Synergistic anticancer activity of HSP70 and HSF1 inhibitors in colorectal cancer cells: A new strategy for combination therapy.

Background: The heat shock response (HSR) is a highly conserved mechanism that maintains intracellular homeostasis in response to various environmental and physiological stresses. Heat shock proteins (HSPs), particularly HSP70, play a pivotal role in this process as molecular chaperones. Although HSP70 inhibitors have demonstrated anti-cancer activity, their therapeutic potential has been limited by the negative feedback mechanism between HSP70 and heat shock factor 1 (HSF1).

Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China.

Background: Over the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC).

L-aspartate ameliorates diet-induced obesity by increasing adipocyte energy expenditure.

Aims: Obesity always leads to profound perturbation of metabolome. Metabolome studies enrich the knowledge on associations between endogenous metabolites and obesity, potentially providing innovative strategies for the development of novel anti-obesity pharmacotherapy. This study aims to identify an endogenous metabolite that regulates energy expenditure and to explore its application for obesity treatment.

sgRNA structure optimization and PTG/Cas9 system synergistically boost gene knockout efficiency in an insect.

Knockouts mediated by CRISPR/Cas9 technology are widely used to study insect gene functions, but the efficiency in Hemiptera is low. New strategies are urgently needed to improve gene knockout efficiency. This study initially explored the impact of modifying the fundamental backbone structure of single guide RNA (sgRNA) on knockout efficiency.

Design, synthesis and structure-activity relationship of novel 2-pyrimidinylindole derivatives as orally available anti-obesity agents.

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study.

The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis.

Objectives: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis.

Methods: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers.

Development of Novel -Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development.

Controllable quantum scars induced by spin-orbit couplings in quantum dots.

Spin-orbit couplings (SOCs), originating from the relativistic corrections in the Dirac equation, offer nonlinearity in the classical limit and are capable of driving chaotic dynamics. In a nanoscale quantum dot confined by a two-dimensional parabolic potential with SOCs, various quantum scar states emerge quasi-periodically in the eigenstates of the system, when the ratio of confinement energies in the two directions is nearly commensurable. The scars, displaying both quantum interference and classical trajectory features on the electron density, due to relativistic effects, serve as a bridge between the classical and quantum behaviors of the system.

Enhancement of Carrier Mobility in Multilayer InSe Transistors by van der Waals Integration.

Two-dimensional material indium selenide (InSe) holds great promise for applications in electronics and optoelectronics by virtue of its fascinating properties. However, most multilayer InSe-based transistors suffer from extrinsic scattering effects from interface disorders and the environment, which cause carrier mobility and density fluctuations and hinder their practical application. In this work, we employ the non-destructive method of van der Waals (vdW) integration to improve the electron mobility of back-gated multilayer InSe FETs.

A lysosome-targeted fluorescent probe based on a BODIPY structure for Cys/Hcy detection.

Cysteine (Cys) and homocysteine (Hcy) are important biothiols in living organisms. They play important roles in a variety of physiological and pathological processes. Therefore, it is very important to design an optical probe for the selective detection of Cys/Hcy.

Microbial pathways driving stable soil organic carbon change in abandoned Moso bamboo forests in southeast China.

Mineral-associated organic carbon (MOC) is a stable component of the soil carbon (C) pool, critical to realize carbon sequestration and coping with climate change. Many Moso bamboo (Phyllostachys edulis) forests in subtropical and tropical areas that used to be intensively managed have been left unmanaged. Still, studies on MOC changes occurring during the transition from intensive management to unmanagement are lacking.

Design, synthesis and evaluation of 2-pyrimidinylindole derivatives as anti-obesity agents by regulating lipid metabolism.

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring.

Risk of thrombotic events in immune thrombocytopenia patients treated with thrombopoietic agents: a systematic review and meta-analysis.

Background: Immune thrombocytopenia (ITP), which is a well-known hemorrhagic disorder characterized by low platelet counts, has been shown to be associated with the risk of thrombosis. Thrombopoietic agents (TAs) are extensively used as second-line treatments for ITP, effectively reducing the risk of hemorrhage. However, thrombosis, a potential adverse effect of TAs, raises clinical challenges.

Design and Synthesis of Bouchardatine Derivatives as a Novel AMP-Activated Protein Kinase Activator for the Treatment of Colorectal Cancer.

