Current Status of Nursing Home Distribution in China: A National Cross-Sectional Study.

AIMS: Population aging is a challenge that the whole world is facing, especially in China. This study aims to investigate the current distribution status of nursing homes in China using spatial epidemiology methods. DESIGN: Cross-sectional study in China. METHODS: The data were obtained from the Integrated Civil Affairs Government Service Platform 'China County Statistical Yearbook' for 2020 and the 'China City Statistical Yearbook' for 2020. Using global Moran's index to test the clustering of nursing homes, inter-group and intra-group Theil index was utilised to differentiate the sources of differences. The coupling coordination analysis was conducted to explore the coordination. Geographically weighted regression was utilised to investigate the impact of economic development and aging on nursing home resources. All analyses were conducted by Arcgis 10.8 and R Studio 4.3.2. RESULTS: Global Moran's index indicated that the distribution of nursing homes in China exhibited clustering. The Theil index values for institutions and beds at the national county were 0.32450 and 0.30675. However, upon comparing provinces and regions, it was found that the differences across the country mainly stem from within provinces (contribution rate: institutions 65.0%; beds 73.0%) and within regions (contribution rate: institutions 99.0%; beds 91.0%). The majority of districts and counties had a coupling coordination index of institutions and bed numbers, both of which were < 0.5. CONCLUSION: The development of nursing home resources in China has been rapid, generally presenting a balanced state, but further optimisation is needed. This study established a foundation for the targeted distribution of essential public services, focusing on nursing home healthcare resources tailored to the needs of older persons. IMPLICATIONS: The study underscored the urgent need for targeted elderly care policies, emphasising the optimisation of resource distribution to enhance the overall quality of care provided to the aging population. NO PATIENTS OR PUBLIC CONTRIBUTION: The study did not involve humans.

Tolvaptan and the role of kidney aquaporin-2 abundance in managing volume overload in patients with CKD.

Objective: This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients. Methods: CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc., were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan. Results: Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output (P < .001) and weight reduction (P < .001). At day 7, Group T maintained more significant diuretic effects (P < .001). More Group C patients required ultrafiltration therapy (P = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy. Conclusion: Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy.This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html).

Supplementation with carnosine, a food-derived bioactive dipeptide, alleviates dexamethasone-induced oxidative stress and bone impairment via the NRF2 signaling pathway.

BACKGROUND: Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3-E1 cells in vitro. RESULTS: Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress. CONCLUSION: Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry.

[High tibial osteotomy on varus knee osteoarthritis with medial meniscus posterior root injury].

OBJECTIVE: To explore clinical effect of distal tibial tubercle-high tibial osteotomy (DTT-HTO) in treating knee osteoarthritis (KOA) with medial meniscus posterior root tear (MMPRT). METHODS: A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021, including 3 males and 18 females, aged from 49 to 75 years old with an average of (63.81±6.56) years old, the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2) years, and 4 patients with grade Ⅱ, 14 patients with grade Ⅲ, and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification. The distance of medial meniscusextrusion (MME) and weight-bearing line ratio (WBLR) of lower extremity were compared before and 12 months after operation. Visual analogue scale (VAS), Western Ontarioand and McMaster Universities (WOMAC) osteoarthritis index, and Lysholm knee score were used to evaluate knee pain and functional improvement before operation, 1, 6 and 12 months after operation, respectively. RESULTS: Twenty-one patients were followed up for 12 to 18 months with an average of (13.52±1.72) months. MME distance was improved from (4.99±1.05) mm before operation to (1.87±0.76) mm at 12 months after operation (P<0.05). WBLR was increased from (15.49±7.04)% before operation to (62.71±2.27)% at 12 months after operation (P<0.05). VAS was decreased from (7.00±1.14) before operation to (2.04±0.80), (0.90±0.62) and (0.61±0.50) at 1, 6 and 12 months after operation. WOMAC were decreased from preoperative (147.90±9.88) to postoperative (103.43±8.52), (74.00±9.54) and (47.62±9.53) at 1, 6 and 12 months, and the difference were statistically significant (P<0.05). Lysholm scores were increased from (46.04±7.34) before oepration to (63.19±8.93), (81.10±6.41) and (89.29±3.04) at 1, 6 and 12 months after operation(P<0.05). CONCLUSION: For the treatment of varus KOA with MMPRT, DTT-HTO could reduce medial meniscus protrusion distance, improve the ratio of lower limb force line, and effectively reduce knee pain and improve knee joint function.

Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis. METHODS: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT. RESULTS: The expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells. CONCLUSIONS: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.

Revealing the spoilage characteristics of refrigerated prepared beef steak by advanced bioinformatics tools.

BACKGROUND: Although microorganisms are the main cause of spoilage in prepared beef steaks, very few deep spoilage mechanisms have been reported so far. Aiming to unravel the mechanisms during 12 days of storage at 4 °C affecting the quality of prepared beef steak, the present study investigated the changes in microbial dynamic community using a combined high-throughput sequencing combined and bioinformatics. In addition, gas chromatography-mass spectrometry combined with multivariate statistical analysis was utilized to identify marker candidates for prepared steaks. Furthermore, cloud platform analysis was applied to determine prepared beef steak spoilage, including the relationship between microbiological and physicochemical indicators and volatile compounds. RESULTS: The results showed that the dominant groups of Pseudomonas, Brochothrix thermosphacta, Lactobacillus and Lactococcus caused the spoilage of prepared beef steak, which are strongly associated with significant changes in physicochemical properties and volatile organic compounds (furan-2-pentyl-, pentanal, 1-octanol, 1-nonanol and dimethyl sulfide). Metabolic pathways were proposed, among which lipid metabolism and amino acid metabolism were most abundant. CONCLUSION: The present study is helpful with respect to further understanding the relationship between spoilage microorganisms and the quality of prepared beef steak, and provides a reference for investigating the spoilage mechanism of dominant spoilage bacteria and how to extend the shelf life of meat products. © 2024 Society of Chemical Industry.

Cooperative defect engineering and ligand modification in UiO-66 to achieve high proton conductivity.

D-UiO-66-NIM with high proton conductivity has been synthesized through the dual strategy of defect engineering and ligand modification. Moreover, D-UiO-66-NIM exhibits good temperature cycling stability and durability in proton conductivity. This work has developed a new method to obtain efficient MOF-based proton conductors.

Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance.

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.

Translation, cross-cultural adaptation, reliability, and validity of the Chinese version of the intensive care unit environment stress scale for pediatric patients.

PURPOSE: There is currently a lack of understanding of children's experience in the pediatric intensive care unit (PICU) environment. Additionally, pediatric patients may experience post-PICU syndrome following discharge. Thus, we aimed to adapt and evaluate the psychometric properties of a tool specifically for use with children in the PICU. DESIGN AND METHODS: According to Brislin's Model, the Intensive Care Unit Environment Stress Scale (ICUESS) was translated both forward and backward and adapted cross-culturally. A total of 210 PICU patients were selected from four hospitals in XXX to analyze the final translated version of the questionnaire, the Pediatric Intensive Care Unit Environmental Stress Scale (PICUESS). Content validity, exploratory factor analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to assess the validity, while reliability was assessed using Cronbach's alpha and split-half reliability analysis. RESULTS: For PICUESS, seven of 42 items were modified. Content validity was high (overall = 0.96, item validity = 0.8 to 1.0). Exploratory factor analysis revealed eight common factors (Kaiser-Meyer-Olkin = 0.857, significant Bartlett's test). The results of the CFA indicate that the scale model fits well across the 8 factors. The entire scale demonstrated excellent internal consistency (Cronbach's alpha = 0.934). The overall split-half reliability was 0.935. CONCLUSIONS: The Chinese version of PICUESS demonstrates good reliability and validity, making it suitable for assessing pediatric patients' perceptions of the PICU environment. PRACTICE IMPLICATIONS: The PICUESS can assist healthcare professionals in providing personalized environment care for PICU patients. It has the potential to serve as a tool for further testing and international comparisons of pediatric patients' perceptions of the PICU environment.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling.

