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Abstract Studies have shown that acute exercise alters the expression of circulating neutrophil and peripheral blood mononuclear cell (PBMC) genes, affecting a wide range of processes from cellular growth to the promotion of inflammatory and anti-inflammatory responses. In this study, we identified differential gene expression associated with acute exercise and PBMC in puberty children through the GEO database. We utilized bioinformatics technology to analyze the impact of acute exercise on PBMC and identified key genes involving the puberty children. Combining two datasets of gene expression, we identified 197 shared differentially expressed genes (DEGs) in PBMC before and after exercise. We conducted pathway analysis of these DEGs and built a gene co-expression network. The identification of hub genes was achieved through the utilization of protein-protein interaction (PPI) networks. 268 shared DEGs were identified in the GSE11761 dataset in pre- and post-exercise groups, while 352 differential genes were identified between the pre- and post-exercise groups of females in the GSE14642 dataset. A total of 197 shared genes were identified between the two datasets. Seven core genes were identified by MCODE and CytoHubba, namely IL2RB, KLRD1, GZMB, TBX21, PRF1, HAVCR2, and GZMA. Bioinformatics techniques are effective in screening and analyzing PBMC-associated DEGs in children undergoing acute pre- and post-exercise puberty. Microarray analysis of PBMCs in children undergoing puberty can identify molecules that may predict acute exercise responses. This study provides insights for further exploration of the mechanisms and targets of acute exercise on the organism.

Abstract Background Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R+ macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R+ macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates. Methods In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients. Results CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R+ macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect. Conclusions Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R+ macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.

Compacted clay liners are extensively used as barriers to control the upward diffusion of vapors of volatile or semi-volatile organic contaminants released from unsaturated contaminated soils at industry-contaminated sites. This study aimed to investigate the gas diffusion barrier performance of compacted clayey soils amended with three agents including attapulgite and diatomite individually, and attapulgite/diatomite mixture. The properties including water retention, volumetric shrinkage, gas diffusion, and unconfined compressive strength were evaluated through a series of laboratory tests of amended compacted clayey soils. The results demonstrate that the decrease in volume proportions of inter-aggregate pores leads to an increase in unconfined compressive strength (qu). Both hydrophilic groups and microstructures of attapulgite and diatomite result in an increase in water retention percent (Wt) of compacted clayey soil specimens after amendment regardless of the type of agent or initial water content (w0). Furthermore, the ratio of the gas diffusion coefficient (De) to the gas diffusion coefficient in the air (Da) was significantly reduced owing to a decrease in volume proportions of inter-aggregate pores, hydrophilic group, and microstructures of attapulgite and diatomite. Scanning electron microscope analyses revealed that rod-shaped attapulgite filled the inter-aggregate pores formed by clay particles, whereas the disc-shaped diatomite particles, characterized by micropores, failed to obstruct the inter-aggregate pores due to their larger particle size. Mercury intrusion porosimetry (MIP) analyses showed a reduction in pore volume in the inter-aggregate pores, leading to a reduction in the total pore volume for both the attapulgite and attapulgite/diatomite mixture amended clays, which is in accordance with the scanning electron microscope (SEM) results. The findings are pertinent to the practical application of compacted clay liners as gas barriers against the upward migration of volatile or semi-volatile organic contaminants at contaminated sites.

