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PurposeThe Chinese Visceral Adiposity Index (CVAI), a measure of visceral adiposity dysfunction, is used to assess visceral fat (VFA) malfunction. This research was performed to evaluate the relationship between CVAI and serum uric acid levels in type 2 diabetes mellitus (T2DM) patients.MethodsA total of 2268 patients with T2DM were enrolled in this study. We collected the general clinical information of patients, measured the basic anthropometric indicators, tested glycolipid metabolism and biochemical indicators, and measured the visceral and subcutaneous fat area with bioelectrical impedance technology. According to the quartiles of the CVAI, the T2DM patients were classified into four groups: group A (CVAI ≤ 94.43), group B (94.43

ObjectiveEpilepsy, a prevalent neurological disorder, has multifaceted etiologies. Next-generation sequencing (NGS) has emerged as a robust diagnostic tool for this condition. This study aims to evaluate the detection efficiencies of different exome-based sequencing techniques.MethodsExome-based epilepsy panel tests, clinical exome sequencing (CES), and whole exome sequencing (WES) were conducted on 259 pediatric patients diagnosed with epilepsy. Single-nucleotide variants (SNVs) and copy number variants (CNVs) were interpreted based on each patient’s phenotypic presentation. Additionally, data concerning clinical symptoms, neuroimaging findings, treatment responses, and prognostic outcomes were collected and analyzed.ResultsThe overall diagnostic yield was 32.8% (85/259), with a diagnostic yield of 40.0% for exome-based epilepsy panels, 30.1% for CES, and 27.8% for WES. We identified 82 cases with pathogenic or likely pathogenic SNVs and 4 cases with pathogenic CNVs, of which one case with both SNV and CNV. The most frequently detected gene was PRRT2, present in 10.0% (9/82) of cases. Epileptic syndromes were diagnosed in 66 patients, predominantly West Syndrome, Dravet Syndrome and Genetic Epilepsy with Febrile Seizures plus.ConclusionNGS is an effective method for uncovering the genetic foundations of pediatric epilepsy, with diagnostic yields varying based on the sequencing approach used. The growing preference for WES underscores its utility in complex cases, pointing to a trend towards more tailored diagnostic strategies.

BackgroundPTC (papillary thyroid cancer) is a lymphotropic malignancy associated with cervical lymph node metastasis (CLNM, including central and lateral LNM), which compromises the effect of treatment and prognosis of patients. Accurate preoperative identification will provide valuable reference information for the formulation of diagnostic and treatment strategies. The aim of this study was to develop and validate a clinical-multimodal ultrasound radiomics model for predicting CLNM of PTC.MethodsOne hundred sixty-four patients with PTC who underwent treatment at our hospital between March 2016 and December 2021 were included in this study. The patients were grouped into a training cohort (n=115) and a validation cohort (n=49). Radiomic features were extracted from the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) and strain elastography-ultrasound (SE-US) images of patients with PTC. Multivariate logistic regression analysis was used to identify the independent risk factors. FAE software was used for radiomic feature extraction and the construction of different prediction models. The diagnostic performance of each model was evaluated and compared in terms of the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value (NPV) and positive predictive value (PPV). RStudio software was used to develop the decision curve and assess the clinical value of the prediction model.ResultsThe clinical-multimodal ultrasound radiomics model developed in this study can successfully detect CLNM in PTC patients. A total of 3720 radiomic features (930 features per modality) were extracted from the ROIs of the multimodal images, and 15 representative features were ultimately screened. The combined model showed the best prediction performance in both the training and validation cohorts, with AUCs of 0.957 (95% CI: 0.918–0.987) and 0.932 (95% CI: 0.822–0.984), respectively. Decision curve analysis revealed that the combined model was superior to the other models.ConclusionThe clinical-multimodal ultrasound radiomics model constructed with multimodal ultrasound radiomic features and clinical risk factors has favorable potential and high diagnostic value for predicting CLNM in PTC patients.

Periodontal disease is a highly prevalent disease worldwide that seriously affects people’s oral health, including gingivitis and periodontitis. Although the current treatment of periodontal disease can achieve good control of inflammation, it is difficult to regenerate the periodontal supporting tissues to achieve a satisfactory therapeutic effect. In recent years, due to the good tissue regeneration ability, the research on Mesenchymal stromal/stem cells (MSCs) and MSC-derived exosomes has been gradually deepened, especially its ability to interact with the microenvironment of the body in the complex immunoregulatory network, which has led to many new perspectives on the therapeutic strategies for many diseases. This paper systematically reviews the immunomodulatory (including bone immunomodulation) properties of MSCs and their role in the periodontal inflammatory microenvironment, summarizes the pathways and mechanisms by which MSCs and MSC-EVs have promoted periodontal regeneration in recent years, lists potential areas for future research, and describes the issues that should be considered in future basic research and the direction of development of “cell-free therapies” for periodontal regeneration.

The combination of hydrophilic arginine residues and hydrophobic tryptophan residues is considered to be the first choice for designing short-chain antimicrobial peptides (AMPs) due to their potent antibacterial activity. Based on this, we designed an arginine- and tryptophan-rich short peptide, VR-12. Peri-implantitis is a significant microbial inflammatory disorder characterized by the inflammation of the soft tissues surrounding an implant, which ultimately leads to the progressive resorption of the alveolar bone. This study found through antibacterial experiments, wound healing promotion experiments, and anti-inflammatory experiments that VR-12 inhibited and killed planktonic peri-implantitis-associated bacteria, inhibited biofilm formation, and disrupted mature biofilms. Additionally, VR-12 exhibited good biocompatibility with RAW264.7 cells and human gingival fibroblasts (HGFs) cells, promoting proliferation of both cell types. Moreover, VR-12 induced HGFs migration by promoting expression of migration-related factors, thereby promoting soft tissue healing. VR-12 also acted on lipopolysaccharide (LPS)-induced RAW264.7 cells, exerting excellent anti-inflammatory properties by affecting the secretion/expression of inflammation-related factors/genes. Therefore, VR-12 may be a good option for both warding off and treatmenting peri-implantitis.

