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Cytokine of interferon-gamma (IFNγ) plays a vital role in the immune response against Mycobacteria tuberculosis (Mtb) infection, yet the specific function of T cells producing IFNγ in this process remains unclear. In this study, we first isolated IFNγ+CD3+ T cells induced by Mtb antigens using surface staining assays. which showed a strong ability to inhibit the growth of intracellular mycobacteria in macrophages. Peripheral blood mononuclear cells (PBMCs) from healthy individuals were then challenged with Bacillus Calmette–Guérin (BCG) or Mtb, respectively, to sort IFNγ-secreting T cells for mRNA sequencing to analyze the gene expression patterns. The results of the integrated data analysis revealed distinct patterns of gene expression between IFNγ+CD3+ T cells induced by the BCG vaccine and those induced by Mtb pathogens. Further, unlike Mtb-induced cells, BCG-induced IFNγ+CD3+ T cells expressed high levels of interleukin-2 (IL-2), which increased the frequencies of these cells and the production of effector cytokines IFNγ and IL-2. Our findings suggested that IFNγ+CD3+ T cells with high IL-2 expression presented potent effector functions to inhibit intracellular Mtb growth, while Mtb infection impaired IL-2 expression in IFNγ+CD3+ T cells.

IntroductionSARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. Cdc42 is involved in the regulation of cellular senescence. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence through Cdc42.MethodsK18-hACE2 mice were infected with SARS-CoV-2 Omicron BA.4 or stimulated with spike protein through the airway, the senescent cells and Cdc42 expression in lung tissue were detected. Overexpression of spike protein or exogenous incubation of spike protein was used to simulate the induction of cellular senescence by spike protein. Mechanistic insights into the role of Cdc42 were mainly explored using Western Blot and qRT-PCR.ResultsSpike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation.DiscussionThis study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases.

BackgroundReproductive tract infections (RTIs) represent a critical public health concern impacting women’s health, particularly pronounced in developing countries. We aim to investigates the prevalence of self-reported RTI symptoms in women aged 18 to 65 and the factors influencing gynecological examination behavior and associated risks are explored.MethodsFrom May 6, 2022, to September 20, 2022, a comprehensive survey engaged 20,864 women aged 18 to 65 in 19 townships in Lueyang, Shaanxi. Each survey team, comprising a gynecologist, two female health center staff, and a master’s student, conducted face-to-face questionnaire surveys in villages and households. The questionnaire featured three sections: prevalence of self-reported RTI symptoms, gynecological examination history, and factors influencing examination behavior.ResultsThe high response rate of 98.69% yielded 20,590 valid questionnaires. Among surveyed women, 42.04% reported RTI symptoms, with a higher prevalence in those aged 30 and above, peaking at 44.88% in the 50–59 age group. Vulvar itching (24.73%), abnormal vaginal discharge (17.41%), and urinary tract irritation signs (11.73%) were most common. Older adult women (≥60) reported higher frequency and longer duration of symptoms. Only 9.88% of symptomatic women underwent gynecological examinations in 2022. Examination likelihood decreased with age, presenting a critical gap in healthcare utilization among older women. Reasons for checkups included routine checkups (47.02%), symptom concerns (41.29%), and the availability of free medical checkup programs (9.82%). Barriers included perceived lack of serious symptoms (23.7%), lack of necessity (4.41%) and lack of time (3.98%). Among those examined, 40.58% had a diagnosis of gynecological disorders, including pelvic inflammatory disease, human papilloma virus infection and cervical cancer.ConclusionWidespread RTI symptoms, particularly in perimenopausal and older women, underscore the need for enhanced healthcare. Barriers to gynecological examinations include awareness, education, and accessibility issues. Strategies must prioritize health education, routine examinations, and improved healthcare infrastructure in underdeveloped regions.

BackgroundThe relationship of systolic blood pressure variability (SBPV) with Alzheimer’s disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions.MethodsLongitudinal data across 96 months (T0 to T4) were derived from the Alzheimer’s disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years).ResultsParticipants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008).ConclusionThese findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health.

BackgroundOsteoporosis is a multifactorial bone disease in which lipid metabolism plays an important role. Bone Mineral Density (BMD) measured by Dual-energy X-ray Absorptiometry (DXA) is a critical indicator for diagnosing osteoporosis. The cardiometabolic index (CMI) is a novel metric that combines two quantitative indicators of blood lipids—triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). This study explores the association between CMI and BMD and seeks to elucidate the role of lipid metabolism in the context of bone health.MethodsBased on the data of the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020-pre-pandemic, weighted multiple linear regression and smooth curve fitting were used to study the relationship between CMI and femoral BMD. Stratified analyses were also conducted for age, gender, BMI, ethnicity, diabetes and hypertension status. And, the saturation threshold effect of CMI was further analyzed using a two-stage linear regression model.ResultThis study enrolled a total of 1,650 participants (48.7% males), with an average age of 63.0 ± 8.6 years. After adjusting for multiple confounding factors, CMI was positively correlated with total femur BMD, trochanter BMD, and intertrochanter BMD, while the correlation with femur neck BMD was not statistically significant. In the fully adjusted model, each unit increase in CMI was associated with a 0.026 (g/cm2) increase in total femur BMD, a 0.022 (g/cm2) increase in trochanter BMD, and a 0.034 (g/cm2) increase in intertrochanter BMD. Subjects in the highest quartile of CMI had a 0.034 (g/cm2) increase in total femur BMD, a 0.035 (g/cm2) increase in trochanter BMD, and a 0.039 (g/cm2) increase in intertrochanter BMD in the fully-adjusted model compared to those in the lowest quartile. In addition, saturation was observed between CMI and total femur BMD, trochanter BMD and intertrochanter BMD, with saturation thresholds of 1.073, 1.431 and 1.073, respectively.ConclusionCMI is strongly associated with BMD, indicating its potential relevance in bone metabolism. However, the role of CMI in the context of bone health, especially regarding osteoporosis risk, requires further investigation in large-scale prospective studies.

BackgroundInsulin resistance (IR) can predict the prognosis of patients suffering from cerebrovascular disorders. The triglyceride–glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio have been confirmed to be easy and reliable indicators of IR. However, the relationships between the TyG index or TG/HDL-C ratio and early neurological deterioration (END) after thrombolysis in patients with acute ischemic stroke (AIS) are uncertain.MethodsA retrospective analysis of 1,187 patients diagnosed with AIS who underwent intravenous thrombolysis between January 2018 and February 2024 was performed. Post-thrombolysis END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥4 within 24 h after thrombolysis. Logistic regression analysis was performed to explore the relationships of the TyG index and TG/HDL-C ratio with post-thrombolysis END. Receiver operating characteristic (ROC) analysis was used to assess the ability of the TyG index and TG/HDL-C ratio to discriminate post-thrombolysis END.ResultsAmong the 1,187 recruited patients, 179 (15.08%) were diagnosed with post-thrombolysis END, and 1,008 (84.92%) were diagnosed with non-END. A binary logistic regression model indicated that the TyG index (odds ratio [OR], 2.015; 95% confidence interval [CI] 1.964–2.414, p = 0.015) and TG/HDL-C ratio (OR, 1.542; 95% CI, 1.160–2.049, p = 0.004) were independent factors for post-thrombolysis END. The area under the curve (AUC) values for the TyG index, TG/HDL-C ratio, and TyG index combined with the TG/HDL-C ratio for post-thrombolysis END were 0.704, 0.674, and 0.755, respectively.ConclusionThis study indicates that the TyG index and TG/HDL-C ratio can be used as prognostic factors to predict post-thrombolysis END.

