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Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.

Abstract Large language models (LLMs) are seen to have tremendous potential in advancing medical diagnosis recently, particularly in dermatological diagnosis, which is a very important task as skin and subcutaneous diseases rank high among the leading contributors to the global burden of nonfatal diseases. Here we present SkinGPT-4, which is an interactive dermatology diagnostic system based on multimodal large language models. We have aligned a pre-trained vision transformer with an LLM named Llama-2-13b-chat by collecting an extensive collection of skin disease images (comprising 52,929 publicly available and proprietary images) along with clinical concepts and doctors’ notes, and designing a two-step training strategy. We have quantitatively evaluated SkinGPT-4 on 150 real-life cases with board-certified dermatologists. With SkinGPT-4, users could upload their own skin photos for diagnosis, and the system could autonomously evaluate the images, identify the characteristics and categories of the skin conditions, perform in-depth analysis, and provide interactive treatment recommendations.

Abstract During early embryonic development, the transition from totipotency to pluripotency is a fundamental and critical process for proper development. However, the regulatory mechanisms governing this transition remain elusive. Here, we conducted a comprehensive genome-wide CRISPR/Cas9 screen to investigate the 2-cell-like cells (2CLCs) phenotype in mouse embryonic stem cells (mESCs). This effort led to the identification of ten regulators that play a pivotal role in determining cell fate during this transition. Notably, our study revealed Mdm2 as a significant negative regulator of 2CLCs, as perturbation of Mdm2 resulted in a higher proportion of 2CLCs. Mdm2 appears to influence cell fate through its impact on cell cycle progression and H3K27me3 epigenetic modifications. In summary, the results of our CRISPR/Cas9 screen have uncovered several genes with distinct functions in regulating totipotency and pluripotency at various levels, offering a valuable resource for potential targets in future molecular studies.

Objective: To improve the contents of various hypoglycemic components in natural mulberry leaves, different fermentation-promoting substances were added to mulberry leaf shoots during their fermentation by means of that drawn on the experience of traditional black tea fermentation process. Method: Based on the single factor experiments, orthogonal optimization test was carried out to determine the optimal addition amount using cellulase, pectinase and tea polyphenols as influencing factors, and the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves as comprehensive evaluation indicators. Results: Compared with natural fermentation, the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves fermented by additives were increased by 61.84%, 45.02% and 28.68%, when the addition amounts of cellulase, pectinase and tea polyphenols were 0.6%, 0.8% and 0.9%, respectively. And their contents were 115.12%, 80.19% and 54.81% higher than those in natural mulberry leaves, respectively. Conclusion: The contents of hypoglycemic components in natural mulberry leaves can be improved by adding substances that promote fermentation, which lays a foundation for its subsequent effective utilization in hypoglycemia.

Abstract The present study investigates the optimization of the steam gasification process for the conversion of palm oil waste into environmentally friendly energy, utilizing the catalytic properties of calcium oxide and coal bottom ash. The objective of our research is to investigate the enhancement of the conversion process by employing a machine-learning approach. Specifically, we utilize a support vector machine (SVM) to model and evaluate the impact of different operational parameters on the resulting gas mixture. One notable feature of this study involves the incorporation of an adaptive marine predator algorithm (AMPA) into the SVM framework, aiming to enhance the predicted precision and efficiency of the model. The primary focus of this study revolves around the development of an intelligent optimization framework that surpasses conventional machine learning techniques, hence providing a more dynamic and efficient strategy for process improvement. The SVM model’s performance, as assessed against experimental benchmarks, exhibits a notable degree of predictive accuracy and substantial concurrence with observed data. This increase in performance indicates that our methodology has the potential to make a significant contribution to the enhancement of renewable catalysts in gasification processes. The findings of this study could potentially have significant ramifications for the advancement of renewable energy production and the creation of intelligent systems in complicated industrial applications.

Abstract Background Chayote is a high economic crop in the Cucurbitaceae family, playing an important role in food production, disease treatment and the production of degradable materials in industries. Due to the harsh environment, such as high temperature, drought and frost, some chayote resources are gradually disappearing. It is crucial to collect, characterize, and conserve chayote resources. However, the genetic diversity of chayote resources in China has not been studied so far. Results In this study, we collected 35 individuals of chayote from 14 provinces in China. Subsequently, we found 363,156 SSR motifs from the chayote genome and designed 57 pairs of SSR primers for validation. Out of these, 48 primer pairs successfully amplified bands, with 42 of them showing polymorphism. These 42 primer pairs detected a total of 153 alleles, averaging 3.64 alleles per locus. The polymorphic information content ranged from 0.03 to 0.78, with an average value of 0.41, indicating a high level of polymorphism. Based on the analysis using STRUCTURE, PCoA, and UPGMA methods, the 35 chayote individuals were divided into two major clusters. Through further association analysis, 7 significantly associated SSR markers were identified, including four related to peel color and three related to spine. Conclusions These molecular markers will contribute to the analysis of genetic diversity and genetic breeding improvement of chayote in the future.

Abstract Infrared thermal imaging camera as a non-contact monitoring of the object to be measured is widely used in fire detection, driving assistance and so on. Although there are many related studies, there is a lack of research on the influence of fog or smoke on infrared imaging under different environmental temperatures. To address this shortcoming, The temperature of both the environment and the target in this experiment is controlled by PID technology. The smoke or fog environment is generated using a smoke cake or an ultrasonic fog machine. The temperature of the target was measured by infrared thermal imaging camera. It was observed that as the temperature of the environment increases, the measured temperature of the target also increases. However, the change in temperature is more pronounced in the fog environment compared to either the smoke environment or the normal environment. It has been found through research that environmental radiation causes temperature changes in fog droplets. Therefore, Infrared radiation is less affected in the smoke environment and more affected in the fog environment. Additionally, when the environmental temperature is close to the target's temperature, the infrared image becomes blurred.

