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Abstract Background The prevalence of non-small cell lung cancer (NSCLC) is notably elevated in individuals diagnosed with idiopathic pulmonary fibrosis (IPF). Secreted phosphoprotein 1 (SPP1), known for its involvement in diverse physiological processes, including oncogenesis and organ fibrosis, has an ambiguous role at the intersection of IPF and NSCLC. Our study sought to elucidate the function of SPP1 within the pathogenesis of IPF and its subsequent impact on NSCLC progression. Methods Four GEO datasets was analyzed for common differential genes and TCGA database was used to analyze the prognosis. The immune infiltration was analyzed by TIMER database. SPP1 expression was examined in human lung tissues, the IPF fibroblasts and the BLM-induced mouse lung fibrosis model. Combined with SPP1 gene gain- and loss-of-function, qRT-PCR, Western blot, EdU and CCK-8 experiments were performed to evaluate the effects and mechanisms of SPP1 in IPF progression. Effect of SPP1 on NSCLC was detected by co-cultured IPF fibroblasts and NSCLC cells. Results Through bioinformatics analysis, we observed a significant overexpression of SPP1 in both IPF and NSCLC patient datasets, correlating with enhanced immune infiltration of cancer-associated fibroblasts in NSCLC. Elevated levels of SPP1 were detected in lung tissue samples from IPF patients and bleomycin-induced mouse models, with partial colocalization observed with α-smooth muscle actin. Knockdown of SPP1 inhibits TGF-β1-induced differentiation of fibroblasts to myofibroblasts and the proliferation of IPF fibroblasts. Conversely, SPP1 overexpression promoted IPF fibroblast proliferation via PI3K/Akt/mTOR pathway. Furthermore, IPF fibroblasts promoted NSCLC cell proliferation and activated the PI3K/Akt/mTOR pathway; these effects were attenuated by SPP1 knockdown in IPF fibroblasts. Conclusions Our findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.

Abstract Background Previous studies have indicated that social connectedness can serve as a protective buffer against negative outcomes associated with online victimization. However, the role of social connectedness between Internet gaming disorder and somatic symptoms is still unclear. This study aims to examine the mediating effect of social connectedness on the association between Internet gaming disorder and somatic symptoms. Methods A cross-sectional design was utilized, using questionnaires for data collection and multi-stage stratified cluster sampling. The general demographic questionnaire, Nine-Item Internet Gaming Disorder Scale–Short Form, Social Connectedness Scale-Revised and Patient Health Questionnaire Physical Symptoms were used to collect data. We adopted Pearson’s correlation analysis and the PROCESS Macro Model in regression analysis to explore the relationships among Internet gaming disorder, social connectedness and somatic symptoms. Results Internet gaming disorder was positively correlated with somatic symptoms (r = 0.20, P

Abstract This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

In China, despite the continuous efforts to preserve traditional villages in recent years, a significant amount of cultural heritages continue to vanish. Commonly observed issues such as the lack of coordination between preservation and development, the imbalance in spatial environment conservation and utilization, are pervasive. Regrettably, there is a conspicuous absence of theoretical underpinning in addressing these challenges. In this study, The evaluation factor of spatial environmental protection was selected, and these factors were weighted through expert surveys and the Analytic Hierarchy Process, and applied the multi-objective linear weighting function method to obtain a comprehensive evaluation calculation formula. Subsequently, we conducted an assessment of 28 representative traditional villages in the southern Chinese regions of Guangdong, Fujian, and Jiangxi. Their current issues were systematically analyzed and cluster analysis was applied to discern 11 distinct typologies of traditional village development. Besides, the temporal evolution patterns of these villages were delved into, and their development were categorized into five stages: initiation, enhancement, prosperity, over-development, and decline. Ultimately, based on the spatial environment characteristics of each development type and evolution stage, corresponding guidelines for spatial environment conservation and utilization are proposed, which provides necessary theoretical frameworks for future work this region.

