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Continuous tobacco monocropping has caused soil degradation and yield reduction in China. Intercropping, as a specific and efficient cropping pattern, is highly associated with the enhancement of soil quality and land-use efficiency. Tobacco (Nicotiana tabacum L.)- Isatis (Isatis tinctoria L.) intercropping can significantly alleviate pests and diseases, and improve soil potential and fertility in tobacco fields. In this study, comparative analysis of three different tobacco-Isatis intercropping (B2, B3, B4) and tobacco monocropping (B1) on the soil nutrients, enzyme activities, and microbial community were conducted. B2, B3, and B4 importantly increased the contents of organic matter, available potassium, and available phosphorus content of the soil by 17.38%, 7.76%, and 2.78%, respectively. Moreover, B2 enhanced the activities of sucrase, urease, and catalase of soil by 2.35 times, 3.16 times, and 4.47 times, respectively, and B3 enhanced the activities of sucrase, urease, and catalase of soil by 2.74 times, 3.22 times, and 3.11 times, respectively. The intercropping pattern also optimized the structure of the soil microbial community. The relative abundances of Acidobacteriota, Chloroflexi, Gemmatimonadota, Planctomycetota, Nitrospirota, and Verrucomicrobiota in B3 and B4 were higher than those in B1. Positive links in soil bacterial correlation networks accounted for 47%, and soil bacteria formed a highly interactive and complex network. And compared with the B1, Ascomycota and Basidiomycota were lower abundance in B2 and B4, Ascomycota were lower abundance in B3 and Mortierellomycota were lower abundance in B2 and B3. Compared with monocropping, the chemical composition of tobacco leaves was harmoniously improved and the total production value of tobacco fields was significantly higher. The content of reducing sugar, total sugar, nicotine, potassium, and two-sugar ratio of leaves were increased after intercropping. The proportion of top-grade tobacco leaves after roasting in B2, B3, and B4 treatments were increased by 8.19%, 16.74%, and 27.32%, respectively. The study constructs insights into microbial community interactions at in tobacco/Isatis intercropping systems, and may facilitate the further development of tobacco/Isatis intercropping systems.

IntroductionGemcitabine and cisplatin remain the cornerstone for the treatment of advanced or unresectable biliary tract cancers, but the incidence rate of the grade 3 or 4 toxic effects is high (70.7%). In recent years, significant progress has been achieved in the systemic treatment of cholangiocarcinoma with immune checkpoint inhibitors (ICIs), targeted therapy, and hepatic artery infusion chemotherapy (HAIC). HAIC may elevate the local drug concentration in the liver to 10–100 times the drug plasma concentration; therefore, it may enhance tumor cytotoxicity while minimizing systemic adverse effects. HAIC combined with immunotherapy and targeted therapy resulted in acceptable tumor responses and tolerable toxic effects in the treatment of hepatocellular carcinoma (HCC). However, whether this combination strategy can benefit patients with unresectable intrahepatic cholangiocarcinoma remains unclear.Methods and AnalysisWe describe a single-arm, open label, prospective clinical trial of HAIC sequential transcatheter arterial embolization (TAE) combined with tislelizumab and surufatinib in patients with unresectable intrahepatic cholangiocarcinoma. TAE + HAIC was performed at an interval of at least 3 weeks, and oxaliplatin (85 mg/m2) and rituximab (3 mg/m2) were infused. TAE was performed using undrugged microspheres. Tislelizumab was infused every 3 weeks and surufatinib was administered orally once a day, with 3-5 capsules (50 mg/capsule) each time. We plan to enroll 28 participants in this study. The primary study endpoint was objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), conversion to surgical resection rate, overall survival (OS), 1-year OS rate, disease control rate (DCR), quality of life (QoL), and incidence of adverse events.Trial registration numberNCT06239532.

BackgroundPeritoneal dialysis-related peritonitis (PDRP) is one of the most common complications of peritoneal dialysis (PD). Understanding the risk factors and etiological characteristics is indispensable for infection prevention and improving the outcome and life quality.MethodsA total of 70 PD patients were separated into the PDRP group (n=25) and the control group (n=45). Variables, including gender, age, body mass index, primary diseases, and history of basic diseases, in the two groups were analyzed to assess the risk factors of PDRP. Metagenomic next-generation sequencing (mNGS) and microbial culture were compared in detecting pathogenic microorganisms. Gut microbiota analysis was performed in 35 PDRP patients based on mNGS data.ResultsDialysis time and times of dialysate change were the risk factors of PDRP, and times of dialysate change was the independent risk factor of PDRP (p = 0.046). mNGS produced higher sensitivity (65.79%) than microbial culture (36.84%) in identifying pathogenic microorganisms. Staphylococcus aureus and Klebsiella pneumoniae (four cases) were the most frequent pathogens causing PDRP, followed by Staphylococcus capitis (three cases). β diversity of the gut microbiota was significantly different between patients with fewer times of dialysate change (≤4) and more (>5), as well as between patients with gram-positive (G+) bacterial and gram-negative (G−) bacterial infection.ConclusionThe dialysis time and times of dialysate changes not only are risk factors for peritonitis in PD patients but also stimulate significant changes in the gut microbiome structure in PDRP patients. These findings may provide a novel viewpoint for the management of patients with PDRP.

ImportanceClinical trials in recent years have shown significant effectiveness of complement inhibitors for geographic atrophy (GA) treatment. Two complement inhibitor drugs have been approved by the Food and Drug Administration (FDA).Objectiveto compare and rank the different complement inhibitors in the treatment of GA secondary to age-related macular degeneration (AMD).Data sourcesA systematic literature search was conducted in the Cochrane Central, Web of Science Core Collection, PubMed, LWW Medical Journals, ClinicalTrials.gov, and WHO ICTRP from inception to October 2023.Study selectionAll randomized clinical trials evaluating the effectiveness of complement inhibitors in patients diagnosed with secondary GA in AMD were identified.Data extraction and synthesisThis study followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) network meta-analysis Checklist of Items and the Cochrane Risk of Bias Assessment Tool for assessing the study quality. Multiple authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Random-effects network meta-analyses were applied. Bayesian network meta-analysis was performed using the BUGSnet package in R (4.2.0).Main outcomes and measuresThe primary efficacy outcome was the change in GA lesion size (mm2) from baseline to month 12. The secondary efficacy outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to month 12. Safety outcome measures included the number of subjects with serious adverse events (SAEs) and macular neovascularization (MNV).ResultsTen randomized controlled trials including 4,405 participants and five complement inhibitors were identified. Comparison with sham and SUCRA analysis showed that avacincaptad pegol 2 mg (MD: −0.58, 95% CrI: −0.97 to −0.18, SUCRA: 93.55), pegcetacoplan monthly (MD: −0.38, 95% CrI: −0.57 to −0.20, SUCRA: 81.37), and pegcetacoplan every other month (MD: −0.30, 95% CrI: −0.49 to −0.11, SUCRA: 70.16) have significant changes in GA lesion reduction. No treatments showed significant changes in BCVA and SAE compared with sham. Pegcetacoplan monthly (OR: 4.30, 95% CrI: 1.48–16.72) increased the risk of MNV. Avacincaptad pegol 2 mg demonstrated favorable outcomes in terms of SAE and MNV.Conclusion and relevanceAvacincaptad pegol 2 mg is the most effective complement inhibitor with better safety for the treatment of GA secondary to AMD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351515, Identifier PROSPERO CRD42022351515.

