. ResultsIn terms of current development status, there were fewer HMAs and user reviews in China compared with the United States. Regarding app functional availability, fewer than 5% (4/91) of the apps achieved a demand fulfillment rate exceeding 80% (8/10). Overall, user satisfaction in both countries was low. ConclusionsIn the United States, user satisfaction was lowest for advertising distribution, data synchronization, and reliability. By contrast, Chinese apps need improvements in cost efficiency and compatibility.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Objective: Polyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass. Methods: We performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI. Results: Regression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI (β = −0.193, 95 % confidence interval (CI): −0.325 to −0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant (β = −0.294, 95 % CI: −0.495 to −0.094), and a similar trend was found in obese individuals (β = −0.512, 95 % CI: −0.762 to −0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses. Conclusions: Our study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.

Rubber suspension bushings have mainly been studied under single- or multi-axis load cycling, while research on rubber suspension bushings under random load cycling is not deep enough. This study conducted uniaxial tensile and fatigue tests on N60 rubber dumbbell-shaped plate samples to obtain stress–strain curves and S–N curves. Using the uniaxial tensile test data, a Mooney–Rivlin hyperelastic constitutive model was fitted using Abaqus software, and a finite element model of the rubber suspension bushing was established. A 3D virtual road surface was constructed using Adams software, and characteristic features of typical road surfaces were extracted for statistical analysis, resulting in the generation of a load spectrum showing variations in force over time. Based on the Miner linear damage accumulation theory, finite element fatigue life prediction of the rubber suspension bushing was conducted using pulses from the 232 s region of the load spectrum. The predicted fatigue life was compared to the results from benchtop fatigue testing, resulting in a relative error of less than 6.443 %. The findings suggest that the method is effective in predicting the fatigue life of rubber suspension bushings under random loads.

Uremic Clearance Granule (UCG) is a traditional Chinese medicines (TCMs) that has been recognized as potentially effective treatment for diabetic nephropathy (DN). However, the chemical composition and the hypoglycemic ingredients of UCG remain unclear. In this experiment, a magnetic ligand fishing protocol combined with HPLC coupled Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR-MS) technology was developed to screen and identify α-Glucosidase inhibitors from UCG. First, constituents of UCG was identified by HPLC-FT-ICR-MS. Next, α-Glucosidase coated Fe3O4@SiO2@NH2 (Fe3O4@SiO2@NH2@α-Glucosidase) nano composites was synthesized. The essential parameters (concentration of Glutaraldehyde (GA), ratio of Fe3O4@SiO2@NH2 to enzyme, crosslinking time and immobilization time) were optimized to obtain maximum enzyme activity and the performance of immobilized enzyme was compared with that of free enzyme. The α-Glucosidase inhibitory activities were then evaluated using autodock and the 4-Nitrophenyl-α-D-glucopyranoside (pNPG) method. As a result, 142 compounds were identified were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. 20 possible α-Glucosidase activity inhibitory components were identified using HPLC-FT-ICR-MS. Molecular docking and inhibition studies showed that 4 compuunds including Limonexic acid, Sanggenol A, Glabrone, Matrine were more likely to stronger α-Glucosidase inhibitory activities than acarbose. In conclusion, the proposed approach, which combined highly specific screening with HPLC-FT-ICR-MS, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicines (TCMs).

Abstract Background Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma‐associated HLH (LA‐HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA‐HLH in the elderly population. Methods We retrospectively analyzed a multicenter cohort of elderly patients with LA‐HLH. Clinicopathological features and treatment information were collected. The impacts of baseline characteristics and treatments on survival outcomes were analyzed. Results A total of 173 elderly patients with LA‐HLH were included. Compared with young patients, elderly patients showed different clinical and laboratory features. Regarding lymphoma subtypes, B‐cell lymphoma was more common in elderly patients (elderly 61.3% vs. young 32.3%, p 1407 U/L), and a higher creatinine level (>96.8 μmol/L) were independent predictors of decreased overall survival and 60‐day survival. A prognostic index was established and demonstrated to be robust in predicting the overall survival and 60‐day survival of elderly patients with LA‐HLH. Conclusions LA‐HLH in elderly patients displayed heterogeneous clinicopathological features and survival outcomes. Treatments need to be optimized to improve the outcomes of elderly patients with LA‐HLH.