Abstract The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti‐HBc compound—colchicine, an alkaloid compound—that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Flood control operation, a non-engineering measure, can efficiently manage flood disasters within a river basin. However, numerous uncertainties exit in the real-time operation of flood control systems, creating risks in decision-making. As an efficient tool to mitigate these risks, risk management has garnered increasing attention in real-time flood control operation. This communication offers a series of suggestions for future research concerning risk management in real-time flood control operation, including risk assessment, risk diagnosis, and risk control methods.

Background: Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers. Methods: Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs. Results: First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-β, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs. Conclusions: This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.

ABSTRACTBackground Pneumococcal vaccines are effective in preventing pneumococcal diseases in adults. The evaluation of the antibodies persistence to the 23-valent pneumococcal polysaccharide vaccine (PPV23) could provide evidence on PPV23 revaccination.Research design and methods Adults aged ≥ 60 years were selected and vaccinated with PPV23 in Shanghai, and followed up for 5 years with blood samples collection of a 1-year interval. The geometric mean concentrations (GMC) of the IgG against 23 pneumococcal serotypes covered by PPV23 were detected using enzyme-linked immunosorbent assay. The antibodies to 23 pneumococcal serotypes among different groups was analyzed using statistical analysis.Results Overall, 517 participants completed all six visits over a 5-year period (2013–2018). The GMC of 23 serotypes in adults aged ≥ 60 years decreased slowly after PPV23 vaccination compared to baseline pre-vaccination (P

Abstract Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins’ expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.

Abstract Background The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap. Methods A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL. Results This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)). Conclusions This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.

Abstract Background This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). Methods This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. Results A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18–41.09; P

Abstract Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

Regular physicochemical and microbiological properties and volatile flavors of Sichuan Wu xiang-style sausages collected from Chengdu City were analyzed and used to reveal the quality characteristics of Sichuan Wu xiang-style sausage. The results showed that moisture content was 11.73%±1.64%, pH value was 5.68±0.06, TBARS value was 1.47±0.48 mg/kg, nitrite content was 1.31±0.12 mg/kg, and L*, a*, and b* was 48.12±1.46, 16.08±0.91, 18.31±0.73 respectively. The aerobic plate count, suspected staphylococci count, suspected lactic acid bacteria count, and Enterobacteriaceae count was 7.09±0.14, 5.74±0.23, 7.64±0.14 and 4.27±0.15 lg CFU/g, respectively. 97 kinds of volatile compounds were totally detected from Sichuan Wu xiang-style sausage samples, and 22 shared volatile compounds with odor activity value (OAV) greater than 1 were regarded as the main volatile flavors. Furthermore, it was showed that (+)-limonene, linalool and artemisia brain contributed most to the typical flavor of Wu xiang-style sausage through the loading plot of principal component analysis, imparting citrus, mint, floral, lavender, liquorice, and aniseed odors. The results obtained revealed the main volatile compounds and typical flavor characteristics of Sichuan Wu xiang-style sausage, and laid foundations for further researches on the flavor characteristics of Sichuan Wu xiang-style sausage.

Abstract Background Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15–21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. Results 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P

As people live longer, the burden of aging-related brain diseases, especially dementia, is increasing. Brain aging increases the risk of cognitive impairment, which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis. Therefore, supplemental dietary lipids have the potential to prevent brain aging. This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives. Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids (PUFAs) in brain health. The results of interventions indicate that phospholipids—including phosphatidylcholine, phosphatidylserine, and plasmalogen—are efficient in alleviating cognitive impairment during aging, with plasmalogen exhibiting higher efficacy than phosphatidylserine. Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons. Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.

