To investigate epigenetic and transcriptional alterations in children with Wiedemann-Steiner syndrome (WDSTS) due to variants of KMT2A gene using genome-wide DNA methylation array and RNA sequencing (RNA-seq), and identify the key pathways and candidate genes. A retrospective study was carried out for 16 children with WDSTS and 10 healthy controls who visited Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine between November 2016 and December 2024. Peripheral blood samples were collected. Genomic DNA and total RNA were extracted using commercially made kits. Genome-wide DNA methylation profiling was conducted to identify differentially methylated positions (DMPs) and annotated genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RNA-seq was performed to identify differentially expressed genes (DEGs) and conduct GO/KEGG functional annotation. Methylation and expression data were integrated to identify overlapping genes showing significant changes at both levels, followed by GO, KEGG and gene-pathway network analyses. This study was approved by the Ethics Committee of the hospital (Ethics No.: GKLW-A-2024-006-01). A total of 2 652 DMPs corresponding to 1 262 genes were identified, which included 833 hypermethylated genes (66%) and 429 hypomethylated genes (34%). Hypermethylated genes were mainly enriched for functions related to cell junctions, while hypomethylated genes were significantly involved in nervous system development and morphogenesis. RNA-seq identified 2 627 DEGs, including 765 up-regulated genes (29%) and 1 862 down-regulated genes (71%). Up-regulated genes were mainly associated with immune-related processes, and down-regulated genes were mainly related to substance transport. Integrative analysis identified 93 overlapping genes with significant changes in both methylation and expression. And these genes were enriched in extracellular matrix-related processes, calcium ion binding, neurodevelopment, and cell adhesion. Key candidate genes, including LAMB1, LAMB2 and NID1, were further prioritized. Integrated analysis of DNA methylation and transcriptome data reveals WDSTS-related epigenetic-transcriptional alterations and provides clues for exploring disease mechanisms and optimizing diagnostic strategies.

To compare the performance of copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) for the analysis of abortive tissues. Tissue samples were collected from 396 patients with missed abortion who were treated at Yancheng Maternal and Child Health Care Hospital between January 2021 and July 2024. A retrospective analysis method was employed to gather relevant clinical data of the patients. 171 samples were detected by CNV-seq combined with short tandem repeat (STR) analysis, and 225 samples were detected by CMA. Differences between the two techniques, including the detection of chromosomal aneuploidies, structural aberrations [detection of CNVs of various lengths and different CNVs types], the types of chromosomal abnormalities across different ages and gestational weeks were comprehensively compared. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2024-LS-KYLX-010). Among the 396 samples, 256 cases were detected with chromosomal abnormalities, which yielded a detection rate of 64.6%. Among the 171 cases undergoing CNV-seq analysis, 107 (62.6%) were found with chromosomal abnormalities. Among the 225 cases undergoing CMA, 149 (66.2%) were found with chromosomal abnormalities. No significant difference was found between the two groups (Χ2 = 0.566, P > 0.05). Among the autosomal number abnormalities, trisomy 16 was the most common in both groups, followed by trisomy 22, and 45,X was the most common among the abnormal number of sex chromosomes. In cases of chromosomal structural abnormalities, the CNV-seq group detected 36 CNVs, while the CMA group detected 27 CNVs. In the comparison of CNVs between the two groups based on different genome lengths, when the genome length was 100 ~ 500 kb, the CNV-seq group detected more than the CMA group, there was a statistically significant difference (Χ2 = 4.974, P < 0.05). When the genome length was greater than 1 000 kb, the CMA group detected more than the CNV-seq group, there was a statistically significant difference (Χ2 = 5.24, P < 0.05). Compared to different types of detected CNVs, the CMA group detected more pathogenic CNVs than the CNV-seq group, there was a statistically significant difference (Χ2 = 10.176, P < 0.05), while the CNV-seq group detected more variants of uncertain significance (VUS) CNVs, there was a statistically significant difference (Χ2 = 9.625, P < 0.05). The comparison of two groups based on different types of chromosomal abnormalities shows that aneuploidy was the most common in both groups. The proportion of polyploidy abnormalities was higher in the CMA group than in the CNV-seq group, there was a statistically significant difference (Χ2 = 8.106, P < 0.05), and the proportion of chimerism was higher in the CNV-seq group than in the CMA group, there was a statistically significant difference (Χ2 = 6.888, P < 0.05). The comparison of chromosome abnormalities distribution by age group between the CNV-seq group and the CMA group showed no statistical significance in the four age groups of ≤ 24 years, 25 ~ 29 years, 30 ~ 34 years, and ≥ 35 years (P > 0.05). Comparison of chromosomal abnormalities detected in the two groups at different gestational weeks showed that the CNV-seq group had a significantly higher detection rate for the first 8 weeks than the CMA group (Χ2 = 8.419, P < 0.05), though no significant difference was found in the proportion of chromosomal abnormalities between the two groups for the 8 ~ 10 weeks, 10 ~ 12 weeks, and weeks after 12 (all P > 0.05). CNV-seq can detect chromosomal aneuploidies, mosaicisms and more VUS. The combination of CNV-seq and STR analysis can effectively detect chromosomal polyploidy. CNV-seq requires low sample quality and genomic DNA content while achieving high success rates. In the clinics, combined CNV-seq and STR analysis can serve an effective tool for genetic diagnosis of miscarriage tissues.

