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ObjectiveTo investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment.MethodsThe serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared.ResultsThe incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P

BackgroundKnee Osteoarthritis (KOA) is a prevalent and debilitating condition affecting millions worldwide, yet its underlying etiology remains poorly understood. Recent advances in neuroimaging and genetic methodologies offer new avenues to explore the potential neuropsychological contributions to KOA. This study aims to investigate the causal relationships between brain-wide morphometric variations and KOA using a genetic epidemiology approach.MethodLeveraging data from 36,778 UK Biobank participants for human brain morphometry and 487,411 UK Biobank participants for KOA, this research employed a two-sample Mendelian Randomization (TSMR) approach to explore the causal effects of 83 brain-wide volumes on KOA. The primary method of analysis was the Inverse Variance Weighted (IVW) and Wald Ratio (WR) method, complemented by MR Egger and IVW methods for heterogeneity and pleiotropy assessments. A significance threshold of p < 0.05 was set to determine causality. The analysis results were assessed for heterogeneity using the MR Egger and IVW methods. Brain-wide volumes with Q_pval < 0.05 were considered indicative of heterogeneity. The MR Egger method was employed to evaluate the pleiotropy of the analysis results, with brain-wide volumes having a p-value < 0.05 considered suggestive of pleiotropy.ResultsOur findings revealed significant causal associations between KOA and eight brain-wide volumes: Left parahippocampal volume, Right posterior cingulate volume, Left transverse temporal volume, Left caudal anterior cingulate volume, Right paracentral volume, Left paracentral volume, Right lateral orbitofrontal volume, and Left superior temporal volume. These associations remained robust after tests for heterogeneity and pleiotropy, underscoring their potential role in the pathogenesis of KOA.ConclusionThis study provides novel evidence of the causal relationships between specific brain morphometries and KOA, suggesting that neuroanatomical variations might contribute to the risk and development of KOA. These findings pave the way for further research into the neurobiological mechanisms underlying KOA and may eventually lead to the development of new intervention strategies targeting these neuropsychological pathways.

Background: Kidney renal clear cell carcinoma (KIRC) is a common and clinically significant subtype of kidney cancer. A potential therapeutic target in KIRC is disulfidptosis, a novel mode of cell death induced by disulfide stress. The aim of this study was to develop a prognostic model to explore the clinical significance of different disulfidptosis gene typings from KIRC.Methods: A comprehensive analysis of the chromosomal localization, expression patterns, mutational landscape, copy number variations, and prognostic significance of 10 disulfide death genes was conducted. Patients were categorized into distinct subtypes using the Non-negative Matrix Factorization (NMF) typing method based on disulfidptosis gene expression patterns. Weighted Gene Co-expression Network Analysis (WGCNA) was used on the KIRC dataset to identify differentially expressed genes between subtype clusters. A risk signature was created using LASSO-Cox regression and validated by survival analysis. An interaction between risk score and immune cell infiltration, tumor microenvironment characteristics and pathway enrichment analysis were investigated.Results: Initial findings highlight the differential expression of specific DRGs in KIRC, with genomic instability and somatic mutation analysis revealing key insights into their role in cancer progression. NMF clustering differentiates KIRC patients into subgroups with distinct survival outcomes and immune profiles, and hierarchical clustering identifies gene modules associated with key biological and clinical parameters, leading to the development of a risk stratification model (LRP8, RNASE2, CLIP4, HAS2, SLC22A11, and KCTD12) validated by survival analysis and predictive of immune infiltration and drug sensitivity. Pathway enrichment analysis further delineates the differential molecular pathways between high-risk and low-risk patients, offering potential targets for personalized treatment. Lastly, differential expression analysis of model genes between normal and KIRC cells provides insights into the molecular mechanisms underlying KIRC, highlighting potential biomarkers and therapeutic targets.Conclusion: This study contributes to the understanding of KIRC and provides a potential prognostic model using disulfidptosis gene for personalized management in KIRC patients. The risk signature shows clinical applicability and sheds light on the biological mechanisms associated with disulfide-induced cell death.

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuV may show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there are many efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton’s resilience against CLCuD.

BackgroundAlthough subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography.MethodsThis meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle–Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models.ResultsSeventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e’ wave (E/e’) had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine.ConclusionIn adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083).Systematic review registrationhttps://inplasy.com/inplasy-2023-2-0083.

BackgroundInterleukin-6 (IL-6) is essential for maintaining intestinal epithelial homeostasis. Although cold water-immersion restraint (CWIR) stress is commonly used to induce in vivo gastric injury, it also affects intestinal epithelial permeability. Although IL-6 is increased in response to acute physiological and psychological stress, its exact effects on the pathophysiology of the intestinal epithelium in response to acute CWIR stress remain unknown.MethodsWe used IL-6 knockout (KO) mice with acute CWIR modeling to investigate the effect of IL-6 deficiency on intestinal epithelial morphology and pathological damage using histological staining assays under the acute stress. We detected jejunal epithelial apoptosis using TUNEL and standard molecular experiments.ResultsCWIR caused intestinal epithelial damage, which was alleviated by the absence of IL-6, as evidenced by morphological changes and goblet cell and intestinal permeability alteration. IL-6 KO also reduced CWIR-mediated inflammatory levels and improved stress defense. Meanwhile, IL-6 deficiency decreased the intestinal epithelial apoptosis induced by CWIR administration. This IL-6 KO-led effect depended more on mitochondrial AIF signaling rather than the traditional caspase pathway.ConclusionAs a result, we concluded that acute CWIR-induced severe intestinal damage and jejunal epithelium apoptosis could be alleviated by IL-6 deficiency, implying a protective effect of IL-6 deficiency on the intestines under acute stress. The findings shed new light on treating CWIR-induced intestinal disorders by inhibiting IL-6 signaling.

Growing evidence has demonstrated that stress triggers gastrointestinal (GI) disorders. This study aimed to investigate how the acute cold water-immersion restraint (CWIR) stress affects intestinal injury and gut microbiota (GM) distribution. Male C57BL/6 mice were used to establish a CWIR animal model. Hematoxylin–eosin and periodic acid–Schiff staining were performed to assess intestinal histopathological changes. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and immunofluorescence staining were used to evaluate the expression of inflammatory cytokines and immune cell infiltration in the intestinal tissues. The gut permeability and intestinal occludin protein expression were determined through fluorescein isothiocyanate-dextran detection and western blot, respectively. GM profiles were analyzed via high-throughput sequencing of the fecal bacterial 16S rRNA genes. Results showed that CWIR induced more severe intestinal mucosal injury compared to the control, leading to a significant increase in tumor necrosis factor-α expression, but no infiltration of neutrophil and T cells. CWIR also resulted in GI disruption and increased the permeability of the intestinal mucosa. GM profiles showed that CWIR reduced GM diversity of mice compared with the control group. Specifically, aerobic and gram-negative bacteria significantly increased after CWIR, which was associated with the severity of gut injury under stress. Therefore, acute CWIR leads to severe intestinal damage with inflammation and disrupts the GM homeostasis, contributing to decreased GM diversity. Our findings provide the theoretical basis for the further treatment of intestinal disorders induced by CWIR.

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.

BackgroundOsteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.MethodsHuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.ResultsKnockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuVmay show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there aremany efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton's resilience against CLCuD. [ABSTRACT FROM AUTHOR]