Mg–3Nd–0.2Zn–0.4Zr (NZ30K, wt.%) alloy is a new kind of high-performance metallic biomaterial. The combination of the NZ30K Magnesium (Mg) alloy and selective laser melting (SLM) process seems to be an ideal solution to produce porous Mg degradable implants. However, the microstructure evolution and mechanical properties of the SLMed NZ30K Mg alloy were not yet studied systematically. Therefore, the fabrication defects, microstructure, and mechanical properties of the SLMed NZ30K alloy under different processing parameters were investigated. The results show that there are two types of fabrication defects in the SLMed NZ30K alloy, gas pores and unfused defects. With the increase of the laser energy density, the porosity sharply decreases to the minimum first and then slightly increases. The minimum porosity is 0.49 ± 0.18%. While the microstructure varies from the large grains with lamellar structure inside under low laser energy density, to the large grains with lamellar structure inside & the equiaxed grains & the columnar grains under middle laser energy density, and further to the fine equiaxed grains & the columnar grains under high laser energy density. The lamellar structure in the large grain is a newly observed microstructure for the NZ30K Mg alloy. Higher laser energy density leads to finer grains, which enhance all the yield strength (YS), ultimate tensile strength (UTS) and elongation, and the best comprehensive mechanical properties obtained are YS of 266 ± 2.1 MPa, UTS of 296 ± 5.2 MPa, with an elongation of 4.9 ± 0.68%. The SLMed NZ30K Mg alloy with a bimodal-grained structure consisting of fine equiaxed grains and coarser columnar grains has better elongation and a yield drop phenomenon.

Abstract Background and aims The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. Methods The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. Results Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). Conclusion Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

Abstract Objective This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated. Methods A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda. Results In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include “skepticism about the accuracy of the model”, “delay in early prediction by the indicator of length of neuro-ICU stay”, and “lack of a proper protocol for clinical application”. Conclusions We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.

Abstract Cloud environment is a virtual, online, and distributed computing environment that provides users with large-scale services. And cloud monitoring plays an integral role in protecting infrastructures in the cloud environment. Cloud monitoring systems need to closely monitor various KPIs of cloud resources, to accurately detect anomalies. However, due to the complexity and highly dynamic nature of the cloud environment, anomaly detection for these KPIs with various patterns and data quality is a huge challenge, especially those massive unlabeled data. Besides, it’s also difficult to improve the accuracy of the existing anomaly detection methods. To solve these problems, we propose a novel Dynamic Graph Transformer based Parallel Framework (DGT-PF) for efficiently detect system anomalies in cloud infrastructures, which utilizes Transformer with anomaly attention mechanism and Graph Neural Network (GNN) to learn the spatio-temporal features of KPIs to improve the accuracy and timeliness of model anomaly detection. Specifically, we propose an effective dynamic relationship embedding strategy to dynamically learn spatio-temporal features and adaptively generate adjacency matrices, and soft cluster each GNN layer through Diffpooling module. In addition, we also use nonlinear neural network model and AR-MLP model in parallel to obtain better detection accuracy and improve detection performance. The experiment shows that the DGT-PF framework have achieved the highest F1-Score on 5 public datasets, with an average improvement of 21.6% compared to 11 anomaly detection models.

Abstract Background Predicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2–5 days conventionally to return the results from doctor's order. Methods It is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture. Results There were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively. Conclusions The machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.

Abstract The rapid advancement of microservice architecture in the cloud has led to the necessity of effectively detecting, classifying, and diagnosing run failures in microservice applications. Due to the high dynamics of cloud environments and the complex dependencies between microservices, it is challenging to achieve robust real-time system fault identification. This paper proposes an interpretable fault diagnosis framework tailored for microservice architecture, namely Multi-scale Learnable Transformation Graph for Fault Classification and Diagnosis(MTG_CD). Firstly, we employ multi-scale neural transformation and graph structure adjacency matrix learning to enhance data diversity while extracting temporal-structural features from system monitoring metrics Secondly, a graph convolutional network (GCN) is utilized to fuse the extracted temporal-structural features in a multi-feature modeling approach, which helps to improve the accuracy of anomaly detection. To identify the root cause of system faults, we finally conduct a coarse-grained level diagnosis and exploration after obtaining the results of classifying the fault data. We evaluate the performance of MTG_CD on the microservice benchmark SockShop, demonstrating its superiority over several baseline methods in detecting CPU usage overhead, memory leak, and network delay faults. The average macro F1 score improves by 14.05%.