Abstract Sclerotinia stem rot (SSR), caused by the necrotrophic fungus Sclerotinia sclerotiorum, is one of the most devastating diseases for several major oil-producing crops. Despite its impact, the genetic basis of SSR resistance in plants remains poorly understood. Here, through a genome-wide association study, we identify a key gene, BnaA07. MKK9, that encodes a mitogen-activated protein kinase kinase that confers SSR resistance in oilseed rape. Our functional analyses reveal that BnaA07.MKK9 interacts with BnaC03.MPK3 and BnaC03.MPK6 and phosphorylates them at the TEY activation motif, triggering a signaling cascade that initiates biosynthesis of ethylene, camalexin, and indole glucosinolates, and promotes accumulation of H2O2 and the hypersensitive response, ultimately conferring resistance. Furthermore, variations in the coding sequence of BnaA07.MKK9 alter its kinase activity and improve SSR resistance by ~30% in cultivars carrying the advantageous haplotype. These findings enhance our understanding of SSR resistance and may help engineer novel diversity for future breeding of oilseed rape.

Abstract Ulcerative colitis (UC) is characterized by an abnormal immune response, and the pathogenesis lacks clear understanding. The cGAS-STING pathway is an innate immune signaling pathway that plays a significant role in various pathophysiological processes. However, the role of the cGAS-STING pathway in UC remains largely unclear. In this study, we obtained transcriptome sequencing data from multiple publicly available databases. cGAS-STING related genes were obtained through literature search, and differentially expressed genes (DEGs) were analyzed using R package limma. Hub genes were identified through protein–protein interaction (PPI) network analysis and module construction. The ConsensuClusterPlus package was utilized to identify molecular subtypes based on hub genes. The therapeutic response, immune microenvironment, and biological pathways of subtypes were further investigated. A total of 18 DEGs were found in UC patients. We further identified IFI16, MB21D1 (CGAS), TMEM173 (STING) and TBK1 as the hub genes. These genes are highly expressed in UC. IFI16 exhibited the highest diagnostic value and predictive value for response to anti-TNF therapy. The expression level of IFI16 was higher in non-responders to anti-TNF therapy. Furthermore, a cluster analysis based on genes related to the cGAS-STING pathway revealed that patients with higher gene expression exhibited elevated immune burden and inflammation levels. This study is a pioneering analysis of cGAS-STING pathway-related genes in UC. These findings provide new insights for the diagnosis of UC and the prediction of therapeutic response.

Abstract Objective This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina. Materials and methods We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion. Results A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 GyEQD2,10 (95% CI: 75.3–96.6 GyEQD2,10). Conclusions A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.

Abstract Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo −/− ) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo −/− Apoe −/− and Apoo −/− Ldlr −/− mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.

Abstract Background RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. Methods Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. Results As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. Conclusions This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

Phenotypic differences between diploid parents and their allotriploid offspring are common in aquaculture breeding. Some allotriploid populations exhibit rapid growth rates and increased body weight, which are significant for supporting fisheries development. Understanding the genetic mechanisms underlying these traits is crucial for implementing diverse breeding strategies to achieve high production in fish farming. Here, we collected the following fish species for our study: red crucian carp (Carassius auratus red var., 2nRR), common carp (Cyprinus carpio L., 2nCC), and two allotriploids (3nR2C and 3 nRC2). These allotriploids were obtained through backcrossing an allotetraploid of C. auratus red var. × C. carpio L. (4nR2C2, ♂) with C. auratus red var. and C. carpio L. (♀), respectively. These allotriploids demonstrated faster growth rates compared to their diploid inbred parents, contributing to the Chinese fisheries industry for several decades. We conducted a systematic comparison of mitochondrial DNA (mtDNA) copy numbers in the liver and muscle tissues of 2nRR, 2nCC, 3nR2C, and 3 nRC2 under different seasons. When entering winter (low water temperature: 13 °C), the triploid fish (3nR2C and 3 nRC2) exhibited lower mtDNA copy numbers in the muscle, indicating a reduction in individual activity and energy expenditure to facilitate weight maintenance when food availability is limited. Furthermore, we analysed the expression levels of three nuclear-regulated mitochondrial genes (tfam, tfb1m, and tfb2m) and observed an imbalance of allelic expression in tfam and tfb1m in the two triploid fish. These findings enhance our understanding of the molecular regulatory mechanisms underlying growth trait differences among fish with different ploidy levels.

BackgroundPrematurity significantly impacts neonatal health worldwide, necessitating effective interventions to improve outcomes for these vulnerable infants. While breastfeeding has emerged as a cornerstone of preterm care, its precise impact on neurodevelopment remains a subject of ongoing inquiry and debate. This systematic review aims to investigate the existing evidence in this area.MethodsOn December 17, 2023, online databases including PubMed, The Cochrane Library, Embase, Web of Science, CNKI, VIP, CBM, and Wan Fang Data were searched. Comparisons were classified into several categories: never breastfeeding (Never-BF) versus exclusive breastfeeding, Never-BF versus any breastfeeding (Any-BF), predominant preterm formula (Pre-PTF) versus predominant breastfeeding (Pre-BF), and Pre-PTF versus predominant donor breast milk (Pre-DBM) groups. Randomized controlled trials and observational studies were analyzed separately through meta-analyses. Each study’s risk of bias was assessed, and the GRADE system was utilized to evaluate the certainty of the findings.ResultsSixteen studies met the inclusion criteria, comprising one RCT and 15 cohort studies. The key findings indicated that infants in the Any-BF groups demonstrated superior long-term cognitive scores compared to those in the Never-BF groups, particularly evident in infants assessed before 18 months in the Pre-BF groups versus Pre-PTF groups. A reduced risk of neurodevelopmental impairment was also observed in preterm infants in the Any-BF groups. Evidence regarding the effect of breastfeeding on motor development was inconclusive, except for potential motor improvement in extremely low birth weight infants in the Any-BF groups. Neither exclusive breastfeeding nor pre-DBM exhibited clear superiority over Pre-PTF in terms of neurodevelopmental outcomes for preterm infants. Caution is warranted due to potential publication bias impacting the assessment of breastfeeding’s impact on motor skills.ConclusionOur systematic review supports current recommendations for breastfeeding in preterm infants, emphasizing its positive effects on cognitive abilities and reduced risk of neurodevelopmental disorders. Further studies are needed to clarify if DHM provides neurodevelopmental benefits comparable to maternal milk, as current evidence does not sufficiently address this question. Additionally, future investigations should prioritize refining our understanding of the influence of breastfeeding on motor development in this vulnerable population.Systematic review registrationPROSPERO, identifier CRD42023492274, Available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023492274.