To explore the clinical phenotypes and genetic etiology of a child with MRXS34 syndrome due to a variant of NONO gene. A child patient who presented at Shanxi Provincial Maternity and Child Care Hospital on September 28, 2020 was selected as study subject. Clinical data of the child were retrospectively collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing of the family members. Pathogenicity of the variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the effect of the NONO gene variant on messenger RNA (mRNA) expression level in the proband, and complementary DNA (cDNA) sequencing was performed to validate the splicing patterns of the NONO gene variant in the proband. Using the keywords "NONO gene" "MRXS34" "developmental delay" "intellectual disability" and "congenital heart disease", a literature search was conducted in databases including the China National Knowledge Infrastructure(CNKI), Wanfang Data and PubMed databases to identify studies on the clinical and genotypic characteristics of children with MRXS34 caused by NONO gene variants. The search period was set from the inception of the databases to April 2025, and a comprehensive analysis of the findings from the identified studies was performed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: IRB-KYHZ-2019-006). The proband, a 3-year-old male, exhibited global developmental delay, intellectual disability, facial dysmorphism, macrocephaly, corpus callosum dysgenesis, cavum septum pellucidum, atrial septal defect, tricuspid valve insufficiency with regurgitation, cryptorchidism, inguinal hernia, and anal cutaneous fistula. The results of WES and Sanger sequencing validation showed that the proband carried a heterozygous variant of the NONO gene c.577_581del (p.Val193fs), while both parents were wild-type, indicating that this variant was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2_Moderate+PM2_Supporting). RT-qPCR results showed that the relative mRNA expression level of the NONO gene in the proband was significantly lower than that in the control group of normal children, and cDNA sequencing results verified that the frameshift variant due to base deletion led to nonsense-mediated mRNA decay (NMD), causing premature termination of transcription without exon skipping at the splice site. Using the literature search strategy established in this study, a total of 15 studies on the clinical and genotypic characteristics of children with MRXS34 caused by NONO gene variants were identified, involving a total of 32 patients. Together with the proband of this study, a total of 33 patients were included in the comprehensive analysis. The results revealed a total of 23 types of variants involving the NONO gene. The main clinical manifestations of MRXS34 included developmental delay/intellectual disability (23/24, 95.8%), cardiovascular abnormalities (23/30, 76.7%), craniofacial/somatic malformations (21/24, 87.5%), and corpus callosum dysgenesis (16/21, 76.2%). The NONO gene variant probably underlay the pathogenesis of MRXS34 in this proband. The findings of this study has expanded of the variant and clinical spectra associated with the NONO gene.

To analyze the clinical phenotype and genetic etiology of patients with Dyggve-Melchior-Clausen syndrome (DMC syndrome). A child with DMC syndrome diagnosed at Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University in August 2020 was selected as study subject. A retrospective analysis was carried out to collect the proband's clinical data. Peripheral blood samples was collected from the proband and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated within the family by Sanger sequencing. Pathogenicity of candidate variants was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the center (Ethics No.: SCMCIRB-K2023024-1). The proband, a 5-year-and-7-month-old girl, presented with short stature (height: -5.5 s) and intellectual disability. Physical examination revealed microcephaly (head circumference: -3.5 s), coarse facial features, long philtrum, pigeon chest, and brachydactyly of both hands. Laboratory findings revealed normal serum insulin-like growth factor-1 (IGF-1) levels (168 ng/mL). Imaging analysis demonstrated dysplasia of corpus callosum and spondyloepiphyseal dysplasia in the proband. WES revealed that she has harbored compound heterozygous variants of the DYM gene, namely c.312-313del (p.His104Glnfs*29) and c.1274A>T (p.Tyr425Phe). Both variants were unreported previously and inherited from her parents who were phenotypically normal. Based on guidelines from the ACMG, the DYM gene variant c.312-313del (p.His104Glnfs*29) was classified as pathogenic (PVS1+PM2_Supporting+PP3+PP4_supporting), while the c.1274A>T (p.Tyr425Phe) variant was classified as likely pathogenic (PM2_Supporting+PP3+PP1+PP4_supporting). By following the pre-set literature search strategy, a total of 20 articles were included, which involved a total of 73 cases of DYM gene variants leading to DMC syndrome. Among these, only one family case was documented in China. Together with proband from this study, a total of 74 DMC syndrome patients due DYM gene variants were included for a comprehensive analysis of clinical phenotypes and genetic characteristics. The age at the time of reporting ranged from 1 to 60 years. The main clinical manifestations included intellectual disability, short stature, and spondyloepiphyseal dysplasia, followed by microcephaly and coarse facial features. By genetic testing, c.1877delA variant was the most common mutation at the nucleotide level. The c.312-313del/c.1274A>T compound heterozygous variants of the DYM gene probably underlay the pathogenesis of DMC syndrome in this proband. Above finding has expanded the mutational and phenotypic spectra of the DMC syndrome.