Since ancient times, plants have provided humans with important bioactive compounds for the treatment of various diseases. Nine compounds were isolated from the roots and rhizomes of Caulophyllum robustum (a plant in the family Panaxaceae), including two new saponins C. Spanion A and C. Spanion B (1-2) and seven known saponins (3-9). The cytotoxicity of these compounds on human cancer cell lines was analyzed using MTT method. Compounds 6 and 9 exhibit cytotoxicity towards these three types of human cancer cells (

ObjectiveThe aim of this study was to explore the clinical characteristics of patients infected with different Omicron subvariants presenting non-severe disease, evaluate the safety and efficacy of Azvudine for treatment of COVID-19, in order to broaden understanding of Omicron subvariant infections.MethodA total of 244 individuals with Omicron subvariant (BA.2.76, n = 158; BA.5.1, n = 86) were included in the study. Demographic, clinical, and laboratory data of the study participants were collected and analyzed.ResultPatients infected with BA.5.1 exhibited a higher incidence of clinical symptoms like fatigue (25.58% vs. 2.53%, p

ObjectiveWith the development of ChatGPT, the number of studies within the nursing field has increased. The sophisticated language capabilities of ChatGPT, coupled with its exceptional precision, offer significant support within the nursing field, which includes clinical nursing, nursing education, and the clinical decision-making process. Preliminary findings suggest positive outcomes, underscoring its potential as a valuable resource for enhancing clinical care. However, a comprehensive analysis of this domain is lacking, and the application of bibliometric methods remains rare. This study aims to describe and predict the developmental trajectory of the discipline, identify research hotspots and trends, and provide a comprehensive framework for the integration of ChatGPT in nursing.MethodsFollowing the development of a search strategy in collaboration with librarians, the implementation of this strategy occurred in the Web of Science Core Collection (WoSCC) on June 30, 2024. For bibliometric and visual analyses—including evaluations of sources, institutions, countries, author collaboration networks, and keywords—Bibliometrix (version 4.4.2) and CiteSpace (version 6.2.R2 Basic) were employed.ResultsA total of 81 articles published by 67 authors were retrieved from the Web of Science Core Collection database, covering the period of June 30, 2024. The number of published studies has exhibited an increasing trend. The “European Journal of Cardiovascular Nursing” emerged as the most productive journals, while the USA, the UK, and China were identified as the leading countries in terms of publication output. The top 10 keywords identified in this study include artificial intelligence, nursing education, large language models, ChatGPT, natural language processing, generative artificial intelligence, care, nursing practice, clinical decision-making, and deep learning.ConclusionChatGPT is an emerging tool in the nursing field, currently in the foundational research phase. While there is significant international collaboration, cooperation among author groups remains somewhat limited. Studies focusing on ChatGPT in nursing primarily concentrate on two key themes: (1) the deep learning of ChatGPT in nursing and (2) the feasibility of its application. It is essential for nurses across various specialties to collaborate in exploring the diverse applications of ChatGPT within their domains, thereby fostering the ongoing development and enhancement of this technology.

Pancreatic cancer remains a highly malignant and challenging tumor with a dismal 5-year survival rate of only 13%. The majority of patients are diagnosed at advanced stages, where surgical options are limited, and prognosis is poor. Immunotherapy, particularly PD-1 inhibitors, has shown limited success in pancreatic cancer due to its unique tumor immune microenvironment. However, certain genetic profiles, such as BRCA1/2 mutations, high tumor mutational burden (TMB), or microsatellite instability-high (MSI-H), may enhance sensitivity to these therapies. This report presents two cases of advanced pancreatic cancer with BRCA1/2 mutations treated with a combination of chemotherapy and immune checkpoint inhibitors. The first patient, with TMB-H and stable microsatellites, achieved complete remission after conversion therapy and remains disease-free for over two years post-surgery. The second patient, with MSI-H and low TMB, experienced significant tumor regression and improved quality of life with a prolonged progression-free survival, although the patient ultimately declined surgery. These cases suggest that combined chemotherapy and immunotherapy may offer a promising treatment option for select pancreatic cancer patients, particularly those with specific genetic profiles, warranting further investigation into personalized approaches to immunotherapy in this malignancy.

The purpose of the study was to demonstrate how soybean peptides (SBP) protect against H2O2 -induced injury in intestinal porcine epithelial cells (IPEC-J2). SBP were prepared by protease hydrolysis, in which the molecular weights of 95.76% SBP were smaller than 3 kDa. Cell experiment included four groups: Control group (IPEC-J2 cells were treated with HGDMEM), SBP group (100 μg/mL SBP incubation for 13 h), H2O2 treatment group (1 mM H2O2 treatment for 1 h), SBP + H2O2 group (100 μg/mL SBP pretreatment for 12 h followed by 1 mM H2O2 treatment for 1 h). This study showed that that treatment with single 1 mM H2O2 for 1 h significantly reduced cell viability to 52.99% (p

BackgroundCongenital tracheal stenosis (CTS) is a rare but life-threatening malformation of the trachea. Surgical reconstruction is the treatment of choice in symptomatic cases which is highly risky and is rarely performed in extremely premature infants. With this, reporting a case of CTS managed by tracheal reconstructive surgery under ECMO in a baby weighing 1.47 kg at 32 + 1 WOG was the first ever case in China.Case presentationA premature newborn with a very low birth weight (VLBW) was admitted to our institute for breathing difficulties, requiring mechanical ventilation, and experienced two unsuccessful attempts of extubation. The team performed tracheal reconstructive surgery supported by ECMO after identifying lower tracheal stenosis through a bronchoscopy examination. One month after the surgery, oxygen support was able to discontinue. The patient's entire hospitalization was incredibly challenging, marked by hemodynamic instability with persistent anemia, and disseminated intravascular coagulation (DIC), which were managed with great care. Despite the difficult stay, a follow-up bronchoscopy revealed no obstruction or tracheal stenosis, leading to a successful discharge.ConclusionAdvancements in diagnostic techniques and innovative management methods have made diagnosing and treating CTS easier, even in premature infants. Our case is the first in China to successfully undergo tracheal reconstructive surgery supported by ECMO, inspiring future achievements in the medical field.

BackgroundUveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2.MethodsThe GEO datasets GSE211763 and GSE149920 were analyzed using GEO2R to identify differentially expressed genes that may be associated with UVM progression and metastasis. A Protein-Protein Interaction Network (PPI) was constructed to identify key molecules. The correlation between PLEK2 expression and overall survival was evaluated via GEPIA2, and clinical characteristics of UVM patients were compared based on PLEK2 levels. PLEK2 expression in UVM cell lines was assessed using the CCLE database and confirmed by qPCR and western blot. A weighted correlation network analysis (WGCNA) was performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, a search for miRNAs potentially regulating PLEK2 expression was performed using TargetScan, miRWalk, and TarBase databases.ResultsComparative analysis of the GEO datasets unveiled 79 commonly up-regulated genes and 238 commonly down-regulated genes. The PPI network identified 9 hub genes, with PLEK2 significantly linked to reduced overall survival. Clinical comparisons indicated significant differences in cancer status (p = 0.013) and tumor diameter (p = 0.039) between high and low PLEK2 expression groups. Elevated PLEK2 mRNA levels were confirmed in UVM cell lines compared to retinal pigment epithelial cells. PLEK2 was enriched in the calcium signaling pathway and associated with the Wnt/Ca2+ signaling pathway. A total of 21 miRNAs potentially regulating PLEK2 were predicted.ConclusionPLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.

BackgroundThere is currently no accurate, readily available, or validated biomarker for assessing disease severity and survival outcomes in sepsis-induced acute kidney injury (SAKI), which limits the ability to conduct effective therapeutic interventions. The neutrophil extracellular traps (NETs) may be involved in the pathophysiology of SAKI. The present study investigated the predictive value of plasma NETs for the survival outcome of patients with SAKI.MethodsThis observational study included 136 SAKI patients, all of whom underwent a 28-day follow-up. According to the follow-up records, SAKI patients were divided into two groups: the non-survivor group (60 subjects) and the survivor group (76 subjects). Blood samples were collected after the diagnosis of AKI to measure three NET markers and 12 inflammatory indices. Correlation analysis, logistic regression analysis, receiver operating characteristic curve analysis, and survival analysis were performed.ResultsCompared to survivors, non-survivors among SAKI patients exhibited significantly higher levels of three plasma NET markers (all p

BackgroundCoronary heart disease (CHD) is a prevalent cardiovascular condition, with its incidence and mortality rates steadily rising over time, posing a significant threat to human health. Studies have indicated that polyphenols exhibit a certain degree of protective effect against coronary heart disease. However, the findings regarding the impact of polyphenol-rich seed foods on patients with CHD have yielded inconsistent results.ObjectiveThis study investigated the effects of polyphenol-rich seed foods on blood lipids and inflammatory markers in patients with coronary heart disease.MethodsThe China National Knowledge Network, China Science and Technology Journal Database, China Biomedical Literature Database, Wanfang Database, PubMed, Cochrane Library, Embase, and Web of Science were searched for articles from the self-built database until March 16, 2024. The quality of the included studies was assessed using Edition 2 of the Cochrane Randomized Trials Risk Bias Tool, and data analysis was conducted using RevMan 5.4.ResultsThe study encompassed seven articles, with a total participation of 324 patients diagnosed with coronary heart disease. The study incorporated three seed foods abundant in polyphenols: Brazil nut, almond, and flaxseed. The meta-analysis findings revealed a significant reduction in triglyceride levels [MD = −20.03, 95% CI (−32.25, −17.44), p < 0.00001] among patients diagnosed with coronary heart disease who incorporated seed-based foods abundant in polyphenols into their diet regimen. Furthermore, a notable enhancement was observed in HDL cholesterol levels [MD = 3.14, 95% CI (1.55, 4.72), p = 0.0001]. Moreover, the type of intervention substance influenced the observed effects. The consumption of almonds has been demonstrated to significantly reduce total cholesterol [MD = −15.53, 95% CI (−21.97, −9.1), p

ObjectiveThis study aims to explore the potential contribution of angiographic characteristics in the increased stroke risk among pediatric patients.MethodsThis study retrospectively enrolled pediatric patients with ischemic, hemorrhagic, and asymptomatic moyamoya disease. Their hemispheres were categorized into five groups for the analysis of angiographic characteristics, which included Suzuki’s stage, moyamoya vessels, lenticulostriate artery, thalamotuberal artery, thalamoperforating artery, anterior choroidal arteries, posterior choroidal arteries, and posterior cerebral artery involvement.ResultsTwo hundred and nineteen pediatric patients with four hundred and thirty-eight hemispheres were enrolled. There was no significant difference in collateral dilatation between asymptomatic and hemorrhagic hemispheres. However, asymptomatic hemispheres had significantly lower incidence of posterior cerebral artery involvement and Suzuki’s stage compared to hemorrhagic (p = 0.008, p = 0.004) and ischemic hemispheres (p = 0.026, p

PurposeThe impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantitatively assess the effects of genetic polymorphisms on dabigatran esters in healthy Chinese subjects employed a population pharmacokinetic (PopPK) approach.MethodsIn total, 1,926 pharmacokinetic (PK) samples from 123 healthy individuals who were given 150 mg of dabigatran orally during a fasting state or postprandially were analyzed using the PopPK model. A two-compartment model with first-order absorption was found to adequately describe the PK data.ResultsThe results showed that covariates food intake and ABCB1 SNP rs4148738 were shown to have statistically significant impacts. Specifically, in postprandial administration increased lag time (ALAG) and clearance (CL) by 2.65% and 0.51%, respectively, and decreased absorption rate constant (KA) by 0.24%. Additionally, in subjects with CT genotype ABCB1 (rs4148738), the central ventricular volume of distribution (V2) was increased by 0.38%.ConclusionIn summary, the PopPK model developed in this study was robust and effectively characterized the pharmacokinetics of dabigatran in healthy Chinese adults, demonstrating that both food and ABCB1 genetic variation significantly influence the absorption and plasma concentration levels of dabigatran.

