Discovery of Novel -Sulfonamide-tetrahydroquinolines as Potent Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists for the Treatment of Psoriasis.

Guided by the mode of action of , our previously discovered RORγt inverse agonist, we conducted five rounds of design syntheses and structure-activity relationship (SAR) studies, ultimately identifying RORγt inverse agonist , which exhibited superior activity compared to . Besides, showed promising therapeutic effects in alleviating psoriasis in mice by intraperitoneal injection. Due to the high lipophilicity and pharmacokinetic properties of , it was formulated into an ointment, which enabled effective skin retention and mitigated systemic side effects.

2'-Fluorinated nucleoside chemistry for new drug discovery: achievements and prospects.

Fluorinated nucleosides are an important class of modified nucleosides that have demonstrated therapeutic potential for treating various human diseases, especially viral infections and cancer. Many fluorinated nucleosides have advanced into clinical trials or have been approved by the FDA for use in patients. Among these fluorinated nucleosides, azvudine, developed by us, has been officially approved by the National Medical Products Administration for the treatment of coronavirus disease 2019 (COVID-19) and human immunodeficiency virus, indicating the therapeutic promise of fluorinated nucleosides.

The next challenge in emissions control for heavy-duty diesel vehicles: From NO to NO.

Vehicle emissions are a major source of greenhouse gases globally. Dual selective catalytic reduction (SCR), an advanced version of single SCR, is crucial under stricter nitrogen oxide (NO) emission standards for heavy-duty diesel vehicles (HDDVs). However, the emission characteristics of nitrous oxide (NO), a byproduct of SCR and a potent greenhouse gas, remain unclear.

Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis.

Background: Lung adenocarcinoma (LUAD) is a highly lethal malignancy. Liquid-Liquid Phase Separation (LLPS) plays a crucial role in targeted therapies for lung cancer and in the progression of lung squamous cell carcinoma. However, the role of LLPS in the progression and prognosis of LUAD remains insufficiently explored.

Mitigative Effect and Mechanism of Caffeic Acid Combined with Umbilical Cord-Mesenchymal Stem Cells on LPS-Induced Mastitis.

Mastitis is an inflammation of the mammary gland tissue that can lead to decreased milk production and altered milk composition, carrying serious implications for the safety of dairy products. Although both caffeic acid (CA) and umbilical cord-mesenchymal stem cells (UC-MSCs) showed potential anti-inflammatory and immunomodulatory properties, little is known about their combined roles in treating mastitis. Here, we report the combined effects and mechanisms of CA and UC-MSCs on lipopolysaccharide (LPS)-induced mastitis.

Molecular Insight into the Electric Field Regulation of N and CH Adsorption in the Trapdoor ZSM-25 Zeolites.

Controlling gas admission by regulating pore accessibility in porous materials has been a topic of extensive research. Recently, the electric field (E-field) has emerged as an external stimulus to alter the adsorption behavior of some microporous adsorbents. However, the mechanism behind this phenomenon is not yet fully understood.

Dysregulated T-cell homeostasis and decreased CD30 Treg proliferating in aplastic anemia.

Aplastic anemia (AA) is an autoimmune hematopoietic disease mediated by autoreactive T cells leading to bone marrow failure. However, the precise role of autoreactive T cells in the development of AA is not fully understood, hindering the advancement of therapeutic and diagnostic strategies. In this study, we conducted a single-cell transcriptome analysis of CD8 T cells, conventional CD4 T (CD4 Tconv) cells, and Treg cells, to elucidate the potential disruption of T cell homeostasis in patients with AA.

Neohesperidin alleviates the inhibitory effect of bisphenol A on the myogenic differentiation of umbilical cord mesenchymal stem cells via the IGF1R/AKT1/RHOA signaling pathway.

Bisphenol A (BPA), a typical environmental endocrine disruptor, has raised concerns among researchers due to its toxicological effects. Whether neohesperidin (NEO) can intervene in the toxic effects of BPA remains unknown. This study aims to investigate the effects and mechanisms of NEO on the myogenic differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) exposed to BPA.

Sestrin2 in POMC neurons modulates energy balance and obesity related metabolic disorders via mTOR signaling.

Sestrin2 is a highly conserved protein that can be induced under various stress conditions. Researches have revealed that the signaling pathway of the mammalian target of rapamycin (mTOR) is essential in modulating both glucose and lipid metabolism. However, the precise involvement of Sestrin2 in the hypothalamus, particularly in pro-opiomelanocortin (POMC) neurons, in control of energy homeostasis remains uncertain.

Prediction of developmental toxic effects of fine particulate matter (PM) water-soluble components via machine learning through observation of PM from diverse urban areas.