BackgroundExploration of the benefits and timing of surgical decompression in spinal cord injury (SCI) has been a research hotspot. However, despite the higher volume and increasing emphasis on quality there remains no bibliometric view on SCI and surgical decompression. In this study, we aimed to perform bibliometric analysis to reveal the core countries, affiliations, journals, authors, and developmental trends in SCI and surgical decompression across the past 50 years.MethodsArticles and reviews were retrieved from web of science core collection between 1975 and 2024. The bibliometrix package in R was used for data analysis and visualizing.ResultsA total of 8,688 documents were investigated, indicating an ascending trend in annual publications. The USA and China played as the leaders in scientific productivity. The University of Toronto led in institutional productions. Core authors, such as Michael G. Fehlings, showed high productivity, and occasional authors showed widespread interests. Core journals like Spine and Spinal Cord served as beacons in this field. The interaction of core authors and international collaboration accentuated the cross-disciplinary feature of the field. Prominent documents emphasized the clinical significance of early decompression in 24 h post SCI.ConclusionBased on comprehensive bibliometric analysis and literature review, we identified the hotspots and future directions of this field: (1) further investigation into the molecular and cellular mechanisms to provide pre-clinical evidence for biological effects of early surgical decompression in SCI animal models; (2) further evaluation and validation of the optimal time window of surgical decompression based on large cohort, considering the inherent heterogeneity of subpopulations in complicated immune responses post SCI; (3) further exploration on the benefits of early decompression on the neurological, functional, and clinical outcomes in acute SCI; (4) evaluation of the optimal surgical methods and related outcomes; (5) applications of artificial intelligence-based technologies in spinal surgical decompression.

Nicosulfuron, a widely utilized herbicide, is detrimental to some maize varieties due to their sensitivity. Developing tolerant varieties with resistance genes is an economical and effective way to alleviate phytotoxicity. In this study, map-based cloning revealed that the maize resistance gene to nicosulfuron is Zm00001eb214410 (CYP81A9), which encodes a cytochrome P450 monooxygenase. qRT- PCR results showed that CYP81A9 expression in the susceptible line JS188 was significantly reduced compared to the resistant line B73 during 0-192 hours following 80 mg/L nicosulfuron spraying. Meanwhile, a CYP81A9 overexpression line exhibited normal growth under a 20-fold nicosulfuron concentration (1600 mg/L), while the transgenic acceptor background material Zong31 did not survive. Correspondingly, silencing CYP81A9 through CRISPR/Cas9 mutagenesis and premature transcription termination mutant EMS4-06e182 resulted in the loss of nicosulfuron resistance in maize. Acetolactate Synthase (ALS), the target enzyme of nicosulfuron, exhibited significantly reduced activity in the roots, stems, and leaves of susceptible maize post-nicosulfuron spraying. The CYP81A9 expression in the susceptible material was positively correlated with ALS activity in vivo. Therefore, this study identified CYP81A9 as the key gene regulating nicosulfuron resistance in maize and discovered three distinct haplotypes of CYP81A9, thereby laying a solid foundation for further exploration of the underlying resistance mechanisms.

Traditional biomass boiler operations predominantly rely on manual control, with adjustments made based on operator experience. This approach not only demands considerable manpower but also leads to suboptimal resource utilization. Addressing the specific operational dynamics of biomass boilers, this study introduces a controller designed around the STM32 microcontroller. This device employs a modular architecture and incorporates cost-effective chips and peripheral components. To enhance energy efficiency and the overall user experience, the controller utilizes pulse width modulation pulse modulation alongside a fuzzy PID control strategy. Capable of toggling between manual and automatic modes for local operations, it also supports data logging directly on the device or in the cloud. Tailored to meet diverse user requirements, the controller facilitates remote monitoring and management. It employs a strategic control mechanism for various motors, ensuring precise hot water temperature measurements within the boiler and enabling data uploads to cloud platforms. This not only conserves energy and reduces labor costs but also promotes environmental sustainability and operational efficiency. Through ongoing refinement and rigorous testing, the controller has achieved a level of maturity that underscores its readiness for widespread implementation.

Mycotoxins are secondary metabolites produced during the growth, storage, and transportation of crops contaminated by fungi and are physiologically toxic to humans and animals. Aflatoxin, zearalenone, deoxynivalenol, ochratoxin, patulin, and fumonisin are the most common mycotoxins and can cause liver and nervous system damage, immune system suppression, and produce carcinogenic effects in humans and animals that have consumed contaminated food. Physical, chemical, and biological methods are generally used to detoxify mycotoxins. Although physical methods, such as heat treatment, irradiation, and adsorption, are fast and simple, they have associated problems including incomplete detoxification, limited applicability, and cause changes in food characteristics (e.g., nutritive value, organoleptic properties, and palatability). Chemical detoxification methods, such as ammonification, ozonation, and peroxidation, pollute the environment and produce food safety risks. In contrast, bioenzymatic methods are advantageous as they achieve selective detoxification and are environmentally friendly and reusable; thus, these methods are the most promising options for the detoxification of mycotoxins. This paper reviews recent research progress on common mycotoxins and the enzymatic principles and mechanisms for their detoxification, analyzes the toxicity of the degradation products and describes the challenges faced by researchers in carrying out enzymatic detoxification. In addition, the application of enzymatic detoxification in food and feed is discussed and future directions for the development of enzymatic detoxification methods are proposed for future in-depth study of enzymatic detoxification methods.

Liangshan Prefecture, located at the northeastern edge of the Hengduan Mountain System and within the southern section of the Sichuan-Yunnan tectonic belt in Sichuan Province, China, a region prone to landslides, collapses and debris flows due to its active tectonics, complex topography and significant river erosion. By analysing a dataset of environment factors and geological hazard catalogue, the research uses the Relief algorithm to identify critical influencing factors for each hazard type, selecting 10, 9 and 9 factors for landslides, collapses and debris flows, respectively. Five models are used to assess the vulnerability of these hazards: the Information Value model, the Evidence Weight model, the Logistic Regression model, and both the Evidence Weight-Logistic Regression and the Information Value-Logistic Regression coupled models. The effectiveness of these models is confirmed by confusion matrix and ROC curve analyses, with the combined models showing particularly high accuracy in assessing susceptibility. High risk zones were identified in specific areas and along major fault zones in Liangshan Prefecture. The research provides significant insights into the susceptibility of geological hazards in mountainous and canyon regions, offering a comprehensive approach that goes beyond the limitations of single model applications. This methodology not only provides more accurate and comprehensive results, but also serves as a fundamental reference for geological hazard mitigation and management in Liangshan Prefecture, potentially benefiting similar regions worldwide.

IntroductionHigh-alkalinity water is a serious health hazard for fish and can cause oxidative stress and metabolic dysregulation in fish livers. However, the molecular mechanism of liver damage caused by high alkalinity in fish is unclear. MethodsIn this study, 180 carp were randomly divided into a control (C) group and a high-alkalinity (A25) group and were cultured for 56 days. High-alkalinity-induced liver injury was analysed using histopathological, whole-transcriptome, and metabolomic analyses. ResultsMany autophagic bodies and abundant mitochondrial membrane damage were observed in the A25 group. High alkalinity decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and the total antioxidant capacity (T-AOC) and increased the malondialdehyde (MDA) content in liver tissues, causing oxidative stress in the liver. Transcriptome analysis revealed 61 differentially expressed microRNAs (miRNAs) and 4008 differentially expressed mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that mammalian target of rapamycin (mTOR), forkhead box O (FoxO), mitogen-activated protein kinase (MAPK), and the autophagy signalling pathway were the molecular mechanisms involved. High alkalinity causes oxidative stress and autophagy and results in autophagic damage in the liver. Bioinformatic predictions indicated that Unc-51 Like Kinase 2 (ULK2) was a potential target gene for miR-140-5p, demonstrating that high alkalinity triggered autophagy through the miR-140-5p–ULK2 axis. Metabolomic analysis revealed that the concentrations of cortisol 21-sulfate and beta-aminopropionitrile were significantly increased, while those of creatine and uracil were significantly decreased. DiscussionThe effects of high alkalinity on oxidative stress and autophagy injury in the liver were analysed using whole-transcriptome miRNA-mRNA networks and metabolomics approaches. Our study provides new insights into liver injury caused by highly alkaline water.