Abstract Cholangiocarcinoma (CCA) was identified as a malignant tumor with rising incidence and mortality rates, and the roles of long noncoding RNA (lncRNA) in CCA remained not entirely clear. In this study, LINC00511 had high expression in CCA, which was closely related to poor prognosis. Knockdown of LINC00511 significantly inhibited cell malignant biological behaviors. It also affected the stemness of CCA, evidenced by decreased SOX2 protein expression. Moreover, the study revealed the interaction of LINC00511, YTHDF2, and SOX2 in CCA. Specifically, LINC00511 facilitated the formation of a complex with YTHDF2 on SOX2 mRNA, which uniquely enhances the mRNA's stability through m6A methylation sites. This stabilization appears crucial for maintaining malignant behaviors in CCA cells. Additionally, LINC00511 modulated SOX2 expression via the PI3K/AKT signaling pathway. Meanwhile, SOX2 can also promote LINC00511 expression as an upstream transcription factor, thereby confirming a positive feedback loop formed by LINC00511, YTHDF2, and SOX2, which plays a significant role in the occurrence and development of CCA. Finally, the study successfully constructed two patient‐derived xenograft models, revealing the vital role of LINC00511 in CCA development. In summary, this research provides a comprehensive understanding of the role of LINC00511 in the pathogenesis of CCA.

AimTo evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension.MethodsThis observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups.ResultsIn total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of −4.63 mm Hg (95% CI, −6.51 to −2.74) at week 8, −6.69 mm Hg (95% CI, −8.54 to −4.85) at week 16, −7.81 mm Hg (95% CI, −9.57 to −6.04) at week 24 for SBP, and −1.83 mm Hg (95% CI, −3.21 to −0.45) at week 8, −2.57 mm Hg (95% CI, −3.97 to −1.17) at week 16, −2.89 mm Hg (95% CI, −4.24 to −1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21–1.72) at week 8, 1.90 (95% CI, 1.59–2.27) at week 16, and 2.24 (95% CI, 1.87–2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p-value >0.05.ConclusionThe HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI therapy.

Along with social development and lifestyle changes, the number of overweight and obese patients worldwide is rising annually. Obesity is a chronic metabolic disease with complex etiology. Dipeptidyl peptidase IV (DPP-IV) is a novel adipokine with significantly elevated expression in the visceral fat of obese patients. DPP-IV is a molecule that regulates metabolic homeostasis and inflammatory processes. Through its enzymatic activity, it plays a significant part in achieving hypoglycemic and weight loss effects through various pathways. DPP-IV and DPP-IV inhibitors also have pleiotropic effects in modulating obesity-related diseases by reducing obesity-related inflammation, ameliorating inflammatory bowel disease (IBD), improving hepatic steatosis and lowering cardiovascular risk, and even decreasing the risk of novel coronavirus disease-19 (COVID-19). This paper reviews the mechanisms of action based on DPP-IV targets in obesity and metabolic homeostasis, as well as their active role in the treatment of chronic diseases associated with obesity.

Drawing upon a comprehensive dataset encompassing Chinese publicly traded enterprises across the two-decade span from 2000 to 2020, this article analyzes the effects of external economic policy variations on the productivity of Chinese enterprises. The consequences show that when facing the aggravation of external variations in economic policy, enterprises prefer to enhance total factor productivity and labor productivity to reduce the risk caused by the expansion of external uncertainty. Moreover, the greater the degree of internationalization of an enterprise, the higher its vulnerability to variations in external economic policies. The mechanism test shows that for enterprises that only participate in domestic circulation, external economic policy fluctuations improve productivity by affecting the operating environment; however, when enterprises join in the dual circulation, the fluctuations will promote productivity by affecting the scale of enterprises’ overseas business instead. First published online 6 November 2024

With the increasing integration of renewable energy sources and the presence of numerous controllable loads such as electric vehicles and energy storage in the modern power system, higher nonlinearities and uncertainty both sources and loads are introduced. These factors pose challenges in achieving fast and accurate emergency frequency control. Therefore, this paper addresses the issue of dual source-load uncertainties in power system and presents an optimization strategy based on the Soft Actor Critic (SAC) algorithm that involves the participation of controllable loads in emergency frequency control. Firstly, the spatio-temporal uncertainties of wind farm power output on power supply side and power demand on the load side are described using Weibull and normal probability distributions, respectively. Secondly, an improved Markov Decision Process (MDP) model for emergency frequency control is established, which considers the characteristics of the dual source-load uncertainties. Finally, an optimization of the SAC algorithm is conducted based on Deep Reinforcement Learning (DRL), aiming to achieve rapid system frequency recovery and minimize the cost of removing controllable loads. The presented approach in the paper enhances the emergency frequency control strategy for uncertain power systems and effectively addresses the issue of source-load uncertainty compounded by fault power shortages.

Objective: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. Methods: Robust rank aggregation (RRA) method was used to integrate NAFLD-related gene expression datasets. For fatty liver study, adeno-associated virus (AAV) delivery and genetic knockout mice were used to create IGFBP2 (Insulin-like growth factor binding protein 2) gain- or loss-of function models. Western blot, Co-immunoprecipitation (Co-IP), immunofluorescent (IF) staining, luciferase assay, molecular docking simulation were performed to reveal the IGFBP2-EGFR-STAT3 axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. Results: By using RRA method, the present study identified IGFBP2 being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. Conclusions: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

As a biologically essential transition metal, copper is widely involved in various enzymatic reactions and crucial biological processes in the body. It plays an increasingly important role in maintaining normal cellular metabolism and supporting the growth and development of the human body. As a trace element, copper maintains the dynamic balance of its concentration in body fluids through active homeostatic mechanisms. Both excess and deficiency of copper ions can impair cell function, ultimately leading to cell damage and death. Cuproptosis is a novel form of cell death where copper ions cause cell death by directly binding to the lipoylated components of the citric acid cycle (CAC) in mitochondrial respiration and interfering with the levels of iron-sulfur cluster (Fe-S cluster) proteins, ultimately causing protein toxic stress. Its primary characteristics are Cu2+ concentration dependence and high expression in mitochondrial respiratory cells. Recent research has revealed that, compared to other forms of programmed cell death such as apoptosis, necrosis, and autophagy, cuproptosis has unique morphological and biochemical features. Cuproptosis is associated with the occurrence and development of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. This article focuses on a review of the relevance of cuproptosis in gastric cancer (GC).