The innovation in ultrasound has greatly promoted the prenatal diagnosis of ventricular septal defect. As a minor lesion of congenital heart disease, the prenatal genetic counseling of isolated ventricular septal defect faces some challenges, including the true genetic correlationship, selection of appropriated testing methods to identify deleterious mutations, and avoidance of overdiagnosis and overintervention. Researchers have explored the prenatal diagnosis efficiency of commonly used cytogenetic and molecular genetic technologies. Small insertions/deletions and monogenic variants with phenotypic heterogeneity play important role and contribute to the comprehend of pathogenesis. Isolated ventricular septal defect fetuses without genetic finding and extracardiac structural abnormality generally have good pregnancy outcome. Long-term follow-up data is needed to describe the comprehensive map, such as the potential missed diagnosis especially late-onset syndromes, the impact on the quality of life and life expectancy. When conducting prenatal genetic counseling, strict adherence to ethical principles is needed to ensure that the rights of all parties involved are fully protected. Clinicians should carefully evaluate the risks and benefits and provide parents with sufficient information and advice to enable them to make informed decisions.

IntroductionThe primary objective of this study was to identify variables that significantly influence the implementation of math Response to Intervention (RTI) at the school level, utilizing the ECLS-K: 2011 dataset.MethodsDue to missing values in the original dataset, a Random Forest algorithm was employed for data imputation, generating a total of 10 imputed datasets. Elastic net logistic regression, combined with nested cross-validation, was applied to each imputed dataset, potentially resulting in 10 models with different variables. Variables for the models derived from the imputed datasets were selected using four methods, leading to four candidate models for final selection. These models were assessed based on their performance of prediction accuracy, culminating in the selection of the final model that outperformed the others.Results and discussionMethod50 and Methodcoef emerged as the most effective, achieving a balanced accuracy of 0.852. The ultimate model selected relevant variables that effectively predicted RTI. The predictive accuracy of the final model was also demonstrated by the receiver operating characteristic (ROC) plot and the corresponding area under the curve (AUC) value, indicating its ability to accurately forecast math RTI implementation in schools for the following year.

IntroductionAcupoint Catgut Embedding (ACE) is an extended and developed form of traditional acupuncture that serves as a composite stimulation therapy for various diseases. However, its local stimulation effects on acupoints remain unclear. Acupuncture can activate mechanically sensitive calcium ion channels, TRPV2 and TRPV4, located on various cell membranes, promoting Ca2+ influx in acupoint tissues to exert effects. Whether ACE can form mechanical physical stimulation to regulate these channels and the related linkage effect requires validation.MethodsThis study investigates the influence of TRPV2 and TRPV4 ion channels on the local stimulation effects of ACE by embedding PGLA suture at the Zusanli (ST36) acupoint in rats and using TRPV2 and TRPV4 inhibitors. Flow cytometry, immunofluorescence, Western blot, and Real-time quantitative PCR were employed to detect intracellular Ca2+ fluorescence intensity, the expression of macrophage (Mac) CD68 and mast cell (MC) tryptase, as well as the protein and mRNA expression of TRPV2 and TRPV4 in acupoint tissues after PGLA embedding.ResultsThe results indicate that ACE using PGLA suture significantly increases the mRNA and protein expression of TRPV2 and TRPV4, Ca2+ fluorescence intensity, and the expression of Mac CD68 and MC tryptase in acupoint tissues, with these effects diminishing over time. The increasing trends are reduced after using inhibitors, particularly when both inhibitors are used simultaneously. Furthermore, correlation analysis shows that embedding PGLA suture at the ST36 acupoint regulates Mac and MC functions through Ca2+ signaling involving not only TRPV2 and TRPV4 but multiple pathways.DiscussionThese results suggest that embedding PGLA suture at the ST36 acupoint generates mechanical physical stimulation and regulates TRPV2 and TRPV4 ion channels, which couple with Ca2+ signaling to form a linkage effect that gradually weakens over time. This provides new reference data for further studies on the stimulation effects and clinical promotion of ACE.

BackgroundKlebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections, classified into carbapenem-sensitive and carbapenem-resistant strains. Understanding the virulence factors and antibiotic resistance of these strains is essential for effective clinical management.ObjectiveThis study compared the virulence genes and antibiotic resistance profiles of 50 CSKP and 50 CRKP strains, examining their expression under antibiotic pressure and the mechanisms contributing to their pathogenicity.MethodsVirulence genes (rmpA, rmpA2, iucA, iutA, Peg-344, ybts, iroB) were detected in both strains using polymerase chain reaction (PCR). Antibiotic susceptibility testing established minimum inhibitory concentrations (MICs) for key antibiotics. Gene expression analysis was performed with quantitative reverse transcription PCR (qRT-PCR) after 10 days of antibiotic exposure.ResultsCSKP strains exhibited significantly higher positivity rates for virulence genes compared to CRKP strains. CRKP strains predominantly expressed resistance genes KPC, SHV, and CTX-M3, whereas no resistance genes were found in CSKP. Antibiotic susceptibility tests showed increased MICs, particularly for ciprofloxacin and imipenem, following antibiotic induction. CSKP demonstrated elevated expression of rmpA and rmpA2, while CRKP showed increased expression of SHV, and KPC after antibiotic exposure.ConclusionThis study highlights the intricate relationship between virulence and resistance in Klebsiella pneumoniae. CSKP strains show strong virulence factor expression, while CRKP strains adapt to antibiotic pressure through altered gene expression patterns. These findings underscore the urgent need for continuous surveillance and innovative therapeutic strategies to combat multidrug-resistant Klebsiella pneumoniae infections.