Background and aimsThe American Heart Association (AHA) recently introduced the Life’s Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes.Methods and ResultsThis cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education.ConclusionCVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.

BackgroundPost-stroke depression (PSD) is a well-established psychiatric complication following stroke. Nevertheless, the relationship between early-onset PSD and homocysteine (Hcy) or fibrinogen remains uncertain.MethodsAcute ischemic stroke (AIS) patients who met the established criteria were enrolled in this study. Early-onset PSD was diagnosed two weeks after the stroke. The severity of depressive symptoms was assessed by the Hamilton Depression Scale-17 items (HAMD-17), with patients scored ≥7 assigned to the early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between Hcy, fibrinogen, and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the relationship between Hcy, fibrinogen, and early-onset PSD. Receiver operating characteristic curve (ROC) analysis was ASSDalso performed to detect the predictive ability of Hcy and fibrinogen for early-onset PSD.ResultsAmong the 380 recruited patients, a total of 106 (27.89%) patients were diagnosed with early-onset PSD. The univariate analysis suggested that patients in the PSD group had a higher admission National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score (mRS), Hcy, and fibrinogen levels than patients in the non-PSD group (P

ObjectiveTo evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China.MethodsA prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study.ResultsOut of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15–0.84; P = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17–1.61; P

Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy.Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software.Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT>MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT>MIC.Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT>MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.

Precision medicine, characterized by the personalized integration of a patient’s genetic blueprint and clinical history, represents a dynamic paradigm in healthcare evolution. The emerging field of personalized anesthesia is at the intersection of genetics and anesthesiology, where anesthetic care will be tailored to an individual’s genetic make-up, comorbidities and patient-specific factors. Genomics and biomarkers can provide more accurate anesthetic protocols, while artificial intelligence can simplify anesthetic procedures and reduce anesthetic risks, and real-time monitoring tools can improve perioperative safety and efficacy. The aim of this paper is to present and summarize the applications of these related fields in anesthesiology by reviewing them, exploring the potential of advanced technologies in the implementation and development of personalized anesthesia, realizing the future integration of new technologies into clinical practice, and promoting multidisciplinary collaboration between anesthesiology and disciplines such as genomics and artificial intelligence.

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction.Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran’s Q statistic was utilized to detect the heterogeneity.Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02–1.21, p = 0.019), and also the genetically determined Crohn’s disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02–1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92–1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity.Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn’s disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction.

In order to quantitatively analyze the roughness of the bench floor during open-pit mine blasting, this study proposes a real-time measuring method for the three-dimensional terrain of the bench floor during the excavation process. Real-time monitoring is conducted at the boundary and discrete internal points of the workbench floor during electric shovel operation, utilizing real-time kinematic global navigation satellite system (RTK-GNSS) positioning technology. An improved convex hull algorithm is introduced to automatically extract the optimal boundary of discrete point clouds based on their spatial distribution characteristics. This study establishes a digital elevation model (DEM) using five interpolation algorithms for 3D terrain visualization simulation. Through cross-validation, a comparative analysis of the DEM accuracy, the simulation results of the ordinary kriging interpolation algorithm were found to be optimized. The optimized interpolation algorithm is applied to simulate the 3D terrain in the Dexing open-pit copper mine, and the relevant terrain parameters were calculated. This dataset can serve as a precise foundation for the real-time path planning of elevation blasting design and ground leveling operations.

IntroductionVillage clinics (VCs) are the foundation of the three-tiered health service system in China, delivering basic and routine outpatient services to citizens in rural China. VC technical efficiency and its convergence play a critical role in policy decisions regarding the distribution of health service resources in rural China.MethodsThis study measured VC technical efficiency (using the slacks-based measure model), its convergence (using the convergence model), and the factors that influence the convergence in Shanxi Province, China. Data were obtained from the Shanxi Rural Health Institute 2014–2018 Health Statistics Report, which involved 3,543 VCs.ResultsThe results showed that VC technical efficiency was low and differed by region. There was no α convergence in VC technical efficiency, but evidence of β convergence was found in Shanxi. The main factors that influence convergence were the building area of each VC (BA), proportion of government subsidies (PGS), and ratio of total expenditure to total income of each VC (RTETI).ConclusionThe government should increase investments in VCs and improve VC technical efficiency. Meanwhile, the government should be aware of and take measures to curb the inequity in VC technical efficiency among different regions and take suitable measures to curb this disparity.

IntroductionStudies have established the benefits of horticultural therapy and activities for human health and well-being. Nonetheless, limited research has been conducted on the potential restorative advantages and distinctions between different types of horticultural activities in terms of stress reduction.MethodsThis study employed a quantitative research method to investigate the stress recovery benefits of five horticultural activities (flower arrangement, sowing and transplanting seeds, kokedama crafting, pressed flower card making, and decorative bottle painting with dried flowers) and one reference activity (short composition writing) for children. The experiment was conducted in a children’s activity center’s multi-purpose classroom with 48 elementary students aged 9–12 years. The subjects first took a stress test to induce stress and then engaged in horticultural activities for 20 min. Physiological stress was assessed using electrocardiograms and electroencephalograms as feedback indicators. Psychological and emotional changes were determined using the Positive and Negative Affect Schedule for Children and Self-Assessment Manikin scales.ResultsThe results demonstrated that horticultural activities greatly reduced physiological fatigue, and their recovery benefits were significantly greater than those of the reference activity. The recovery effects from different horticultural activities were similar across physiological indicators, although flower arrangement and sowing and transplanting seeds exhibited relatively robust recovery benefits. The heart rate and α-EEG-based generalized estimating equation revealed that horticultural activities offered significantly better relative recovery at each time phase of operation than the reference activity, with girls showing a 3.68% higher relative recovery value than boys. Flower arrangement and kokedama crafting offered better physiological recovery for students with prior horticultural experience, and these two activities received the highest scores in terms of positive effects and the “pleasure” dimension. Students believed that participating in horticultural activities resulted in a noteworthy increase in personal confidence and a greater sense of achievement.ConclusionThe study suggests that horticultural activities that involve real and vibrant plants or natural materials and are more attractive have more stress-relieving benefits. We conclude that horticultural activities are beneficial leisure activities that aid in stress relief for children and that it is important to consider the attributes of activities when developing horticultural programs for elementary students.