ObjectiveThis study investigates the significance of systemic pan-immune inflammation value (PIV) prior to concurrent chemoradiotherapy (CCRT) in predicting the therapeutic efficacy as well as prognosis of patients with locally advanced cervical squamous cell carcinoma.MethodsA retrospective analysis was conducted on the clinical data of 847 patients with locally advanced cervical cancer (LACC) treated at the Second Hospital of Jilin University between 2016 and 2020. All patients underwent radical CCRT, including platinum-based sensitizing chemotherapy. The PIV was measured as given by: (platelet count × neutrophil count × monocyte count)/lymphocyte count. Logistic regression analysis was utilized to study the effect of PIV on therapeutic response in LACC patients and Kaplan–Meier survival together with Cox proportional hazard model to assess its impact on prognosis.ResultsWith the therapeutic effect as the endpoint, the optimal cutoff of PIV (356.0099) was signified via the receiver operating characteristics curve, and patients were grouped and compared based on this value. PIV was determined as an independent predictor of the therapeutic effect in CCRT for LACC (hazard ratio (HR) 1.696, 95% confidence interval (CI) 1.111–2.590). PIV was also an independent predictor of overall survival (OS) (HR 0.540, 95% CI 0.409–0.713, p

Background Axial symptoms (AS) represent one of the primary complications after cervical spondylotic myelopathy (CSM) surgery. Traditional Chinese Medicine (TCM), as a complementary and alternative therapy, is widely used in the treatment of postoperative AS in CSM. However, it lacks standardised treatment protocols, uniform therapeutic criteria, assessment methods and a sufficiently in-depth understanding of its mechanisms of action. These shortcomings impact the credibility of TCM treatment in clinical practice.Methods and analysis We will conduct comprehensive searches, both manual and electronic, on literature published up to 31 July 2024, and database searches will commence after the publication of this agreement, with an estimated commencement date of 1 October 2024 and the end date of 31 March 2025, without language restrictions. Key databases such as MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, WHO International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wanfang Database will be explored. In addition, we will include resources such as library journals and conference abstracts. After identifying and screening all randomised controlled trials focused on TCM for postoperative AS of CSM, the two investigators will conduct a meta-analysis of the included studies. The results will be summarised as the risk ratio for binary data and the standardised or weighted average difference for continuous data.Ethics and dissemination Ethical approval is not required since this review does not involve individual patient data. The review’s findings will provide clinicians with evidence on using TCM treatment for AS post-CSM surgery, disseminated through peer-reviewed publications or conferences.PROSPERO registration number CRD42024505160.

Implant surface designs have advanced to address challenges in oral rehabilitation for healthy and compromised bone. Several studies have analyzed the effects of altering material surfaces on osteogenic differentiation. However, the crucial role of osteoclasts in osseointegration has often been overlooked. Overactive osteoclasts can compromise implant stability. In this study, we employed a silanization method to alter pure titanium to produce a surface loaded with the antimicrobial peptide GL13K that enhanced biocompatibility. Pure titanium (Ti), silanization-modified titanium, and GL13K-modified titanium (GL13K-Ti) were co-cultured with macrophages. Our findings indicated that GL13K-Ti partially inhibited osteoclastogenesis and expression of osteoclast-related genes and proteins by limiting the formation of the actin ring, an important structure for osteoclast bone resorption. Our subsequent experiments confirmed the epigenetic role in regulating this process. GL13K-Ti was found to impact the degree of methylation modifications of H3K27 in the NFATc1 promoter region following RANKL-induced osteoclastic differentiation. In conclusion, our study unveils the potential mechanism of methylation modifications, a type of epigenetic regulatory modality, on osteoclastogenesis and activity on the surface of a material. This presents novel concepts and ideas for further broadening the clinical indications of oral implants and targeting the design of implant surfaces.

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is a highly prevalent liver disease globally, with a significant risk of progressing to cirrhosis and even liver cancer. Efferocytosis, a process implicated in a broad spectrum of chronic inflammatory disorders, has been reported to be associated with the pathogenesis of MASH; however, its precise role remains obscure. Thus, we aimed to identify and validate efferocytosis linked signatures for detection of MASH.MethodsWe retrieved gene expression patterns of MASH from the GEO database and then focused on assessing the differential expression of efferocytosis-related genes (EFRGs) between MASH and control groups. This analysis was followed by a series of in-depth investigations, including protein–protein interaction (PPI), correlation analysis, and functional enrichment analysis, to uncover the molecular interactions and pathways at play. To screen for biomarkers for diagnosis, we applied machine learning algorithm to identify hub genes and constructed a clinical predictive model. Additionally, we conducted immune infiltration and single-cell transcriptome analyses in both MASH and control samples, providing insights into the immune cell landscape and cellular heterogeneity in these conditions.ResultsThis research pinpointed 39 genes exhibiting a robust correlation with efferocytosis in MASH. Among these, five potential diagnostic biomarkers—TREM2, TIMD4, STAB1, C1QC, and DYNLT1—were screened using two distinct machine learning models. Subsequent external validation and animal experimentation validated the upregulation of TREM2 and downregulation of TIMD4 in MASH samples. Notably, both TREM2 and TIMD4 demonstrated area under the curve (AUC) values exceeding 0.9, underscoring their significant potential in facilitating the diagnosis of MASH.ConclusionOur study comprehensively elucidated the relationship between MASH and efferocytosis, constructing a favorable diagnostic model. Furthermore, we identified potential therapeutic targets for MASH treatment and offered novel insights into unraveling the underlying mechanisms of this disease.

Heated cigarettes are becoming trendy due to their advantage of not burning the tobacco material and thus reducing the amount of harmful ingredients released, while being able to leave the nicotine and tar content of the smoke untouched. However, the high temperature of the smoke as it enters the human mouth can affect the user experience. Therefore, the development of adsorption cooling materials for use in heated cigarettes is gradually becoming a hot topic. In this work, an adsorption cooling material based on embossed rod powder was prepared. It was found that compared with the commercial Yoga cooling material, the embossed rod powder based adsorption cooling material was able to reduce the maximum smoke temperature to 45.16 °C. In addition, it reduced the adsorption of nicotine by the cooling material, and increased the glycerol and nicotine content in the cooled smoke, which effectively promoted the taste of the smoke. Furthermore, the molecular simulation results found that the higher specific surface area and rich microscopic pore structure could increase the heat conduction area of the high-temperature flue gas, which enhanced the heat transfer effect of the flue gas. Finally, the periodic characteristic velocity pulsation destroyed the boundary layer formed by the fluid in the wall region, which increased the convective heat transfer effect between the fluid and the particles. The optimum sample 03 had the largest specific surface area and the lowest crystallinity, and thus had the best cooling effect. This work could provide some reference significance for the development of cooling materials for heating cigarettes.