Abstract Background Fournier’s Gangrene is a severe surgical infectious disease, and various risk factors can increase its mortality rate. The purpose of this study is to retrospectively analyze the clinical characteristics and laboratory data of Fournier’s Gangrene patients, followed by an analysis of mortality-related risk factors. This study has no secondary objectives. Methods This study included 46 hospitalized patients diagnosed with Fournier’s Gangrene at Suzhou Traditional Chinese Medicine Hospital from December 2013 to March 2024. Clinical data for all patients were extracted from the electronic medical records system. The collected data included gender, age, duration of illness, length of hospital stay, sites of infection involvement, comorbidities, white blood cell count, hematocrit, albumin, blood glucose, creatinine, serum sodium, serum potassium upon admission, microbial culture results, and patient outcomes (survival/death). The Simplified Fournier Gangrene Severe Index (SFGSI) was used to score all patients. Patients were categorized into survival and death groups based on clinical outcomes. Differences between categorical variables were compared using the χ² test or Fisher’s exact test. Differences between numerical variables were compared using Student’s t-test or the Mann-Whitney U test. Binary logistic regression was employed to analyze the risk factors for mortality in Fournier’s Gangrene. Results Among the 46 Fournier’s Gangrene patients, 39 were male (84.8%) and 7 were female (15.2%). The age ranged from 17 to 86 years, with a median age of 61 years. Fourteen cases (30.4%) were confined to the perianal area, 26 cases (56.5%) had fascial necrosis involving the perianal, perineal, and genital regions, while 6 cases (13.0%) extended to the abdominal wall. At a 3-month postoperative follow-up, 43 patients (93.5%) survived, while 3 patients (6.5%) died shortly after admission due to severe illness. Based on the outcome, patients were divided into survival and death groups with 43 and 3 cases, respectively. Significant differences were observed between the two groups in terms of age (P2 (P

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Trace element levels in the circulation (blood, serum, plasma) are believed to play a role in the pathophysiologic processes of Alzheimer’s disease (AD); however, there is heterogeneity in the available findings. This study conducted a systematic review and meta-analysis of trace elements (including: copper (Cu), iron (Fe), zinc (Zn), selenium (Se), lead (Pb), cadmium (Cd), mercury (Hg), manganese (Mn), aluminum (Al), arsenic (As), and magnesium (Mg)) in AD patients and controls to assess the variation of trace elements in the circulation of AD patients. By systematically screening case–control studies on circulatory trace element levels in AD patients from 2000 to the present in the PubMed, Web of Science, and MEDLINE databases, 52 studies were included in the final meta-analysis. The results of the random-effects model showed significantly elevated circulatory levels of Cd (SMD = 0.79, 95% CI: 0.35, 1.24), Hg (SMD = 0.59, 95% CI: 0.03, 1.16), and Cu (SMD = 0.70, 95% CI: 0.37, 1.04) in AD patients, while levels of Fe (SMD = − 0.58, 95% CI: − 1.03, − 0.13), Se (SMD = − 0.53, 95% CI: − 0.85, − 0.21), and Zn (SMD = − 0.99, 95% CI: − 1.52, − 0.46) were significantly lower. The database formed in this study provides reliable population-based research evidence for exploring changes in circulating trace element levels in AD patients. Monitoring and stabilization of circulatory trace element levels in the elderly may be a potential preventive target for AD.

Abstract The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K–L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

Abstract Background Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

Abstract Co-combustion is a technology that enables the simultaneous and efficient utilization of biomass and coal gangue (CG). Nevertheless, the factors that affect the combustibility of co-pyrolytic char, which represents the rate-determining step of the entire co-combustion process, remain unclear. This study investigates the impact of the physicochemical properties of co-pyrolytic char, including pore structure, carbon structure, and alkali metals, on the combustion characteristics. The TGA analysis indicates that the ignition and burnout temperatures of the co-pyrolytic char increase as the CG mixing ratio increases, resulting in a prolonged combustion. This is due to the fact that the carbon structure of the co-pyrolytic char becomes increasingly aromatic, accompanied by a reduction in aliphatic hydrocarbons and oxygen-containing groups as the CG mixing ratio increases. Furthermore, the high ash content of the CG is another significant factor contributing to the observed reduction in combustibility. The reaction between mullite, quartz in CG, and alkali metals in biomass results in the formation of aluminosilicate, which reduces the catalytic ability of alkali metals. Furthermore, the char combustion kinetics are analyzed by the KAS method, and the results indicate that the introduction of CG increases the activation energy of the entire char combustion process. The activation energy of the 80RS20CG is within the range of 102.22–164.99 kJ/mol, while the RS char is within the range of 89.87–144.67 kJ/mol.