ObjectiveThe aim of this study was to assess the association between adherence to Mediterranean diet and the presence of atrial fibrillation (AF) in a Northern Chinese population.MethodsThis study was a single center, case–control study. A total of 952 low risk participants in Beijing Anzhen Hospital from 2016 to 2021 were collected, including 476 patients with first diagnosed of atrial fibrillation and 476 age and sex matched controls. According to the food frequency questionnaire (FFQ), the alternate Mediterranean diet score (AMED) was calculated, which was 0–9 points, indicating the adherence to the Mediterranean diet from low to high.ResultsThe average age of the participants was 57.6 ± 9.1 years old, and 70.2% were men. After analyzing every component of AMED, vegetable consumption shows a negative correlation with the risk of AF, whereas alcohol consumption demonstrates a positive correlation with it (OR = 0.61, 95% CI 0.44–0.80, p

BackgroundSystemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD).MethodsWe obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes.ResultsBy intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD.ConclusionThis study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

BackgroundAntipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia.MethodsStructural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17).ResultsML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences.ConclusionOur study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy.

Sleep disorders are becoming more and more common, leading to many health problems. However, most of current available medications to treat sleep disorders are addictive and even impair cognitive abilities. Therefore, it is important to find a natural and safe alternative to treat sleep disorders. In this study, twenty-four 8-week-old male ICR mice (25 ± 2 g) were equally divided into three groups: the control group (gavage of 0.9% saline), the eucalyptus essential oil (EEO) group (10 mg/kg B.W.), and the diazepam group (1 mg/kg B.W.). Firstly, open field test and sleep induction test were used to determine the sedative-hypnotic effect of EEO. Secondly, the effect of EEO on neurotransmitters in the mice brain was determined. Finally, based on the gut microbiota-brain axis (GMBA), the effect of EEO on the intestinal flora of mice was explored. It was found that EEO significantly reduce the activity and prolong the sleep duration of mice, exhibiting a good sedative-hypnotic effect. In the brain, EEO could increase the levels of sleep-promoting neurotransmitters, such as glutamine, Gamma-aminobutyric acid (GABA), glycine, tryptophan, N-acetylserotonin, and 5-hydroxyindoleacetic acid (5-HIAA). In the intestine, EEO was found to increase the diversity of gut microbes, the abundance of short chain fatty acid (SCFA) producing flora, and the abundance of functional flora synthesizing GABA and glycine neurotransmitters. These studies suggested that EEO exerted a sedative-hypnotic effect by acting on gut microbes and neurotransmitters in the brain. EEO has the potential to become a natural and safe alternative to traditional hypnotic sedative drugs.

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

IntroductionThe activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear.MethodsOur current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model.ResultsOur results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 (Azin1) and editing events in lincRNAs such as maternally expressed gene 3 (Meg3), AW112010, and macrophage M2 polarization regulator (Mm2pr). Importantly, geranylgeranyl diphosphate synthase 1 (Ggps1) and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 (Gch1) and non-coding RNA activated by DNA damage (Norad), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs.DiscussionThe findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.

BackgroundArtesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation.MethodsPotential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice.ResultsResearch has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM.ConclusionThis study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

BackgroundThe Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician’s concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood.MethodsHere, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS).ResultsEmploying mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens.ConclusionOverall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

Recent advances in immunotherapy represent a breakthrough in solid tumor treatment but the existing data indicate that immunotherapy is not effective in improving the survival time of patients with glioblastoma. The tumor microenvironment (TME) exerts a series of inhibitory effects on immune effector cells, which limits the clinical application of immunotherapy. Growing evidence shows that phosphate and tension homology deleted on chromosome ten (PTEN) plays an essential role in TME immunosuppression of glioblastoma. Emerging evidence also indicates that targeting PTEN can improve the anti-tumor immunity in TME and enhance the immunotherapy effect, highlighting the potential of PTEN as a promising therapeutic target. This review summarizes the function and specific upstream and downstream targets of PTEN-associated immune cells in glioblastoma TME, providing potential drug targets and therapeutic options for glioblastoma.

This study investigated the effects of hot air drying (HAD), infrared-assisted hot air drying (IR-HAD), vacuum freeze drying (VFD), and pulsed-vacuum drying (PVD) on the drying characteristics, color, microstructure, total phenolic content (TPC), total flavonoid content (TFC), vitamin C (Vc) content, and the odor analysis using electronic nose of sea buckthorn pomace. The results showed that IR-HAD exhibited the highest drying rate and the shortest drying time (250 min). PVD exhibited the highest TPC, TFC, and Vc content while maintaining a color difference ΔE value closest to that of the fresh sample. PVD microstructure exhibited no collapse, fewer pores, and smaller cracks than the IR-HAD and VFD microstructures. Furthermore, the PVD pomace displayed the lowest reactivity to sulfides and ethanol compounds. The comprehensive analysis suggests that PVD holds promise as a drying method for sea buckthorn pomace and provides valuable insights for selecting an appropriate drying method for sea buckthorn pomace.