IntroductionThis study explores the effectiveness of music therapy in repairing psychological trauma in bereaved families, aiming to provide a comprehensive understanding of its potential therapeutic impact. It begins with an analysis of the current situation faced by bereaved families, identifying the psychological challenges they experience.MethodsThe research design included the recruitment of participants from bereaved families, who were then divided into an experimental group and a control group. An optimized Long Short-Term Memory (LSTM) network model was constructed to analyze music therapy data, tailored specifically to capture the nuances of this therapeutic process. The experimental procedure detailed the specific operations involved in the music therapy sessions and established a clear comparison framework between the two groups.ResultsThe performance of the proposed LSTM model demonstrated high accuracy (0.85), precision (0.86), recall (0.84), and F1-score (0.85), indicating its effectiveness in predicting treatment outcomes. When compared to the Self-Reporting Inventory-90 (SCL-90) scale, the model captured the trend of treatment effects with a high level of accuracy and reliability. Notably, participants numbered 2, 6, and 8 in the experimental group showed substantial improvement rates of 67.21%, 71.45%, and 75.67%, respectively, in their psychological health issues.DiscussionThe comparative analysis between the experimental and control groups confirmed that the music therapy approach, as guided by the proposed LSTM model, led to a more significant improvement in psychological health issues for bereaved families. This suggests that the model offers a promising avenue for enhancing the effectiveness of music therapy in this context.

Object: This study aims to evaluate the value of super resolution (SR) technology in augmenting the quality of digestive endoscopic images. Methods: In the retrospective study, we employed two advanced SR models, i.e., SwimIR and ESRGAN. Two discrete datasets were utilized, with training conducted using the dataset of the First Affiliated Hospital of Soochow University (12,212 high-resolution images) and evaluation conducted using the HyperKvasir dataset (2,566 low-resolution images). Furthermore, an assessment of the impact of enhanced low-resolution images was conducted using a 5-point Likert scale from the perspectives of endoscopists. Finally, two endoscopic image classification tasks were employed to evaluate the effect of SR technology on computer vision (CV). Results: SwinIR demonstrated superior performance, which achieved a PSNR of 32.60, an SSIM of 0.90, and a VIF of 0.47 in test set. 90 % of endoscopists supported that SR preprocessing moderately ameliorated the readability of endoscopic images. For CV, enhanced images bolstered the performance of convolutional neural networks, whether in the classification task of Barrett's esophagus (improved F1-score: 0.04) or Mayo Endoscopy Score (improved F1-score: 0.04). Conclusions: SR technology demonstrates the capacity to produce high-resolution endoscopic images. The approach enhanced clinical readability and CV models’ performance of low-resolution endoscopic images.

The emergence of metacommunity theory has provided a framework for studying the spatial structure of biological communities. To unravel the underlying driving mechanisms of macroinvertebrate metacommunity structure and diversity, this paper evaluates macroinvertebrate data from a water body in eastern China using variance decomposition and stratified partitioning. The results suggest that spatial processes dominate macroinvertebrate metacommunity structure, while the combined effects of spatial processes, aquatic environment, and geoclimatic factors also explain part of the macroinvertebrate community structure. Spatial processes, aquatic environment, and geoclimatic factors significantly influenced macroinvertebrate alpha diversity and indirectly influenced beta diversity through alpha diversity. Therefore, the significant effects of spatial processes and geoclimatic variables cannot be ignored in biological assessments, especially biodiversity assessments. Our findings elucidate the metacommunity dynamics in the region and provide crucial information for conservation planning in riverine ecosystems.

BackgroundThyroid disease (TD) is a prominent endocrine disorder that raises global health concerns; however, its comorbidity patterns remain unclear. ObjectiveThis study aims to apply a network-based method to comprehensively analyze the comorbidity patterns of TD using large-scale real-world health data. MethodsIn this retrospective observational study, we extracted the comorbidities of adult patients with TD from both private and public data sets. All comorbidities were identified using ICD-10 (International Classification of Diseases, 10th Revision) codes at the 3-digit level, and those with a prevalence greater than 2% were analyzed. Patients were categorized into several subgroups based on sex, age, and disease type. A phenotypic comorbidity network (PCN) was constructed, where comorbidities served as nodes and their significant correlations were represented as edges, encompassing all patients with TD and various subgroups. The associations and differences in comorbidities within the PCN of each subgroup were analyzed and compared. The PageRank algorithm was used to identify key comorbidities. ResultsThe final cohorts included 18,311 and 50,242 patients with TD in the private and public data sets, respectively. Patients with TD demonstrated complex comorbidity patterns, with coexistence relationships differing by sex, age, and type of TD. The number of comorbidities increased with age. The most prevalent TDs were nontoxic goiter, hypothyroidism, hyperthyroidism, and thyroid cancer, while hypertension, diabetes, and lipoprotein metabolism disorders had the highest prevalence and PageRank values among comorbidities. Males and patients with benign TD exhibited a greater number of comorbidities, increased disease diversity, and stronger comorbidity associations compared with females and patients with thyroid cancer. ConclusionsPatients with TD exhibited complex comorbidity patterns, particularly with cardiocerebrovascular diseases and diabetes. The associations among comorbidities varied across different TD subgroups. This study aims to enhance the understanding of comorbidity patterns in patients with TD and improve the integrated management of these individuals.