Abstract Background Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P

Abstract Objective There were few reports in the literature regarding hidden blood loss following surgery for developmental dysplasia of the hip in children. This study aimed to evaluate the volume of hidden blood loss and its risk factors among children undergoing hip reconstruction for developmental dysplasia of the hip. Methods A retrospective analysis of clinical data from 42 patients (58 hips), who underwent Pemberton and femoral osteotomies between March 2020 and March 2023, was conducted. Serial complete blood count assays were conducted on the day of admission and four days post-surgery. Preoperative and postoperative hematocrit levels were documented to calculate hidden blood loss utilizing the Gross formula. Pearson and Spearman correlation analyses, along with multivariable linear regression, were employed to ascertain associations between patient characteristics and hidden blood loss. Results The mean hidden blood loss was recorded as 283.06 ± 271.05 mL, constituting 70.22% of the total blood loss. Multiple linear regression analysis identified weight and surgical duration as independent risk factors contributing to hidden blood loss. Conclusions A relevant amount of postoperative hidden blood loss occurs after Pemberton osteotomy and femoral osteotomy for developmental dysplasia of the hip. Surgeons should be aware that patients who require blood transfusions and have longer surgical durations are at a higher risk of developing more hidden blood loss. Therefore, attention should be given to hidden blood loss to ensure patient safety during the perioperative period for those undergoing Pemberton and femoral osteotomies. Level of evidence IV.

Tropical cyclones (TCs) can cause severe wind and rain hazards. Unusual TC tracks and their extreme precipitation forecasts have become two difficult problems faced by conventional models of primitive equations. The case study in this paper finds that the numerical computation of the climatological component in conventional models restricts the prediction of unusual TC tracks. The climatological component should be a forcing quantity, not a predictor in the numerical integration of all models. Anomaly-based variable models can overcome the bottleneck of forecast time length or the one-week forecasting barrier, which is limited to less than one week for conventional models. The challenge in extreme precipitation forecasting is how to physically get the vertical velocity. The anomalous moisture stress modulus (AMSM), as an indicator of heavy rainfall presented in this paper, considers the two conditions associated with vertical velocity and anomalous specific humidity in the lower troposphere. Vertical velocity is produced by the orthogonal collision of horizontal anomalous airflows.

In this study, the complete mitochondrial genome of Anidiocerus bimaculatus was sequenced and annotated for the first time, which belongs to the subfamily Eurymelinae. The mitogenome of A. bimaculatus was 15,267 bp in length and contained 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one non-coding control region. In this mitogenome, all the PCGs are initially encoded by ATT, ATA, ATG, or TTG, and terminated by TAA, or single T. The overall base composition of A. bimaculatus is 43.6% adenines, 36.0% thymines, 9.1% guanines, and 11.3% cytosines. ML phylogenetic analyses confirmed that Idiocerini forms a monophyletic clade and the newly sequenced A. bimaculatus clustered within the Idiocerini clade based on 13 protein-coding genes and two rRNA genes.

Abstract Background Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice. Methods The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα −/−) mice were used to confirm the CP-mediated pathway. Results CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect. Conclusion This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.

Abstract Current induced spin–orbit torque (SOT) manipulation of magnetization is pivotal in spintronic devices. However, its application for perpendicular magnetic anisotropy magnets, crucial for high‐density storage and memory devices, remains nondeterministic and inefficient. Here, a highly efficient approach is demonstrated to generate collinear spin currents by artificial modulation of interfacial symmetry, achieving 100% current‐induced field‐free SOT switching in CoFeB multilayers with perpendicular magnetization on stepped Al2O3 substrates. This field‐free switching is primarily driven by the out‐of‐plane anti‐damping SOT generated by the planar spin Hall effect (PSHE), resulting from reduced interface symmetry due to orientation‐determined steps. Microscopic theoretical analysis confirms the presence and significance of PSHE in this process. Notably, this method for generating out‐of‐plane spin polarization along the collinear direction of the spin‐current with artificial modulation of interfacial symmetry, overcomes inherent material symmetry constraints. These findings provide a promising avenue for universal control of spin–orbit torque, addressing challenges associated with low crystal symmetry and highlighting its great potential to advance the development of energy‐efficient spintronic devices technology.