Abstract Various substances in the blood plasma serve as prognostic indicators of the progression of COVID-19. Consequently, multi-omics studies, such as proteomic and metabolomics, are ongoing to identify accurate biomarkers. Cytokines and chemokines, which are crucial components of immune and inflammatory responses, play pivotal roles in the transition from mild to severe illness. To determine the relationship between plasma cytokines and the progression of COVID-19, we used four study cohorts to perform a systematic study of cytokine levels in patients with different disease stages. We observed differential cytokine expression between patients with persistent-mild disease and patients with mild-to-severe transformation. For instance, IL-4 and IL-17 levels significantly increased in patients with mild-to-severe transformation, indicating differences within the mild disease group. Subsequently, we analysed the changes in cytokine and chemokine expression in the plasma of patients undergoing two opposing processes: the transition from mild to severe illness and the transition from severe to mild illness. We identified several factors, such as reduced expression of IL-16 and IL-18 during the severe phase of the disease and up-regulated expression of IL-10, IP-10, and SCGF-β during the same period, indicative of the deterioration or improvement of patients’ conditions. These factors obtained from fine-tuned research cohorts could provide auxiliary indications for changes in the condition of COVID-19 patients.

Social animals frequently exhibit huddling sleep behaviors in response to nocturnal ecological pressures. However, there remain significant gaps in our understanding of the decision-making process promoting huddle sleep. Exploring how such decision-making processes are initiated and programmed in nonhuman primates offers additional insights into various animals, with a particular focus on humans. The present research examined the social factors and individual influences involved in initiating huddle sleep among a population of wild Tibetan macaques (Macaca thibetana) at Mt. Huangshan in Anhui, China. The results showed that social rank, age, and social centrality were involved in the decision-making process for huddle sleep. Individuals with higher rank and greater social centrality not only tended to act as leaders but also frequently took on followers. Younger individuals were more inclined to be followers. If an individual consistently followed a specific member during huddles, we referred to her/him as a fan. Individuals with more fans (fandom) and those that were consistently fans of others were also more socially central in their group. Such different selection factors fostered coordination among individuals and promoted huddle formation. The study has enhanced our understanding of nocturnal huddling behavior in social nonhuman primates and the intricate mechanisms involved in decision-making. The findings provide valuable insights into the sleep behavior of wild animals, thereby increasing our understanding of how monkeys maintain long-term survival. The analysis of sleep behavior has significant theoretical and practical implications for the conservation of Tibetan macaques.

Background As a powerful tool, bioinformatics analysis is playing an increasingly important role in many fields. Osteogenic differentiation is a complex biological process involving the fine regulation of numerous genes and signaling pathways. Method Osteogenic differentiation-related genes are collected from the online databases. Then, we proposed two indexes Jaccard similarity and Sorensen-Dice similarity to measure the topological relevance of genes in the human PPI network. Furthermore, we selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation. Subsequently, we performed functional a enrichment analysis of these top-ranked genes to check whether these candidate genes identified by similarity-based metrics are enriched in some specific biological functions and states. we performed a permutation test to investigate the similarity score with four well-known osteogenic differentiation-related pathways including hedgehog signaling pathway, BMP signaling, ERK pathway, and Wnt signaling pathway to check whether these osteogenic differentiation-related pathways can be regulated by FOXA1. Lentiviral transfection was used to knockdown and overexpress gene FOXA1 in human bone mesenchymal stem cells (hBMSCs). Alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS) were employed to investigate osteogenic differentiation of hBMSCs. Result After data collection, human PPI network involving 19,344 genes is included in our analysis. After simplifying, we used Jaccard and Sorensen-Dice similarity to identify osteogenic differentiation-related genes and integrated into a final similarity matrix. Furthermore, we calculated the sum of similarity scores with these osteogenic differentiation-related genes for each gene and found 337 osteogenic differentiation-related genes are involved in our analysis. We selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation and performed functional enrichment analysis of these top-ranked 50 genes. The results collectively demonstrate that these candidate genes can indeed capture osteogenic differentiation-related features of hBSMCs. According to the novel analyzing method, we found that these four pathways have significantly higher similarity with FOXA1 than random noise. Moreover, knockdown FOXA1 significantly increased the ALP activity and mineral deposits. Furthermore, overexpression of FOXA1 dramatically decreased the ALP activity and mineral deposits. Conclusion In summary, this study showed that FOXA1 is a novel significant osteogenic differentiation-related transcription factor. Moreover, our study has tightly integrated bioinformatics analysis with biological knowledge, and developed a novel method for analyzing the osteogenic differentiation regulatory network.