Background: Parkinson's disease (PD) is a common central neurodegenerative disease in middle-aged and elderly people. The progressive degeneration and death of dopaminergic neurons leads to insufficient dopamine (DA) neurotransmitters. Acupuncture and moxibustion can alleviate the aging of neurons. Therefore, studying the neuroprotective effects of electroacupuncture (EA) in PD mice is particularly important. Methods: Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was used to establish a PD mouse model, and lipopolysaccharide (LPS) was used to induce microglia polarization. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Nissl staining and immunohistochemistry were used to detect neuronal apoptosis and injury, α-syn expression and microglial accumulation in PD mice. In addition, the levels of inflammatory factors were determined using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the Ca2+ content. The fluorescein isothiocyanate (FITC) labeling method was used to assess glucose uptake. A reagent kit was used to detect glucose and lactate levels. Results: MPTP induced the selective loss of DA neurons in the SN of mice, altered Ca2+ homeostasis, and induced an inflammatory response. In addition, maintaining Ca2+ homeostasis depends on the activity of transient receptor potential channel 1 (TRPC1). EA therapy promotes TRPC1 expression, which has a negative regulatory effect on sodium–glucose cotransporter 1 (SGLT1). Under the action of EA, TRPC1 protein expression increased, Ca2+ concentrations increased, and the effect of SGLT1 was inhibited, thereby facilitating glucose metabolism, blocking the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, restraining M1 polarization of microglia, and alleviating the PD process. Conclusion: EA promotes TRPC1/Ca2+ pathway activation, inhibits SGLT1-mediated regulation of glucose metabolism and PI3K/AKT pathway activation, inhibits microglial M1 polarization, and alleviates PD.

The spatial gradients of protein and starch in wheat grains affected the grain milling characteristics and flour utilization. The increase in compound heat stress and drought stress (HDS) due to global climate change threatens wheat grain yield and quality parameters, but the impacts of extreme climate events on the gradients of protein and starch in wheat grains remain unclear. In this study, two-year, environment-controlled experiments with four heat stress levels (17/27, 21/31, 25/35, and 29/39°C) and three drought stress levels (30 %, 55 %, and 75 % field capacity) were conducted to investigate the effects of HDS on the gradients of protein and starch concentrations within the five grain layers. The results showed that HDS resulted in significantly greater protein concentrations, while resulting in lower starch concentrations in the wheat grain layers. Among the five layers, the endosperm layers exhibited the greatest increase in protein concentration under HDS, but the starch concentration under HDS decreased in the order of husk > aleurone > endosperm layer. HDS unevenly altered the protein and starch concentrations of the five grain layers. There was significant linear relationship between relative protein and starch concentration with accumulated heat degree days (AHDD). With a 1°C·d increase in AHDD, the protein concentration in the five grain layers increased by 1.17–2.19 %, while the starch concentration decreased by 0.62–0.90 %, depending on the drought stress levels. A significant linear relationship was also observed between the relative protein and starch concentrations and evapotranspiration (ET). A 1 mm increase in ET led to a protein concentration decrease of 0.58–0.76 % in P1-P5, with a corresponding starch concentration increase of 0.28–0.46 %, depending on cultivar and treatment stages. Our results indicate that HDS significantly impacts the grain quality parameters for the flour milling process and human diet and will provide important insights into adapting wheat quality to climate change.

Climate anomalies such as drought may lead to cascading effects on river ecosystems, ultimately resulting in the change of aquatic biocenosis. Here, we investigated functional assemblies of fish communities at three sites below the Gezhouba Dam of the middle Yangtze River in China before and during a drought event from 2021 to 2022. As the drought proceeded, the richness of the fish functional groups decreased, and the abundance of demersal/invertivore species increased. These changes might indicate adaptive responses of fish communities to the reduction in water volume and shrinkage in habitat areas. The shifts in functional structure also caused fish communities to become more similar during the drought. The null model based on functional traits showed a distance effect of the fish community assembly rules. The communities close to the dam were structured more stochastically under drought stress, which may be attributed to the impact of ecological operation by cascade hydro-junctions. In contrast, the communities far away from the dam were structured by environmental filtering. Our results support the hypothesis that the natural hydrological regime is the main force driving the spatiotemporal dynamic of riverine fish assemblages, and the drought stress on fish communities may need more attention to cope with future biodiversity loss under global climate changes.

Background and objective: The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Methods: The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function. Conclusions: The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.

Abstract 2D van der Waals (vdW) magnets have recently emerged as a promising material system for spintronic device innovations due to their intriguing phenomena in the reduced dimension and simple integration of magnetic heterostructures without the restriction of lattice matching. However, it is still challenging to realize Curie temperature far above room temperature and controllable magnetic anisotropy for spintronics application in 2D vdW magnetic materials. In this work, the pressure‐tuned dome‐like ferromagnetic‐paramagnetic phase diagram in an iron‐based 2D layered ferromagnet Fe3GaTe2 is reported. Continuously tunable magnetic anisotropy from out‐of‐plane to in‐plane direction is achieved via the application of pressure. Such behavior is attributed to the competition between intralayer and interlayer exchange interactions and enhanced DOS near the Fermi level. The study presents the prominent properties of pressure‐engineered 2D ferromagnetic materials, which can be used in the next‐generation spintronic devices.

Abstract Lysine lactylation (Kla) plays a vital role in several physiological processes. However, the cancer‐specific modulation of Kla in gastrointestinal (GI) tumors requires systematic elucidation. Here, global lactylome profiling of cancerous and adjacent tissues is conducted from 40 patients with GI cancer and identified 11698 Kla sites. Lactylome integration revealed that Kla affects proteins involved in hallmark cancer processes, including epigenetic rewiring, metabolic perturbations, and genome instability. Moreover, the study revealed pan‐cancer patterns of Kla alterations, among which 37 Kla sites are consistently upregulated in all four GI cancers and are involved in gene regulation. It is further verified that lactylation of CBX3 at K10 mediates its interaction of CBX3 with the epigenetic marker H3K9me3 and facilitates GI cancer progression. Overall, this study provides an invaluable resource for understanding the lactylome landscape in GI cancers, which may provide new paths for drug discovery for these devastating diseases.

BackgroundAn adrenal collision tumor (ACT) denotes the presence of distinct tumors with diverse behavioral, genetic, and histological features independently co-existing within the adrenal tissue without intermingling, and occurrences of such cases are infrequent. The concurrent occurrence of adrenal schwannoma and adrenal ganglioneuroma is exceedingly rare, and the diagnosis of these ACTs has been notably challenging due to their atypical clinical manifestations and imaging characteristics.Case summaryA 37-year-old man presented to the hospital 3 weeks after a computed tomography (CT) examination that revealed a left adrenal mass. Physical examination findings were unremarkable. Both CT and magnetic resonance imaging scans indicated the presence of a left adrenal mass. Plasma cortisol, adrenocorticotropic hormone, and renin–angiotensin–aldosterone system tests yielded normal results. Preoperative imaging confirmed the diagnosis of left adrenal pheochromocytoma. After thorough surgical preparation, a laparoscopic partial left adrenalectomy was performed. Subsequent postoperative pathological analysis identified adrenal schwannoma in conjunction with adrenal ganglioneuroma. The patient recovered well and was discharged on postoperative day 4. A routine urology clinic visit was included in his postoperative care plan. During follow-up assessments, CT scans of the left adrenal gland revealed no abnormalities.ConclusionAdrenal schwannoma combined with ganglioneuroma represents an exceptionally rare collision tumor characterized by the absence of typical clinical or imaging features, leading to potential misdiagnosis. Adrenal incidentalomas present as multifaceted conditions, and this case serves to heighten awareness of their intricate nature. Due to the challenges in preoperative differentiation of various adrenal mass types, postoperative pathological analysis is imperative for guiding the subsequent treatment course for the patient.

BackgroundKidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair.MethodsDuring the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-β and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels.ResultsOur analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid β precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-β triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo.ConclusionOur study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.

IntroductionWith the growing interest in the psychological basis of language learning, this study aims to validate the Chinese version of the Language Mindset Inventory (LMI) among Chinese university students.MethodsA sample of 476 students from various universities in mainland China was used. The translation process followed the forward-backward method. Confirmatory factor analyses (CFAs) were conducted to evaluate the factor structure. The internal consistency of the LMI was assessed using Cronbach's alpha, and convergent validity was examined through correlations with established mindset measures.ResultsCompared with the one-factor model, the two-factor model which distinguishes between fixed and growth mindsets, showed an acceptable and better fit index. The overall Cronbach's alpha for the full scale was 0.954, with 0.929 for the fixed mindset dimension and 0.903 for the growth mindset dimension. AVE values for the fixed and growth dimensions were 0.597 and 0.510, respectively. Correlations showed that the growth mindset dimension was significantly positively associated with the 8-Item Growth Mindset Scale (r = 0.186, p < 0.01) and the Mindset Scale for Learning English (r = 0.149, p < 0.01), while the fixed mindset dimension was negatively associated with both scales (r = −0.228 and r = −0.169, p < 0.01).DiscussionThis study confirms the reliability and validity of the Chinese version of the LMI, making it a relevant tool for assessing language learning mindsets among Chinese university students. The findings support the integration of LMI into educational strategies to promote resilience and adaptability, enhancing language education outcomes.

Since time immortal, people have used the well-known Chinese Chaenomeles fruit Xuan-Mugua for both traditional medicine and nourishment. With an aim to explore the digestive and antioxidant properties of the phenolics, Xuan-Mugua peel and pulp were extracted, digested and analyzed in vitro. Our results indicated that the total phenolics content (TPC), total flavonoids content (TFC) and the antioxidant activity of the peel were 3.24–8.89 times higher than that of pulp. The contents and activity of the peel and pulp consistently dropped in the sequence of oral, gastric, and small intestine digestions, from 22.78 % to 52.16 %. With a level of 1.590 ± 0.060 and 0.395 ± 0.015 mg g−1 dried weight in the peel and pulp, respectively, chlorogenic acid was the primary phenolic ingredient in Xuan-Mugua, with a promising recovery (81.39–82.23 %) during the digestion. According to these results, Xuan-Mugua exhibited an appreciable level of phenolic content and antioxidant activity during digestion, making it a suitable ingredient for use in functional foods.

Background In recent years, the incidence of spinal metastasis (SM) has been increasing steadily. In response to this serious public health problem, researchers have made progress by using the integration of traditional Chinese and Western medicine. However, considerable heterogeneity in the definition and measurement of outcomes across clinical research studies, along with the lack of uniform measurement standards for study data, makes it difficult for researchers to compare different treatments. Therefore, it is crucial to accurately evaluate clinical research on the integration of traditional Chinese and Western medicine for SM.Methods This study protocol outlines a comprehensive research programme based on the Core Outcome Set Standards Protocol Items. The study consists of four phases: a literature review, semistructured interviews, a two-round modified Delphi survey, a consensus meeting. Phase 1 involves a comprehensive literature review to extract outcomes used in current clinical studies of integrated traditional Chinese and Western medicine or Western medicine for the treatment of SM. A semistructured interview format will be used to survey patients and caregivers in phase 2 to collect suggestions from the patient perspective. Phase 3 involves a two-round modified Delphi survey to complete a prioritisation evaluation of outcomes to generate a candidate list for core outcome set (COS). Finally, phase 4 involves a face-to-face consensus meeting to review and establish the COS.Ethics and dissemination Conducted in response to the current dilemma of SM, the study was endorsed by the Spine Oncology Group of the Orthopaedic Surgeons Branch of the Chinese Physicians’ Association. It will be developed and reported through a rigorous process, with the results of the study to be published in a peer-reviewed journal.Registration: COMET Registry: COMET 2938; https://www.comet-initiative.org/Studies/Details/2938.

Background: RNA modifications represent a novel category of biological molecule alterations, characterized by three primary classes of proteins: writers, erasers, and readers. Numerous studies indicate that the dysregulation of these RNA modifications is linked to cancer development and may offer new therapeutic avenues for treatment. In our research, we focused on eight specific genes associated with RNA modifications (RMRGs) to comprehensively analyze their distinct functions in gastric cancer (GC). Furthermore, we aimed to elucidate the roles of RMRGs concerning clinicopathological characteristics, tumor microenvironment, and patient prognosis. Methods: In this study, we examined the expression and mutations of RMRGs in gastric cancer (GC) using data from TCGA-STAD (The Cancer Genome Atlas; Stomach adenocarcinoma) and the gene expression omnibus (GSE66229). We identified two subtypes of RMRGs and three gene clusters through consensus clustering analysis, assessing their differences in prognosis and immune cell infiltration patterns. Subsequently, we developed an RMRGs score to evaluate GC prognosis and highlight general immune features within the tumor microenvironment (TME). Lastly, we focused on MAMDC2 to validate its expression in GC and explore the effects of a MAMDC2 inhibitor on GC tumor cells. Results: We discovered 94 differentially expressed RMRGs common to both the TCGA-STAD and GEO datasets. Notable differences in prognosis and immune cell infiltration were observed between the two RMRGs subtypes and three gene clusters. The RMRGs score emerged as an independent prognostic factor related to the tumor microenvironment (TME) characteristics in gastric cancer (GC). Reducing MAMDC2 levels enhanced cell migration and invasion while decreasing proliferation in vitro. Conclusions: In conclusion, this study comprehensively analyzed the role of RMRGs on GC. Our study firstly proposed RMRGs score and demonstrated its potential to be biomarkers for prognosis and immune characteristics. Consequently, RMRGs score is of great clinical significance and can be utilized to develop individualized.

