The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Objective Based on TLR4/NF-κB/MLCK pathway,the therapeutic effect and mechanism of Baihe Dihuang Decoction on insomnia with intestinal flora disturbance in mice induced by p-chlorophenlalanine(PCPA)and multi-factor stimulation were studied.The aim is to provide theoretical basis for clinical use.Methods Eighty-four KM mice were randomly divided into normal group,model group,positive group(Diazepam,1.38 mg·kg-1),Baihe group(2.25 g·kg-1),Dihuang group(2.25 g·kg-1)and Baihe Dihuang Decoction group(4.5 g·kg-1).Insomnia mouse model was established by intraperitoneal injection of PCPA for 2 days combined with 4 weeks of multi-factor stimulation,including stimulating the tail with forceps clip for 2 minutes,reversing day and night for 24 hours,wetting the padding for 24 hours,tilting the cage at 45° for 24 hours,alternating the cages for 24 hours,fasting food for 24 hours,and getting cold bath for 3 minutes,etc.After successfully modeling,corresponding drug treatment was given.The anxiety-like behavior of mice was observed by elevated cross maze system.The latency and duration of sleep were observed by righting reflex experiment.16sRNA sequencing was used to analyze the composition and structure of intestinal flora in mice.The concentration changes of γ-aminobutyric acid(GABA),glutamic acid(Glu),tryptophan(Trp),5-hydroxytryptophan(5-HTP)and 5-hydroxytryptamine(5-HT)in brain and colon were detected by liquid chromatography-mass spectrometry(LC-MS).Immunohistochemical method was used to detect the expressions of zona atresia protein 1(ZO-1)and Occludin in colon.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the genes including interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),ZO-1,Occludin,Toll-like receptor 4(TLR4),nuclear factor κB(NF-κB)and myosin light chain kinase(MLCK)in colonic tissue.Western Blot was used to detect the expressions of TLR4,NF-κB,phosphorylated nuclear factor κB(p-NF-κB),MLCK,myosin light chain(MLC)and phosphorylated myosin light chain(p-MLC)in colonic epithelial tissue.Results Compared with the normal group,the distance of entering the open arm and the duration of stay in the open arm of model group in the elevated cross maze were significantly shortened(P＜0.05).The sleep latency was significantly prolonged,and the sleep duration was significantly shortened(P＜0.05).The richness and uniformity of intestinal flora were decreased(P＜0.05,P＜0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in the brain decreased significantly(P＜0.01),while the concentration of Glu increased significantly(P＜0.01).The concentration of GABA and Glu in colon decreased significantly(P＜0.01),while the concentration of Trp,5-HTP and 5-HT increased significantly(P＜0.01).The expression levels of inflammatory factors IL-1β,IL-6 and TNF-α in colonic tissue were significantly increased(P＜0.01),and the expression levels of ZO-1 and Occludin genes and proteins were significantly decreased(P＜0.01).The gene expression levels of TLR4,NF-κB and MLCK were significantly increased(P＜0.01),and the protein expression levels of TLR4,p-NF-κB,MLCK and p-MLC were significantly increased(P＜0.01).Compared with the model group,Baihe Dihuang Decoction could significantly prolong the distance of entering the open arm and the duration of stay in the open arm of insomnia mice in the elevated cross maze(P＜0.05).The sleep latency was significantly shortened,and the sleep duration was significantly increased(P＜0.05).The richness and uniformity of intestinal flora were increased(P＜0.05,P＜0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in brain was increased(P＜0.05,P＜0.01),and the concentration of Glu was decreased(P＜0.01).The concentration of GABA and Glu in colon was increased(P＜0.01),while the concentration of Trp,5-HTP and 5-HT was decreased(P＜0.05,P＜0.01).The expression levels of IL-1β,IL-6 and TNF-α genes were down-regulated(P＜0.01),the expression levels of ZO-1 and Occludin genes and proteins were up-regulated(P＜0.01),TLR4,NF-κB,MLCK gene expression levels and TLR4,p-NF-κB,MLCK,p-MLC protein expression levels were down-regulated in the pathway(P＜0.01).Conclusion Baihe Dihuang Decoction can effectively treat insomnia with intestinal flora disorders.Its mechanism of action may be related to the regulation of brain and intestinal neurotransmitter disorders,down-regulating TLR4/NF-κB/MLCK signaling pathway,and up-regulating tight junction proteins expression,reducing inflammatory responses,and then repairing the mechanical barrier of intestinal mucosa.

Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.
Animals ; Male ; Goats ; Stem Cells ; Spermatogonia/metabolism* ; Cell Proliferation ; Flow Cytometry ; Testis/metabolism*

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.

Objective:To investigate the effects of patelloplasty combined with cartilage surface resection on early function and anterior knee pain during total knee arthroplasty(TKA).Methods:This is a prospective controlled study, 100 patients with knee osteoarthritis(KOA) who received TKA treatment in Zoucheng People′s Hospital of Shandong Province from February 2021 to April 2022 were selected and divided into the combined group and the control group using the random number table method, 50 cases in each group. The combined group received patelloplasty combined with cartilage surface resection during TKA, while the control group only received patelloplasty. Preoperative osteoarthritis Kellgren-Lawrance (K-L) grade, joint motion (ROM), the operation time and the decrease of hemoglobin in two groups were recorded.Knee function was evaluated by Hospital for Special Surgery(HSS) knee score at 1, 3, 6, and 12 months after surgery. Anterior knee pain during stair climbing was evaluated by visual analogue scale(VAS), and recovery of patellofemoral joint was evaluated by Feller score system. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test. Results:There was no significant difference in preoperative K-L grading and ROM between the two groups ( P> 0.05). The operation time of the combined group was longer than that of the control group[(71.49±9.34) min vs (66.27±8.22) min], the difference was statistically significant ( P <0.05), and there was no statistical significance in the decrease of hemoglobin between the two groups ( P>0.05). At 3, 6 and 12 months after treatment, the HSS scores of the combined group were higher than those of the control group [3 months: (76.93±8.26) vs (71.74±7.84), 6 months: (85.72±6.27) vs (81.47±6.19), 12 months: (88.64±5.27) vs (85.72±4.85)], the difference were statistically significant ( P <0.05). At 1, 3, 6 and 12 months after treatment, the VAS scores of anterior knee pain in combined group were lower than those in control group [1 months: (2.54±0.48) vs (2.77±0.63), 3 months: (2.02±0.53) vs (2.58±0.45), 6 months: (1.32±0.35) vs (1.97±0.38), 12 months: (1.14±0.33) vs (1.75±0.35)], the difference were statistically significant ( P <0.05). The incidence of anterior knee pain at 3, 6 and 12 months after operation in combined group was lower than that in control group [3 months: 20.0% vs 38.0%, 6 months: 14.0% vs 32.0%, 12 months: 10.0% vs 28.0%], the difference were statistically significant ( P <0.05). At 3, 6 and 12 months after treatment, the patellar Feller score in the combined group was higher than that in the control group[3 months: (18.63±3.52) vs (15.36±3.28), 6 months: (22.27±3.18) vs (19.63±3.48), 12 months: (25.82±3.27) vs (22.47±3.47)], the difference were statistically significant ( P <0.05). Conclusion:Patelloplasty combined with cartilage surface resection during TKA can effectively prevent the occurrence of postoperative anterior knee pain and improve the therapeutic effect.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

The cultivation and production of cucumber are seriously affected by downy mildew caused by Pseudoperonospora cubensis. Downy mildew damages leaves, stems and inflorescences, and then reduces the yield and quality of cucumber. This review summarized the research advances in cucumber downy mildew, including pathogen detection and defense pathways, regulatory factors, mining of pathogens-resistant candidate genes, proteomic and genomic analysis, and development of QTL remarks. This review may facilitate clarifying the resistance mechanisms of cucumber to downy mildew.
Cucumis sativus/genetics* ; Oomycetes/genetics* ; Peronospora ; Plant Diseases/genetics* ; Proteomics