PurposeObesity, particularly abdominal obesity, is seen as a risk factor for diabetic complications. The weight-adjusted-waist index (WWI) is a recently developed index for measuring adiposity. Our goal was to uncover the potential correlation between the WWI index and diabetic kidney disease (DKD) risk.MethodsThis cross-sectional study included adults with type 2 diabetes mellitus (T2DM) who participated in the NHANES database (2007-2018). The WWI index was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). DKD was diagnosed based on impaired estimated glomerular filtration rate (eGFR30 mg/g), or both in T2DM patients. The independent relationship between WWI index and DKD risk was evaluated.ResultsA total of 5,028 participants with T2DM were included, with an average WWI index of 11.61 ± 0.02. As the quartile range of the WWI index increased, the prevalence of DKD gradually increased (26.76% vs. 32.63% vs. 39.06% vs. 42.96%, P

BackgroundInflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear.MethodsAIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score

The maturity of kiwifruit is widely gauged by its soluble solids content (SSC), with accurate assessment being essential to guarantee the fruit’s quality. Hyperspectral imaging offers a non-destructive alternative to traditional destructive methods for SSC evaluation, though its efficacy is often hindered by the redundancy and external disturbances of spectral images. This study aims to enhance the accuracy of SSC predictions by employing feature engineering to meticulously select optimal spectral features and mitigate disturbance effects. We conducted a comprehensive investigation of four spectral pre-processing and nine spectral feature selection methods, as components of feature engineering, to determine their influence on the performance of a linear regression model based on ordinary least squares (OLS). Additionally, the stacking generalization technique was employed to amalgamate the strengths of the two most effective models derived from feature engineering. Our findings demonstrate a considerable improvement in SSC prediction accuracy post feature engineering. The most effective model, when considering both feature engineering and stacking generalization, achieved an RMSEp of 0.721, a MAPEp of 0.046, and an RPDp of 1.394 in the prediction set. The study confirms that feature engineering, especially the careful selection of spectral features, and the stacking generalization technique are instrumental in bolstering SSC prediction in kiwifruit. This advancement enhances the application of hyperspectral imaging for quality assessment, offering benefits that extend across the agricultural industry.

BackgroundPancreatic cancer remains an extremely malignant digestive tract tumor, posing a significant global public health burden. Patients with pancreatic cancer, once metastasis occurs, lose all hope of cure, and prognosis is extremely poor. It is important to investigate liver metastasis of Pancreatic cancer in depth, not just because it is the most common form of metastasis in pancreatic cancer, but also because it is crucial for treatment planning and prognosis assessment. This study aims to delve into the mechanisms of pancreatic cancer liver metastasis, with the goal of providing crucial scientific groundwork for the development of future treatment methods and drugs.MethodsWe explored the mechanisms of pancreatic cancer liver metastasis using single-cell sequencing data (GSE155698 and GSE154778) and bulk data (GSE71729, GSE19279, TCGA-PAAD). Initially, Seurat package was employed for single-cell data processing to obtain expression matrices for primary pancreatic cancer lesions and liver metastatic lesions. Subsequently, high-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify genes associated with liver metastasis. Machine learning algorithms and COX regression models were employed to further screen genes related to patient prognosis. Informed by both biological understanding and the outcomes of algorithms, we meticulously identified the ultimate set of liver metastasis-related gene (LRG). In the study of LRG genes, various databases were utilized to validate their association with pancreatic cancer liver metastasis. In order to analyze the effects of these agents on tumor microenvironment, we conducted an in-depth analysis, including changes in signaling pathways (GSVA), cell differentiation (pseudo-temporal analysis), cell communication networks (cell communication analysis), and downstream transcription factors (transcription factor activity prediction). Additionally, drug sensitivity analysis and metabolic analysis were performed to reveal the effects of LRG on gemcitabine resistance and metabolic pathways. Finally, functional experiments were conducted by silencing the expression of LRG in PANC-1 and Bx-PC-3 cells to validate its influence to proliferation and invasiveness on PANC-1 and Bx-PC-3 cells.ResultsThrough a series of algorithmic filters, we identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis elucidated the activation of the TGF-beta signaling pathway by PAK2 to promote the occurrence of liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis revealed that overexpression of PAK2 promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. CCK8 experiments showed that silencing PAK2 led to a decrease in the proliferative capacity of pancreatic cancer cells and scratch experiments demonstrated that low expression of PAK2 decreased invasion capability in pancreatic cancer cells. Flow cytometry reveals that PAK2 significantly inhibited apoptosis in pancreatic cancer cell lines. Molecules related to the TGF-beta pathway decreased with the inhibition of PAK2, and there were corresponding significant changes in molecules associated with EMT.ConclusionPAK2 facilitated the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-beta signaling pathway. Simultaneously, it decreased the differentiation level of cancer cells, consequently enhancing their malignancy. Additionally, PAK2 fostered communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. In summary, PAK2 emerged as a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis.

Tomatoes are susceptible to damage from cold temperatures in all stages of growth. Therefore, it is important to identify genetic resources and genes that can enhance tomato’s ability to tolerate cold. In this study, a population of 223 tomato accessions was used to identify the sensitivity or tolerance of plants to cold stress. Transcriptome analysis of these accessions revealed that SUS3, a member of the sucrose synthase gene family, was induced by cold stress. We further investigated the role of SUS3 in cold stress by overexpression (OE) and RNA interference (RNAi). Compared with the wild type, SUS3-OE lines accumulated less MDA and electrolyte leakage and more proline and soluble sugar, maintained higher activities of SOD and CAT, reduced superoxide radicals, and suffered less membrane damage under cold. Thus, our findings indicate that SUS3 plays a crucial role in the response to cold stress. This study indicates that SUS3 may serve as a direct target for genetic engineering and improvement projects, which aim to augment the cold tolerance of tomato crops.

Background: Ubiquitination and deubiquitination modifications play pivotal roles in eukaryotic life processes, regulating protein dynamics via the ubiquitin-proteasome pathway. Dysregulation can impact disease development, including cancer and neurodegenerative disorders. Increasing evidence highlights their role in tumorigenesis, modulating key proteins. OTUD3, a deubiquitinase, stabilizes PTEN, suppressing tumor growth by inhibiting PI3K-AKT signaling. Yet, further OTUD3 substrates remain underexplored.Methods: We employed the In vivo ubiquitination assay to investigate the ubiquitination role of OTUD3 on KPTN within the cellular context. Additionally, CRISPR/Cas9 editing and Immunofluorescence were utilized to study the impact of OTUD3 on the mTOR signaling pathway in cells. Furthermore, Cell proliferation assay and NMR were employed to explore the effects of OTUD3 on cellular growth and proliferation.Results: OTUD3 serves as a deubiquitinase for KPTN. OTUD3 interacts with KPTN, facilitated by the OTU domain within OTUD3. Further investigations confirmed KPTN’s ubiquitination modification, primarily at lysine residue 49. Ubiquitination experiments demonstrated OTUD3’s ability to mediate KPTN’s deubiquitination without affecting its protein levels. This suggests KPTN’s ubiquitination is a function-regulated, non-degradable modification. Under various amino acid starvation or stimulation conditions, overexpressing OTUD3 reduces mTORC1 signaling activation, while knocking out OTUD3 further enhances it. Notably, OTUD3’s regulation of mTORC1 signaling relies on its deubiquitinase activity, and this effect is observed even in PTEN KO cells, confirming its independence from PTEN, a reported substrate. OTUD3 also promotes GATOR1’s lysosomal localization, a process requiring KPTN’s involvement. Ultimately, OTUD3 affects cellular metabolic pool products by downregulating the mTORC1 pathway, significantly inhibiting tumor cell growth and proliferation.Discussion: Our experiments shed light on an alternative perspective regarding the intrinsic functions of OTUD3 in inhibiting tumor development. We propose a novel mechanism involving KPTN-mediated regulation of the mTORC1 signaling pathway, offering fresh insights into the occurrence and progression of tumor diseases driven by related genes. This may inspire new approaches for drug screening and cancer treatment, potentially guiding future therapies for relevant tumors.

Listeria monocytogenes (Lm) is associated with severe foodborne infections and ubiquitous in the nature. Identification of characteristics of Lm transmission through trading of food products is essential for rapidly tracking Lm sources and controlling dissemination of listeriosis. In this study, a total of 44 Lm strains were isolated from food products originating from 14 countries/regions during 2003-2018 at the Shanghai port. The genomes of these Lm strains were sequenced by high-throughput sequencing. Multilocus sequence typing (MLST) analysis showed that 43 isolates were divided into 17 sequence types (STs). The distribution of STs was decentralized, with the dominant ST2 accounting for only 18.18% of the strains. The LM63 strain did not match with any of the existing STs. Core-genome MLST (cgMLST) analysis based on 1748 core genes categorized the 44 strains into 30 cgMLST types (CTs), with CT10153 and CT7892 as the most predominant CTs. Notably, LM63 and LM67 shared the same CT in the cgMLST analysis. The phylogenetic analysis based on single-copy homologous genes revealed that the 44 Lm strains were primarily classified into two lineages. The SNP analysis also indicated that these strains were roughly divided into two clades, with strains in the first clade mainly collected earlier than those in the second clade, which were predominantly collected from 2010 onwards. The analysis using the virulence factor database (VFDB) indicated that the virulence gene inlJ was the most prevalent among these 44 strains. Notably, ddrA, msbA, and sugC were enriched in this dataset, requiring further clarification of their roles in Listeria through future studies. These results might provide a clue for understanding of the global epidemiology and surveillance of Lm and present insights for implementing effective measures to reduce or prevent Listeria contamination outbreaks in imported food products.

ObjectivePrimary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics.MethodsA four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method.Results47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers.ConclusionThis study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.

G2/M cell cycle checkpoint protein WEE1 kinase is a promising target for inhibiting tumor growth. Although various WEE1 inhibitors have entered clinical investigations, their therapeutic efficacy and safety profile remain unsatisfactory. In this study, we employed a comprehensive virtual screening workflow, which included Schrödinger-Glide molecular docking at different precision levels, as well as the utilization of tools such as MM/GBSA and Deepdock to predict the binding affinity between targets and ligands, in order to identify potential WEE1 inhibitors. Out of ten molecules screened, 50% of these molecules exhibited strong inhibitory activity against WEE1. Among them, compounds 4 and 5 showed excellent inhibitory activity with IC50 values of 1.069 and 3.77 nM respectively, which was comparable to AZD1775. Further investigations revealed that compound 4 displayed significant anti-proliferative effects in A549, PC9, and HuH-7 cells and could also induce apoptosis and G1 phase arrest in PC9 cells. Additionally, molecular dynamics simulations unveiled the binding details of compound 4 with WEE1, notably the crucial hydrogen bond interactions formed with Cys379. In summary, this comprehensive virtual screening workflow, combined with in vitro testing and computational modeling, holds significant importance in the development of promising WEE1 inhibitors.

Objective: The treatment for posterolateral tibial plateau fractures (PTPF) have been subjects of controversy. We conducted a study to improve the fixation of PTPF through a lateral approach.Methods: We utilized 40 synthetic tibias and categorized the fracture models into five groups based on the locking compression plate (LCP) and T-distal radius plate (TPP) via various forms of fixation with screws through the posterolateral (PL) fracture fragments. I: Two-screw fixation using two locking screws (LPTL). Ⅱ: Two-screw fixation with both variable angle locking screws (LPTV). Ⅲ: One-screw fixation with one locking screw (LPOL). Ⅳ: One-screw fixation with one locking screw and two anteroposterior lag screws (LPOLTL). Ⅴ: a distal radius plate with three locking screws (TPP). Biomechanical tests were conducted to observe the axial compression displacement of the PL fracture fragments at force levels of 250 N, 500 N, and 750 N, as well as to determine the failure load and the axial stiffness for each respective group.Results: Under a 750 N load condition, the displacements within the five experimental groups exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. However, there were no significant differences between Group V and Group II, Group I and Group IV (p > 0.05), and only Group Ⅲ demonstrated a displacement exceeding 3 mm. The failure load and the axial stiffness exhibited the same trend. Conversely, statistical significance was identified among the remaining group compared with Group Ⅲ (p < 0.05). Regarding the finite element analysis, the maximum displacements for the five models under the load of 750 N exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. The following trends were observed in maximum von Mises stresses for these models under the load of 750 N: Ⅴ < Ⅱ < Ⅳ< Ⅰ < Ⅲ.Conclusion: It is crucial to address the inadequate mechanical strength associated with single screw fixation of LCP for fixing PL fractures in a clinical setting. The biomechanical strength of two-screw fixation surpasses that of single-screw fixation. Introducing variable-angle screws can further enhance the fixation range. Furthermore, the addition of two lag screws threaded from anterior to posterior can compensate the mechanical stability, when PL fracture is fixed with single screw in clinic.

Introduction“Probiotic therapy” to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases.MethodsIn this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis.ResultsWe confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis.ConclusionTherefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.

β-Alanine is the only naturally occurring β-type amino acid in nature, and it is also one of the very promising three-carbon platform compounds that can be applied in cosmetics and food additives and as a precursor in the chemical, pharmaceutical and material fields, with very broad market prospects. β-Alanine can be synthesized through chemical and biological methods. The chemical synthesis method is relatively well developed, but the reaction conditions are extreme, requiring high temperature and pressure and strongly acidic and alkaline conditions; moreover, there are many byproducts that require high energy consumption. Biological methods have the advantages of product specificity, mild conditions, and simple processes, making them more promising production methods for β-alanine. This paper provides a systematic review of the chemical and biological synthesis pathways, synthesis mechanisms, key synthetic enzymes and factors influencing β-alanine, with a view to providing a reference for the development of a highly efficient and green production process for β-alanine and its industrialization, as well as providing a basis for further innovations in the synthesis of β-alanine.

ObjectiveA high-sodium diet is an important risk factor for hypertension in the Chinese population, which can increase the risk of cardiovascular and cerebrovascular diseases. Although a large number of related studies have been carried out in Anhui province, clear, effective salt reduction interventions and policies that can be widely promoted have not yet been formed. This study sought to understand the prevalence and precise measures of salt reduction behavior, the variables affecting salt reduction behavior, and the reasons why salt reduction behavior was not practiced in Anhui Province, China.MethodsThe total number of participants in the study was 3,378. Using a multi-stage stratified cluster random sampling method, residents between the ages of 18 and 69 years in 10 counties and districts were selected from March to October 2019. A survey questionnaire and physical measurements were given to each participant. The influencing factors of residents' salt reduction behavior were examined using a multi-factor unconditional logistic regression analysis. The chi-squared (χ2) test was used to analyze the implementation of salt reduction behaviors among different age groups and gender, the factors influencing the implementation of salt reduction measures, and the reasons for not implementing salt reduction measures.ResultsA history of hypertension was associated with salt reduction strategies (P = 0.014). Patients with hypertension were more likely to adopt salt reduction behaviors than those without hypertension (OR = 1.218, P = 0.040). The influence of eating out on the adoption of salt-reduction measures varied by age group (χ2 = 50.463, P < 0.001) and gender (χ2 = 81.348, P < 0.001).ConclusionIn summary, residents of the Anhui Province are not very knowledgeable about salt reduction. Age, gender, education level, hypertension, and marital status are the main determinants. Our findings have significant implications for policymakers who want to devise salt reduction strategies.

