mTORC2 Regulates Non-homologous End Joining Through Modulating the Temporal Dynamics of 53BP1.

DNA damage repair is a critical biological process that maintains genomic integrity, and its dysregulation is closely related to tumorigenesis. To reveal the roles of mammalian target of rapamycin complex 2 (mTORC2) in DNA damage response (DDR), we investigated the temporal changes of cellular protein phosphorylation in mTORC2 deficient renal cancer cells in response to DNA double-strand break (DSB) induced by ionizing radiation (IR) using quantitative phosphoproteomics. The results showed that knockdown of Rictor, a specific component of mTORC2, induced profound changes in the dynamics of protein phosphorylation in response to IR.

Discovery and evaluation of novel Benzohydroxamic acid-indole derivatives as dual inhibitors of ADAM17 and HDAC2 with antitumor activity.

Hepatocellular carcinoma (HCC) has garnered significant attention from researchers due to its high recurrence rate and invasive characteristics. The design of drugs with dual-target combined effects represents a promising strategy in cancer treatment. Our observations suggest that ADAM17 and HDAC may inhibit the unfavorable prognostic signaling pathway Notch1 in HCC through distinct mechanisms, thereby suppressing tumor cell proliferation and metastasis.

Discovery of novel oxindole derivatives as TRPA1 antagonists with potent analgesic activity for pain treatment.

Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in detecting harmful stimuli and endogenous ligands, primarily expressed in sensory neurons. Due to its role in pain and itch, TRPA1 is a potential drug target. We identified an oxindole core structure via high-throughput screening, modified it, and tested the modified compounds in vitro and in vivo.

CRISPR-AsCas12f1 couples out-of-protospacer DNA unwinding with exonuclease activity in the sequential target cleavage.

Type V-F CRISPR-Cas12f is a group of hypercompact RNA-guided nucleases that present a versatile in vivo delivery platform for gene therapy. Upon target recognition, Acidibacillus sulfuroxidans Cas12f (AsCas12f1) distinctively engenders three DNA break sites, two of which are located outside the protospacer. Combining ensemble and single-molecule approaches, we elucidate the molecular details underlying AsCas12f1-mediated DNA cleavages.

Toxicity Evaluation of Potassium Sorbate In Vivo with Drosophila Melanogaster.

Potassium sorbate (PS) is a preservative widely used in the food, pharmaceutical, and cosmetics industries. Improper and careless use of PS can lead to various health issues and potential environmental problems. is capable of making rapid and sensitive responses to stress or other stimuli.

Efficacy and safety of glucagon-like peptide-1 receptor agonists in the treatment of polycystic ovary syndrome-A systematic review and meta-analysis.

Context: Polycystic ovary syndrome (PCOS) is an endocrine gynaecological disorder that affects many women of childbearing age.

Objective: To evaluate the efficacy and safety of glucose-like peptide-1 receptor agonists for obese women with PCOS.

Methods: We searched the PubMed, Embase, WOS, and Cochrane Libarary databases up to June 2023.

sp. nov., an iron-reducing bacterium isolated from mangrove sediment.

A novel facultatively anaerobic and Gram-stain-negative bacterium, designated FJH33, was isolated from mangrove sediment sampled in Zhangzhou, PR China. Cells of strain FJH33 were rod-shaped or slightly curved-shaped, with widths of 0.3-0.

Multi-Omics Characterization of Type 2 Diabetes Mellitus-Induced Cognitive Impairment in the db/db Mouse Model.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder frequently accompanied by cognitive impairment. Contributing factors such as modern lifestyle, genetic predisposition, and gene environmental interactions have been postulated, but the pathogenesis remains unclear. In this study, we attempt to investigate the potential mechanisms and interventions underlying T2DM-induced cognitive deficits from the brain-gut axis perspective.

Biosynthesis Pathways, Transport Mechanisms and Biotechnological Applications of Fungal Siderophores.

Iron (Fe) is the fourth most abundant element on earth and represents an essential nutrient for life. As a fundamental mineral element for cell growth and development, iron is available for uptake as ferric ions, which are usually oxidized into complex oxyhydroxide polymers, insoluble under aerobic conditions. In these conditions, the bioavailability of iron is dramatically reduced.

Variants in Causes Occipital Cortical Malformation.

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.

A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease.

Alexander disease (AxD) is a cerebral white matter disease affecting a wide range of ages, from infants to adults. In the present study, two cases of bulbospinal form AxD were reported, and a preliminary exploration of AxD was conducted thorough clinical, functional magnetic resonance imaging (fMRI) and functional analyses. In total, two de novo mutations in the glial fibrillary acidic protein () gene (c.

Inflammatory pathways in Alzheimer's disease mediated by gut microbiota.

In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron.

The Prevalence and Risk Factors of Cerebral Microbleeds: A Community-Based Study in China.

Introduction: Cerebral microbleeds (CMBs) are frequently found in the healthy elderly. However, data on the prevalence and risk factors of CMBs in the general population of China are lacking.

Methods: A cross-sectional study focusing on the prevalence and risk factors of CMBs was conducted in stroke-free elderly from Shanghai Wuliqiao community.

Neurodevelopmental disorder caused by a truncating de novo variant of IRF2BPL.

Background: Mutations in the IRF2BPL gene can cause neurodevelopmental disorders. We describe the clinical and genetic characteristics of a Chinese patient with a novel abnormality in this gene, explore the potential pathogenic mechanism and summarize the clinical characteristics of 25 patients with IRF2BPL mutations.

Methods: We identified the gene mutation sites by whole-exome and Sanger sequencing.

c.1263+1G>A Is a Latent Hotspot for CYP27A1 Mutations in Chinese Patients With Cerebrotendinous Xanthomatosis.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are crucial for early diagnosis and treatment.

Objectives And Methods: Four CTX families with mutations in the CYP27A1 gene were enrolled in our study.

Altered structural and functional connectivity in CSF1R-related leukoencephalopathy.

CSF1R-related leukoencephalopathy is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few studies have investigated the intrinsic brain alternations of patients with CSF1R-related leukoencephalopathy. We aim to evaluate the structural and functional changes in those patients.

Facile and Scalable Fabrication of Highly Efficient Lead Iodide Perovskite Thin-Film Solar Cells in Air Using Gas Pump Method.

Control of the perovskite film formation process to produce high-quality organic-inorganic metal halide perovskite thin films with uniform morphology, high surface coverage, and minimum pinholes is of great importance to highly efficient solar cells. Herein, we report on large-area light-absorbing perovskite films fabrication with a new facile and scalable gas pump method. By decreasing the total pressure in the evaporation environment, the gas pump method can significantly enhance the solvent evaporation rate by 8 times faster and thereby produce an extremely dense, uniform, and full-coverage perovskite thin film.

An early warning and control system for urban, drinking water quality protection: China's experience.

An event-driven, urban, drinking water quality early warning and control system (DEWS) is proposed to cope with China's urgent need for protecting its urban drinking water. The DEWS has a web service structure and provides users with water quality monitoring functions, water quality early warning functions, and water quality accident decision-making functions. The DEWS functionality is guided by the principles of control theory and risk assessment as applied to the feedback control of urban water supply systems.