The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Both carcinoembryonic antigen and CA19-9 are considered as predictive markers of intestinal cancer recurrence and metastasis.In addition,CA19-9 elevation is considered as a predictive marker of connective tissue disease-related interstitial lung disease.The incidence of oxaliplatin and capecitabine-associated interstitial lung disease is low,and there is no report about CA19-9 as a predictive marker of oxaliplatin and capecitabine-associated interstitial lung disease.This paper reports a case of interstitial lung disease with CA19-9 elevation caused by oxaliplatin and capecitabine adjuvant therapy for ileocecal carcinoma.The change trend of serum carcinoembryonic antigen in this patient was consistent with tumor recurrence and metastasis,and that of serum CA19-9 was consistent with the severity of interstitial lung disease.Therefore,CA19-9 elevation after intestinal cancer surgery does not necessarily indicate the tumor recurrence and metastasis,and attention should be paid to the possibility of oxaliplatin and capecitabine-associated interstitial lung disease.
Humans ; CA-19-9 Antigen/blood* ; Capecitabine ; Cecal Neoplasms/drug therapy* ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage* ; Fluorouracil/administration & dosage* ; Lung Diseases, Interstitial/blood* ; Organoplatinum Compounds/administration & dosage* ; Oxaliplatin

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Objective:To investigate the clinical characteristics of residual dizziness（RD） after repositioning in patients with benign paroxysmal positional vertigo（BPPV）, identify its potential risk factors, and develop a predictive risk model. Methods:A total of 137 patients diagnosed with BPPV at the First Affiliated Hospital of Xi'an Jiaotong University between January 2023 and June 2023 were enrolled. Based on the presence or absence of subjective discomfort within 3 months after successful repositioning, patients were divided into the non-RD group（NRD, n=93） and the RD group（n=44）. Differences in demographic characteristics, comorbidities, and disease-related features were compared between groups. Multivariate logistic regression analysis was used to identify independent risk factors for RD, and a nomogram was constructed based on these factors. The predictive performance of the model was assessed using the area under the curve（AUC）. Results:The RD group showed significantly higher values in body mass index, prevalence of diabetes and motion sickness history, dizziness duration before repositioning, history of repositioning at external hospitals, number of treatments, and recurrence（all P<0.001）. Multivariate logistic regression revealed that diabetes（adjusted OR=8.73, P=0.039）, motion sickness history（adjusted OR=23.08, P<0.001）, dizziness duration ≥30 days before repositioning（adjusted OR=15.16, P<0.001）, and recurrence（adjusted OR=15.72, P=0.001） were independent risk factors for RD. The nomogram model based on these variables demonstrated good predictive ability, with an AUC of 0.804（95%CI 0.684-0.924）. Conclusion:Diabetes, motion sickness history, dizziness duration ≥30 days, and recurrence are independent risk factors for RD after repositioning in patients with BPPV. The nomogram model based on these variables shows good predictive performance, with recurrence having the highest predictive value. This model can aid in early identification of high-risk patients and guide individualized intervention strategies.
Humans ; Nomograms ; Benign Paroxysmal Positional Vertigo/therapy* ; Dizziness/etiology* ; Risk Factors ; Risk Assessment ; Multivariate Analysis ; Male ; Female ; Logistic Models ; Middle Aged ; Patient Positioning ; Adult

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. Conclusion The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.

This study aimed to determine the drug resistance phenotype and genetic characteristics of Listeria monocytogenes ST5 LK100 isolated from a neonate,which provided a basis for the diagnosis and treatment of L.monocyto-genes infection and to enhance the understanding of the genomic characteristics of this strain.A suspected L.monocytogenes strain was isolated from the gastric juice sample of an infected neonate,and identified with a VITEK2 Compact automatic mi-crobial identification instrument and 16S RNA sequencing.Five drug sensitivity tests were conducted on the identified strain with the E-test method.Additionally,the whole genome of the strain was sequenced using a third-generation sequencing plat-form.The antibiotic resistance elements of the strain were identified by BlastN with the CARD antibiotic resistance gene data-base.The multilocus sequence typing(MLST),serotyping,and virulence genes of the strain was determined by Pasteur da-tabase,the virulence gene distribution was analyzed using the virulence analysis website.The prophages of the strain were predicted and annotate by PHASTER online website.The strain(LK100)isolated from the neonate was identified as L.monocytogenes.This strain was sensitive to penicillin,ampicil-lin,meropenem,erythromycin,and trimethoprim-sulfame-thoxazole antibiotics.The MLST type and serotype was ST5 and 1/2b-3b,respectively.The total length of the chromoso-mal genome of LK100 was 3 032 582 bp with a GC content of 37.91％,and it contained a complete circular plasmid with a se-quence length of 52 822 bp.The strain LK100 carried complete InlA protein,LIPI-1 pathogenicity island,SSI-1 stress survival island,and an LGI2 genomic island.The intrinsic antibiotic resistance genes were mainly located on the chromosome.Five prophage sequences were predicted in the LK100 genome.This study identified a strain of ST5 L.monocytogenes LK100 from an infected neonate and characterized its genome and antibiotic sensitivity,laying the foundation for further research on ST5 L.monocytogenes.