To explore the clinical phenotype and genetic etiology of a fetus with autosomal dominant intellectual disability type 72 (MRD72) resulting from a variant of the SRRM2 gene. A Chinese pedigree with MRD72 (fetus) who had visited the Affiliated Women and Children's Hospital of Ningbo University in November 2024 was selected as study subject. Clinical data of the pedigree were collected. Amniotic fluid and peripheral blood samples were collected from the fetus and its parents for genomic DNA extraction. Whole-exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing of the family members and rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on MRD72 were searched in domestic and international databases for a review. This study was approved by the hospital (Ethics No.: EC2023-094). The proband was a fetus of 25 weeks of gestation. Fetal echocardiography revealed a relatively small left atrium and left ventricle, along with a diminished aortic-to-pulmonary artery ratio. WES revealed that the fetus has harbored a heterozygous nonsense variant of the SRRM2 gene. Sanger sequencing confirmed both parents carried the wild-type alleles. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting) and has not been recorded in public databases. Bioinformatic analysis predicted amino acid 512 to be highly conserved across various species. According to the pre-set literature search strategy, 4 publications were retrieved, which involved 30 MRD72 patients from 27 pedigrees, In addition to this study, a total of 31 cases were included. Analysis of clinical features and genetic etiology showed that patients with MRD72 presented mainly with clinical manifestations such as mental and motor development delay, special facial features, speech/intellectual development delay, and obesity. The genetic etiology was all variants at relevant loci of the SRRM2 gene. The SRRM2 variant identified in this study is implicated as the genetic cause of MRD72 in the proband. Above results have expanded the mutational and phenotypic spectra of the SRRM2 gene.

Dopaminergic system gene polymorphisms associated with severe obesity and related outcomes: A case-control study in Brazil.

Low-dose aspirin (LDA) is an intervention recommended to prevent the development of hypertensive disorders of pregnancy (HDP) in high-risk pregnancies. Maternal conditions such as HDP have been associated with cord blood epigenetic changes including those related to cardiovascular processes; however, it is unclear whether maternal aspirin therapy may impact neonatal epigenetics in otherwise healthy high-risk pregnancy. This study aimed to determine if maternal LDA exposure in utero leads to altered DNA methylation in umbilical cord blood cells in term neonates compared with controls not exposed to aspirin, and to identify if these methylation changes alter key pathways in the development of chronic disease. Umbilical cord blood was collected from 10 neonates without LDA exposure and 13 neonates with LDA exposure in utero. Patients with hypertensive disorders of pregnancy, COVID-19, and chorioamnionitis were excluded. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC assay. A total of 155 differentially methylated loci (81 genes were hypermethylated and 74 were hypomethylated) were identified in LDA-exposed neonatal umbilical cord blood compared with the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to Th1 and Th2 signaling and classical (M1) macrophage activation. The genes affected by LDA exposure were associated with cardiac and renal systems. LDA exposure led to differential DNA methylation in umbilical cord blood. The differentially methylated genes were related to inflammatory pathways as well as cardiac and renal toxicity pathways. LDA exposure in utero may promote altered health programming in the neonate in areas impacting cardiovascular health. · Maternal aspirin exposure is associated with differential DNA methylation in cord blood.. · Cord blood epigenetic changes associated with maternal aspirin relate to anti-inflammatory pathways.. · Research on potential protective impact of maternal aspirin on neonatal epigenetics is warranted..