The global health implications of fine particulate matter (PM) underscore the imperative need for research into its toxicity and chemical composition. In this study, zebrafish embryos exposed to the water-soluble components of PM from two cities (Harbin and Hangzhou) with differences in air quality, underwent microscopic examination to identify primary target organs. The Harbin PM induced dose-dependent organ malformation in zebrafish, indicating a higher level of toxicity than that of the Hangzhou sample.

Robustness of coupled networks with multiple support from functional components at different scales.

Robustness is an essential component of modern network science. Here, we investigate the robustness of coupled networks where the functionality of a node depends not only on its connectivity, here measured by the size of its connected component in its own network, but also the support provided by at least M links from another network. We here develop a theoretical framework and investigate analytically and numerically the cascading failure process when the system is under attack, deriving expressions for the proportion of functional nodes in the stable state, and the critical threshold when the system collapses.

MolProphet: A One-Stop, General Purpose, and AI-Based Platform for the Early Stages of Drug Discovery.

Artificial intelligence (AI) is an effective tool to accelerate drug discovery and cut costs in discovery processes. Many successful AI applications are reported in the early stages of small molecule drug discovery. However, most of those applications require a deep understanding of software and hardware, and focus on a single field that implies data normalization and transfer between those applications is still a challenge for normal users.

Large Organic Polar Molecules Tailored Electrode Interfaces for Stable Lithium Metal Battery.

Lithium (Li) metal batteries (LMBs) are deemed as ones of the most promising energy storage devices for next electrification applications. However, the uneven Li electroplating process caused by the diffusion-limited Li transportation at the Li metal surface inherently promotes the formation of dendritic morphology and instable Li interphase, while the sluggish Li transfer kinetic can also cause lithiation-induced stress on the cathode materials suffering from serious structural stability. Herein, a novel electrolyte designing strategy is proposed to accelerate the Li transfer by introducing a trace of large organic polar molecules of lithium phytate (LP) without significantly altering the electrolyte structure.

A Triple-Responsive Polymeric Prodrug Nanoplatform with Extracellular ROS Consumption and Intracellular HO Self-Generation for Imaging-Guided Tumor Chemo-Ferroptosis-Immunotherapy.

High reactive oxygen species (ROS) levels in tumor microenvironment (TME) impair both immunogenic cell death (ICD) efficacy and T cell activity. Furthermore, tumor escapes immunosurveillance via programmed death-1/programmed death ligand-1 (PD-L1) signal, and the insufficient intracellular hydrogen peroxide weakens ferroptosis efficacy. To tackle the above issues, a glutathione (GSH)/ROS/pH triple-responsive prodrug nanomedicine that encapsulates FeO nanoparticle via electrostatic interaction is constructed for magnetic resonance imaging (MRI)-guided multi-mode theranostics with chemotherapy/ferroptosis/immunotherapy.

HvBGlu3, a GH1 β-glucosidase enzyme gene, negatively influences β-glucan content in barley grains.

HvBGlu3, a β-glucosidase enzyme gene, negatively influences β-glucan content in barley grains by mediating starch and sucrose metabolism in developing grains. Barley grains are rich in β-glucan, an important factor affecting end-use quality. Previously, we identified several stable marker-trait associations (MTAs) and novel candidate genes associated with β-glucan content in barley grains using GWAS (Genome Wide Association Study) analysis.

Prevalence of, risk factors for, and target organ damage from metabolic syndrome among people living with HIV on ART: A cross-sectional analysis in Chongqing, China.

Introduction: The incidence of metabolic syndrome (MetS) in people living with HIV is significantly higher than in people without HIV. MetS is not only a major driver of cardiovascular disease (CVD) but is also closely related to the development of chronic kidney disease (CKD). The aim of this study was to investigate the prevalence of and risk factors for MetS and to further understand the degree of damage to target organs.

Discovery of Biaryl Amide Derivatives as Potent, Selective, and Orally Bioavailable RORγt Agonists for Cancer Immunotherapy.

The master transcription factor receptor retinoic acid receptor-related orphan receptor γt (RORγt) regulates the differentiation of T-helper 17 (Th17) cells and the production of interleukin-17 (IL-17). Activation of RORγt T cells in the tumor microenvironment promotes immune infiltration to more effectively inhibit tumor growth. Therefore, RORγt agonists provide a reachable approach to cancer immunotherapy.

On the Durability of Tin-Containing Perovskite Solar Cells.

Tin (Sn)-containing perovskite solar cells (PSCs) have gained significant attention in the field of perovskite optoelectronics due to lower toxicity than their lead-based counterparts and their potential for tandem applications. However, the lack of stability is a major concern that hampers their development. To achieve the long-term stability of Sn-containing PSCs, it is crucial to have a clear and comprehensive understanding of the degradation mechanisms of Sn-containing perovskites and develop mitigation strategies.