Breast cancer is the most common malignant tumor in women. Due to the high heterogeneity of breast cancer cells, traditional in vitro research models still have major limitations. Therefore, it is urgent to establish an experimental model that can accurately simulate the characteristics of human breast cancer. Breast cancer organoid technology emerged as the times required, that is, to construct tissue analogs with organ characteristics by using a patient’s tumor tissue through 3D culture in vitro. Since the breast cancer organoid can fully preserve the histology and genetic characteristics of the original tumor, it provides a reliable model for preclinical drug screening, establishment of breast cancer organoid biobanks, research into the mechanisms of tumor development, and determination of cancer targets. It has promoted personalized treatment for clinical breast cancer patients. This article mainly focuses on recent research progress and applications of organoid technology in breast cancer, discussing the current limitations and prospects of breast cancer organoid technology.

Transactive memory system (TMS) makes learning and transferring knowledge easy and efficient. This study has constructed a conceptual model of TMS to reveal the crucial factors influencing the formation of a TMS in online asynchronous learning to foster knowledge sharing and collaboration and enhance knowledge transfer effectiveness. The conceptual model of TMS is built upon theoretical foundations concerning the creation of TMS and the variables influencing them. The study has put forth a set of hypotheses to predict the expected effects of group factors, individual factors, task interdependence, the degree of intellectual silence, and knowledge management on the formation of TMS. In this study, a total of 229 questionnaire data were collected from undergraduate, master's, and doctoral students in Northeast China who had experience with an online asynchronous learning TMS. Structural equation modeling has been employed to identify the key indicators involved and their influence on the formation of TMS. The empirical study was carried out using statistical analysis of SPSS data, with the results indicating that each factor has varying impacts on knowledge management, ultimately affecting the formation of TMS. These findings provide a more nuanced understanding of how these factors shape online asynchronous learning environments.

ObjectiveTo preliminarily explore the risk factors for post-infectious bronchiolitis obliterans (PIBO) complicating adenovirus pneumonia (ADVP) in children through a meta-analysis.MethodsA systematic search was conducted on three English-language databases (PubMed, Web of Science and The National Library of Medicine) and two Chinese-language databases (China National Knowledge Infrastructure and the Wanfang Database) between database inception and 1 January 2023. Data analysis was conducted using Stata 15.1 software.ResultsA total of 10 articles, reporting 14 risk factors, were included in the analysis, with 8 risk factors taken into consideration. Through the meta-analysis, 5 risk factors were identified for PIBO complicating ADVP in paediatric patients: hypoxaemia [odds ratio (OR) = 9.37, 95% CI: 4.22, 20.77, p

The group product-harm crisis has much greater and longer negative impact, and its governance has become an important issue. To address this issue, this study proposed a new construct: industry governance. On the basis of clarifying the dimensions and measurements of industry governance, this study constructed a reflective–formative hierarchical model and collected data through a questionnaire. Utilizing convenience sampling, 329 valid samples at the University in Wuhan, China collected by survey were used to verify the hypotheses. With the help of Smart PLS 3.0, this study finds that the industry governance has a significant and positive impact on consumer's trust (enterprise trust, industry trust and government trust) after the group product-harm crisis. Industry governance plays an important role in the governance of group product-harm crisis. This study is the first time to explore the structure and measurement of industry governance, and verifies the impact of industry governance on group product-harm crisis, which enriches governance theory, and perfects product-harm crisis theory, providing a new direction and guidance for managers to better manage product-harm crisis.

Abstract Background Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD. The present research aims to explore the potential neuroprotective properties of APHD and its underlying mechanisms. Methods The possible mechanism of APHD was predicted using a combination of molecular docking and network pharmacological analysis. PC12 cells were induced by H2O2 and oxygen–glucose deprivation/reoxygenation (OGD/R), respectively. Western blot, flow cytometry, immunofluorescence staining, and qRT-PCR were used to investigate the antioxidant activity of APHD. The HO-1 inhibitor ZnPP and Nrf2 gene silencing were employed to confirm the influence of APHD on the signaling cascade involving HO-1, Nrf2, and Keap1 in vitro. Results APHD exhibited antioxidant activity in both PC12 cells subjected to H2O2 and OGD/R conditions by downregulating the release of LDH, the concentrations of MDA, and ROS, and upregulating SOD, GSH-Px, and GSH concentrations. APHD could potentially initiate the Keap1-Nrf2/HO-1 signaling cascade, according to the findings from network pharmacology evaluation and molecular docking. Furthermore, APHD was observed to increase Nrf2 and HO-1 expression at both mRNA and protein levels, while downregulating the protein concentrations of Keap1. Both Nrf2 silencing and treatment with ZnPP reversed the neuroprotective effects of APHD. Conclusions APHD activated antioxidant enzymes and downregulated the levels of LDH, MDA, and ROS in two cell models. The neuroprotective effect is presumably reliant on upregulation of the Keap1-Nrf2/HO-1 pathway. Taken together, APHD from brown algae of the genus Dictyota shows potential as a candidate for novel neuroprotective agents.