This study was designed to investigate the effects of adding a novel yeast culture, Saccharomyces cerevisiae refermented sorghum distiller's dried grains with solubles (SSDDGS), to the diets of lactating female goats on lactation performance and lamb growth performance. We divided 10 lactating Dazu black goats of similar age, weight, and offspring into two groups: one fed a pelleted diet with 50 g/day SSDDGS (ET), and the other without SSDDGS as a control (EC) for 7 weeks. We monitor the weight changes of each goat and collect blood and milk samples from experimental ewes at specific times for hormone and milk composition determination. We use ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to detect metabolites in the serum of lactating ewes. Our results showed that SSDDGS supplementation significantly reduced female goats' average daily weight loss during weeks 2–4 of lactation and increased serum IGF-1 and prolactin levels at week 4 (p < 0.05). SSDDGS supplementation in early lactation significantly increased milk protein, lactose, and ash content (p < 0.05). UPLC-MS/MS analysis showed that SSDDGS changed the levels of 58 metabolites in the serum of lactating goats. These metabolites were mainly involved in the sohingolipid signaling pathway, and cysteine, methionine, and sphingolipid metabolism. In summary, Yeast culture SSDDGS reduced weight loss, enhanced milk quality, and modified metabolic profiles in early lactation goats, providing insight into the potential regulatory role and mechanism of yeast culture in lactation female goats.

IntroductionThe endometrium plays a crucial role in early human pregnancy, particularly in embryo implantation, survival, and growth. However, invasion and infection by pathogens can lead to endometritis, infertility, and poor reproductive outcomes. Understanding the mechanisms of endometritis and its impact on fertility remains limited. An infection model using patient-derived endometrial epithelial gland organoids (EEGOs) was established to advance in vitro studies on endometritis and related infertility.MethodsAn EEGOs infection model was constructed and characterized from human endometrium, treating the organoids with estrogen and progesterone to observe changes in the proliferative and secretory phases. The organoids were infected with E. coli, and the release of inflammatory cytokines in the supernatant was detected using ELISA. RNA-seq was employed to analyze the differences before and after E. coli treatment, and differential gene mRNA expression was validated using real-time quantitative PCR. Additionally, the effect of E2 in alleviating inflammation was assessed through markers of receptivity (PAEP, LIF, ITGβ), proliferation (Ki67), and barrier repair (ZO-1).ResultsThe constructed human EEGOs exhibited long-term expansion capability, genetic stability, and characteristic hormonal responses, strongly expressing epithelial markers (MUC1, E-Cadherin). After E. coli infection, the expression levels of inflammatory cytokines TNF-α, IL-8, and IFN-γ increased significantly (P

ObjectivePrevious observational studies have suggested associations between various inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy. However, the causal association remains uncertain.MethodSummary statistics for type 2 diabetes mellitus and diabetic nephropathy were obtained from a publicly available genome-wide association study. Data on inflammatory cytokines were sourced from a genome-wide association study on protein quantitative trait loci. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted mode, and weighted median method were employed as supplementary analyses. Sensitivity analyses were performed to detect heterogeneity and potential horizontal pleiotropy in the study.ResultGenetic evidence indicated that elevated levels of fibroblast growth factor 19 levels promoted the occurrence of type 2 diabetes mellitus, and increased concentrations of fibroblast growth factor 21 levels, C-C motif chemokine 19 levels, eotaxin levels, and interleukin-10 mitigated the risk of developing type 2 diabetes mellitus, while type 2 diabetes mellitus did not exert a significant influence on said proteins. Elevated levels of tumor necrosis factor ligand superfamily member 14 and TNF-related activation-induced cytokine were associated with an increased risk of diabetic nephropathy, and increased concentrations of interleukin-1-alpha and transforming growth factor-alpha were potentially correlated with a diminished risk of diabetic nephropathy. Sensitivity analyses further ensure the robustness of our findings.ConclusionMendelian randomization analysis highlights a causal association between inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy, offering valuable evidence and reference for future research.

PurposeCurrently, chemoimmunotherapy is effective only in a subset of patients with advanced non-squamous non-small cell lung cancer. Robust biomarkers for predicting the efficacy of chemoimmunotherapy would be useful to identify patients who would benefit from chemoimmunotherapy. The primary objective of our study was to develop an artificial intelligence-based immunoscore and to evaluate the value of patho-immunoscore in predicting clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (NSCLC).MethodsWe have developed an artificial intelligence–powered immunoscore analyzer based on 1,333 whole-slide images from TCGA-LUAD. The predictive efficacy of the model was further validated in the CPTAC-LUAD cohort and the biomarker cohort of the ORIENT-11 study, a randomized, double-blind, phase 3 study. Finally, the clinical significance of the patho-immunoscore was evaluated using the ORIENT-11 study cohort.ResultsOur immunoscore analyzer achieved good accuracy in all the three cohort mentioned above (TCGA-LUAD, mean AUC: 0.783; ORIENT-11 cohort, AUC: 0.741; CPTAC-LUAD cohort, AUC: 0.769). In the 259 patients treated with chemoimmunotherapy, those with high patho-immunoscore (n = 146) showed significantly longer median progression-free survival than those with low patho-immunoscore (n = 113) (13.8 months vs 7.13 months, hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.38 – 0.73; p < 0.001). In contrast, no significant difference was observed in patients who were treated with chemotherapy only (5.07 months vs 5.07 months, HR: 1.04, 95% CI: 0.71 – 1.54; p = 0.83). Similar trends were observed in overall survival.ConclusionOur study indicates that AI-powered immunoscore applied on LUAD digital slides can serve as a biomarker for survival outcomes in patients with advanced non-squamous NSCLC who received chemoimmunotherapy. This methodology could be applied to other cancers and facilitate cancer immunotherapy.