Probiotic supplementation is gaining attention for its role in maintaining health and enhancing the quality of life of the elderly. Leukocyte telomere length (LTL) is a biomarker of cellular aging, with shorter LTL associated with cardiovascular morbidity and mortality. This study explored whether probiotics could counteract LTL attrition in an ethnically homogeneous cohort of older adults over a 6-month period. Samples were selected from the PROBIOSENIOR trial, a randomized, double-blind, placebo-controlled study involving 46 participants (≥60 years). Participants were randomized to receive either SYNBIO® probiotics (5 × 109 CFU/daily dose) or a placebo for 6 months. Genomic DNA was extracted from blood samples at baseline, and 6 months later, LTL measures were obtained via quantitative PCR. A general linear model assessed the "treatment x time" interaction as the main outcome. LTL was successfully assessed for all participants (N = 46 × 2 time points). Statistical analysis revealed a significant "treatment x time" interaction (P = .034), indicating a reduced LTL attrition rate in the probiotic group compared with the placebo group. A 6-month supplementation with SYNBIO probiotics significantly reduced LTL attrition in an ethnically homogeneous cohort of elderly adults. These findings suggest that probiotics may serve as a simple and effective intervention to mitigate cellular aging and promote healthy aging.

Genome-wide association study for the detection of genetic variants associated with the antibody response upon viral hemorrhagic septicemia virus vaccination in Paralichthys olivaceus.

Preliminary screening reveals HPV-derived cDNA in the HNCF-PI 52 cell line originally derived from normal cervical tissue.

Persistent soil resistome expansion following bacterial inoculation despite successful antibiotic bioremediation.

Advances in radiation-based sterile insect technique: A comprehensive review of mechanisms, influencing factors, and its potential for sustainable pest control.

Mitochondrial RNA helicase DDX28 promotes cell cycle and DNA repair programs and shapes an immunosuppressive microenvironment in acute myeloid leukemia.

267 Background: Lung cancer, especially non-small cell lung cancer (NSCLC), exhibits significant molecular heterogeneity that influences treatment response and clinical outcomes. This study aims to explore genetic variations and actionable alterations in Indian NSCLC patients to enhance precision medicine approaches. Methods: FFPE tumor tissue samples from 227 Indian lung cancer patients were analyzed using the 1Cell.Ai OncoTarget panel, a targeted NGS assay covering 126 genes associated with multi-cancer mutations, driver fusions, and microsatellite instability. Genomic DNA extraction, library preparation, and sequencing were performed on the Illumina NextSeq platform. Variant calling and clinical interpretation were conducted using the AI-driven iCARE software to identify somatic mutations, gene fusions, copy number variations (CNVs), and other genomic alterations. Therapeutic recommendations followed ACMG, AMP, ASCO, and CAP guidelines. Results: Comprehensive molecular profiling revealed frequent alterations in TP53 (116 cases; 51.1%), EGFR (98 cases; 43.2%), PIK3CA (20 cases; 8.8%), KRAS (15 cases; 6.6%), APC (12 cases; 5.3%), and ALK (11 cases; 4.8%). A clinically significant TP53–EGFR dual-mutation signature was observed in lung adenocarcinoma, with a high co-occurrence rate of approximately 59% (65 cases), defining a distinct molecular subtype characterized by differential responses to EGFR tyrosine kinase inhibitors, an increased propensity for accelerated therapeutic resistance, and a higher risk of aggressive disease progression. Additionally, KRAS co-mutation with TP53 was identified in 10 cases (66.67%), a pattern associated with adverse clinical outcomes, poorer prognosis, and reduced responsiveness to immunotherapy. Importantly, the detection of the KRAS G12C subtype highlights eligibility for targeted therapies such as sotorasib and adagrasib. Among evaluable cases for therapeutic recommendations (n = 160), EGFR mutations were present in 41.66% (67/160) and demonstrated favourable responses to EGFR-directed TKIs, although TP53 co-mutations contributed to resistance in a subset, while ALK fusions (15.63%; 25/160) showed marked sensitivity to ALK inhibitor–based targeted therapies. Conclusions: This study demonstrates the diverse genomic landscape of Indian NSCLC patients, highlighting TP53 and EGFR as key drivers. Notably, 160 of 227 patients (70.48%) received therapy recommendations based on genomic alterations, underscoring the translational value of targeted NGS panels in advancing precision medicine beyond conventional chemotherapy.

Development and analytical validation of the first LAMP assays for the detection of Echinococcus vogeli.

Clamp the LAMP: a photoelectrochemical platform for KRAS mutation detection via wild-type blocking.

Analytical performance of cfDNA quantification methods in pediatric acute lymphoblastic leukemia plasma.

Novel mudskippers CXCL14-derived peptides with broad-spectrum antibacterial activity protect against Edwardsiella tarda infection.

Prevalence of human T-lymphotropic virus type 1 (HTLV-1) infection among patients attending a dermatology clinic in Northeastern Brazil.

Human cytomegalovirus terminase inhibitors letermovir, tomeglovir, and the halogenated benzimidazoles modify DNA cleavage/packaging to generate a super-genomic DNA species by cleavage site skipping.