Parkinson's disease (PD) is characterized by the accumulation of misfolded α-synuclein protein and the loss of dopaminergic neurons in the substantia nigra. Abnormal α-synuclein aggregates form toxic Lewy bodies, ultimately inducing neuronal injury. Mitochondrial dysfunction was reported to be involved in the neurotoxicity of α-synuclein aggregates in PD. However, the specific mechanism by which abnormal α-synuclein aggregates cause mitochondrial disorders remains poorly defined. Previously, we found that cofilin-1, a member of the actin-binding protein, regulates α-synuclein pathogenicity by promoting its aggregation and spreading in vitro and in vivo. In this study, we further investigated the effect of cofilin-1 on α-synuclein induced mitochondrial damage. We discovered that α-synuclein aggregates accelerate the translocation of cofilin-1 to mitochondria, promote its combination with the mitochondrial outer membrane receptor Tom 20, and ultimately activate the oxidative damage and apoptosis pathway in mitochondria. All these results demonstrate the important regulatory role of cofilin-1 in the mitochondrial neurotoxicity of pathological α-synuclein during the progression of PD.

Patients with Osteoarthritis (OA) often also suffer from Sleep Apnea Syndrome (SAS), and many scholars have started to notice this link, although the relationship between the two is still unclear. In this review, we aim to summarize the current literature on these two diseases, integrate evidence of the OA and OSA connection, explore and discuss their potential common mechanisms, and thus identify effective treatment methods for patients with both OA and SAS. Some shared characteristics of the two conditions have been identified, notably aging and obesity as mutual risk factors. Both diseases are associated with various biological processes or molecular pathways, including mitochondrial dysfunction, reactive oxygen species production, the NF-kB pathway, HIF, IL-6, and IL-8. SAS serves as a risk factor for OA, and conversely, OA may influence the progression of SAS. The effects of OA on SAS are underreported in the literature and require more investigation. To effectively manage these patients, timely intervention for SAS is necessary while treating OA, with weight reduction being a primary requirement, alongside combined treatments such as Continuous positive airway pressure (CPAP) and medications. Additionally, numerous studies in drug development are now aimed at inhibiting or clearing certain molecular pathways, including ROS, NF-KB, IL-6, and IL-8. Improving mitochondrial function might represent a viable new strategy, with further research into mitochondrial updates or transplants being essential.

Griffithsin (GRFT) is a highly effective, broad-spectrum, safe, and stable viral inhibitor used to suppress a variety of viruses. However, little information is available on whether GRFT can prevent plant viral diseases. In this study, we constructed a GRFT overexpression vector containing the sweetpotato storage cell signal peptide and generated exogenous GRFT overexpression lines through genetic transformation. The transgenic plants showed notable resistance to sweetpotato virus disease in the virus nursery. To verify the antiplant virus function of GRFT, transient expression in tobacco leaves showed that GRFT inhibited the sweetpotato leaf curl virus (SPLCV). The replication of SPLCV was entirely inhibited when the concentration of GRFT reached a certain level. The results of pulldown and BIFC assays showed that GRFT did not interact with the six components of SPLCV. In addition, the mutated GRFTD/A without the binding ability of carbohydrate and anticoronavirus function, in which three aspartate residues at carbohydrate binding sites were all mutated to alanine, also inhibited SPLCV. Quantitative reverse-transcription PCR analyses showed that the tobacco antiviral-related genes HIN1, ICS1, WRKY40, and PR10 were overexpressed after GRFT/GRFTD/A injection. Furthermore, HIN1, ICS1, and PR10 were more highly expressed in the leaves injected with GRFTD/A. The results suggest that sweetpotato is able to express GRFT exogenously as a bioreactor. Moreover, exogenous GRFT expression inhibits plant viruses by promoting the expression of plant antiviral genes.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies in the world. With the rapid pace of life and changes in diet structure, the incidence and mortality of CRC increase year by year posing a serious threat to human health. As the most complex and largest microecosystem in the human body, intestinal microecology is closely related to CRC. It is an important factor that affects and participates in the occurrence and development of CRC. Advances in next-generation sequencing technology and metagenomics have provided new insights into the ecology of gut microbes. It also helps to link intestinal flora with CRC, and the relationship between intestinal flora and CRC can be continuously understood from different levels. This paper summarizes the relationship between intestinal flora and CRC and its potential role in the diagnosis of CRC providing evidence for early screening and treatment of CRC.

The Permian Capitanian-Changhsingian black shale formed in intra-platform basins are the major source rocks in Southwest China. However, the depositional conditions and organic matter accumulation of these black shales are not well understood. In this study, geochemical characteristics comprise TOC, major, trace and REEs from sixty-two samples from the studied outcrop in Northern Nanpanjiang Basin, Southwest China are systematically investigated to determine silicon source, paleo-ocean productivity, and paleo-redox conditions to reveal their influence on organic matter enrichment under 3rd-order sequence. The Capitanian-Changhsingian black shale in the study area is the result of the combined effects of active extensional activity, high paleo-productivity maintained by volcanic activity, and dysoxic and anoxic conditions represented by biological extinction events. There are differences in the factors controlling organic matter accumulation in black shale at different stages. The controlling factors for the organic enrichment during Capitanian (SQ2) are the rapidly deepening water mass of extensional rifts and the high productivity induced by volcanic ash in the igneous provinces, as well as the global anoxic event represented by “negative carbon isotope shift.” The controlling factors during Changhsingian are the deepening of water mass under the reactivation of extensional rifts, resulting in a dysoxic environment, and the high productivity maintained by volcanic activity in South China. The Wuchiapingian black shale was formed under dysoxic conditions under the stagnation of extensional activity, and intermittent volcanic activity in South China maintained the high paleo-productivity level of the Wuchiapingian stage.