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

Background Gynecological cancers (GC) pose a severe threat to the health and safety of women’s lives, and organoids, as in-vitro research models, have demonstrated significant advantages in simulating tissue characteristics and drug screening. In recent years, there has been a rapid increase in research outcomes related to organoids in GC. However, there has been no bibliometric study concerning.Methods Publications related to GC and organoids from 2010-2023 were retrieved from the Web of Science Core Collection (WoSCC). We conducted a bibliometric analysis and visualization using CiteSpace, VOSviewer, and the Bibliometrix R Package. This analysis included the spatiotemporal distribution, author, sources, references, and keywords.Results A total of 333 publications were included. The number of annual publications indicated an explosive phase of development since 2019. The USA was the most important country in terms of cooperation, publication output, citation and centrality. University of California system ranked first in productivity among institutions, and HIPPO Y is the most relevant author in the research field. CANCERS published the most documents, and NATURE is the most cited sources. Analysis of Keywords and References, it is possible to establish the trend, and find the hotspots in the research field.Conclusion This bibliometric analysis delineated global landscapes and progress trends in GC organoids research. This study emphasized that organoids can effectively replicate the original tissue or tumors, providing a good in-vitro model for research on tumor-related mechanisms and showing significant advantages in drug screening and efficacy clinical prediction. Additionally, as preclinical models, they provide compelling evidence for personalized therapy and prediction of patient drug responses.

BackgroundShort video addiction (SVA) among college students is influenced by personality traits, namely, neuroticism and agreeableness. However, the role of depression and anxiety as mediators remains unclear.ObjectiveThis study aims to explore the mediating role of comorbid depression and anxiety in the relationship between different dimensions of university students’ personalities and SVA.MethodsThe SPSS PROCESS was utilized to analyze data from 804 university students across seven universities in China.ResultsThe findings show that neuroticism, agreeableness, and extraversion in the personalities of Chinese university students are all significantly linked to SVA; neuroticism and agreeableness in the personalities of university students have a greater impact on SVA; both neuroticism and agreeableness can first induce depression and then lead to anxiety and SVA, whereas only agreeableness can first lead to anxiety and then result in depression and SVA.ConclusionThis study uncovers the intricate relationship between personality traits and SVA among college students, emphasizing depression and anxiety as critical chain mediators in this relationship. It reveals that neuroticism and agreeableness significantly influence SVA through specific pathways involving depression and anxiety, indicating that interventions targeting these traits are essential.

BackgroundCardiomyocyte senescence plays a crucial role as a pathological mechanism in heart failure (HF). However, the exact triggering factors and underlying causes of HF onset and progression are still not fully understood.ObjectivesBy integrating multi-omics data, this study aimed to determine the genetic associations between cardiomyocyte and HF using cell senescence-related genes (SRGs).MethodsThe study utilized the CellAge database and the SenMayo dataset, combined with high-resolution single-cell RNA sequencing (scRNA-seq) data, to identify SRG and examine differences in cardiac cell expression. To explore the causal relationship with HF using Mendelian Randomization (MR). Genetic variations influencing gene expression, DNA methylation, and protein expression (cis-eQTL, cis-mQTL, and cis-pQTL) were analyzed using the two-sample MR (TSMR) and summary-data-based MR (SMR). Additionally, Bayesian colocalization analysis, germline genetic variation, and bulk RNA data were employed to strengthen the reliability of the results. The application potential of therapeutic targets is ultimately assessed by evaluating their druggability.ResultsThe expression of 39 SRGs in cardiomyocytes was identified. In the discovery set revealed that CDKN1A (OR = 1.09, 95% confidence interval (CI) 1.02–1.15, FDR = 0.048) could be causally related to HF, and the results are also replicated in the validation set (OR = 1.20, 95% confidence interval (CI) 1.10–1.30, FDR

Low temperature chilling is one of the major abiotic stresses affecting growth and yield of Triticum aestivum L. With global climate change, the risk of cold damage in wheat production has increased. In recent years, with the extensive research on wheat chilling resistance, especially the development of genetic engineering technology, the research on wheat chilling resistance has made great progress. This paper describes the mechanism of wheat cold damage, including cell membrane injury, cytoplasmic concentration increased as well as the imbalance of the ROS system. Mechanisms of cold resistance in wheat are summarised, including hormone signalling, transcription factor regulation, and the role of protective enzymes of the ROS system in cold resistanc. Functions of cloned wheat cold resistance genes are summarised, which will provide a reference for researchers to further understand and make use of cold resistance related genes in wheat. The current cold resistant breeding of wheat relies on the agronomic traits and observable indicators, molecular methods are lacked. A strategy for wheat cold-resistant breeding based on QTLs and gene technologies is proposed, with a view to breeding more cold-resistant varieties of wheat with the deepening of the research.

This case report describes a rare instance of extrarenal clear cell renal cell carcinoma (ccRCC) in a 48-year-old woman who presented with a loss of consciousness. Abdominal CT revealed a 24 × 31 mm mass in the left adrenal region, with no kidney involvement. The mass was surgically excised, and histopathological examination confirmed the diagnosis of ccRCC. Immunohistochemical analysis revealed positive markers, including CA9, CD10, PAX-8, and vimentin. The patient did not undergo adjuvant therapy, and a 6-month follow-up showed no signs of recurrence or metastasis. This case emphasizes the importance of considering extrarenal ccRCC in differential diagnoses of adrenal masses.

Salmonella enterica ser. Typhimurium is a common pathogen that poses a considerable public health threat, contributing to severe gastrointestinal diseases and widespread foodborne illnesses. The virulence of S. Typhimurium is regulated by quorum sensing (QS) and the type III secretion system (T3SS). This study investigated the inhibitory effects and anti-QS activity of epigallocatechin gallate (EGCG), which is a bioactive ingredient found in green tea, on the virulence of S. Typhimurium. In vitro bacterial experiments demonstrated that EGCG inhibited the production of autoinducers, biofilm formation, and flagellar activity by downregulating the expression of AI-1, AI-2, Salmonella pathogenicity islands (SPI)-1, SPI-2, and genes related to flagella, fimbriae, and curli fibers. In a mouse model of S. Typhimurium-induced enteritis, EGCG considerably reduced intestinal colonization by S. Typhimurium and alleviated intestinal damage. In conclusion, EGCG protects the intestines of mice infected with S. Typhimurium by inhibiting QS-induced virulence gene expression, demonstrating its potential as a therapeutic agent for controlling S. Typhimurium infections.