RationaleGanoderma lucidum (G. lucidum) is a popular medicinal fungus that has been used in traditional medicine for decades, with its provenance influencing its medicinal and commercial worth. The amount of active ingredients and the price of G. lucidum from different origins vary significantly; hence, fraudulent labeling is common. Reliable techniques for G. lucidum geographic verification are urgently required to safeguard the interests of consumers, producers, and honest dealers. A stable isotope is widely acknowledged as a useful traceability technique and could be developed to confirm the geographical origin of G. lucidum.MethodsG. lucidum samples from various sources and in varying stages were identified by using δ13C, δD, δ18O, δ15N, C, and N contents combined with chemometric tools. Chemometric approaches, including PCA, OPLS-DA, PLS, and FLDA models, were applied to the obtained data. The established models were used to trace the origin of G. lucidum from various sources or track various stages of G. lucidum.ResultsIn the stage model, the δ13C, δD, δ18O, δ15N, C, and N contents were considered meaningful variables to identify various stages of G. lucidum (bud development, growth, and maturing) using PCA and OPLS-DA and the findings were validated by the PLS model rather than by only four variables (δ13C, δD, δ18O, and δ15N). In the origin model, only four variables, namely δ13C, δD, δ18O, and δ15N, were used. PCA divided G. lucidum samples into four clusters: A (Zhejiang), B (Anhui), C (Jilin), and D (Fujian). The OPLS-DA model could be used to classify the origin of G. lucidum. The model was validated by other test samples (Pseudostellaria heterophylla), and the external test (G. lucidum) by PLS and FLDA models demonstrated external verification accuracy of up to 100%.ConclusionC, H, O, and N stable isotopes and C and N contents combined with chemometric techniques demonstrated considerable potential in the geographic authentication of G. lucidum, providing a promising method to identify stages of G. lucidum.

Background and aimsWhether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer.MethodsThis study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality.ResultsHigh ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose–response manner (all Pnonlinearity

Immune checkpoint inhibitors (ICIs) modulate the body’s immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis (ICIP) is a serious immune-related adverse event (irAE). Immunotherapy is currently approved as a first-line treatment for non-small cell lung cancer (NSCLC), and the incidence of ICIP in NSCLC patients can be as high as 5%-19% in clinical practice. ICIP can be severe enough to lead to the death of NSCLC patients, but there is a lack of a gold standard for the diagnosis of ICIP. Radiomics is a method that uses computational techniques to analyze medical images (e.g., CT, MRI, PET) and extract important features from them, which can be used to solve classification and regression problems in the clinic. Radiomics has been applied to predict and identify ICIP in NSCLC patients in the hope of transforming clinical qualitative problems into quantitative ones, thus improving the diagnosis and treatment of ICIP. In this review, we summarize the pathogenesis of ICIP and the process of radiomics feature extraction, review the clinical application of radiomics in ICIP of NSCLC patients, and discuss its future application prospects.

With the rapid development of the photovoltaic (PV) industry, the problem of the blind construction of PV power plants is becoming increasingly prominent. Thus, the scientific evaluation of the suitability of regional PV products, power generation potential, and emission reduction benefits is of great significance to the sustainable development of the PV industry. In this study, geographic information sensing and multi-criteria decision making methods are to be combined to calculate a PV development suitability index based on meteorology, topography, location, and vegetation to characterize the spatial patterns of the PV development in the Inner Mongolia Autonomous Region. Subsequently, the power generation potential and emission reduction benefits under different development scenarios were quantitatively assessed. The particularly suitable, and more suitable areas for the PV development in the Inner Mongolia Autonomous Region are 23.66% of the total area. Among these, the more suitable areas are the most extensive. The suitability of PV development in the western part of the Inner Mongolia Autonomous Region is more than that in the central and eastern parts. The suitable areas are mainly distributed in the Alashan League and Bayannur City in the west. Thus, the Inner Mongolia Autonomous Region has enormous potential for electricity generation. The development of 12.57% of the particularly suitable areas can meet the electricity consumption of the Inner Mongolia Autonomous Region in 2021. Moreover, sensitivity analysis is conducted to investigate the impacts of system efficiency variation on energy output. The distribution of the power generation potential and electricity demand in the Inner Mongolia Autonomous Region has robust spatial heterogeneity. PV power generation can achieve remarkable energy saving and emission reduction. If all particularly suitable areas are developed, the annual carbon emission reduction of the Inner Mongolia Autonomous Region will be approximately 2,446,621,000 t, which is 4.46 times the total carbon emission of the Autonomous Region and 21.2% of the total carbon emission of China in 2021. Therefore, this study provides a scientific reference and guide for selecting suitable sites for PV power plants and their sustainable development in the Inner Mongolia Autonomous Region.

Proteases (proteinases or peptidases) are a class of hydrolases that cleave peptide chains in proteins. Endopeptidases are a type of protease that hydrolyze the internal peptide bonds of proteins, forming shorter peptides; exopeptidases hydrolyze the terminal peptide bonds from the C-terminal or N-terminal, forming free amino acids. Microbial proteases are a popular instrument in many industrial applications. In this review, the classification, detection, identification, and sources of microbial proteases are systematically introduced, as well as their applications in food, detergents, waste treatment, and biotechnology processes in the industry fields. In addition, recent studies on techniques used to express heterologous microbial proteases are summarized to describe the process of studying proteases. Finally, future developmental trends for microbial proteases are discussed.

Intracerebral hemorrhage (ICH), the most devastating subtype of stoke, is of high mortality at 5 years and even those survivors usually would suffer permanent disabilities. Fortunately, various preclinical active drugs have been approached in ICH, meanwhile, the therapeutic effects of these pharmaceutical ingredients could be fully boosted with the assistance of nanotechnology. In this review, besides the pathology of ICH, some ICH therapeutically available active drugs and their employed nanotechnologies, material functions, and therapeutic principles were comprehensively discussed hoping to provide novel and efficient strategies for ICH therapy in the future.

BackgroundIn order to investigate the impact of Treg cell infiltration on the immune response against pancreatic cancer within the tumor microenvironment (TME), and identify crucial mRNA markers associated with Treg cells in pancreatic cancer, our study aims to delve into the role of Treg cells in the anti-tumor immune response of pancreatic cancer.MethodsThe ordinary transcriptome data for this study was sourced from the GEO and TCGA databases. It was analyzed using single-cell sequencing analysis and machine learning. To assess the infiltration level of Treg cells in pancreatic cancer tissues, we employed the CIBERSORT method. The identification of genes most closely associated with Treg cells was accomplished through the implementation of weighted gene co-expression network analysis (WGCNA). Our analysis of single-cell sequencing data involved various quality control methods, followed by annotation and advanced analyses such as cell trajectory analysis and cell communication analysis to elucidate the role of Treg cells within the pancreatic cancer microenvironment. Additionally, we categorized the Treg cells into two subsets: Treg1 associated with favorable prognosis, and Treg2 associated with poor prognosis, based on the enrichment scores of the key genes. Employing the hdWGCNA method, we analyzed these two subsets to identify the critical signaling pathways governing their mutual transformation. Finally, we conducted PCR and immunofluorescence staining in vitro to validate the identified key genes.ResultsBased on the results of immune infiltration analysis, we observed significant infiltration of Treg cells in the pancreatic cancer microenvironment. Subsequently, utilizing the WGCNA and machine learning algorithms, we ultimately identified four Treg cell-related genes (TRGs), among which four genes exhibited significant correlations with the occurrence and progression of pancreatic cancer. Among them, CASP4, TOB1, and CLEC2B were associated with poorer prognosis in pancreatic cancer patients, while FYN showed a correlation with better prognosis. Notably, significant differences were found in the HIF-1 signaling pathway between Treg1 and Treg2 cells identified by the four genes. These conclusions were further validated through in vitro experiments.ConclusionTreg cells played a crucial role in the pancreatic cancer microenvironment, and their presence held a dual significance. Recognizing this characteristic was vital for understanding the limitations of Treg cell-targeted therapies. CASP4, FYN, TOB1, and CLEC2B exhibited close associations with infiltrating Treg cells in pancreatic cancer, suggesting their involvement in Treg cell functions. Further investigation was warranted to uncover the mechanisms underlying these associations. Notably, the HIF-1 signaling pathway emerged as a significant pathway contributing to the duality of Treg cells. Targeting this pathway could potentially revolutionize the existing treatment approaches for pancreatic cancer.

