Novel oral compound Z526 mitigates cancer-associated cachexia via intervening NF-κB signaling and oxidative stress.

Cancer-associated cachexia (CAC) is a severe metabolic disorder syndrome mainly characterized by muscle and fat loss, which accounts for one-third of cancer-related deaths. No effective therapeutic approach that could fully reverse CAC is available. NF-κB signaling and oxidative stress play vital roles in both muscle atrophy and fat loss in CAC.

Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.

Due to the importance of 4R tau (with four microtubule-binding-repeat domains) in the pathogenicity of primary tauopathies, it has been challenging to model these diseases in induced pluripotent stem cell (iPSC)-derived neurons, which express very low levels of 4R tau. To address this, we have developed a panel of isogenic iPSC lines carrying MAPT splice-site mutations, S305S, S305I, or S305N, derived from four different donors. All mutations significantly increase 4R tau expression in iPSC neurons and astrocytes.

Cytokine-induced reprogramming of human macrophages toward Alzheimer's disease-relevant molecular and cellular phenotypes .

Myeloid cells including brain-resident (microglia) and peripheral macrophages play a crucial role in various pathological conditions, including neurodegenerative disorders like Alzheimer's disease (AD). They respond to disruption of tissue homeostasis associated with disease conditions by acquiring various transcriptional and functional states. Experimental investigation of these states is hampered by the lack of tools that enable accessible and robust reprogramming of human macrophages toward Alzheimer's disease-relevant molecular and cellular phenotypes .

Solid-State Reversible Phase Transition and Photoluminescence Properties of Organic-Inorganic Hybrid Halide: (BTPA)MnBr.

Multifunctional materials have long been a popular research area, with organic-inorganic hybrids frequently utilized due to their diverse properties and versatile assembly techniques. In this context, a novel Mn-based organic-inorganic hybrid compound (BTPA)MnBr() was prepared, with strong green photoluminescence, phase transition under thermal stimulation, and two reversible dielectric-state switches. This compound exhibits strong green photoluminescence under ultraviolet excitation, boasting a quantum yield of 44.

A microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression reveals physiological characteristics similar to depression.

The diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression.

Clinical and laboratory features of neurosyphilis: A single-center, retrospective study of 402 patients.

Neurosyphilis is a serious global health issue and a big challenge in developing countries, related risk factors should be taken seriously. Although there are a certain number of studies describing the clinical and laboratory features and risk factors for symptomatic neurosyphilis (SNS), but some risk factors are still controversial. The aim of this research is to investigate the association between asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS) and identify risk factors for SNS.

Identification of Potential Hub Genes Related to Acute Pancreatitis and Chronic Pancreatitis via Integrated Bioinformatics Analysis and In Vitro Analysis.

Acute pancreatitis (AP) and chronic pancreatitis (CP) are considered to be two separate pancreatic diseases in most studies, but some clinical retrospective analyses in recent years have found some degree of correlation between the two in actual treatment, however, the exact association is not clear. In this study, bioinformatics analysis was utilized to examine microarray sequencing data in mice, with the aim of elucidating the critical signaling pathways and genes involved in the progression from AP to CP. Differential gene expression analyses on murine transcriptomes were conducted using the R programming language and the R/Bioconductor package.

BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues.

Genetic and experimental evidence suggests that Alzheimer's disease (AD) risk alleles and genes may influence disease susceptibility by altering the transcriptional and cellular responses of macrophages, including microglia, to damage of lipid-rich tissues like the brain. Recently, sc/nRNA sequencing studies identified similar transcriptional activation states in subpopulations of macrophages in aging and degenerating brains and in other diseased lipid-rich tissues. We collectively refer to these subpopulations of microglia and peripheral macrophages as DLAMs.

Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.

Genome-wide association studies (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified noncoding polymorphisms within the gene. encodes GIRK2, a subunit of a G-protein-coupled inwardly rectifying potassium channel that regulates neuronal excitability. We studied the effect of upregulating using an isogenic approach with human glutamatergic neurons derived from induced pluripotent stem cells (male and female donors).

ncRNAs-mediated overexpression of predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.

Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 () is a DNA demethylase.

Shallow Marine High-Resolution Optical Mosaics Based on Underwater Scooter-Borne Camera.

Optical cameras equipped with an underwater scooter can perform efficient shallow marine mapping. In this paper, an underwater image stitching method is proposed for detailed large scene awareness based on a scooter-borne camera, including preprocessing, image registration and post-processing. An underwater image enhancement algorithm based on the inherent underwater optical attenuation characteristics and dark channel prior algorithm is presented to improve underwater feature matching.

Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis.

Background: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-).

Methods: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.

Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome.

Purpose: To identify new mutations in DNAH17 that cause male infertility and analyze intracytoplasmic sperm injection (ICSI) outcomes in patients with DNAH17 mutations.

Methods: A total of five cases of new DNAH17 mutations exhibiting the multiple morphological abnormalities of the sperm flagella (MMAF) phenotype were identified through semen analysis and genetic testing. They were recruited at our reproductive medicine center from September 2018 to July 2022.

Computational biology-based study of the molecular mechanism of spermidine amelioration of acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory gastrointestinal disease, the mortality and morbility of which has been on the increase in the past years. Spermidine, a natural polyamine, has a wide range of pharmacological effects including anti-inflammation, antioxidation, anti-aging, and anti-tumorigenic. This study aimed to investigate the reliable targets and molecular mechanisms of spermidine in treating AP.

Bacillus licheniformis prevents and reduces anxiety-like and depression-like behaviours.

As common mental disorders, depression and anxiety impact people all around the world. Recent studies have found that the gut microbiome plays an important role in mental health. It is becoming possible to treat mental disorders by regulating the composition of the gut microbiota.

Exploring the therapeutic mechanisms of Gleditsiae Spina acting on pancreatic cancer network pharmacology, molecular docking and molecular dynamics simulation.

Pancreatic cancer is one of the most aggressive tumors and also has a low survival rate. The dried spines of Gleditsia sinensis Lam are known as "Gleditsiae Spina" and they mostly contain flavonoids, phenolic acids, terpenoids, steroids, and other chemical components. In this study, the potential active components and molecular mechanisms of Gleditsiae Spina for treating pancreatic cancer were systematically revealed by network pharmacology, molecular docking and molecular dynamics simulations (MDs).

ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida.

Study Question: Does a homozygous nonsense mutation in ACR lead to total fertilization failure (TFF) resulting in male infertility in humans?

Summary Answer: A novel homozygous nonsense mutation of ACR (c.167G>A, p.Trp56X) was identified in two infertile brothers and shown to cause human TFF.

Upregulated GIRK2 counteracts ethanol-induced changes in excitability & respiration in human neurons.

Unlabelled: Genome-wide association analysis (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified non-coding polymorphisms within the gene. encodes GIRK2, a subunit of a G protein-coupled inwardly-rectifying potassium channel that regulates neuronal excitability. How changes in GIRK2 affect human neuronal excitability and the response to repeated ethanol exposure is poorly understood.

Visualizing Higher-Fold Topology in Chiral Crystals.

Novel topological phases of matter are fruitful platforms for the discovery of unconventional electromagnetic phenomena. Higher-fold topology is one example, where the low-energy description goes beyond standard model analogs. Despite intensive experimental studies, conclusive evidence remains elusive for the multigap topological nature of higher-fold chiral fermions.

BHLHE40/41 regulate macrophage/microglia responses associated with Alzheimer's disease and other disorders of lipid-rich tissues.

Background: Genetic and experimental evidence strongly implicates myeloid cells in the etiology of AD and suggests that AD-associated alleles and genes may modulate disease risk by altering the transcriptional and cellular responses of macrophages (like microglia) to damage of lipid-rich tissues (like the brain). Specifically, recent single-cell/nucleus RNA sequencing (sc/nRNA-seq) studies identified a transcriptionally distinct state of subsets of macrophages in aging or degenerating brains (usually referred to as disease-associated microglia or DAM) and in other diseased lipid-rich tissues (e.g.

DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.

The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility.