To identify the bacterial pathogens in a case of goat respiratory disease in Yunnan prov-ince,three Gram-negative,rod-shaped bacteria strains,YN240861,YN240862 and YN240863,were isolated from lung samples of three diseased goats with respiratory disease,and the identifications of the biochemical and the sequence similarity and phylogeny of 16S rDNA gene,and the analyses of the pathogenicity and antimicrobial susceptibility were studied.The results of the bacterial iden-tification indicated that the most biochemical characteristics of the three isolates were identical with those of the Histophilus somni(H.somni)type stain ATCC 43625T and the other reference strains of H.somni.The three strains had the 16S rDNA sequence similarity of 97.7％with H.som-ni type strain ATCC 43625T,and shared the 16S rDNA sequence similatiies of 99.4％-99.9％with the other H.somni reference strains.The three strains formed the same branch with all the H.som-ni reference strains in the 16S rDNA gene sequence phylogenetic tree.Based on these identification results,the three strains were identified as H.somni.The mouse pathogenicity test showed that each of the three strains had the median lethal dose(LD50)≤7.6×10 5 CFU in mice,which indica-ted that the three stains have higher pathogenicity to mice.The results of the antimicrobial suscep-tibility test indicated that the three strains were sensitive to ampicillin of penicillins,cefazolin and ceftriaxone of cephalosporins,chloramphenicol and florfenicol of chloramphenicols,kanamycin and gentamicin of aminoglycosides,and ofloxacin of quinolones.The strain YN240862 was resistant to sulfamethoxazole of sulfonamides.To our knowledge,this is the first isolation of Hi.somni in Chi-na,and confirmed the presence of H.somni infection in goats in China,which provides the basic da-ta for the prevention and treatment of H.somni infection in goats in China.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

To identify the bacterial pathogens in a case of goat respiratory disease in Yunnan prov-ince,three Gram-negative,rod-shaped bacteria strains,YN240861,YN240862 and YN240863,were isolated from lung samples of three diseased goats with respiratory disease,and the identifications of the biochemical and the sequence similarity and phylogeny of 16S rDNA gene,and the analyses of the pathogenicity and antimicrobial susceptibility were studied.The results of the bacterial iden-tification indicated that the most biochemical characteristics of the three isolates were identical with those of the Histophilus somni(H.somni)type stain ATCC 43625T and the other reference strains of H.somni.The three strains had the 16S rDNA sequence similarity of 97.7％with H.som-ni type strain ATCC 43625T,and shared the 16S rDNA sequence similatiies of 99.4％-99.9％with the other H.somni reference strains.The three strains formed the same branch with all the H.som-ni reference strains in the 16S rDNA gene sequence phylogenetic tree.Based on these identification results,the three strains were identified as H.somni.The mouse pathogenicity test showed that each of the three strains had the median lethal dose(LD50)≤7.6×10 5 CFU in mice,which indica-ted that the three stains have higher pathogenicity to mice.The results of the antimicrobial suscep-tibility test indicated that the three strains were sensitive to ampicillin of penicillins,cefazolin and ceftriaxone of cephalosporins,chloramphenicol and florfenicol of chloramphenicols,kanamycin and gentamicin of aminoglycosides,and ofloxacin of quinolones.The strain YN240862 was resistant to sulfamethoxazole of sulfonamides.To our knowledge,this is the first isolation of Hi.somni in Chi-na,and confirmed the presence of H.somni infection in goats in China,which provides the basic da-ta for the prevention and treatment of H.somni infection in goats in China.

Objective Through project performance management,to mobilize the enthusiasm of hospital information de-partment engineers and ensure the quality of hospital information project construction.Methods Change the traditional perform-ance allocation scheme,with the project as the main KPI value,and evaluate the comprehensive score through three dimensions:project stage coefficient,difficulty coefficient,and plan completion degree,to obtain the activity coefficient for performance allo-cation.Results Following the principle of"more work,more pay"and"better work,more pay",employees who have the cour-age to undertake information technology projects have received higher performance-based salaries.Conclusion By changing the performance allocation plan,the success rate of information technology projects has been improved,and the overall technical level and professional literacy of the information department have been improved.

Metabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.
Chromatin ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Histones/metabolism* ; Humans ; Neoplasms/therapy*

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

OBJECTIVE: To determine the carrier rate of deafness-related genetic variants among 53 873 newborns from Zhengzhou. METHODS: Heel blood samples of the newborns were collected with informed consent from the parents, and 15 loci of 4 genes related to congenital deafness were detected by microarray. RESULTS: In total 2770 newborns were found to carry deafness-related variants, with a carrier rate of 5.142%. 1325 newborns (2.459%) were found to carry heterozygous variants of the GJB2 gene, 1071 (1.988%) were found with SLC26A4 gene variants, 205 were found with GJB3 gene variants (0.381%), and 120 were found with 12S rRNA variants (0.223%). Five newborns have carried homozygous GJB2 variants, two have carried homozygous SLC26A4 variants, five have carried compound heterozygous GJB2 variants, and four have carried compound heterozygous SLC26A4 variants. 33 neonates have carried heterozygous variants of two genes at the same time. CONCLUSION The carrier rate of deafness-related variants in Zhengzhou, in a declining order, is for GJB2, SLC26A4, GJB3 and 12S rRNA. The common variants included GJB2 235delC and SLC26A4 IVS7-2A>G, which are similar to other regions in China. To carry out genetic screening of neonatal deafness can help to identify congenital, delayed and drug-induced deafness, and initiate treatment and follow-up as early as possible.

Objective: To describe the MICM (morphology, immunology, cytogenetics and molecular biology) characteristics of a case of acute myelomonocytic leukemia M 4C . Methods: The medical history data of the case of M 4C admitted to our hospital was reviewed. The results of bone marrow cell morphology, cytochemical stains, bone marrow biopsy, immunophenotype, cytogenetics, molecular test and NGS (next-generation sequencing) of the case were analyzed. Results: The bone marrow smear showed markedly active proliferation of bone marrow cells in which the myelomonocytic cells accounted for 85.6%. Cytochemical stains showed peroxidase (POX) stain partially and weakly positive; specific esterase AS-DCE partially positive; non-specific esterase α-NBE partially positive and smothered by sodium fluoride; non-specific esterase AS-DAE partially positive and smothered by sodium fluoride. Bone marrow biopsy showed hyperproliferative cells and diffused hyperplasia of blasts. Immunophenotype analysis showed that the abnormal cell population was positive for CD11B, CD64, CD56, cMPO, CD33, CD41, CD61, CD38 and CD58, but negative for CD13, CD34, CD117, CD7, CD123, HLA-DR, CD10, CD19, CD20, CD2, CD14, CD235, CD15, CD303, CD304, CD25, cCD79a, cCD3, cCD22, CD1a and TDT. Cytogenetic analysis showed 47, XY, t(9;11) (p22;q23),+mar. The molecular test for leukemia showed MLLT3/KMT2A gene rearrangement. NGS showed NRAS and TET2 mutation. The case was finally diagnosed as AML (acute myelomonocytic leukemia) M 4C with t(9;11)(p22;q23), MLLT3-KMT2A. Conclusion Leukemia M 4C may show the characteristics of both granulocytes and monocytes with complex morphological features. The combined examination of MICM should be necessary for the diagnosis of M 4C with great significance.

Objective To explore the role of college students' emotion regulation strategies in the relationship between emotion experiences and physical health.Method A total of 2 000 college students from a college in Hebei Province were tested randomly with the depression anxiety stress scale-21 (DASS-21),the emotion regulation questionnaire (ERQ) and the EuroQoL five-dimension questionnaire(EQ-5D).Results (1) Depression,anxiety and stress and expression suppression of male students (1(0,5),1(0,6),2(0,7),16.61±5.34,respectively) were higher than those of females(0(0,2),1(0,3),1(0,4),15.68±5.l0,respectively) (Z=-6.162,-3.108,-2.846,t=3.814,P＜0.01);and cognitive reappraisal,visual analogue scales (EQ-VAS) and EQ-5D value indexes(EQ-5D) of male students(27.74±7.56,81.17 ± 18.29,0.94 ± 0.15,respectively)were lower than those of females (28.69 ± 6.34,84.23 ± 16.43,0.96 ± 0.11,respectively) (t=-2.967,-3.812,-3.837,P＜0.01).(2) The scores of depression,anxiety and stress were positively correlated with expression suppression (r=0.096,0.080,0.066,P＜0.01),and negatively correlated with cognitive reappraisal(r=-0.176,-0.160,-0.174,P＜0.01) and EQ-VAS (r=-0.410,-0.437,-0.422,P＜0.01).(3) Cognitive reappraisal played a moderating role in the effect of stress on physical health (R2 =0.191,P＜0.01);and expression inhibition exerted a positive moderating role in that of depression on physical health (R2 =0.163,P＜0.01).Conclusion College students' emotion regulation strategies play a moderating role in the effect of emotional state on physical health.