Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective To search,evaluate and summarise the best evidence on pre-rehabilitation before surgery for elderly patients with hip fracture so as to provide an evidence-based basis for further standardisation in clinical practice.Methods Based on the"6S Pyramid"evidence model,desktop searches were conducted across databases and websites including Medlive,BMJ Best Practice,UpToDate,the World Health Organization,the Guidelines International Network(GIN),British National Institute for Health and Care Excellence(NICE),American National Guideline Clearinghouse(NGC),Canadian Medical Association:Clinical Practice Guidelines Infobase(CMA),Scottish Intercollegiate Guidelines Network(SIGN),the Registered Nurses'Association of Ontario(RNAO),American College of Sports Medicine(ACSM),American Academy of Orthopaedic Surgeons(AAOS),European Society for Clinical Nutrition and Metabolism(ESPEN),American Society for Parenteral and Enteral Nutrition(ASPEN),the Enhanced Recovery After Surgery Society(ERASS),Cochrane Library,Joanna Briggs Institute,PubMed,CINAHL,Web of Science,Embase,Scopus,Science Direct,CNKI,Wanfang Data,Vip,and SinoMed.The research targeted evidence on pre-rehabilitation in elderly patients with hip-fracture before surgery,encompassing clinical decisions,guidelines,evidence summaries,best practices,expert consensus,systematic reviews and randomized controlled trials(RCTs).The search items spanned from the inception of database to 31st December,2023.Two researchers trained with evidence-based knowledge evaluated the quality of the included literature and extracted and summarised the evidence.Results A total of 14 documents were included,consisting of 2 clinical decisions,4 guidelines,1 best practice,4 expert consensus and 3 systematic reviews.Evidence was summarised into 7 domains from 25 pieces of evidence:multidisciplinary management,preoperative assessment,preoperative health education,multi-modal analgesia,nutritional management,exercise intervention and assessment and prevention of complication risks.Conclusion The best evidence summarised in this study provides a basis for pre-rehabilitation in elderly patients with hip fracture before surgery.Nurses should adapt the findings to specific contexts,standardise the preoperative rehabilitation procedures,and improve clinical outcomes for the patients.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

ObjectiveTo investigate the quality markers of Xiaoqinglong granules（XQLG） for treating bronchial asthma using the analytic hierarchy process（AHP）-entropy weight method（EWM）， network pharmacology and high performance liquid chromatography（HPLC） content determination. MethodsEffectiveness， testability and peculiarity component data of XQLG in treating bronchial asthma were constructed through database retrieval， literature review， and network pharmacology. Subsequently， AHP-EWM was used to quantitatively identify and weight the control layer and element layer， the relevant compounds were selected as candidate quality markers based on comprehensive scores. Further comparison of reference substances and establishment of HPLC content determination method were used to determine the potential quality markers of XQLG， which were verified by molecular docking with disease targets. ResultsA total of 13 components， including glycyrrhizic acid， paeoniflorin， schisandrol A， isoliquiritigenin， 6-gingerol， ephedrine， liquiritin， albiflorin， liquiritigenin， 6-shogaol， pseudoephedrine， cinnamic acid and cinnamaldehyde， were identified as potential quality markers of XQLG by AHP-EWM. Quantitative analysis indicated that all aforementioned quality markers could be detected in 13 batches of XQLG， indicating that it had stable testability as a quality marker. Among these 13 batches of samples， ephedrine and paeoniflorin exhibited good consistency in content， while pseudoephedrine and cinnamaldehyde showed poor consistency. Molecular docking analysis revealed that the 13 compounds exhibited binding energies with the core targets -2.11 kcal·mol^-1， indicating that the 13 compounds could spontaneously bind to the disease targets， which may be the material basis for the treatment of bronchial asthma with XQLG. ConclusionIn this study， 13 compounds were screened by AHP-EWM combined with network pharmacology and HPLC as quality markers for the treatment of bronchial asthma by XQLG， laying the foundation for enhancing the quality standards of this preparation.

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

Multiple sclerosis(MS)is a chronic central nervous system inflammatory demyelinating disease caused by autoim-mune diseases.Intermittent fasting(IF)is a dietary pattern with periodic energy limitation.Studies have shown that IF can delay the occurrence and development of MS and experimental allergic encephalomyelitis(EAE).Its mechanism of action includes repairing nerve damage,promoting myelin regeneration,regulating gut microbiota,and reversing immune inflammation.The use of IF can re-duce the severity,recurrence time,and lesion size of MS patients clinically,which brings new ideas for the treatment and prevention of MS.This article provides a review of the effects and mechanisms of IF in treating MS,with the aim of gaining new insights into the treatment of MS and providing reference for the application of IF in the treatment of MS patients.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Objective To search,evaluate and summarise the best evidence on pre-rehabilitation before surgery for elderly patients with hip fracture so as to provide an evidence-based basis for further standardisation in clinical practice.Methods Based on the"6S Pyramid"evidence model,desktop searches were conducted across databases and websites including Medlive,BMJ Best Practice,UpToDate,the World Health Organization,the Guidelines International Network(GIN),British National Institute for Health and Care Excellence(NICE),American National Guideline Clearinghouse(NGC),Canadian Medical Association:Clinical Practice Guidelines Infobase(CMA),Scottish Intercollegiate Guidelines Network(SIGN),the Registered Nurses'Association of Ontario(RNAO),American College of Sports Medicine(ACSM),American Academy of Orthopaedic Surgeons(AAOS),European Society for Clinical Nutrition and Metabolism(ESPEN),American Society for Parenteral and Enteral Nutrition(ASPEN),the Enhanced Recovery After Surgery Society(ERASS),Cochrane Library,Joanna Briggs Institute,PubMed,CINAHL,Web of Science,Embase,Scopus,Science Direct,CNKI,Wanfang Data,Vip,and SinoMed.The research targeted evidence on pre-rehabilitation in elderly patients with hip-fracture before surgery,encompassing clinical decisions,guidelines,evidence summaries,best practices,expert consensus,systematic reviews and randomized controlled trials(RCTs).The search items spanned from the inception of database to 31st December,2023.Two researchers trained with evidence-based knowledge evaluated the quality of the included literature and extracted and summarised the evidence.Results A total of 14 documents were included,consisting of 2 clinical decisions,4 guidelines,1 best practice,4 expert consensus and 3 systematic reviews.Evidence was summarised into 7 domains from 25 pieces of evidence:multidisciplinary management,preoperative assessment,preoperative health education,multi-modal analgesia,nutritional management,exercise intervention and assessment and prevention of complication risks.Conclusion The best evidence summarised in this study provides a basis for pre-rehabilitation in elderly patients with hip fracture before surgery.Nurses should adapt the findings to specific contexts,standardise the preoperative rehabilitation procedures,and improve clinical outcomes for the patients.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.