BackgroundHelicobacter pylori (H. pylori) infection poses a global health challenge, necessitating diverse treatment strategies. This network meta-analysis aimed to assess various treatment regimens for H. pylori in East and Southeast Asian populations.MethodsA systematic search was conducted in PubMed, Embase, and the Cochrane Library databases from inception to 20 Dec 2023, to identify relevant randomized controlled trials (RCTs) on H. pylori treatment interventions in East Asian and Southeast Asian populations. The primary outcome focused on effectiveness, specifically the rate of H. pylori eradication, while the secondary outcome evaluated overall safety, including the incidence of total and serious adverse effects. Network geometry plots were generated to illustrate direct and indirect treatment comparisons, using triple therapy (TT) as the reference standard. Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models to account for study heterogeneity and consistency models for indirect comparisons. The treatment hierarchy was assessed using the ranking probabilities and surface under the cumulative ranking curve (SUCRA) values.Results79 studies met the inclusion criteria, with 99 paired comparisons. The included studies, conducted in Southeast Asia and among East Asian populations, included 29,903 patients. Significant outcomes in treat effectiveness were observed in various comparisons, such as sequential therapy vs. TT, bismuth quadruple therapy (BQT) vs. TT, high-dose dual therapy (HDDT) vs. TT, concomitant therapy vs. TT, P-CAB-based therapy vs. TT, and R-HT/HT vs. TT. R-HT/HT was the top choice based on rankograms and SUCRA values (SUCRA = 96.5). Regarding overall safety, significant results were noted in comparisons involving BQT, HDDT, concomitant therapy, sequential therapy, and P-CAB-based therapy. HDDT achieved the highest overall safety based on rankograms and SUCRA values (SUCRA = 0.0). HDDT demonstrated the lowest incidence of serious adverse events, according to global rankograms and SUCRA values (SUCRA = 19.7).ConclusionThis network meta-analysis highlights the complexity of treating H. pylori in East and Southeast Asia. R-HT/HT emerged as the most effective regimen, while HDDT proved to be the safest, with the lowest incidence of serious adverse events. These findings are crucial for optimizing treatment protocols in these regions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023435318.

BackgroundFunctional constipation in children is a worldwide problem that impacts both children's gastrointestinal function and the quality of family life. The treatment of this condition often depends on parental involvement to administer rectal interventions to their children to stimulate defecation. However, adherence to rectal interventions is currently suboptimal. We sought to explore the factors that facilitate and hinder parents from adherence to rectal interventions.MethodsA descriptive qualitative study was conducted involving semi-structured interviews with parents of infants and young children with functional constipation requiring rectal interventions from March to May 2023. The data were analyzed using content analysis.ResultsFourteen parents participated in the study. Parents reported the main facilitators of adherence to prescribed rectal interventions as recognition of illness severity, support from family and friends, and medical resource support and e-health literacy. Parents reported the primary barriers as information barriers, family conflict, cognitive misalignment, and difficulties in accessing healthcare services.ConclusionRectal interventions are often essential in managing constipation in young children, with parental compliance being crucial for effective treatment. Healthcare providers must consider the psychosocial aspects of parents’ perceptions, adhere to guidelines to standardize communication, and ensure comprehensive education to improve medication literacy.

ObjectiveTo investigate the potential correlation between body mass index (BMI) and the 28-day mortality rate among sepsis patients and the gender difference in this association.DesignThe current research was a retrospective cohort study.ParticipantsA total of 14,883 male and female cohorts of sepsis patients were included in the Medical Information Mart for Intensive Care IV (MIMIC-IV V2.2) database. Patients in each gender cohort were further classified as underweight, normal weight, overweight, or obese according to BMI and the World Health Organization (WHO) BMI categories.OutcomesThe 28-day mortality from the date of ICU hospitalization was the primary outcome measure.ResultsThe BMI and 28-day mortality exhibited an L-shaped relationship (p for nonlinearity

The abundance of specific hydrocarbon-oxidizing bacteria (MV value) in surface soil is closely linked to the concentration of thermogenic light hydrocarbons found in the underlying layers. The identification of these bacteria using specific detection techniques offers unique insights into microbiological anomalies associated with oil and gas, underscoring the significance of delineating microbiological geochemical anomalies in the exploration process. Accurate determination of the anomaly range is crucial for forecasting potential oil and gas reservoirs. In this study, a variety of fractal and geological statistical methods were employed to analyze microbiological geochemical data from the Taiwan Strait Basin. The multifractal approach allows for the simultaneous assessment of spatial autocorrelation and singularity in geochemical fields, with the fractal distribution reflecting the localized enrichment and depletion patterns of microbiological geochemical elements in rocks and other substrates. Geological statistical methods, such as the variation function, enable the assessment of spatial autocorrelation in geochemical and geophysical fields. The results indicate that microbiological anomalies in the Jiulongjiang Depression are mainly concentrated in the southwestern part of the study area, with some anomalies also observed in the central region. Conversely, microbiological anomalies in the Jinjiang Depression are predominantly located in the southern portion of the study area. Microbiological anomalies in the study area (Jinjiang Depression and Jiulongjiang Depression) exhibit a northeast-southwest strip distribution, aligning with the trend of the depressions and faults, suggesting that faults could influence the distribution of oil and gas resources in the region. Based on microbiological statistical analyses, the Jiulongjiang Depression shows better potential for oil and gas prospects compared to the Jinjiang Depression, guiding future research efforts in the Jiulongjiang Depression.

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.

BackgroundsCrush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures.MethodsMice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols.ResultsThe results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state.ConclusionWe successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI.

IntroductionTo investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms.Methods56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR.Results654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI.DiscussionThis study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock.