BackgroundThere is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear.MethodsThe differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes. Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed.ResultsWe identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD.ConclusionOur study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.

IntroductionLong-term care assistants are taking on more important roles in the healthcare system. The purpose of this study was to investigate what demographic factors influence the core competencies of nursing assistants, as well as to investigate the levels of organizational support, self-efficacy, and core competencies among nursing assistants in China, to explore the relationship between them.MethodsThis is a cross-sectional study with prospective data collection based on a self-report questionnaire. A total of 320 long-term care assistants from two healthcare institutions. We collected socio-demographic characteristics and measured their perceived organizational support, self-efficacy, and core competency levels of the participants. Pearson correlation tests were conducted to examine the relationships among three variables, and a structural equation model was developed to test the interrelationships among these variables.ResultsThe results indicated that age, employment type, licensing status, monthly income, pre-job training, and training methods were associated with core competency, with nursing knowledge identified as a weak area in core competencies. There were significant associations among each dimension of perceived organizational support, self-efficacy, and core competencies (p

IntroductionThe causality between personality and psychiatric traits and lung cancer (LC) remains unclear. Therefore, we aimed to elucidate the causality between these traits and LC.MethodsBidirectional two-sample Mendelian randomization (MR) and bibliometric approaches were conducted to estimate the causality between personality (neuroticism, extraversion, agreeableness, conscientiousness, and openness) and psychiatric (schizophrenia, attention-deficit/hyperactivity disorder [ADHD], major depressive disorder, autism spectrum disorder, bipolar disorder, insomnia, and anxiety) traits and LC and its subtypes (lung squamous cell carcinoma, lung adenocarcinoma, and small cell LC). Summary data of these traits were extracted from large datasets (17,375–462,341 participants). Inverse variance weighting was used as the primary MR analysis, with supplementary models, including MR-Egger and weighted medians. Sensitivity analyses were conducted to detect pleiotropy. Bibliometric data were retrieved from the Web of Science Core Collection, Scopus, and PubMed. The main mapping techniques adopted were co-word, collaboration, and citation analyses.ResultsSchizophrenia was associated with an increased risk of LC (odds ratio [OR] = 1.077, 95% confidence interval [CI] = 1.030–1.126, P = 0.001). Moreover, LC increased the risk of ADHD (OR = 1.221, 95% CI = 1.096–1.362, P < 0.001). No significant bidirectional associations were observed between other mental traits and LC and its subtypes. Causality, psychiatry, and psychiatric comorbidity are emerging keywords. Research dynamics and landscapes were revealed.ConclusionThis study suggests that schizophrenia is a risk factor for LC and that LC is a risk factor for ADHD. Furthermore, causality, psychiatry, and psychiatric comorbidity have become emerging research trends in related fields.

BackgroundLung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear.MethodsThis study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses.ResultsThe MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.).ConclusionThis study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidence-based medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications.

