Osmundacetone ameliorates Alzheimer's-like pathologies by inhibiting β-amyloid fibrillation, oxidative damage and neuroinflammation in APP/PS1 transgenic mice.

Background: β-Amyloid (Aβ) fibrillation is critical for Aβ deposition and cytotoxicity during the progression of Alzheimer's disease (AD). Consequently, anti-Aβ monoclonal antibody drugs targeting Aβ oligomers and aggregation are considered potential therapeutic strategies for AD treatment. Similar to the working mechanisms of anti-Aβ monoclonal antibody drugs, our study identified osmundacetone (OAC), a small-molecule compound isolated from the traditional Chinese medicine Rhizoma Osmundae, as exerting anti-AD effects by targeting Aβ.

Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides.

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of VBPO from the brown seaweed and VBPO from the red seaweed , which produce ()- and ()-sulfoxides, respectively.

Specific growth velocity reference charts for monochorionic twin pregnancies.

Objective: We aimed to create specific growth velocity reference charts for monochorionic (MC) twin pregnancies and provide additional information for assessing fetal growth in MC twins.

Study Design: This retrospective study collected data from uncomplicated MC twins with serial ultrasound parameters. The four ultrasound parameters, including biparietal diameter, femur length, head circumference, and abdominal circumference, were used to calculate the estimated fetal weight (EFW).

Effect of electroacupuncture on the intestinal flora-short chain fatty acid metabolism axis in simple obesity rats.

Objectives: To observe the effect of electroacupuncture (EA) on the intestinal flora-short chain fatty acids (SCFAs) metabolism axis in rats with simple obesity, so as to explore the underlying mechanism of EA in reducing obesity.

Methods: Male SD rats were randomly divided into control group, model group and EA group, with 6 rats in each group. The obesity model was established by feeding the rats with high-fat diet.

Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.

The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905.

Exploring the clinical implications of novel SRD5A2 variants in 46,XY disorders of sex development.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2, and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region.

Vortex Spin Liquid with Fractional Quantum Spin Hall Effect in Moiré Chern Bands.

Recently there is a report of the experimental signatures of a fractional quantum spin hall (FQSH) state at hole filling n=3 in a twisted MoTe_{2} bilayer. Previous theories of FQSH phases simply considered a decoupled pair of a fractional quantum Hall phase and its time reversal partner. Here, we show the first construction of an FQSH phase beyond the decoupling picture.

Drug-drug interactions of simnotrelvir/ritonavir: an open-label, fixed-sequence, two-period clinical trial.

Objectives: Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp.

Analysis of gut microbiota-derived metabolites regulating pituitary neuroendocrine tumors through network pharmacology.

Pituitary neuroendocrine tumors (PitNETs) are a special class of tumors of the central nervous system that are closely related to metabolism, endocrine functions, and immunity. In this study, network pharmacology was used to explore the metabolites and pharmacological mechanisms of PitNET regulation by gut microbiota. The metabolites of the gut microbiota were obtained from the gutMGene database, and the targets related to the metabolites and PitNETs were determined using public databases.

Michael Acceptor Pyrrolidone Derivatives and Their Activity against Diffuse Large B-cell Lymphoma.

Objective: This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma (DLBCL), a common and heterogeneous malignancy of the adult lymphohematopoietic system. Given the limitations of current therapies, there is a pressing need to develop new and effective drugs for DLBCL treatment.

Methods: A series of pyrrolidone derivatives were synthesized, and their antitumor activities were assessed, particularly against DLBCL cell lines.

A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors.

Design and activity evaluation of new EGFR tyrosine kinase inhibitors containing cyclic polyamines.

The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells.

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone.

Methods: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization.

Antifungal Activity and Mechanism of Diaporthein B against in Prevention of Apple Ring Rot.

Apple ring rot, caused by the pathogenic fungus , has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against , with an EC value of 8.8 μg/mL.

Melatonin mitigates matrix stiffness-induced intervertebral disk degeneration by inhibiting reactive oxygen species and melatonin receptors mediated PI3K/AKT/NF-κB pathway.

Intervertebral disk degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, potentially contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; however, its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its underlying mechanisms.

Spatially structured exchange of metabolites enhances bacterial survival and resilience in biofilms.

Biofilm formation enhances bacterial survival and antibiotic tolerance, but the underlying mechanisms are incompletely understood. Here, we show that biofilm growth is accompanied by a reduction in bacterial energy metabolism and membrane potential, together with metabolic exchanges between the inner and outer regions in biofilms. More specifically, nutrient-starved cells in the interior supply amino acids to cells in the periphery, while peripheral cells experience a decrease in membrane potential and provide fatty acids to interior cells.

circRNA18_46222157_46248185 inhibits melanogenesis by targeting miR-211/EP300 pathway in goat melanocytes.

Objective: This study investigated the effects of circRNA18_46222157_46248185 (named circRNA18) on goat melanogenesis, which differs significantly in goat skins isolated from white and brown coat-colored skins.

Methods: Expression patterns of circRNA18 in goat skin and melanocytes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. The circRNA18 interference vector was designed and synthesized to transfect melanocytes and detect the effect of circRNA18 interference on melanin production.

Highly reversible Zn anodes enabled by in-situ construction of zincophilic zinc polyacrylate interphase for aqueous Zn-ion batteries.

The irreversibility and low utilization of Zn anode stemming from the corrosion and dendrite growth have largely limited the commercialization of aqueous zinc batteries. Here, a carbonyl-rich polymer interphase of zinc polyacrylate (ZPAA) is spontaneously in-situ constructed on Zn anode to address the above-mentioned dilemmas. The ZPAA interlayer enables fast transport kinetics of Zn and tailors the interfacial electric field for realizing the uniform Zn deposition due to superior zincophilicity, high Zn transference number and inherent ion-diffusion channel.

Machine Learning in Identifying Marker Genes for Congenital Heart Diseases of Different Cardiac Cell Types.

Congenital heart disease (CHD) represents a spectrum of inborn heart defects influenced by genetic and environmental factors. This study advances the field by analyzing gene expression profiles in 21,034 cardiac fibroblasts, 73,296 cardiomyocytes, and 35,673 endothelial cells, utilizing single-cell level analysis and machine learning techniques. Six CHD conditions: dilated cardiomyopathy (DCM), donor hearts (used as healthy controls), hypertrophic cardiomyopathy (HCM), heart failure with hypoplastic left heart syndrome (HF_HLHS), Neonatal Hypoplastic Left Heart Syndrome (Neo_HLHS), and Tetralogy of Fallot (TOF), were investigated for each cardiac cell type.

Health Risk Assessment of Employees Exposed to Chlorination By-products of Recreational Water in Large Amusement Parks in Shanghai.

Objective: Chlorination is often used to disinfect recreational water in large amusement parks; however, the health hazards of chlorination disinfection by-products (DBPs) to occupational populations are unknown. This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks.

Methods: Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire.

A novel method of identification of in-ring decay and its application in the half-life estimates of Ru.

Isochronous Mass Spectrometry is a practical approach for studying decays of short-lived isomers. However, solely relying on the time stamps between the isomer and ground state does not provide clear sign of decay. To address this issue, we proposed a method for extracting decay time point by analyzing the residuals of time stamps within a window of (20μs, 180μs) after the start of data acquisition.