BackgroundThis study aims to explore the association between sleep duration and the prevalence of chronic musculoskeletal pain (CMP).MethodsA cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010, which involved multiple centers across the United States. The study included 3,904 adults selected based on age and complete data availability. Demographic variables such as gender, age, race, and socioeconomic status (represented by the poverty-to-income ratio) were considered.ResultsOf the participants, 1,595 reported less than 7 h of sleep, 2,046 reported 7–8 h, and 263 reported more than 9 h of sleep. Short sleep duration was associated with higher odds of CMP (OR, 1.611, 95% CI: 1.224–2.120, p = 0.005). Long sleep duration also showed a higher prevalence (OR, 1.751; 95% CI, 0.923 to 3.321; p = 0.059), although this result was not statistically significant. A U-shaped relationship emerged (Effective degree of freedom (EDF) = 3.32, p

Pseudorabies virus (PRV) exhibits a complex interplay of host-pathogen interactions, primarily by modulating host cell death pathways to optimize its replication and spread in Neuro-2a cells. Using high-throughput RNA sequencing, we identified 2,382 upregulated differentially expressed genes (DEGs) and 3,998 downregulated DEGs, indicating a intricate interaction between viral pathogenesis and host cellular responses. This research offers valuable insights into the molecular processes involved in PRV infection, highlighting the substantial inhibition of crucial cell death pathways in Neuro-2a cells, including necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. Cells infected with PRV exhibit decreased expression of genes critical in these pathways, potentially as a mechanism to avoid host immune reactions and ensure cell survival to support ongoing viral replication. This extensive inhibition of apoptosis and metabolic alterations highlights the sophisticated tactics utilized by PRV, enhancing our comprehension of herpesvirus biology and the feasibility of creating specific antiviral treatments. This research contributes to our understanding of how viruses manipulate host cell death and presents potential opportunities for therapeutic interventions to disrupt the virus’s lifecycle.

Long-term continuous cropping of tobacco causes dysbiosis of soil microbial communities, the imbalance of soil nutrients, and the increase of pathogenic bacteria, which will slow the growth and development of tobacco plants, reduce the production quality, and cause significant losses to tobacco production and tobacco farmers. The application of Potassium fulvic acid can not only provide nutrients, but also inhibit the propagation of pathogens in soil along with raising the amount of organic matter in the soil, which is an effective way to improve soil health. In this experiment, Tobacco variety SNT60 was used as the test material, and 6 treatments were set up by pot test, they were: no fertilisation control group (CK), tobacco special fertiliser (NPK), 3.45 g/kg of potassium fulvic acid fertiliser (T1), 4.65 g/kg of potassium fulvic acid fertiliser (T2), 5.85 g/kg of potassium fulvic acid fertiliser (T3), 7.05 g/kg of potassium fulvic acid fertiliser (T4), Ten replications were set up for each treatment and the soil and fertiliser were mixed and potted before transplanting, 70% as basal fertiliser and 30% as supplementary fertiliser. We also analyzed soil properties, soil microorganisms and agronomic traits of tobacco plants in different treatments to provide reference for mitigating tobacco succession barrier. The test results are as follows: 4.65 g/kg of potassium fulvic acid fertiliser (T2) treatment was the best, soil organic matter, quick nitrogen, phosphorus, potassium, pH, soil catalase, soil sucrase, and soil urease content, compared to CK control, increased by 22.04%, 43.12%, 96.21%, 381.79%, 25.43%, 91.69%, 262.07% and 93.16%. In terms of microbial community, application of potassium fulvic acid fertiliser significantly increased the relative abundance of Ascomycetes, Chlorobacterium, Bacillus, Proteobacteria and Tephritobacterium in the soil. Meanwhile, 4.65 g/kg of potassium fulvic acid fertiliser (T2) promoted the growth of tobacco plants, improved leaf photosynthetic capacity, and enhanced plant disease resistance. This experiment provides practical measures to improve the microbial community of tobacco continuous cropping soils and to reduce the incidence of diseases.

Plant growth, crop yield, and pest and disease control are enhanced by PGPR (Plant growth promoting rhizobacteria), which are beneficial microorganisms found in a close symbiosis with plant roots. Phytohormones are secreted, nutrient uptake is improved, and soil properties along with the microbiological environment are regulated by these microorganisms, making them a significant focus in agricultural research. In this study, the efficient PGPR strain T1 was isolated and screened from tobacco inter-root soil, and identified and confirmed by ITS sequencing technology. Tobacco growth indicators and soil property changes were observed and recorded through potting experiments. The activities of key enzymes (e.g., sucrase, catalase, urease) in soil were further determined. High-throughput sequencing technology was utilized to sequence the soil microbial community, and combined with macro-genomics analysis, the effects of T1 strain on soil microbial diversity and metabolic pathways were explored. Following the application of T1, significant improvements were observed in the height, leaf length, and width of tobacco plants. Furthermore, the physical and chemical properties of the soil were notably enhanced, including a 26.26% increase in phosphorus availability. Additionally, the activities of key soil enzymes such as sucrase, catalase, and urease were significantly increased, indicating improved soil health and fertility. Comprehensive joint microbiomics and macrogenomics analyses revealed a substantial rise in the populations of beneficial soil microorganisms and an enhancement in metabolic pathways, including amino acid metabolism, synthesis, and production of secondary metabolites. These increase in beneficial microorganisms and the enhancement of their metabolic functions are crucial for plant growth and soil fertility. This study provides valuable references for the development of innovative microbial fertilizers and offers programs for the sustainable development of modern agriculture.

ObjectiveCirculating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial.Research design and methodsA subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years.ResultsIn fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models.DiscussionThis study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

BackgroundParkinson’s disease is characterized by symptoms such as bradykinesia and rigidity, which worsen as the disease progresses, significantly impacting patients’ independence and quality of life. This study utilizes a network meta-analysis approach to quantify information gathered from randomized controlled trials (RCTs) regarding motor interventions that effectively improve the motor function of Parkinson’s disease patients, aiming to provide evidence for selecting appropriate exercise intervention strategies for patients.MethodsA systematic search strategy for randomized controlled trials (RCTs) restricted to English was constructed based on multiple biomedical databases. Databases searched included PubMed, Embase, Cochrane, Web of Science, CINAHL, CBM, China National Knowledge Infrastructure (CNKI), Wan fang, VIP, etc., with searches conducted from inception to July 9, 2023. Two authors screened all studies, extracted data, and used frequency domain analysis methods. Network meta-analysis was performed using STATA software version 18.0 to compare and rank exercises that could effectively improve the motor function of Parkinson’s disease patients (measured by indicators such as MDS-UPDRS-III, TUG, BBS, Mini-BES Test, 6MWT scores). Additionally, a series of analyses and evaluations were conducted, such as assessing the methodological quality of included studies using the Cochrane risk of bias tool.ResultsThe network meta-analysis included a total of 111 studies involving 5,358 participants, 133 intervention experiments, and 31 intervention measures. Although most exercise interventions showed effectiveness, cumulative ranking curves under the surface (SUCRA) values showed that archery exercise significantly improved patients’ MDS-UPDRS-III scores (SUCRA = 95.6%), significantly superior to routine care [standardized mean difference (SMD = 16.92, 95%CI = −28.97, −4.87)]. High-intensity and agility exercise (High strength and agility) referred to as high-intensity exercise or agility training or a combination of both, collectively termed as high-intensity agility training, significantly improved patients’ completion time for the time-up-and-go test (SUCRA = 99.7%), (SMD = −7.88, 95%CI = −9.47, −6.28). Dance and Tai Chi exercises significantly improved patients’ balance abilities: Mini-Balance Evaluation Systems Test (SUCRA = 77.9%), (SMD = 5.25, 95%CI = −0.42, 10.92) for dance intervention and Berg Balance Scale (SUCRA = 94.7%), (SMD = 11.22, 95%CI = 3.26, 19.18) for Tai Chi intervention. Dance also significantly improved patients’ walking ability in the 6-min walk test (SUCRA = 80.5%), (SMD = 71.31, 95%CI = 13.77, 128.84).ConclusionCompared to other exercises, archery, dance, Tai Chi, and high-intensity agility exercises demonstrate superior efficacy in improving the motor function of Parkinson’s disease patients.

IntroductionThe impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients.MethodsThis epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections.ResultsIn total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates.ConclusionVaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important.Clinical Trial registrationClinicalTrails.gov, NCT05888909.

Among the largest transcription factor families in plants, bZIPs are crucial for various developmental and physiological processes, particularly abiotic stress resistance. Setaria italica has become a model for understanding stress resistance mechanisms. In this study, we identified 90 bZIP transcription factors in the Setaria italica genome. SibZIPs were classified into 13 groups based on references to Arabidopsis bZIPs. Members in the same group shared similar motifs and gene structure pattern. In addition, gene duplication analysis indenfied 37 pairs of segmental duplicated genes and none tandem duplicated genes in S. italica suggesting segmental duplication contributed to the expansion of the S. italica bZIP gene family. Moreover, the number of SibZIPs genes (39) exhibiting higher expression in roots was significantly more than that in other organs. Twelve SibZIP genes were upregulated in response to dehydration stress. In conclusion, our study advances the current understanding of SibZIP genes and provide a number of candidates for functional analysis of drought tolerance in S. italica.

BackgroundThis study conducts a systematic review through meta-analysis, comparing the composition and diversity of the gut microbiome in patients with esophageal cancer and healthy individuals, and explores the relationship between risk factors and related factors of esophageal cancer.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library. In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, Egger’s test, and Begg’s test to assess the risk of bias.ResultsIn this study, a total of 328 studies were identified through the literature search. Among them, 117 duplicate studies were removed, and 202 studies were excluded based on inclusion and exclusion criteria. Finally, 9 studies were included in the analysis, involving a total of 216 patients with esophageal carcinoma and 352 healthy controls. Four studies provided Chao1 index for quantitative consolidation (ES = 637.41, 95% CI: 549.16 to 725.66, p = 0.000, I2 = 98.2%). Two studies [27, 29] reported ACE index (ES = 438.89, 95% CI: 362.42 to 515.35, p = 0.000, I2 = 97%). Seven studies [26,27,29,30,32] reported the Shannon index for quantitative consolidation (ES = 4.38, 95% CI: 3.95 to 4.81, p = 0.000, I2 = 99%). At the phylum level, the abundance of Bacteroidetes(ES = 37.8, 95% CI: 25.75 to 49.85, p = 0.000, I2 = 87.2%) and Proteobacteria(ES = 7.48, 95% CI: 5.02 to 8.85, p = 0.04, I2 = 2.4%) have statistical difference between ESCC and HC. There was no significant difference between ESCC and HC in the abundance of genera(p>0.05).ConclusionsThis observational meta-analysis revealed that changes in the GM were correlated with esophageal carcinoma, and variations in some advantageous GM might involve regional differences. Additionally, the study aims to facilitate early diagnosis of esophageal cancer and improve screening and diagnostic efficiency.

When multiple CCHP microgrids are integrated into an active distribution network (ADN), the microgrids and the distribution network serve as distinct stakeholders, making the economic optimal dispatch of the system more complex. This paper proposes a distributed dispatch model of ADN with CCHP multi-microgrid, and refines the objective functions of each region. The analytical target cascading approach (ATC) is employed to model the power transaction as virtual sources/loads, and solve the optimal dispatch in parallel. Case studies demonstrate the proposed distributed model is capable of achieving economic optimization for both stakeholders.

Introduction:Gan–jiang–ling–zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated.Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction.Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression.Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC–CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in the context of chronic liver disease, such as hepatitis B or C infection, and cirrhosis. Advanced unresectable HCC (uHCC) presents significant treatment challenges due to its advanced stage and inoperability. One efficient treatment method for advanced uHCC is the use of hepatic arterial infusion chemotherapy (HAIC) combined with transcatheter arterial embolization (TAE).Patients and MethodsIn this study, we conducted a retrospective collection of clinical data, including basic information, radiological data, and blood test parameters, for patients with advanced uHCC who underwent TAE + HAIC treatment from August 2020 to February 2023. A total of 743 cases involving 262 patients were included. Ultimately, the covariates included in the analysis were the Child-Pugh score, extrahepatic metastasis, tumor number, tumor size, and treatment method.ResultsIn the study, we performed univariable and multivariable analysis on 23 clinical factors that were screened by LASSO regression, indicating that the five variables aforementionedly were identified as independent factors influencing patient prognosis. Then we developed a nomogram of the sensitive model and calculated concordance indices of prognostic survival models.ConclusionBased on the uHCC patient cohort, we have developed a prognostic model for OS in patients who received TAE + HAIC treatment. This model can accurately predict OS and has the potential to assist in personalized clinical decision-making.

According to the hypothesis that strange quark matter may be the true ground state of matter at extremely high densities, strange quark stars should be stable and could exist in the Universe. It is possible that pulsars may actually be strange stars, but not neutron stars. Here we present a short review on recent progresses in the field of strange quark stars. First, three popular phenomenological models widely used to describe strange quark matter are introduced, with special attention being paid on the corresponding equation of state in each model. Combining the equation of state with the Tolman-Oppenheimer-Volkov equations, the inner structure and mass-radius relation can be obtained for the whole sequence of strange stars. Tidal deformability and oscillations (both radial and non-radial oscillations), which are sensitive to the composition and the equations of state, are then described. Hybrid stars as a special kind of quark stars are discussed. Several other interesting aspects of strange stars are also included. For example, strong gravitational wave emissions may be generated by strange stars through various mechanisms, which may help identify strange stars via observations. Especially, close-in strange quark planets with respect to their hosts may provide a unique test for the existence of strange quark objects. Fierce electromagnetic bursts could also be generated by strange stars. The energy may come from the phase transition of neutron stars to strange stars, or from the merger of binary strange stars. The collapse of the strange star crust can also release a huge amount of energy. It is shown that strange quark stars may be involved in short gamma-ray bursts and fast radio bursts.