IntroductionMembers of the plant-specific B3 transcription factor superfamily play crucial roles in various plant growth and developmental processes. Despite numerous valuable studies on B3 genes in other species, little is known about the B3 superfamily in pearl millet.Methods and resultsHere, through comparative genomic analysis, we identified 70 B3 proteins in pearl millet and categorized them into four subfamilies based on phylogenetic affiliations: ARF, RAV, LAV, and REM. We also mapped the chromosomal locations of these proteins and analyzed their gene structures, conserved motifs, and gene duplication events, providing new insights into their potential functional interactions. Using transcriptomic sequencing and real-time quantitative PCR, we determined that most PgB3 genes exhibit upregulated expression under drought and high-temperature stresses, indicating their involvement in stress response regulation. To delve deeper into the abiotic stress roles of the B3 family, we focused on a specific gene within the RAV subfamily, PgRAV-04, cloning it and overexpressing it in tobacco. PgRAV-04 overexpression led to increased drought sensitivity in the transgenic plants due to decreased proline levels and peroxidase activity.DiscussionThis study not only adds to the existing body of knowledge on the B3 family’s characteristics but also advances our functional understanding of the PgB3 genes in pearl millet, reinforcing the significance of these factors in stress adaptation mechanisms.

BackgroundSarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients.MethodsPatients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA).ResultsA total of 480 patients with RA were included in the study (90% female, with the largest number in the 45–59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795–0.9498) and 0.907 (95% CI: 0.8552–0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility.ConclusionThis study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

Toxic epidermal necrolysis (TEN) is a rare but serious immune-mediated life-threatening skin and mucous membrane reaction that is mainly caused by drugs, infections, vaccines, and malignant tumors. A 74-year-old woman presented with a moderate fever of unknown cause, which was relieved after 2 days, but with weakness and decreased appetite. Red maculopapules appeared successively on the neck, trunk, and limbs, expanding gradually, forming herpes and fusion, containing a yellow turbidous liquid and rupturing to reveal a bright red erosive surface spreading around the eyes and mouth. The affected body surface area was >90%. The severity of illness score for toxic epidermal necrolysis was 2 points. The drug eruption area and severity index score was 77. She was diagnosed with TEN caused by hepatitis A virus and treated with 160 mg/day methylprednisolone, 300 mg/day cyclosporine, and 20 g/day gammaglobulin. Her skin showed improvements after 3 days of treatment and returned to nearly normal after 1 month, and liver function was completely normal after 2 months.

Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as β-site amyloid precursor protein-cleaving enzyme 1 and γ-secretase or enhancing amyloid-β clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.

IntroductionCorpus callosum injury is a rare type of injury that occurs after a stroke and can cause lower limb dysfunction and a decrease in activities of daily living ability. Furthermore, there are no studies that focus on the progress in rehabilitation of the lower limb dysfunction caused by infarction in the corpus callosum and the effective treatment plans for this condition. We aimed to present a report of two patients with lower limb dysfunction caused by corpus callosum infarction after a stroke and a walking training method.MethodsWe implemented a walking training method that prioritizes bilateral symmetry and increases lateral swaying before the patients established sitting/standing balance. The plan is a rapid and effective method for improving walking dysfunction caused by corpus callosum infarction.Case characteristicsFollowing sudden corpus callosum infarction, both patients experienced a significant reduction in lower limb motor function scores and exhibited evident gait disorders. Scale evaluations confirmed that walking training based on symmetrical and increased lateral sway for patients with lower limb motor dysfunction after corpus callosum infarction led to significant symptom improvement.ConclusionWe report two cases of sudden motor dysfunction in patients with corpus callosum infarction. Symmetrical and increased lateral sway-based walking training resulted in substantial symptom improvement, as confirmed by scale assessments.

BackgroundSelf-leadership has proven to adjust individual psychological states and promote active behaviors to mitigate stress perception and negative lifestyle. This study aims to investigate the relationship between self-leadership, epidemic risk perception, and quality of life among the general public in post-pandemic mainland of China.MethodsTwo online self-reported questionnaire surveys were carried out with 3,098 and 469 people in the Chinese mainland in February 2021 and December 2022, respectively. The univariate analysis, structural equation modeling, and fuzzy-set qualitative comparative analysis were used to analyze the data which was collected by Revised Self-Leadership Questionnaire, Perceived Risk of COVID-19 Pandemic Scale and World Health Organization Quality of Life Brief Scale.ResultsThe Self-leadership was directly, moderately, and positively correlated with quality of life (Standardized path coefficients: 0.383 and 0.491, respectively; p 0.9; RSMEA = 0.058, 0.064

PurposeTo explore the rehabilitation effect and compliance of lumbar and abdominal muscle rehabilitation training in patients with osteoporotic vertebral compression fracture (OVCF) after percutaneous balloon vertebroplasty (PKP).MethodsA total 177 elderly patients with OVCF were divided into rehabilitation group (n = 104) and control group (n = 73) according to whether they received psoas and abdominal muscle rehabilitation training for 3 months after PKP. The differences of general data, orthopaedic rehabilitation, prognosis and bone metabolism were compared between the two groups. All the patients were divided into compliance group (68 cases) and non-compliance group (36 cases) according to compliance. Orthopaedic rehabilitation indicators, prognostic indicators of PKP, and bone metabolism-related parameters were collected for analysis of Chi-square test and Logistic regression. ROC curve was used to analyze the predictive value of bone metabolism related indicators in the compliance of lumbar and abdominal muscle rehabilitation training.ResultsThere was no significant difference in the general data between the rehabilitation training group and the control group (All p > 0.05). Compared with the control group, the Berg balance scale score was significantly increased, while the Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score and the proportion of new fractures were significantly decreased in the rehabilitation training group (All p 75 years, severe anxiety, severe pain and postoperative complications were significantly associated with the compliance of psoas and abdominal muscle rehabilitation training in patients with OVCF after PKP. ROC curve analysis showed that BMD T value, OCN, P1NP, β-CTX, or 25-OH-D levels predicted the AUC of rehabilitation training compliance in patients with OVCF after PKP were 0.821, 0.835, 0.736, 0.715, and 0.748, respectively.ConclusionRehabilitation training of lumbar and abdominal muscles can significantly improve the efficacy of PKP, reduce the degree of osteoporosis and improve the prognosis of patients with OVCF. Age, anxiety, pain and postoperative complications were independent risk factors affecting the compliance of psoas and abdominal rehabilitation training in patients with OVCF after PKP.