This study was aimed at understanding the molecular characteristics of Plasmodium ovale curtisi and Plasmodi-um ovale wallikeri imported cases in Chongqing,to provide data to support monitoring and control efforts.In a retrospective analysis,26 Plasmodium ovale archival blood samples were characterized with respect to five molecular markers(Cox1,Cytb,Tra,Dhfr,and K13)from 2013 to 2023.PCR amplification of partial fragments of the Cox1,Cytb,and Tra genes of Plas-modium ovale was performed to distinguish the two subspecies.The drug-resistance Dhfr and K13 genes of Plasmodium ovale were amplified with PCR assays followed by DNA sequencing,and the sequences were aligned.The differentiation of 26 cases of Plasmodium ovale(14 cases of curtisi subspecies and 12 cases of wallikeri subspecies)according to ssrRNA was consistent with the classification results of Cox1,Cytb,and TRA genes.Thirteen single nucleotide dimorphism sites were identified in Cox 1,including the 145 and 153 loci,with only variations in amino acids M176I and I288V at loci 528 and 862,and N337H mutation in one sample.Twelve base substitutions were found among Cytb gene subspecies,with only the M248I mutation in amino acid 248.A total of 49 nucleotide dimorphism sites in Tra gene,resulting in 18 amino acid mutations,were identified be-tween the two subspecies.In the curtisi type sample,the poc1 type had more PINTINPINTIN and TITPIS amino acid units than the poc2 type.The mutation rate of the Dhfr gene was rel-atively high:25％of the samples showed S58R mutations.The K13 gene subspecies was not homozygous,and one sample was heterozygous.This study confirmed the dimorphism and mutation sites between Plasmodium ovale curtisi and wallikeri sub-species in Cox1,Cytb,Tra,Dhfr,and K13 gene fragments of imported Plasmodium ovale in Chongqing,thus enriching knowledge regarding gene polymorphisms in Plasmodium ovale curtisi and wallikeri imported cases.

Objective:To investigate the correlation between clinical outcomes of congenital diaphragmatic hernia (CDH) and chromosomal abnormalities.Methods:This was a retrospective study involving 101 fetuses who underwent invasive prenatal diagnosis and chromosomal analysis for CDH at the Prenatal Diagnosis Center of Guangzhou Medical University Affiliated Women and Children's Medical Center from January 1, 2010, to December 31, 2021. According to ultrasound results, they were divided into the isolated CDH group and the complex CDH group. The results of chromosomal karyotype analysis or chromosomal microarray analysis (CMA) and birth outcomes were analyzed. For live-born children, follow-up results were analyzed. Statistical analysis was performed using t-test or Chi-square (or Fisher's exact) test. Results:(1) The mean age of the mothers of the 101 fetuses was (29.6±5.3) years, ranging from 20 to 47 years, and 16 mothers (15.8%) were over 35 years old. The mean gestational age at invasive prenatal diagnosis was (27.1±5.0) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days; the mean gestational age at first diagnosis of CDH was (26.6±4.8) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days. (2) The 101 fetuses were divided into isolated CDH group (81 cases, 80.2%) and complex CDH group (20 cases, 19.8%) based on whether they had other ultrasound abnormalities. Among the 20 complex cases, 13 had more than two types of malformations, with cardiovascular system malformations being the most common (11 cases, including seven chromosomal abnormalities). The highest proportion of chromosomal abnormalities was found in fetuses with central nervous system malformations (3/4). (3) Among the 101 CDH fetuses, 31 (30.7%) underwent chromosomal karyotype analysis alone, 39 (38.6%) underwent CMA alone, and 31 (30.7%) underwent both tests. The rate of chromosomal abnormalities was 13.9% (14/101). The detection rates of abnormalities by chromosomal karyotype analysis and CMA were 16.1% (10/62) and 14.3% (10/70), respectively. The additional detection rate by CMA was 2.8% (2/70). (4) The gestational age at diagnosis in the complex CDH group was earlier than that in the isolated CDH group [(22.7±4.2) weeks vs. (27.7±4.6) weeks, t=4.47, P<0.001]. The total detection rate, as well as the detection rates by chromosomal karyotype analysis and CMA, were higher in the complex CDH group than those in the isolated CDH group [45.0% (9/20) vs. 6.2% (5/81), χ2=17.13; 7/15 vs. 6.4% (3/47), χ2=10.82; 5/11 vs. 8.8% (5/57), χ2=7.55; all P<0.01]. (5) Among the 101 CDH fetuses, two were lost to follow-up, and 99 (98.0%) were successfully followed up. Among these 99 cases, 48 were terminated, and 51 were live births. The chromosomal abnormality rate in the 48 terminated fetuses was 25.0% (12/48), including 28 isolated cases and 20 complex cases. All 51 live births were isolated cases, with 45 (88.2%) cured by postnatal surgery and six (11.8%) having adverse clinical outcomes (including two preoperative deaths, three postoperative deaths, and one postoperative recurrence). Conclusions:The rate of chromosomal abnormalities in CDH is high, and it is higher in complex CDH than in isolated CDH. When prenatal diagnosis reveals fetal CDH, invasive prenatal diagnosis is recommended to exclude chromosomal karyotype abnormalities, with CMA recommended as the preferred chromosomal testing method.