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

BackgroundTo assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants.MethodsA single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax).ResultsGL Glargine U300 demonstrated comparable PK parameters (AUC0–24h, Cmax, AUC0–12h, and AUC12–24h of M1) and PD responses [AUCGIR.0–24h, GIRmax, AUCGIR.0–12h, and AUCGIR.12–24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events.ConclusionThe PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®.Clinical trial registrationhttps://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Summary: Glioblastoma (GBM) is characterized by high morbidity, mortality, and low cure rates. Recent studies suggest that TSPAN4 is recognized as a marker protein for migrasomes, a vesicular organelle associated with cell migration. However, the intrinsic role of TSPAN4 in cancers has not been clarified, especially in GBM. Here, we report that TSPAN4 promotes GBM progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Clinically, TSPAN4 is highly expressed in GBM and is significantly correlated with poor prognosis. Functionally, TSPAN4 knockdown dramatically inhibits GBM cell proliferation and invasion in vitro, as well as tumorigenicity in vivo. Conversely, overexpression of TSPAN4 facilitates GBM progression. Mechanistically, TSPAN4 knockdown disrupts interaction with EGFR, destabilizing its expression and inactivating EGFR and downstream signaling pathways, such as MEK/ERK, STAT3, and AKT. Our study reveals that TSPAN4 drives GBM progression through regulating EGFR stability and could be a potential target for cancer therapy.

Abstract Purpose To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. Methods A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. Results In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. Conclusion HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

Abstract Emerging evidence has highlighted that dysregulation of lipid metabolism in clear cell renal cell carcinoma (ccRCC) is associated with tumor development and progression. HIF-2α plays an oncogenic role in ccRCC and is involved in abnormal lipid accumulation. However, the underlying mechanisms between these two phenomena remain unknown. Here, MED15 was demonstrated to be a dominant factor for HIF-2α-dependent lipid accumulation and tumor progression. HIF-2α promoted MED15 transcriptional activation by directly binding the MED15 promoter region, and MED15 overexpression significantly alleviated the lipid deposition inhibition and malignant tumor behavior phenotypes induced by HIF-2α knockdown. MED15 was upregulated in ccRCC and predicted poor prognosis. MED15 promoted lipid deposition and tumor progression in ccRCC. Mechanistic investigations demonstrated that MED15 acts as SREBP coactivator directly interacting with SREBPs to promote SREBP-dependent lipid biosynthesis enzyme expression, and promotes SREBP1 and SREBP2 activation through the PLK1/AKT axis. Overall, we describe a molecular regulatory network that links MED15 to lipid metabolism induced by the SREBP pathway and the classic HIF-2α pathway in ccRCC. Efforts to target MED15 or inhibit MED15 binding to SREBPs as a novel therapeutic strategy for ccRCC may be warranted.

Abstract Objectives This study aims to compare the efficacy of peripheral add multifocal soft contact lenses (SCLs) (excluding bifocal SCLs) with single vision contact lenses or spectacles in controlling myopia progression. Method A comprehensive literature search was conducted in the Pubmed, EMBASE, Web of Science, and Cochrane Library databases until October 2023. The literature was thoroughly screened based on predetermined eligibility criteria. Pooled odds ratios (ORs) were calculated for dichotomous data and weighted mean differences (WMD) for continuous data. Results A total of 11 articles comprising 787 participants were included in this meta-analysis. Our pooled results demonstrated that the peripheral add multifocal SCLs groups exhibited significantly reduced refraction progression (MD = 0.20; 95%CI, 0.14 ∼ 0.27; P

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. Methods We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. Results Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. Conclusion The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.

The uncertainty principle for vector-valued functions of $ L^2({\mathbb{R}}^n, {\mathbb{R}}^m) $ with $ n\ge 2 $ are studied. We provide a stronger uncertainty principle than the existing one in literature when $ m\ge 2 $. The phase and the amplitude derivatives in the sense of the Fourier transform are considered when $ m = 1 $. Based on these definitions, a generalized uncertainty principle is given.