Pine wilt disease (PWD) is a highly destructive infectious disease that affects pine forests. Therefore, an accurate and effective method to monitor PWD infection is crucial. However, the majority of existing technologies can detect PWD only in the later stages. To curb the spread of PWD, it is imperative to develop an efficient method for early detection. We presented an early stage detection method for PWD utilizing UAV remote sensing, hyperspectral image reconstruction, and SVM classification. Initially, employ UAV to capture RGB remote sensing images of pine forests, followed by labeling infected plants using these images. Hyperspectral reconstruction networks, including HSCNN+, HRNet, MST++, and a self-built DW3D network, were employed to reconstruct the RGB images obtained from remote sensing. This resulted in hyperspectral images in the 400-700nm range, which were used as the dataset of early PWD detection in pine forests. Spectral reflectance curves of infected and uninfected plants were extracted. SVM algorithms with various kernel functions were then employed to detect early pine wilt disease. The results showed that using SVM for early detection of PWD infection based on reconstructed hyperspectral images achieved the highest accuracy, enabling the detection of PWD in its early stage. Among the experiments, MST++, DW3D, HRNet, and HSCNN+ were combined with Poly kernel SVM performed the best in terms of cross-validation accuracy, achieving 0.77, 0.74, 0.71, and 0.70, respectively. Regarding the reconstruction network parameters, the DW3D network had only 0.61M parameters, significantly lower than the MST++ network, which had the highest reconstruction accuracy with 1.6M parameters. The accuracy was improved by 27% compared to the detection results obtained using RGB images. This paper demonstrated that the hyperspectral reconstruction-poly SVM model could effectively detect the Early stage of PWD. In comparison to UAV hyperspectral remote sensing methods, the proposed method in this article offers a same precision, but a higher operational efficiency and cost-effectiveness. It also enables the detection of PWD at an earlier stage compared to RGB remote sensing, yielding more accurate and reliable results.

Background: Post-stroke epilepsy (PSE) is a critical complication that worsens both prognosis and quality of life in patients with ischemic stroke. An interpretable machine learning model was developed to predict PSE using medical records from four hospitals in Chongqing. Methods: Medical records, imaging reports, and laboratory test results from 21,459 ischemic stroke patients were collected and analyzed. Univariable and multivariable statistical analyses identified key predictive factors. The dataset was split into a 70% training set and a 30% testing set. To address the class imbalance, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors was employed. Nine widely used machine learning algorithms were evaluated using relevant prediction metrics, with SHAP (SHapley Additive exPlanations) used to interpret the model and assess the contributions of different features. Results: Regression analyses revealed that complications such as hydrocephalus, cerebral hernia, and deep vein thrombosis, as well as specific brain regions (frontal, parietal, and temporal lobes), significantly contributed to PSE. Factors such as age, gender, NIH Stroke Scale (NIHSS) scores, and laboratory results like WBC count and D-dimer levels were associated with increased PSE risk. Tree-based methods like Random Forest, XGBoost, and LightGBM showed strong predictive performance, achieving an AUC of 0.99. Conclusions: The model accurately predicts PSE risk, with tree-based models demonstrating superior performance. NIHSS score, WBC count, and D-dimer were identified as the most crucial predictors. Funding: The research is funded by Central University basic research young teachers and students research ability promotion sub-projec t(2023CDJYGRH-ZD06), and by Emergency Medicine Chongqing Key Laboratory Talent Innovation and development joint fund project (2024RCCX10).