Abstract Background The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). Methods 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. Results Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P

Displacement cascade behaviors of Ti-6Al-4V alloys are investigated using molecular dynamics (MD) simulation. The embedded atom method (EAM) potential including Ti, Al and V elements is modified by adding Ziegler-Biersack-Littmark (ZBL) potential to describe the short-range interaction among different atoms. The time evolution of displacement cascades at the atomic scale is quantitatively evaluated with the energy of primary knock-on atom (PKA) ranging from 0.5 keV to 15 keV, and that for pure Ti is also computed as a comparison. The effects of temperature and incident direction of PKA are studied in detail. The results show that the temperature reduces the number of surviving Frenkel pairs (FPs), and the incident direction of PKA shows little correlation with them. Furthermore, the increasing temperature promotes the point defects to form clusters but reduces the number of defects due to the accelerated recombination of vacancies and interstitial atoms at relatively high temperature. The cluster fractions of interstitials and vacancies both increase with the PKA energy, whereas the increase of interstitial cluster is slightly larger due to their higher mobility. Compared to pure Ti, the presence of Al and V is beneficial to the formation of interstitial clusters and indirectly hinders the production of vacancy clusters.

The MS6.8 earthquake occurred in Luding County, Ganzi Prefecture, Sichuan Province, China at 12:52 p.m. on Sept. 5, 2022, is preliminarily analyzed in terms of regional tectonics, historical earthquakes, sequence characteristics and focal mechanism solutions. The results show that: 1) The magnitude difference ΔM between the main shock and the maximum aftershock, the energy ratio ER of the main shock to the aftershocks, the p-value and the estimated Mmax-value indicate that the MS6.8 Luding earthquake sequence can be divided into the main shock-aftershock type (MAT). 2) The spatial distribution of the aftershocks, their corresponding b-value and expected maximum magnitude are obviously segmented, which reflect the complexity of the seismogenic tectonics. 3) According to the focal mechanisms obtained from the HASH program, the geometry distribution of the sequence, and the relationship between the sequence and the nearby faults, it can be inferred that the Moxi fault segment of the Xianshuihe fault zone is the seismogenic tectonics of the MS6.8 Luding earthquake sequence.

Abstract Blackwater constitutes a primary component of environmental pollution posing serious risk to human health; however, reusing the nutrients found in blackwater diminishes the associated pollution and promotes resource recycling. Conventional green-wall systems are not suitable for in situ treatment of high-concentration wastewater. Thereby, a novel multi-unit green-wall system with six independent treatment units was designed to achieve a cost-effective and eco-friendly in situ treatment of blackwater with high organic load. Zeolite carriers were selected for the matrix with carrier depth of 14.5 cm, ivy and chlorophytum were selected as the greening plants. Various pollutants were rapidly reduced at the initial stage and the concentration of the pollutants decreased as the number of treatment units increased. Overall, the green-wall system was more effective in removing COD and NH4 +–N with the removal rates of 98.5% and 98%, which may be due to the good buffering capacity of the media and the roles of Firmicutes and Bacteroidetes in COD degradation and ammoniated nitrification reactions. In addition, the maximum TP and TN removal rates were observed with a value of 85% and 42%, respectively. Consequently, the novel multi-unit green-wall system is an effective method for in situ blackwater reuse. Graphical Abstract

Abstract Background miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. Methods To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. Results miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. Conclusions Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.