Ethnopharmacological relevanceDanggui Buxue decoction (DBD) is a traditional Chinese herbal formula. According to the theory of traditional Chinese medicine, the combination of Astragali Radix (AR) and Angelica sinensis (AS) is a classic prescription of tonifying qi and enriching blood. DBD has the functions of hematopoietic, immune enhancement and inflammation inhibition, usually used to treat qi and blood deficiency symptoms.Aim of the studyCyclophosphamide (CY) can inhibit humoral and cellular immunity, leading to the overall immune disorder of the body, resulting in immunosuppressive (IS). Pre-laboratory studies confirmed the immunomodulatory effects of DBD, but its mechanisms have not been thoroughly studied. In this study, the main purpose was to determine the effects of DBD on the immune function and intestinal mucosal barrier function of IS mice induced by CY, and initially explored the immunomodulatory mechanism of DBD.Materials and methods100 g of AR and 20 g of AS were accurately weighed and 0.5 g/mL of the DBD was obtained by boiling, filtration and rotary evaporation. Then, mice in the DBD group were administered 5 g/kg of DBD by gavage, positive group were administered 40 mg/kg of levamisole hydrochloride, whereas those in the control and model groups were given the corresponding volume of normal saline by gavage for 1 week. At the end of the experiment, blood, spleen, thymus, ileum and cecum contents of all the experimental mice were collected aseptically. IS mouse model induced by intraperitoneal injection of 80 mg/kg CY for three consecutive days. Pathomorphology was used to observe the physical barrier of the intestine, flow cytometry to detect splenic lymphocytes, immunohistochemistry to determine the content of intestinal barrier-associated proteins, ELISA to measure the secretion of ileal SIgA, qRT-PCR to detect the mRNA expression of immune-related genes in the intestine, and high-throughput sequencing and analysis of cecum contents.ResultsDBD alleviated spleen tissue damage and restored impaired immune functions, such as increased thymus index and CD4+/CD8+ subsets of spleen lymphocytes. In addition, DBD could increase ileum villi length and the ratio of villi length to crypt depth (V/C), and decrease crypt depth. Moreover, DBD administration up-regulated the expression of ZO-1, Occludin, Claudin-1, MUC-2 mRNA in ileum. And the secretions of sIgA and ZO-1 in ileum were also significantly improved. Furthermore, the administration of DBD can increase the diversity of gut microbiota, improve the composition of intestinal flora and increase the relative abundance of beneficial genus, such as Bacteroides.ConclusionDBD alleviated CY-induced immune damage by decreasing the ratio of spleen index to CD4+/CD8+ of T lymphocyte subsets. And the intestinal barrier function of mice was by improves improving the intestinal morphology of the ileum and up-regulating the expression levels of ZO-1, MUC-2 and SIgA. DBD regulates CY-induced gut microbiota dysregulation in mice by increasing species diversity and richness, regulating the phylum, class and order levels of Bacteroidetes.

ObjectivesAn increasing number of studies have shown that third (CB3)- and fourth-generation cryoballoons (CB4) have been used to treat various types of atrial fibrillation (AF), but previous research regarding the safety and efficacy of CB3 or CB4 ablation remains controversial. Therefore, a meta-analysis was performed to further evaluate the safety and efficacy of pulmonary vein isolation (PVI) using the CB3 and CB4 in the treatment of AF.MethodsWe searched PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Clinicaltrials.gov up to December 2023 for qualified trials and data extraction according to inclusion and exclusion criteria. All analyses were carried out using Review Manager 5.3 software.ResultsThe meta-analysis included 13 observational studies consisting of 3,281 subjects and did not include a randomized controlled trial. Overall analyses indicated that the CB3 significantly reduced total procedure time [weighted mean difference (WMD) = −8.69 min, 95% confidence interval (CI) = −15.45 to −1.94 min, I2 = 93%], increased the PVI recording [relative risk (RR) = 1.24, 95% CI = 1.03–1.49, I2 = 90%], and increased the mean nadir temperature of overall PVs (WMD = 2.80°C, 95% CI = 1.08–4.51°C, I2 = 89%) compared with the CB2. Moreover, the CB4 significantly reduced the total procedure time (WMD = −14.50 min, 95% CI = −20.89 to −8.11 min, I2 = 95%), reduced the fluoroscopy time (WMD = −2.37 min, 95% CI = −4.28 to −0.46 min, I2 = 95%), increased the PVI recording (RR = 1.40, 95% CI = 1.15–1.71, I2 = 90%) compared with the CB2. Time-to-isolation, the success rate of PVI, AF recurrence, and complications in the CB3 and CB4 were not significantly different compared with the CB2.ConclusionThese findings demonstrated that the CB3 and CB4 tended to be more effective than the CB2 in the treatment of AF, with shorter procedure times, more PVI recording, and similar safety endpoints.

BackgroundAlport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations.MethodsThree Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals’ peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members.ResultsBoth probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A’s mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C>T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects.ConclusionThe novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C>T may present NS as their primary clinical manifestation.

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.

PurposeThe impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients.MethodsA total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE).ResultsGlobal longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P

Background and aimsTranscatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR.MethodsThis study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups.ResultsAt baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups.ConclusionsThe mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