IntroductionImmune checkpoint inhibitors (ICIs) are important systemic therapeutic agents for hepatocellular carcinoma (HCC), among which T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) is considered an emerging target for ICI therapy. This study aims to evaluate the prognostic value of Tim-3 expression and develop a predictive model for Tim-3 infiltration in HCC.MethodsWe collected data from 424 HCC patients in The Cancer Genome Atlas (TCGA) and data from 102 pathologically confirmed HCC patients from our center for prognostic analysis. Multivariate Cox regression analyses were performed on both datasets to determine the prognostic significance of Tim-3 expression. In radiomics analysis, we used the K-means algorithm to cluster regions of interest in arterial phase enhancement and venous phase enhancement images from patients at our center. Radiomic features were extracted from three subregions as well as the entire tumor using pyradiomics. Five machine learning methods were employed to construct Habitat models based on habitat features and Rad models based on traditional radiomic features. The predictive performance of the models was compared using ROC curves, DCA curves, and calibration curves.ResultsMultivariate Cox analyses from both our center and the TCGA database indicated that high Tim-3 expression is an independent risk factor for poor prognosis in HCC patients. Higher levels of Tim-3 expression were significantly associated with worse prognosis. Among the ten models evaluated, the Habitat model constructed using the LightGBM algorithm showed the best performance in predicting Tim-3 expression status (training set vs. test set AUC 0.866 vs. 0.824).DiscussionThis study confirmed the importance of Tim-3 as a prognostic marker in HCC. The habitat radiomics model we developed effectively predicted intratumoral Tim-3 infiltration, providing valuable insights for the evaluation of ICI therapy in HCC patients.

BackgroundOptimizing the diagnosis and treatment of hematological diseases is a challenging yet crucial research area. Effective treatment plans typically require the comprehensive integration of cell morphology, immunology, cytogenetics, and molecular biology. These plans also consider patient-specific factors such as disease stage, age, and genetic mutation status. With the advancement of artificial intelligence (AI), more “AI + medical” application models are emerging. In clinical practice, many AI-assisted systems have been successfully applied to the diagnosis and treatment of hematological diseases, enhancing precision and efficiency and offering valuable solutions for clinical practice.ObjectiveThis study summarizes the research progress of various AI-assisted systems applied in the clinical diagnosis and treatment of hematological diseases, with a focus on their application in morphology, immunology, cytogenetics, and molecular biology diagnosis, as well as prognosis prediction and treatment.MethodsUsing PubMed, Web of Science, and other network search engines, we conducted a literature search on studies from the past 5 years using the main keywords “artificial intelligence” and “hematological diseases.” We classified the clinical applications of AI systems according to the diagnosis and treatment. We outline and summarize the current advancements in AI for optimizing the diagnosis and treatment of hematological diseases, as well as the difficulties and challenges in promoting the standardization of clinical diagnosis and treatment in this field.ResultsAI can significantly shorten turnaround times, reduce diagnostic costs, and accurately predict disease outcomes through applications in image-recognition technology, genomic data analysis, data mining, pattern recognition, and personalized medicine. However, several challenges remain, including the lack of AI product standards, standardized data, medical–industrial collaboration, and the complexity and non-interpretability of AI systems. In addition, regulatory gaps can lead to data privacy issues. Therefore, more research and improvements are needed to fully leverage the potential of AI to promote standardization of the clinical diagnosis and treatment of hematological diseases.ConclusionOur results serve as a reference point for the clinical diagnosis and treatment of hematological diseases and the development of AI-assisted clinical diagnosis and treatment systems. We offer suggestions for further development of AI in hematology and standardization of clinical diagnosis and treatment.