Abstract Activatable afterglow luminescence nanoprobes enabling switched “off-on” signals in response to biomarkers have recently emerged to achieve reduced unspecific signals and improved imaging fidelity. However, such nanoprobes always use a biomarker-interrupted energy transfer to obtain an activatable signal, which necessitates a strict distance requisition between a donor and an acceptor moiety (

γ-aminobutyric acid (GABA) is a non-protein amino acid discovered in animals, plants, and microorganisms that was approved as the "new resource food" by the National Health Commission of the People's Republic of China (NHC) in 2009. It has a wide range of applications in food, medicine, feed, and other industries, and the research has grown increasingly popular in recent years. The paper reviews the bio-synthesis and metabolic processes of GABA, summarizes the methods of chemical synthesis, plant enrichment, and present GABA detection techniques, and discusses their advantages and limitations. Furthermore, the main physiological functions and mechanism of GABA are summarized, and GABA’s research and development trend is also presented, in order to provide reference for future research and application of GABA.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Abstract Different exogenous electric fields (EF) can guide cell migration, disrupt proliferation, and program cell development. Studies have shown that many of these processes were initiated at the cell membrane, but the mechanism has been unclear, especially for conventionally non-excitable cells. In this study, we focus on the electrostatic aspects of EF coupling with the cell membrane by eliminating Faradaic processes using dielectric-coated microelectrodes. Our data unveil a distinctive biphasic response of the ERK signaling pathway of epithelial cells (MCF10A) to alternate current (AC) EF. The ERK signal exhibits both inhibition and activation phases, with the former triggered by a lower threshold of AC EF, featuring a swifter peaking time and briefer refractory periods than the later-occurring activation phase, induced at a higher threshold. Interestingly, the biphasic ERK responses are sensitive to the waveform and timing of EF stimulation pulses, depicting the characteristics of electrostatic and dissipative interactions. Blocker tests and correlated changes of active Ras on the cell membrane with ERK signals indicated that both EGFR and Ras were involved in the rich ERK dynamics induced by EF. We propose that the frequency-dependent dielectric relaxation process could be an important mechanism to couple EF energy to the cell membrane region and modulate membrane protein-initiated signaling pathways, which can be further explored to precisely control cell behavior and fate with high temporal and spatial resolution.

Abstract Background This pilot study examined the preliminary effectiveness of the PREVENT digital intervention that supports health care teams in delivering health behavior counseling on cancer survivors’ motivation to change behavior, their physical activity and food intake behaviors, and cardiovascular health (CVH). Methods Clinicians (physicians, nurse practitioners) at three urban cancer survivorship clinics were trained to use PREVENT. Patients were randomized to the PREVENT intervention or a wait-list routine care control group. Eligibility criteria for patients included: between ages 12–39, overweight or obese, were at least 6-months post-active cancer treatment, and had sufficient English proficiency. Results Fifty-five participants were enrolled; 27 were randomized to the PREVENT intervention and 28 to wait-list routine care control. The majority of the participants (82%) identified as non-Hispanic white, with an average age of 19.8 (SD ± 5.2) years. Patients that received the PREVENT intervention had greater increases in their self-efficacy, vigorous activity and number of food recommendations met than those who received routine clinical care. Changes in willingness, knowledge, and CVH outcomes were not significant. Conclusions The PREVENT digital intervention may provide improvements in preventive behaviors among AYA cancer survivors by supporting care teams with delivering evidence-based, tailored behavior change recommendations and resources to support patient health. Trial registration This trial ( NCT04623190 ) was registered on 11/02/2022.

The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

ABSTRACTBackground Sarcopenia and knee osteoarthritis are common age-related diseases that have become important public health issues worldwide. Few studies have reported the association between muscle mass loss and knee osteoarthritis. This may be due to the high level of heterogeneity between studies stemming from different definitions of muscle mass loss.Methods The systematic searches were carried out in PubMed and Web of Science from the inception of the databases until 13 January 2023, by two independent researchers. Pooled odds ratios (ORs) for overall and subgroup analyses were obtained using either a random effects model (I2 >50%) or fixed effects model (I2 ≤50%) in Stata.Results Of the 1,606 studies identified, we ultimately included 12 articles on the association between muscle mass and knee osteoarthritis (prospective: n = 5; cross-sectional: n = 7). Low-quality evidence indicated that low muscle mass index and sarcopenic obesity increase the odds of knee osteoarthritis (low muscle mass index OR: 1.36, 95% CI: 1.13–1.64; sarcopenic obesity OR: 1.78, 95% CI: 1.35–2.34). However, no association was observed between general sarcopenia or low muscle mass with knee osteoarthritis.Conclusion This systematic review and meta-analysis revealed that low muscle mass index and sarcopenic obesity were associated with an increased risk of developing knee osteoarthritis.