In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan’s adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.

Yaks inhabit high-altitude, low-oxygen regions, where ion transport functions play a crucial role in maintaining intracellular and extracellular ionic balance and regulating pulmonary vascular tension. These functions affect pulmonary ventilation and blood flow rate, aiding tissue development and enhancing oxygen transfer efficiency, thus facilitating better adaptation to hypoxic environments. To investigate the regulatory mechanisms of ion transport-related factors on the growth and development of yak lungs, we employed RNA sequencing (RNA-seq)for sequencing the transcriptome in the lung tissues of neonatal (1-day-old), juvenile (1-year-old), and adult (4-year-old) yaks. We also performed differential gene expression and functional analyses. The results yielded 26 genes associated with ion transport, mainly enriched in the salivary and pancreatic secretion pathways. Finally, we used several methods including quantitative polymerase chain reaction (qRT-PCR), and Western blotting (WB), immunohistochemical (IHC) and immunofluorescence (IF) staining to determine the distribution of the expression of the ion transport genes FOXI1, KCNMA1, and SLC12A2 in yak lung tissues. qRT-PCR and WB results indicated that mRNA and protein relative expression levels of FOXI1 and SLC12A2 were significantly higher in neonatal yaks than in juvenile and adult yaks (all p

BackgroundThis study aimed to systematically evaluate the clinical efficacy of Jingjin (muscle region of the meridian, sinew/tendon/fascia) acupuncture therapy for the treatment of spastic cerebral palsy.MethodsComputer searches of the Cochrane Library, Web of Science, PubMed, Embase, Chinese Biomedical Literature (CBM) Database, Wanfang database, Wipu (VIP) database, and China National Knowledge Infrastructure (CNKI) database for published randomized controlled trial (RCT) studies on Jingjin acupuncture treatment of cerebral palsy from the beginning of the database construction until 30 November 2023 were performed, and the quality of the papers was assessed through independent data extraction by two individuals and then meta-analyzed using RevMan5.4 software. A total of 20 RCTs involving 1,453 patients were included.ResultsThe overall effective rate of Jingjin acupuncture therapy was better than that of conventional therapy, with a combined odds ratio (OR) of 4.70 and a 95% confidence interval (CI) of [3.05, 7.24]. The Modified Ashworth Spasticity (MAS) Scale, Gross Motor Function Measure (GMFM), Fine Motor Function Measure (FMFM), and Comprehensive Spasticity Scale (CSS) scores are superior to conventional therapy.ConclusionJingjin acupuncture therapy is effective in treating spastic cerebral palsy and has better overall efficacy than conventional therapy. Due to the low quality of some of the literature in this study type, more high-quality, well-designed clinical studies are needed to validate it.

PIN-FORMED (PIN) proteins, which function as efflux transporters, play many crucial roles in the polar transportation of auxin within plants. In this study, the exogenous applications of auxin IAA and TIBA were found to significantly prolong and shorten the florescence of tree peony (Paeonia suffruticosa Andr.) flowers. This finding suggests that auxin has some regulatory influence in petal senescence and abscission. Further analysis revealed a total of 8 PsPINs distributed across three chromosomes, which could be categorized into two classes based on phylogenetic and structural analysis. PsPIN1, PsPIN2a-b, and PsPIN4 were separated into the “long” PIN category, while PsPIN5, PsPIN6a-b, and PsPIN8 belonged to the “short” one. Additionally, the cis-regulatory elements of PsPIN promoters were associated with plant development, phytohormones, and environmental stress. These genes displayed tissue-specific expression, and phosphorylation sites were abundant throughout the protein family. Notably, PsPIN4 displayed distinct and elevated expression levels in roots, leaves, and flower organs. Expression patterns among the abscission zone (AZ) and adjacent areas during various flowering stages and IAA treatment indicate that PsPIN4 likely influences the initiation of peony petal abscission. The PsPIN4 protein was observed to be co-localized on both the plasma membrane and the cell nucleus. The ectopic expression of PsPIN4 reversed the premature flower organs abscission in the Atpin4 and significantly protracted florescence when introduced to Col Arabidopsis. Our findings established a strong basis for further investigation of PIN gene biological functions, particularly concerning intrinsic relationship between PIN-mediated auxin polar

Root rot is a major disease that causes decline of alfalfa production, and Fusarium is a major pathogen associated with root rot. In this study, 13 Fusarium isolates were obtained from alfalfa with root rot in Gansu Province, the major alfalfa production region in China. The isolates were characterized by molecular genotyping (ITS, TEF 1-α and RPB2 fragments) and identified as six species, which included the F. acuminatum, F. incarnatum, F. oxysporum, F. proliferatum, F. redolens, and F. solani. We found that their morphology varied significantly at both the macro- and micro-levels, even for those from the same species. We developed a low cost and fast pathogenicity test and revealed that all isolates were pathogenic to alfalfa with typical root rot symptoms such as leaf yellowing and brown lesions on the root and stem. However, the virulence of the isolates differed. We also found that the conidia of all isolates germinated as early as 24 hours post inoculation (hpi), while hyphae colonized the root extensively and invaded the xylem vessel by 48 hpi. Together our results reveal that different virulent Fusarium isolates use a similar invasion strategy in alfalfa. This natural plant-fungus pathosystem is intriguing and warrants further examination, particularly with regard to efforts aimed at mitigating the impact of multiple similar vascular pathogens on infected alfalfa plants.

BackgroundCreatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function.MethodsWe selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively.ResultsAmongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P