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Electroacupuncture protects the intestinal mucosal barrier in diarrhea-predominant Irritable Bowel Syndrome rats by regulating the MCs/Tryptase/PAR-2/MLCK pathway.

OBJECTIVE: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. METHODS: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. RESULTS: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). CONCLUSION: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.

Pseudomonas weihenstephanensis through the iron metabolism pathway promotes in situ spoilage capacity of prepared beef steaks during cold storage.

In this study, we evaluated the histomorphology, reactive oxygen species (ROS), protein degradation, and iron metabolism characteristics and differential expression analysis of genes for siderophores synthesis and protease secretion in prepared beef steaks inoculated alone or co-inoculated with P. weihenstephanensis, B. thermotrichothrix and M. caseolyticus at 4 °C for 12 days. The results showed that the P. weihenstephanensis was the key bacteria that degraded protein in the process of prepared beef steaks spoilage, which led to protein oxidation by promoting ferritin degradation to release free iron and inducing ROS accumulation. The highest expression of FpvA and AprE was detected in the P. weihenstephanensis group by comparing qRT-PCR of the different inoculation groups. Both qRT-PCR and Western blot revealed that ferritin heavy polypeptide and ferritin light chain polypeptide gene and protein expressions were significantly higher in the P. weihenstephanensis inoculation group compared to the other inoculation groups. Results suggested that FpvA and AprE might play roles in meat spoilage and were potential positional, physiological and functional candidate genes for improving the quality traits of prepared beef steaks. This work may provide insights on controlling food quality and safety by intervening in spoilage pathways targeting iron carrier biosynthesis or protease secretion genes.

Achieving High Proton Conductivity in MIL-91(Al) Aerogel.

The processability and sustainability of proton conductors are two important indicators of their application. Here, MIL-91(Al) with an intrinsic proton conduction framework originating from protonated phosphonate groups was cross-linked with poly(vinyl alcohol) (PVA) to obtain MIL-91(Al) aerogel through freeze-drying. This simple and inexpensive strategy not only facilitated the processing of MIL-91(Al) powder but also resulted in a molded MIL-91(Al) aerogel having a high proton conductivity of 1.02 × 10-2 S cm-1 at 70 °C and 100% relative humidity. Furthermore, MIL-91(Al) aerogel was recyclable and reusable, in line with the principles of environmental protection and sustainability. To the best of our knowledge, this is the first example of using a metal-organic framework aerogel as a proton conductor, which may develop a new model system in this field.

Artificial light at night causes community instability of bacterial community in urban soils.

Urban soils host diverse bacteria crucial for ecosystem functions and urban health. As urbanization rises, artificial light at night (ALAN) imposes disturbances on soil ecosystems, yet how ALAN affects the structure and stability of soil bacterial community remains unclear. Here we coupled a short-term incubation experiment, community profiling, network analysis, and in situ field survey to assess the ecological impacts of ALAN. We showed that ALAN influenced bacterial compositions and shifted the bacterial network to a less stable phase, altering denitrification potential. Such transition in community stability probably resulted from an ALAN-induced decrease in competition and/or an increase in facilitation, in line with the Stress Gradient Hypothesis. Similar destabilizing effects were also detected in bacterial networks in multiple urban soils subjected to different levels of ALAN stress, supporting the action of ALAN on naturally-occurring soil bacterial communities. Overall, our findings highlight ALAN as a new form of anthropogenic stress that jeopardizes the stability of soil bacterial community, which would facilitate ecological projection of expanding ALAN exposure.

Insight into the autochthonous bacterial strains as starter cultures for improving the flavor profiles of dry-cured duck: Changes in microbial diversity and metabolic profiles.