Sustainable Development Goal-14 (SDG-14) directly demands the protection, conservation, restoration, and sustainable management of the global mangrove ecosystem. Assessment of the development Pakistan has made toward the sustainable management of mangrove ecosystems necessitates the remote sensing-based evaluation of national-level mangrove cover. Using Google Earth Engine (GEE) for geoprocessing 12,000+ 10-m high-spatial resolution Sentinel-2 time-series images (2016–23) and applying random forest (RF) classifier, the current research provides the latest spatial distribution of mangroves along Pakistan’s coastline and changes observed for a duration of 8 years. Additionally, this research provides the first spatiotemporal health assessment of Pakistan’s national mangrove cover as well. Rational analysis of the results indicated splitting the entire timeline based on two seasons (Jan–Jun and Jul–Dec). Results revealed an overall increase of 1,210 km2 (2023) in the mangrove cover on the national-level; a 3.42 km2 average annual increase from 2016 (1,186 km2). Mangrove gain/loss assessment based on the land use land cover (LULC) transition matrix illustrated 223 km2 gain and 199 km2 loss; a 24 km2 net gain. Declines of 20.28% and 7.91% were found in maximum- and mean-NDVI (2016-23), depicting the deteriorating mangrove health conditions. Likewise, significant Sen’s slope analysis (p < 0.05) indicated that 88.8% of all the mangrove-NDVI pixels exhibited an overall decrease, whereas 11.2% pixels showed an overall increase (2016-23). It was concluded that despite showing a growth in the extent, mangrove cover in Pakistan has shown a decline in health, primarily due to deforestation for urban operations and sea-level rise, still making them vulnerable and potentially leading to a disrupted ecosystem, including carbon release in the atmosphere. This study will assist in the formulation of mangrove conservation and management strategies, whereas future research can explore the potentials of land surface temperature (LST) and evapotranspiration in combination to the NDVI for an in-depth analysis of the health status of mangroves.

Epoxy resins, known for their excellent properties, are widely used thermosetting resins, but their tendency towards brittle fracture limits their applications. This study addresses this issue by preparing graphene oxide via the Hummer method, modifying it with hyperbranched polyamide ester, and reducing it with hydrazine hydrate to obtain functionalized graphene. This functionalized graphene improves compatibility with epoxy resin. Using a novel two-phase extraction method, different ratios of functionalized graphene/epoxy composites were prepared and tested for mechanical properties and thermal stability. The results showed significant improvements: the tensile strength of composites with 0.1 wt% functionalized graphene increased by 77% over pure epoxy resin, flexural strength by 56%, and glass transition temperature by 50°C. These enhancements, attributed to the improved compatibility between graphene and epoxy resin, demonstrate the potential of functionalized graphene to mitigate the brittleness of epoxy resins, expanding their application potential.

ObjectiveTo explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits.MethodsThe data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community.ResultsThe LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the “persistently unreasonable diet group” (p

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

IntroductionWe previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models.MethodsATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson’s disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish.ResultsCells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson’s disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio.ConclusionThis study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

The quality of fermented plant leaves is closely related to the interleaf microorganisms and their metabolic activities. In this experiment, a multi-omics analysis was applied to investigate the link between the structural composition of the phyllosphere microbial community and the main metabolites during the fermentation process. It was found that the whole fermentation process of cigar leaves could be divided into three stages, in which the Mid-Stage was the most active period of microbial metabolic activities and occupied an important position. Staphylococcus, Brevundimonas, Acinetobacter, Brevibacterium, Pantoea, Aspergillus, Wallemia, Meyerozyma, Sampaiozyma, Adosporium and Trichomonascus played important roles in this fermentation. Staphylococcus and Aspergillus are the microorganisms that play an important role in the fermentation process. Staphylococcus were strongly correlated with lipids and amino acids, despite its low abundance, Stenotrophomonas is importantly associated with terpene and plays a significant role throughout the process. It is worth noting that Wapper exists more characteristic fungal genera than Filler and is more rapid in fermentation progress, which implies that the details of the fermentation process should be adjusted appropriately to ensure stable quality when faced with plant leaves of different genotypes. This experiment explored the relationship between metabolites and microorganisms, and provided a theoretical basis for further optimizing the fermentation process of plant leaves and developing techniques to improve product quality. Biomarker is mostly present in the pre-fermentation phase, but the mid-fermentation phase is the most important part of the process.

In modern agriculture, Controlled environment agriculture (CEA) stands out as a contemporary production mode that leverages precise control over environmental conditions such as nutrient, temperature, light, and other factors to achieve efficient and high-quality agricultural production. Numerous studies have demonstrated the efficacy of manipulating these environmental factors in the short period before harvest to enhance crop yield and quality in CEA. This comprehensive review aims to provide insight into various pre-harvest practices employed in CEA, including nutrient deprivation, nutrient supply, manipulation of the light environment, and the application of exogenous hormones, with the objective of improving yield and quality in horticultural crops. Additionally, we propose an intelligent pre-harvest management system to cultivate high-quality horticultural crops. This system integrates sensor technology, data analysis, and intelligent control, enabling the customization of specific pre-harvest strategies based on producers’ requirements. The envisioned pre-harvest intelligent system holds the potential to enhance crop quality, increase yield, reduce resource wastage, and offer innovative ideas and technical support for the sustainable development of CEA.

Osteosarcoma (OS) is an aggressive and highly lethal bone tumor, highlighting the urgent need for further exploration of its underlying mechanisms. In this study, we conducted analyses utilizing bulk transcriptome sequencing data of OS and healthy control samples, as well as single cell sequencing data, obtained from public databases. Initially, we evaluated the differential expression of four tumor microenvironment (TME)-related gene sets between tumor and control groups. Subsequently, unsupervised clustering analysis of tumor tissues identified two significantly distinct clusters. We calculated the differential scores of the four TME-related gene sets for Clusters 1 (C1) and 2 (C2), using Gene Set Variation Analysis (GSVA, followed by single-variable Cox analysis. For the two clusters, we performed survival analysis, examined disparities in clinical-pathological distribution, analyzed immune cell infiltration and immune evasion prediction, assessed differences in immune infiltration abundance, and evaluated drug sensitivity. Differentially expressed genes (DEGs) between the two clusters were subjected to Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA). We conducted Weighted Gene Co-expression Network Analysis (WGCNA) on the TARGET-OS dataset to identify key genes, followed by GO enrichment analysis. Using LASSO and multiple regression analysis we conducted a prognostic model comprising eleven genes (ALOX5AP, CD37, BIN2, C3AR1, HCLS1, ACSL5, CD209, FCGR2A, CORO1A, CD74, CD163) demonstrating favorable diagnostic efficacy and prognostic potential in both training and validation cohorts. Using the model, we conducted further immune, drug sensitivity and enrichment analysis. We performed dimensionality reduction and annotation of cell subpopulations in single cell sequencing analysis, with expression profiles of relevant genes in each subpopulation analyzed. We further substantiated the role of ACSL5 in OS through a variety of wet lab experiments. Our study provides new insights and theoretical foundations for the prognosis, treatment, and drug development for OS patients.

We herein present a case of a ruptured giant omphalocele with congenital short small intestine. Vacuum-sealing drainage and carboxymethylcellulose silver dressing promoted wound healing after repair, avoided abdominal compartment syndrome, and reduced the risks of multiple procedures. We review the perioperative management of omphaloceles in congenital short small intestines.