Cognitive impairment (CI) is a prodrome of many neurodegenerative diseases with complex and unclear pathogenesis. Metal exposure has been found to be associated with CI, but existing population studies are scarce and have the limitations of single outcome and ignoring mixed exposures. This cross-sectional study was conducted in Shanghai, China, enrolling 836 seniors aged over 60 years to investigate the relationship between combined metal exposure (Lead (Pb), cadmium (Cd), and mercury (Hg)) and CI in the elderly and the mediating effect of oxidative stress. It was found that there were significant differences in urinary Pb, Cd, Hg and blood Pb levels between the CI and normal groups. Urinary Pb and Cd levels were significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score, amyloid β42 (Aβ42), and Aβ42/40, while urinary Cd, Hg and blood Hg were significantly positively correlated with phosphorylated tau protein (P-tau). Weighted quantile sum (WQS) regression indicated that combined metal exposure had a more significant effect on CI than individual exposure. Mediation modeling revealed that plasma superoxide dismutase (SOD) was involved in the effects of urinary Cd on Aβ42/40 and P-tau, with mediation effects accounting for 20 % of the total effect. This study emphasized the combined exposure to metals, and the results can help to properly understand the association between mixed metals exposure and CI in the elderly, as well as provide population data and theoretical basis for identifying early environmental risk factors and discovering potential mechanisms of CI.

Abstract Correlation between echocardiographic and pathoanatomic variables and their prognostic value in murine cardiomyopathy models remain unknown. Using echocardiography, morphometrics, and survival monitoring, we characterized transgenic (TG) mice with dilated cardiomyopathy due to cardiac overexpression of β2‐adrenoceptors focusing on predicting heart failure (HF) risk and HF mortality. In 12‐month‐old non‐TG and TG mice, echocardiography was performed to determine left ventricular (LV) dimensions (d), wall thickness (h), and fractional shortening (FS). Animals were monitored for 3 months for survival. Organ weights and pathological events indicating left HF were determined. TG mice (n = 76) had reduced FS and enlarged LV, and 79% died of HF or likely arrhythmias during the follow‐up period while all non‐TG mice (n = 26) survived. These mice with left HF also had pulmonary congestion and hypertrophy/dilatation of the right ventricle (RV). Weights of lungs, RV, and atria were intercorrelated (r = 0.79–0.83) and also negatively correlated with FS × (h/d) index (r = −0.502 to −0.609). By FS × (h/d) tertiles, TG mice of low tertiles were identified with the highest mortality (96%) largely due to HF (76%). In conclusion, in aged cardiomyopathy mice a good correlation existed between echocardiographic and pathoanatomic variables. Echocardiography‐derived LV function and remodeling were useful in identifying a subgroup of TG mice with a high risk of HF and HF fatality.

ObjectivesThe objective of this study was to profile the transcriptional profiles of peripheral blood mononuclear cells (PBMCs) and their immune repertoires affected by anti-synthetase syndrome (ASS) at the single-cell level.MethodsWe performed single-cell RNA sequencing (scRNA-seq) analysis of PBMCs and bulk RNA sequencing for patients with ASS (N=3) and patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM, N=3) along with healthy controls (HCs, N=4). As ASS and MDA5+ DM have similar organ involvements, MDA5+ DM was used as a disease control. The immune repertoire was constructed by reusing the same scRNA-seq datasets. Importantly, flow cytometry was performed to verify the results from the scRNA-seq analysis.ResultsAfter meticulous annotation of PBMCs, we noticed a significant decrease in the proportion of mucosal-associated invariant T (MAIT) cells in ASS patients compared to HCs, while there was a notable increase in the proportion of proliferative NKT cells. Compared with MDA5+ DM patients, in their PBMCs ASS patients presented substantial enrichment of interferon pathways, which were primarily mediated by IFN-II, and displayed a weak immune response. Furthermore, ASS patients exhibited more pronounced metabolic abnormalities, which may in turn affect oxidative phosphorylation pathways. Monocytes from ASS patients appear to play a crucial role as receptive signaling cells for the TNF pathway. Immunophenotyping analysis of PBMCs from ASS patients revealed an increasing trend for the clone type CQQSYSTPWTF.ConclusionUsing single-cell genomic datasets of ASS PBMCs, we revealed a distinctive profile in the immune system of individuals with ASS, compared to that with MDA5+ DM or healthy controls.