Abstract Background The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. Methods The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. Results A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups. Conclusions Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Background: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. Methods: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. Results: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50–0.80). Conclusion: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

In this study, headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) and other techniques were used to analyze the regular physical-chemical and microbiological properties, the content and aroma pattern of main volatile flavors, and the sensory evaluation of fermented sausages made with the inoculation of the mixed culture Lactobacillus plantarum L77 and Staphylococcus xylosus S120 (L77-S120) and the individual culture Lactobacillus plantarum 77 (L77), with the non-inoculated group as blank. The results showed that the TBARS value, nitrite content and Enterobacteriaceae count of the L77-S120 group were significantly lower than those of the blank and L77 group (P

In the present work, the diffusion behavior of the Ag–Cu–Ni alloys was comprehensively studied for the first time. Twelve solid-solid diffusion couples were prepared and annealed at 1023, 1123, and 1223K, respectively. Based on the measured composition-distance profiles, the interdiffusion coefficients in FCC Ag–Cu–Ni alloys at different temperatures were then calculated by both the Matano-Kirkaldy (MK) and numerical inversion (NI) methods. The atomic mobilities of the Ag–Cu–Ni alloys were also optimized. The results indicate that the model-predicted diffusion behavior shows reasonable agreement with the experimental data, validating the reliability of the two versions of atomic mobility obtained in this work and demonstrating the accuracy and efficiency of the NI method. Ag diffuses faster than Ni in the Cu matrix alloy. The pre-exponential factor D0Ag and the activation energy QAgAgCu show a slight change with the Ag, but significantly increase with the Ni. The variation of the pre-exponential factor D0Ni and the activation energy QNiNiCu with the concentration of Ag and Ni were presented with a 3-D planes and discussed in detail. The accurate diffusivities and atomic mobilities of FCC Ag–Cu–Ni alloys obtained in this work will provide crucial input for the development and design of multi-component low-Ag brazing filler metals.

Abstract Cellular senescence represents an irreversible state of cell-cycle arrest during which cells secrete senescence-associated secretory phenotypes, including inflammatory factors and chemokines. Additionally, these cells exhibit an apoptotic resistance phenotype. Cellular senescence serves a pivotal role not only in embryonic development, tissue regeneration, and tumor suppression but also in the pathogenesis of age-related degenerative diseases, malignancies, metabolic diseases, and kidney diseases. The senescence of renal tubular epithelial cells (RTEC) constitutes a critical cellular event in the progression of acute kidney injury (AKI). RTEC senescence inhibits renal regeneration and repair processes and, concurrently, promotes the transition of AKI to chronic kidney disease via the senescence-associated secretory phenotype. The mechanisms underlying cellular senescence are multifaceted and include telomere shortening or damage, DNA damage, mitochondrial autophagy deficiency, cellular metabolic disorders, endoplasmic reticulum stress, and epigenetic regulation. Strategies aimed at inhibiting RTEC senescence, targeting the clearance of senescent RTEC, or promoting the apoptosis of senescent RTEC hold promise for enhancing the renal prognosis of AKI. This review primarily focuses on the characteristics and mechanisms of RTEC senescence, and the impact of intervening RTEC senescence on the prognosis of AKI, aiming to provide a foundation for understanding the pathogenesis and providing potentially effective approaches for AKI treatment.

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS. Methods In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates. Results Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54–0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47–0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487–0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515–0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491–0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470–0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536–0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days. Conclusion This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment.

Abstract Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Abstract Recent advances in surface-patterning techniques of liquid crystals have enabled the precise creation of topological defects, which promise a variety of emergent applications. However, the manipulation and application of these defects remain limited. Here, we harness the moiré effect to engineer topological defects in patterned nematic liquid crystal cells. Specifically, we combine simulation and experiment to examine a nematic cell confined between two substrates of periodic surface anchoring patterns; by rotating one surface against the other, we observe a rich variety of highly tunable, novel topological defects. These defects are shown to guide the three-dimensional self-assembly of colloids, which can conversely impact defects by preventing the self-annihilation of loop-defects through jamming. Finally, we demonstrate that certain nematic moiré cells can engender arbitrary shapes represented by defect regions. As such, the proposed simple twist method enables the design and tuning of mesoscopic structures in liquid crystals, facilitating applications including defect-directed self-assembly, material transport, micro-reactors, photonic devices, and anti-counterfeiting materials.

Abstract Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Background Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60–65%), CALR (20–25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations.Case presentation A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved.Conclusions The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

Objective High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear.Methods Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression.Results Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6–72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405–0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202–0.648; p