BackgroundPreoperative assessment of the presence of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) remains difficult. We aimed to develop a practical prediction model based on preoperative pathological data and inflammatory or nutrition-related indicators.MethodsThis study retrospectively analyzed the clinicopathological characteristics of 1,061 patients with EGC who were randomly divided into the training set and validation set at a ratio of 7:3. In the training set, we introduced the least absolute selection and shrinkage operator (LASSO) algorithm and multivariate logistic regression to identify independent risk factors and construct the nomogram. Both internal validation and external validation were performed by the area under the receiver operating characteristic curve (AUC), C-index, calibration curve, and decision curve analysis (DCA).ResultsLNM occurred in 162 of 1,061 patients, and the rate of LNM was 15.27%. In the training set, four variables proved to be independent risk factors (p < 0.05) and were incorporated into the final model, including depth of invasion, tumor size, degree of differentiation, and platelet-to-lymphocyte ratio (PLR). The AUC values were 0.775 and 0.792 for the training and validation groups, respectively. Both calibration curves showed great consistency in the predictive and actual values. The Hosmer–Lemeshow (H-L) test was carried out in two cohorts, showing excellent performance with p-value >0.05 (0.684422, 0.7403046). Decision curve analysis demonstrated a good clinical benefit in the respective set.ConclusionWe established a preoperative nomogram including depth of invasion, tumor size, degree of differentiation, and PLR to predict LNM in EGC patients and achieved a good performance.

Treponema phagedenis, a human commensal spirochete, has been reported world-wide as a key factor in the pathogenesis of bovine digital dermatitis. Here we report a case of T. phagedenis sequence detection in the cerebrospinal fluid (CSF) of a patient. The patient was diagnosed with neurosyphilis, and T. phagedenis was detected as the only microorganism in his CSF by metagenomic sequencing. The patient went through a round of penicillin therapy previously (2.4 million units of Benzathine Penicillin intramuscularly once a week for three weeks) that did not resolve the symptoms; after the diagnosis of neurosyphilis he was treated with Penicillin G Sodium 4.0 million units q4h intravenous for 14 days then his symptoms resolved. To the best of our knowledge, T. phagedenis has never been reported to be detected in a human’s CSF before. This was also the first time it was detected by metagenomic next-generation sequencing. We propose that more etiological tests should be performed including culture and sequencing for more patients with syphilis, which will contribute to a deeper understanding of the pathogenicity of the spirochete.

IntroductionSome studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear.MethodsIn this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS.ResultsThe results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman’s correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α).DiscussionIn conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.

BackgroundPregnant women with gestational diabetes mellitus (GDM) require more analgesics after cesarean delivery than those who do not have GDM. Uncontrolled pain following cesarean delivery is a major problem in women with GDM. We investigate the efficacy of low-dose esketamine combined with sufentanil intravenous patient-controlled analgesia (PCA)for postcesarean analgesia in women with GDM.MethodsOne hundred forty pregnant women with GDM were enrolled participate in this randomized controlled trial and were randomized into two groups (70 in each group). The esketamine (S) group was given esketamine +sufentanil + ondansetron, and the control (C) group was given sufentanil +ondansetron. The primary outcome is sufentanil consumption at 24 hours postoperatively, the secondary outcomes are sufentanil consumption at 6 hours postoperatively, pain scores at 6, 24 and 48 hours postoperatively.ResultsCompared with group C, group S had significantly lower sufentanil consumption at 6 and 24 hours postoperatively (P= 0.049 and P0.05). The time to first lactation was not significantly different between the two groups (P>0.05). There was no significant difference in neonatal neurobehavioral scores between the two groups (P>0.05).ConclusionCompared to sufentanil PCA, adding low dose of esketamine significantly reduced the consumption of sufentanil while providing equally effective post cesarean analgesia in the patients with gestational diabetes.

BackgroundGastric cancer continues to be a significant global healthcare challenge, and its burden remains substantial. The development of gastric cancer (GC) is closely linked to chronic atrophic gastritis (CAG), yet there is a scarcity of research exploring the underlying mechanisms of CAG-induced carcinogenesis.MethodsIn this study, we conducted a comprehensive investigation into the oncogenes involved in CAG using both bulk transcriptome and single-cell transcriptome data. Our approach employed hdWGCNA to identify pathogenic genes specific to CAG, with non-atrophic gastritis (NAG) serving as the control group. Additionally, we compared CAG with GC, using normal gastric tissue as the control group in the single-cell transcriptome analysis. By intersecting the identified pathogenic genes, we pinpointed key network molecules through protein interaction network analysis. To further refine the gene selection, we applied LASSO, SVM-RFE, and RF techniques, which resulted in a set of cancer-related genes (CRGs) associated with CAG. To identify CRGs potentially linked to gastric cancer progression, we performed a univariate COX regression analysis on the gene set. Subsequently, we explored the relationship between CRGs and immune infiltration, drug sensitivity, and clinical characteristics in gastric cancer patients. We employed GSVA to investigate how CRGs regulated signaling pathways in gastric cancer cells, while an analysis of cell communication shed light on the impact of CRGs on signal transmission within the gastric cancer tumor microenvironment. Lastly, we analyzed changes in metabolic pathways throughout the progression of gastric cancer.ResultsUsing hdWGCNA, we have identified a total of 143 pathogenic genes that were shared by CAG and GC. To further investigate the underlying mechanisms, we conducted protein interaction network analysis and employed machine learning screening techniques. As a result, we have identified 15 oncogenes that are specifically associated with chronic atrophic gastritis. By performing ROC reanalysis and prognostic analysis, we have determined that GADD45B is the most significant gene involved in the carcinogenesis of CAG. Immunohistochemical staining and differential analysis have revealed that GADD45B expression was low in GC tissues while high in normal gastric tissues. Moreover, based on prognostic analysis, high expression of GADD45B has been correlated with poor prognosis in GC patients. Additionally, an analysis of immune infiltration has shown a relationship between GADD45B and the infiltration of various immune cells. By correlating GADD45B with clinical characteristics, we have found that it primarily affects the depth of invasion in GC. Through cell communication analysis, we have discovered that the CD99 signaling pathway network and the CDH signaling pathway network are the main communication pathways that significantly alter the microenvironment of gastric tissue during the development of chronic atrophic gastritis. Specifically, GADD45B-low GC cells were predominantly involved in the network communication of the CDH signaling pathway, while GADD45B-high GC cells played a crucial role in both signaling pathways. Furthermore, we have identified several metabolic pathways, including D-Glutamine and D-glutamate metabolism and N-Glycan biosynthesis, among others, that played important roles in the occurrence and progression of GC, in addition to the six other metabolic pathways. In summary, our study highlighted the discovery of 143 pathogenic genes shared by CAG and GC, with a specific focus on 15 oncogenes associated with CAG. We have identified GADD45B as the most important gene in the carcinogenesis of CAG, which exhibited differential expression in GC tissues compared to normal gastric tissues. Moreover, GADD45B expression was correlated with patient prognosis and is associated with immune cell infiltration. Our findings also emphasized the impact of the CD99 and CDH signaling pathway networks on the microenvironment of gastric tissue during the development of CAG. Additionally, we have identified key metabolic pathways involved in GC progression.ConclusionGADD45B, an oncogene implicated in chronic atrophic gastritis, played a critical role in GC development. Decreased expression of GADD45B was associated with the onset of GC. Moreover, GADD45B expression levels were closely tied to poor prognosis in GC patients, influencing the infiltration patterns of various cells within the tumor microenvironment, as well as impacting the metabolic pathways involved in GC progression.

