MYRF Variants in Patients With 46,XY Differences/Disorders of Sex Development and Literature Review.

46,XY differences/disorders of sex development (DSD) are genetically heterogeneous conditions characterized by atypical development of the reproductive system. MYRF, a gene encoding a transcription factor, has been identified as a potential causative gene for DSD and cardiac urogenital syndrome (CUGS). This study aims to delineate the clinical manifestations of patients with 46,XY DSD and MYRF mutations, encompassing both from our cohort and cases reported in the literature.

The difference of oropharyngeal microbiome during acute respiratory viral infections in infants and children.

Acute respiratory infections (ARI) with multiple types of viruses are common in infants and children. This study was conducted to assess the difference of oropharyngeal microbiome during acute respiratory viral infection using whole-genome shotgun metagenomic sequencing. The overall taxonomic alpha diversity did not differ by the types of infected virus.

ZBP1-mediated PANoptosis is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury.

UVB irradiation induces diverse modalities of regulatory cell death in keratinocytes. Recently, the pattern of coexistence of pyroptosis, apoptosis, and necroptosis has been termed PANoptosis; however, whether PANoptosis occurs in keratinocytes in UVB-induced skin injury remains unclear. We observed that the key molecules of GSDMD-mediated pyroptosis, apoptosis, and necroptosis, which are N-terminal GSDMD, cleaved caspase-3/PARP, and phosphorylated MLKL, respectively, were elevated in keratinocytes of UVB-challenged mice and human skin tissue.

The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.

Establishment of a Yeast Two-Hybrid-Based High-Throughput Screening Model for Selection of SARS-CoV-2 Spike-ACE2 Interaction Inhibitors.

The recent coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted considerable impact on global health. To prepare for rapidly mutating viruses and for the forthcoming pandemic, effective therapies targeting the critical stages of the viral life cycle need to be developed. Viruses are dependent on the interaction between the receptor-binding domain (RBD) of the viral Spike (S) protein (S-RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor to efficiently establish infection and the following replicate.

The role of programmed cell death in organ dysfunction induced by opportunistic pathogens.

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis.

LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells.

Background: The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved.

Hepatocellular CMPK2 promotes the development of metabolic dysfunction-associated steatohepatitis.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive subtype of metabolic dysfunction-associated steatotic liver disease (MASLD), has limited pharmacological treatment options. Therefore, we aimed to identify novel therapeutic targets.

Methods: The Gene Expression Omnibus (GEO) database and human liver tissues obtained from patients with MASH were used to identify differentially expressed genes in MASH.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how variants contribute to the spectrum of axial skeletal disorders is not well understood.

Clinical Diagnosis and Differential Diagnosis Between CSF1R- and AARS2-Related Leukoencephalopathy.

CSF1R-related leukoencephalopathy (CSF1R-L) and AARS2-related leukoencephalopathy (AARS2-L) were two disease entities sharing similar phenotype and even pathological changes. Although clinically, radiologically, and pathologically similar, they were caused by mutation of two different genes. As the rarity of the two diseases, the differential diagnosis of them was difficult.

A Study on the Induction of Multi-Type Immune Responses in Mice via an mRNA Vaccine Based on Hemagglutinin and Neuraminidase Antigen.

Background: The Influenza A virus (IAV), a pathogen affecting the respiratory system, represents a major risk to public health worldwide. Immunization remains the foremost strategy to control the transmission of IAV. The virus has two primary antigens: hemagglutinin (HA) and neuraminidase (NA).

Genome Sequencing Providing Molecular Evidence of Tetrapolar Mating System and Heterothallic Life Cycle for Edible and Medicinal Mushroom Fr.

is a species whose sclerotia have been extensively employed in traditional Chinese medicine, which has diuretic, antitumor, anticancer, and immune system enhancement properties. However, prolonged asexual reproduction has resulted in significant homogenization and degeneration of seed sclerotia. In contrast, sexual reproduction has emerged as an effective strategy to address these challenges, with a distinct mating system serving as the foundation for the implementation of sexual breeding.

Potential Mechanisms and Effects of Dai Bai Jie Ethanol Extract in Preventing Acute Alcoholic Liver Injury.

This study investigated the protective effect of Dai Bai Jie (DBJ) extract against acute alcoholic liver injury (AALI) and elucidated its potential mechanism. The total saponin level in the DBJ extracts was measured using vanillin-chloroform acid colorimetry. To observe the preventive and protective effects of DBJ on AML-12 cells in an ethanol environment, the effective components of DBJ were identified.

A Multi-Level Multiple Contrastive Learning Method for Single-Lead Electrocardiogram Atrial Fibrillation Detection.

Atrial fibrillation (AF) is the most common persistent arrhythmia, and it is crucial to develop generalizable automatic AF detection methods. However, supervised AF detection is often limited in performance due to the difficulty in obtaining labeled data. To address the gap between limited labeled data and the requirements for model robustness and generalization in single-lead ECG AF detection, we proposed a semi-supervised contrastive learning method named MLMCL for AF detection.

Bone marrow mesenchymal stem cells derived cytokines associated with AKT/IAPs signaling ameliorate Alzheimer's disease development.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition affecting around 50 million people worldwide. Bone marrow-derived mesenchymal stem cells (BMMSCs) have emerged as a promising source for cellular therapy due to their ability to differentiate into multiple cell types and their paracrine effects. However, the direct injection of BMMSCs can lead to potential unpredictable impairments, prompting a renewed interest in their paracrine effects for AD treatment.