The purpose of this study was to reveal the effect of inoculating autochthonous bacterial strains (Lactobacillus and Staphylococcus simulans) on the flavor profiles, microbial community, and metabolites, and to elucidate the potential mechanism of flavor formation in dry-cured duck. The results indicated that the inoculation of bacterial strains could improve the amount of lactic acid bacteria and Staphylococcus and reduce the counts of Enterobacteria. There was a significant difference in flavor profiles between samples inoculated with different strains. Hexanal-D, acetone, 3-methyl-1-butanol-D, thiophene, hexanal-M, propanal, pentanal, (Z)-2-penten-1-ol and ethanol-D were the potential biomarkers. A total of 70 differential metabolites were screened and identified. Amino acid metabolism and lipid metabolism were the key pathways for the production of flavor and metabolites in dry-cured duck. The results of this study will improve our understanding of the mechanism of flavor formation regarding the inoculation of autochthonous starter cultures.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

Safety, tolerability, and pharmacokinetics of TG-1000, a new molecular entity against influenza virus: first-in-human study.

Background: The cap-snatching mechanism of influenza virus mRNA transcription is strongly suppressed by TG-1000, a prodrug rapidly metabolized into TG-0527, is a potent cap-dependent nucleic acid endonuclease inhibitor. Herein, we aimed to assess the safety, tolerability, and pharmacokinetics of TG-1000 in healthy participants and the effect of food on the pharmacokinetics and safety of TG-1000. Method: The study was divided into 2 parts: Part A [Single Ascending-Dose (SAD) study, 10-160 mg] and Part B [Food-Effect (FE) study, 40 mg] were launched sequentially. The study included 66 participants for both investigations. We administered different TG-1000 capsules or placebo doses per the study protocol and collected blood samples for pharmacokinetic assessments at specific times. In plasma, TG-1000 and its active metabolite TG-0527 were assayed, and PK parameters were determined. Results: In SAD, the increase in AUC was less than the proportional increase in dose over the 20-160 mg dose range, while the increase in Cmax was proportional to the increase in dose. In the 10-160 mg dose range, T1/2, λz and Tmax of TG-0527 were dose-independent; and T1/2 and Tmax were within 33.8-39.4 h and 3.02-6 h, respectively. In FE, the AUC0-inf, AUC0-last, and Cmax of TG-0527 decreased by approximately 17.52%, 18.76%, and 41.35%, respectively, and the Tmax delay was around 1.50 h. No serious adverse events occurred during the studies. Conclusion: Overall, TG-1000 was well tolerated and exhibited an acceptable safety and PK profile, supporting further clinical investigation of TG-1000 for the treatment of influenza.

Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma.

Lower-grade glioma (LGG), a prevalent malignant tumor in the central nervous system, requires accurate prediction and treatment to prevent aggressive progression. We aimed to explore the role of disulfidptosis-related genes (DRGs) in LGG, a recently discovered form of programmed cell death characterized by abnormal disulfide accumulation. Leveraging public databases, we analyzed 532 LGG tumor tissues (The Cancer Genome Atlas), 1,157 normal samples (Genotype-Tissue Expression), and 21 LGG tumor samples with 8 paired normal samples (GSE16011). Our research uncovered intricate relationships between DRGs and crucial aspects of LGG, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we identified significant heterogeneity among disulfidptosis sub-clusters and elucidated specific differential gene expression in LGG, with myeloid cell leukemia-1 (MCL1) as a key candidate. Machine learning techniques validated the relevance of MCL1, considering its expression patterns, prognostic value, diagnostic potential, and impact on immune infiltration. Our study offers opportunities and challenges to unravel potential mechanisms underlying LGG prognosis, paving the way for personalized cancer care and innovative immunotherapeutic strategies. By shedding light on DRGs, particularly MCL1, we enhance understanding and management of LGG.

[Clinical study of intercondylar fossa formation to prevent intercondylar fossa impingement after high tibia osteotomy].

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION: Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.