Exploring how environmental changes induce alterations in the phenology matching between plants and pollinators is significant for predicting species’ reproductive output and population dynamics. Our study focused on the invasive poisonous weed Stellera chamaejasme, widely distributed in the Qilian Mountains, China. By continuously monitoring its flowering phenology and flower visitors’ activities across different elevational ranges, we compared phenological matching patterns between S. chamaejasme and its potential pollinators across years with varying environmental temperatures. We found that S. chamaejasme, a typical early-flowering alpine species, begins its flowering in early June. Despite variations in the composition of flower-visiting insects across elevations and years, it maintained stable interactions with four major groups: Meloidae, Tachinidae, Scarabaeidae, and Noctuidae. Phenological mismatches between the peak flowering period of S. chamaejasme and the peak abundance of major potential pollinators were generally observed across its range, with higher phenological matching at higher elevations. This enhanced matching at higher elevations may drive the rapid invasion of S. chamaejasme in these areas. In the year with higher ambient temperature, phenological matching increased across its range, and its elevational sensitivity decreased, potentially contributing to its ongoing expansion in different elevations. The results of our study advance a new insight into the population expansion of invasive species in mountain ecosystems.

IntroductionProliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a chronic glomerular disease caused by monoclonal gammopathy. IgG (mainly IgG3) is the most commonly involved isotype of PGNMID. Here we illustrated a novel medication regimen for the rare variant of PGNMID with deposition of monoclonal immunoglobulin light chain only (PGNMID-LC). Daratumumab has been proved effective in the treatment of plasma cell myeloma while its effect for PGNMID-LC has rarely been reported.MethodsA daratumumab combination therapy (D-VCd regimen, specifically are daratumumab + dexamethasone + bortezomib + cyclophosphamide) was adopted to treat a patient diagnosed with PGNMID-LC.ResultsThe utility of D-VCd regimen showed a favorable effect in this patient. After the fixed course, his clinical symptom, laboratory parameters, neoplastic plasma cells clonity all restored to normal range, and no obvious disease progression was observed throughout the treatment. After a follow up of 14 months, no significant renal or hematological disease progression has been observed.ConclusionThis case underscores the utility of D-VCd regimen in treatment of PGNMID-LC, and it’s inferred that daratumumab regimen has clinical effects in the disease primarily through targeting tumor clonity. However, data on the use of daratumumab (either in monotherapy or in combination) in clinical trials of PGNMID-LC is currently so limited that that more experiments are needed to support the inference.

Abstract Backgroud Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell‐free DNA (cfDNA) in patients with non‐small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell‐free RNA (cfRNA) is critical for resolving the issue. Methods A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT‐qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi‐gene mutations detection by RT‐qPCR. Results Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4‐ALK, ROS1, RET fusions, and MET ex14 skipping. Conclusion These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA‐based assay.

IntroductionPulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH.MethodsEighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure.ResultsPlasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients.DiscussionFindings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

Abstract Purpose Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations. Methods We searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639. Results Ten prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I 2 = 72.39%, P

Abstract Background Cardiovascular disease continues to be a leading cause of mortality worldwide, highlighting the need to explore innovative approaches to improve cardiovascular health outcomes. Time-restricted fasting (TRF) is a dietary intervention that involves limiting the time window for food consumption. It has gained attention for its potential benefits on metabolic health and weight management. This study aims to investigate the impact of TRF on key risk factors, including body weight, glucose metabolism, blood pressure, and lipid profile. Methods We conducted a systematic search in five databases (Scopus, Embase, PubMed, Cochrane, and Web of Science) for relevant studies up to January 2023. After applying inclusion criteria, 12 studies were eligible for analysis. Quality assessment was conducted using the ROB-2.0 tool and ROBINS-I. Risk of bias was mapped using Revman 5.3, and data analysis included Hartung-Knapp adjustment using R 4.2.2. Results The group that underwent the TRF intervention exhibited a significant decrease in body weight (SMD: -0.22; 95%CI: -0.41, -0.04; P 0.05). Conclusion TRF has shown potential as a treatment strategy for reducing total body weight by targeting adipose tissue, with potential improvements in cardiometabolic function.