Clarification of the biosynthetic gene cluster involved in the antifungal prodrug echinocandin B and its robust production in engineered Aspergillus pachycristatus.

Echinocandin antifungals exhibit high efficacy against drug-resistant strains due to their unique mechanism of action. The production of their semi-synthetic precursors relies solely on microbial metabolism, leading to elevated production costs. Anidulafungin, an excellent echinocandin drug, is derived from echinocandin B (ECB), which is industrially produced by Aspergillus pachycristatus.

Multi-center real-world data-driven web calculator for predicting outcomes in IDH-mutant gliomas: Integrating molecular subtypes and treatment modalities.

Background: Isocitrate dehydrogenase (IDH)-mutant gliomas generally have a better prognosis than IDH-wild-type glioblastomas, and the extent of resection significantly impacts prognosis. However, there is a lack of integrated tools for predicting outcomes based on molecular subtypes and treatment modalities. This study aimed to identify factors influencing gross total resection (GTR) rates and to develop a clinical prognostic tool for IDH-mutant gliomas.

Clonal hematopoiesis of indeterminate potential and type 2 diabetes mellitus among patients with STEMI: from a prospective cohort study combing bidirectional Mendelian randomization.

Aim: Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications and prognostic significance of CHIP and T2DM in patients diagnosed with ST-segment elevation myocardial infarction (STEMI).

Methods: Deep-targeted sequencing employing a unique molecular identifier (UMI) for the analysis of 42 CHIP mutations-achieving an impressive mean depth of coverage at 1000 × -was conducted on a cohort of 1430 patients diagnosed with acute myocardial infarction (473 patients with T2DM and 930 non-DM subjects).

Hypervirulent Klebsiella pneumoniae have better clinical outcomes than classical Klebsiella pneumoniae for lower respiratory tract infection patients.

Background: The clinical outcomes and microbiological features of lower respiratory tract infections (LRTIs) caused by hypervirulent Klebsiella pneumoniae (hvKp) and classical Klebsiella pneumoniae (cKp) have not been well understood.

Methods: This study collected 287 non-repetitive Klebsiella pneumoniae isolates from 287 LRTI patients. All these strains underwent annotation for resistance and virulence factors, with 141 strains undergoing mouse infection experiments to assess their virulence.

Multiple Enzymes Expressed by the Gut Microbiota Can Transform Typhaneoside and Are Associated with Improving Hyperlipidemia.

The mechanism of multiple enzymes mediated drug metabolism in gut microbiota is still unclear. This study explores multiple enzyme interaction process of typhactyloside (TYP) with gut microbiota and its lipid-lowering pharmacological activity. TYP, with bioavailability of only 2.

miR-32533 Reduces Cognitive Impairment and Amyloid-β Overload by Targeting CREB5-Mediated Signaling Pathways in Alzheimer's Disease.

MicroRNAs (miRNAs) are associated with amyloid-β (Aβ) dysmetabolism, a pivotal factor in the pathogenesis of Alzheimer's disease (AD). This study unveiled a novel miRNA, microRNA-32533 (miR-32533), featuring a distinctive base sequence identified through RNA sequencing of the APPswe/PSEN1dE9 (APP/PS1) mouse brain. Its role and underlying mechanisms were subsequently explored.

A Universal Therapeutic Vaccine Leveraging Autologous Pre-Existing Immunity to Eliminate in Situ Uniformly Engineered Heterogeneous Tumor Cells.

Tumor vaccines that activate the autologous immune system to eliminate tumor cells represent a promising approach in cancer immunotherapy. However, challenges such as tumor heterogeneity, limited antigen selection, insufficient antigen presentation, and the slow onset of de novo immune responses have resulted in poor universality and suboptimal response rates. In contrast, pathogen-specific pre-existing immunity acquired through infection or vaccination, can rapidly generate a more potent and enduring immune response upon re-encounter with the same antigen.

Comprehensive single-cell atlas of colorectal neuroendocrine tumors with liver metastases: unraveling tumor microenvironment heterogeneity between primary lesions and metastases.

Background: Colorectal neuroendocrine tumors with liver metastases (CRNELM) are associated with a poorer prognosis compared to their nonmetastatic counterparts. A comprehensive understanding of the tumor microenvironment (TME) heterogeneity between primary lesions (PL) and liver metastases (LM) could provide crucial insights for enhancing clinical management strategies for these patients.

Methods: We utilized single-cell RNA sequencing to analyze fresh tissue samples from CRNELM patients, aiming to elucidate the variations in TME between PL and LM.

Efficacy and safety of gut microbiome-targeted treatment in patients with depression: a systematic review and meta-analysis.

Background: The study aimed to comprehensively analyze and establish a framework for evaluating the efficacy of microbiome-targeted treatment (MTT) for depression.

Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and the Chinese National Knowledge Infrastructure database for randomized controlled trials (RCTs) on MTT in treating depression until October 19, 2023. A meta-analysis was conducted to evaluate the efficacy and safety of MTT.

Spatial transcriptomics and single-cell RNA-sequencing revealed dendritic cell-mediated inflammation in keratoconus.

Keratoconus (KC) is a corneal disorder characterized by central corneal protrusion and thinning. In this study, spatial transcriptomics was employed to investigate molecular and cellular variations in KC, revealing a distinct pattern of inflammatory responses across the cornea. Upregulation of inflammatory processes was observed in the central cornea, while downregulation was noted in the periphery, indicating complex regional inflammatory changes in the KC cornea.