ObjectivesAlthough studies have researched the mental effects of intergenerational care, little is known about the impact of transformations in caregiving intensity on depression. This study explores grand-parents’ depressive symptom outcomes in terms of changes over time in grandparental childcare, with considerations for subgroup differences.MethodUsing data from the 2015–2018 China Health and Retirement Longitudinal Study on grandparents aged 45 and older, we adopted generalized estimating equations to estimate the effects of seven category changes [(1) continued to provide high-intensity or (2) low-intensity care at both waves; (3) never provided care; (4) started caregiving; (5) ended caregiving; (6) provided less intensive care; and (7) provided more intensive care] over time in grandparental childcare on depressive symptoms among 17,701 grandparents with at least one grandchild, as well as how the impact varies by gender and urban/rural areas.ResultsGrandparents who decreased the intensity of care, stopped childcare, or offered continuous low-intensity care were associated with a lower level of depression compared with those providing no childcare. In addition, the benefit of continuous caregiving on mental health was especially noticeable in urban grandmothers.ConclusionProviding continuous low-intensity, decreased-intensity grandparenting and the cessation of caregiving were associated with a decreased level of depression for Chinese grandparents; however, there were complex interactions at play. Policies aimed at supporting grandparenting should consider caregiving intensity transitions relevant to gender and urban/rural residence.

ObjectiveThe aim of this study was to examine the factors influencing the prognosis of patients diagnosed with acute basilar artery occlusion (BAO) who receive endovascular treatment. Our particular emphasis was on the predictive implications of the time window for treatment (from symptom onset to femoral artery puncture) and preoperative symptoms for prognosis.MethodsA retrospective analysis of data collected from 51 BAO patients who received endovascular treatment at the Neurosurgery Department of Jinhua Central Hospital from April 2018 to October 2021 was undertaken. The data included immediate post-interventional recanalization rates and the 90-day clinical prognoses of the patients. We used the Modified Rankin Scale (mRs) to categorize patients into two prognosis groups: a favorable prognosis group (mRs score ≤2) and an unfavorable prognosis group (mRs score >2). Preoperative symptoms were gauged using the Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores. A logistic regression analysis was conducted to identify risk factors affecting the prognosis of BAO patients following endovascular treatment.ResultsThe procedure resulted in complete recanalization in all patients (100%). However, four patients (7.8%) passed away during the postoperative hospitalization period. The remaining 47 patients were followed up for 3 months. It was found that 15 patients (31.91%) had a favorable prognosis, while 32 (68.09%) had an unfavorable prognosis. It was generally observed that patients with an unfavorable prognosis had notably higher preoperative GCS and NIHSS scores (p < 0.05). Logistic regression analysis revealed that preoperative symptom severity, as indicated by NIHSS score, and treatment time window were significant prognostic risk factors for patients undergoing endovascular treatment for BAO (p < 0.05).ConclusionEndovascular intervention for BAO appears to be safe and effective, with greater likelihood of a favorable prognosis in patients treated within ≤6 h. The chances of favorable prognosis could potentially be linked to the severity of the patient's preoperative symptoms.

ObjectiveSeveral studies have demonstrated that anti-carbamylation protein antibodies (Anti-CarPA) are persistent in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSC), primary Sjögren’s syndrome (pSS), and interstitial lung disease associated with RA (RA-ILD). However, the relationship between anti-CarPA and other rheumatic diseases (RDs) and non-RA-ILD is not known till now. This study sought to examine the presence of anti-CarPA in Chinese Han patients with RDs and its clinical significance.MethodsThe study included 90 healthy controls (HCs) and 300 patients with RDs, including RA, SLE, polymyositis/dermatomyositis (PM/DM), pSS, SSC, spondyloarthritis (SpA), anti-neutrophil cytoplasmic autoantibodies associated with vasculitis (AAV), undifferentiated connective tissue disease (UCTD), and Behcet’s disease (BD). Antibodies against carbamylated human serum albumin were detected using commercial enzyme-linked immunosorbent assay kits. Correlations between clinical and laboratory parameters were analyzed.ResultSerum levels of anti-CarPA in RA (34.43 ± 33.34 ng/ml), SLE (21.12 ± 22.23 ng/ml), pSS (16.32 ± 13.54 ng/ml), PM/DM (30.85 ± 17.34 ng/ml), SSC (23.53 ± 10.70 ng/ml), and UCTD (28.35 ± 21.91 ng/ml) were higher than those of anti-CarPA in the HCs (7.30 ± 5.05 ng/ml). The concentration of serum anti-CarPA was higher in patients with rheumatic disease-related interstitial lung disease (RD-ILD), especially RA-ILD, PM/DM-ILD, and pSS-ILD. Patients with RD-ILD who tested positive for anti-CarPA were more likely to have a more severe radiographic classification (grades II, p = 0.045; grades III, p = 0.003). Binary logistic regression analysis suggested that anti-CarPA had an association with ILD in RA (p = 0.033), PM/DM (p = 0.039), and pSS (p = 0.048). Based on receiver operating characteristics (ROC) analysis, anti-CarPA cutoffs best discriminated ILD in RA (>32.59 ng/ml, p = 0.050), PM/DM (>23.46 ng/ml, p = 0.038), and pSS (>37.08 ng/ml, p = 0.040). Moreover, serum levels of anti-CarPA were correlated with antibodies against transcription intermediary factor 1 complex (anti-TIF1) (R = –0.28, p = 0.044), antibodies against glycyl-transfer ribonucleic acid synthetase (anti-EJ) (R = 0.30, p = 0.031), and antibodies against melanoma differentiation-associated gene 5 (anti-MDA5) (R = 0.35, p = 0.011).ConclusionSerum anti-CarPA could be detected in patients with RA, PM/DM, pSS, SSC, and UCTD among the Chinese Han population. And it may also assist in identifying ILD in patients with RA, PM/DM, and pSS, which emphasized attention to the lung involvement in anti-CarPA-positive patients.

Microbes are crucial to the quality formation of Sichuan South-road Dark Tea (SSDT) during pile-fermentation, but their mechanism of action has not yet been elucidated. Here, the glycoside hydrolase (GH) gene family and microbial function of Debaryomyces hansenii Y4 during solid-state fermentation were analyzed, and the results showed that many GH genes being distributed in comparatively abundant GH17, GH18, GH76, GH31, GH47, and GH2 were discovered in D. hansenii. They encoded beta-galactosidase, alpha-D-galactoside galactohydrolase, alpha-xylosidase, mannosidase, etc., and most of the GHs were located in the exocellular space and participated in the degradation of polysaccharides and oligosaccharides. D. hansenii Y4 could develop the mellow mouthfeel and “reddish brown” factors of SSDT via increasing the levels of water extracts, soluble sugars and amino acids but decreasing the tea polyphenols and caffeine levels, combined with altering the levels of thearubiins and brown index. It may facilitate the isomerization between epicatechin gallate and catechin gallate. Moreover, the expression levels of DEHA2G24860g (Beta-galactosidase gene) and DEHA2G08602g (Mannan endo-1,6-alpha-mannosidase DFG5 gene) were sharply up-regulated in fermentative anaphase, and they were significantly and negatively correlated with epicatechin content, especially, the expression of DEHA2G08602g was significantly and negatively correlated with catechin gallate level. It was hypothesized that D. hansenii Y4 is likely to be an important functional microbe targeting carbohydrate destruction and catechin transformation during SSDT pile-fermentation, with DEHA2G08602g as a key thermotolerant functional gene.