The article Study on Dynamic Response Characteristics of Offshore Floating Wind Turbine Pitch System has been retracted at the request of EAI's Research Integrity Committee on the grounds of plagiarism.

IntroductionThis study investigates the experiences of leading Chinese companies in environmental conservation under varying extreme climate conditions, focusing on the role of artificial intelligence (AI) and governmental assistance.MethodsA survey was conducted involving 200 participants to assess recognition and endorsement of AI’s role in environmental protection and to explore the adoption of AI technologies by firms for enhancing environmental management practices.ResultsThe survey revealed widespread recognition of Tencent’s green initiatives and strong support for AI’s role in environmental protection. Many firms are considering adopting AI technologies to optimize energy management, deploy intelligent HVAC systems, and improve the operations of data centers and smart lighting systems.DiscussionThe findings highlight a strong belief in AI’s potential to advance environmental protection efforts, with a call for increased governmental support to foster this development. The study underscores the importance of a partnership between businesses and governments to leverage AI for environmental sustainability, contributing significantly to conservation efforts.

For receiving-end power systems with multi-infeed HVDCs and large-scale renewable energy generation, the challenges of weak reactive power support and limited anti-interference capacity pose a threat to the power system voltage stability. To enhance the voltage stability under large disturbances, this paper proposes a data-driven method for coordinated emergency control strategy against voltage instability in multi-infeed hybrid AC/DC systems based on the squeeze and excitation (SE) module and convolutional neural network (CNN). Firstly, the SE module and CNN are integrated to intuitively capture correlations among various feature channels and extract key features related to voltage stability levels. Secondly, a voltage stability evaluation method is proposed based on the SE-CNN model, utilizing a dual channel structure to unveil the quantitative relationship between key response characteristics and voltage stability margin. Finally, regarding the control measures containing load shedding and DC modulation, the emergency control sensitivity index is proposed to assess the stability margin improvement effect of various control objects, and the optimal emergency control strategy is formulated to coordinate multiple voltage stability emergency control measures. Case studies were conducted on a typical China local region receiving-end power grid test system with voltage instability problems, and the simulation results verified the effectiveness of the proposed method. © 2017 Elsevier Inc. All rights reserved.

Regular recreational activities in urban park green spaces are beneficial to the physical and mental health of residents. The supply capacity of, the residents’ demand for, and the actual flow of recreational services must be distinguished and evaluated to promote the fair and reasonable layout of urban park green spaces. However, the unit dimensions of the supply, demand, and flow indexes of recreational services are often inconsistent or only in simple semiquantitative forms, which cannot be directly compared and analyzed. Thus, this study constructed a research framework of “potential supply/demand–pressure/accessibility–actual supply/demand” for recreational services, and the framework was tested using the central urban area of Xuchang as the experimental area. Results show the following: (1) A spatial mismatch exists in the supply–demand relationship of recreational services in the study area; this relationship is reflected in the semicircular layer structure from the central and southern areas to the periphery, changing from shortage of supply to oversupply. (2) The actual supply of recreational services is highly correlated with the number of people served, which can explain 50.38% of the change in the actual supply. (3) The potential demand for recreational services is highly correlated with the actual demand. It can explain 78.96% of the change in the actual demand. (4) Accessibility is a non-critical factor affecting the travel rate of residential quarters, while supply pressure is a key factor affecting the utilization rate of park green space. The framework can effectively identify important or low-utilization service-providing areas, unmet service-demanding areas, and important service-connecting areas. It is suitable for the study of the relationship between the supply, demand, and flow of user movement-related services.

Background: Previous studies have indicated a correlation between maternal imbalances in essential trace elements during pregnancy and the occurrence of spontaneous abortion (SA). Nonetheless, the impact of these elements from both partners and during the preconception period remains unexplored. Objective: This study sought to evaluate the relationship between preconception essential trace elements and spontaneous abortion (SA) based on husband–wife dyads. Methods: This study selected 390 couples with spontaneous abortion (SA) and 390 matched couples with live births from a preconception cohort of 33,687 couples. Urine samples collected prior to pregnancy were analyzed for ten essential trace elements (Se, Cr, Mo, Cu, Zn, Fe, Mn, V, Co, and Ni) using inductively coupled plasma mass spectrometry (ICP-MS). Results: Multivariate conditional logistic regression analysis identified that elevated concentrations of Zn (OR = 0.73) and Ni (OR = 0.69) in couples were associated with a reduced risk of SA, whereas elevated levels of Cr (OR = 1.30) and Mn (OR = 1.39) were linked to an increased risk. Restricted cubic spline models suggested a U-shaped association between couples’ Cu and Co concentrations and SA. Bayesian Kernel Machine Regression further supported a U-shaped relationship between the mixture of ten elements and SA, showing significant protection at the 50th and 55th percentiles compared to the 10th percentile. Additionally, the effects of Cr, Zn, Mn, and Ni on SA varied when the concentrations of the other nine elements were held constant at their 25th, 50th, and 75th percentiles. Stratified analysis revealed that maternal Cu (OR = 0.43) and Fe (OR = 0.63) reduced the risk of SA when paternal Cu and Fe were in the lower quartile. Conversely, maternal Cu (OR = 2.03) and Fe (OR = 1.77) increased the risk of SA when paternal concentrations were in the higher quartile. Similar patterns were observed for Cr, Mn, Co, and Zn. Conclusion: Elevated urinary concentrations of Zn and Ni in couples were associated with a reduced risk of SA, while higher levels of Cr and Mn were linked to an increased risk. Cu, Co, and a mixture of ten essential trace elements exhibited a U-shaped relationship with SA. The impact of certain essential trace elements (Cu, Fe, Cr, Mn, Co, and Zn) on SA in one partner was influenced by their concentrations in the other partner.