Metabolic reprogramming is a crucial hallmark of tumorigenesis. Modulating the reprogrammed energy metabolism is an attractive anticancer therapeutic strategy. We previously found a natural product, , modulated aerobic metabolism and inhibited proliferation in the colorectal cancer cell (CRC).

CRISPR/Cas9-mediated genome editing of gustatory receptor NlugGr23a causes male sterility in the brown planthopper Nilaparvata lugens.

Gustatory receptors (Grs) have an essential role in chemical recognition so as to evaluate food quality. Insect Grs also participate in non-gustatory functions, such as olfaction, temperature sensing, and mating. In this study, we knocked out NlugGr23a, a putative fecundity-related Gr, using the CRISPR/Cas9 system in the brown planthopper Nilaparvata lugens, a serious insect pest of rice.

BiOI-SnO Heterojunction Design to Boost Visible-Light-Driven Photocatalytic NO Purification.

The efficient, stable, and selective photocatalytic conversion of nitric oxide (NO) into harmless products such as nitrate (NO) is greatly desired but remains an enormous challenge. In this work, a series of BiOI/SnO heterojunctions (denoted as %B-S, where % is the mass portion of BiOI compared with the mass of SnO) were synthesized for the efficient transformation of NO into harmless NO. The best performance was achieved by the 30%B-S catalyst, whose NO removal efficiency was 96.

Matrine counteracts obesity in mice via inducing adipose thermogenesis by activating HSF1/PGC-1α axis.

Promoting energy expenditure is known to curb obesity and can be exploited for its treatment. Our previous study has demonstrated that activation of HSF1/PGC-1α axis efficiently induced mitochondrial biogenesis and adaptive oxidation and thus ameliorating lipid accumulation, however, whether it can be a therapeutic approach for metabolic disorders treatment needs explored. Here, a high-efficient and specific HSF1/PGC-1α activator screening system was established and the natural clinical liver-protecting agent matrine was identified as a robust HSF1/PGC-1α activator.

Palladium oxidative addition complex-enabled synthesis of amino-substituted indolyl-4(3)-quinazolinones and their antitumor activity evaluation.

The indolyl-4(3)-quinazolinone core is an important structural motif in functional molecules. However, few methods exist for its direct modification, which limits its potential application. Reported herein is a palladium-mediated amination of halogen-containing indolyl-4(3)-quinazolinones with a variety of primary and secondary amines the corresponding palladium oxidative addition complexes.

A novel HSF1 activator ameliorates non-alcoholic steatohepatitis by stimulating mitochondrial adaptive oxidation.

Background And Purpose: Non-alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH.

Experimental Approach: The correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin-immunoprecipitation sequencing.

Hierarchical Self-Distilled Feature Learning for Fine-Grained Visual Categorization.

Fine-grained visual categorization (FGVC) relies on hierarchical features extracted by deep convolutional neural networks (CNNs) to recognize closely alike objects. Particularly, shallow layer features containing rich spatial details are vital for specifying subtle differences between objects but are usually inadequately optimized due to gradient vanishing during backpropagation. In this article, hierarchical self-distillation (HSD) is introduced to generate well-optimized CNNs features for accurate fine-grained categorization.

Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.

The gut bacterium has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model.

CRISPR/Cas9-mediated knockout of the NlCSAD gene results in darker cuticle pigmentation and a reduction in female fecundity in Nilaparvata lugens (Hemiptera: Delphacidae).

In insects, cuticular pigmentation genes have been exploited as potential visible markers for constructing genetic manipulation systems. Here, we cloned cysteine sulfinic acid decarboxylase (CSAD), an orthologue of melanin metabolism pathway genes, and performed RNAi experiments in the brown planthopper Nilaparvata lugens (Hemiptera: Delphacidae). The results showed that a decrease in the level of transcription of NlCSAD increased melanin deposition in the body compared to the control group, resulting in darker cuticle pigmentation.

Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders.

Discovery of novel anti-obesity agents is a challenging and promising research area. Based on our previous works, we synthesized 40 novel β-indoloquinazoline analogues by altering the skeleton and introducing preferential side chains, evaluated their lipid-lowering activity and summarized the structure-activity relationships. In combination with an evaluation of the lipid-lowering efficacies, AMP-dependent activated protein kinase (AMPK) activating ability and liver microsomal stability, compound 23 (named as IQZ23) was selected for further studies.

Bouchardatine analogue alleviates non-alcoholic hepatic fatty liver disease/non-alcoholic steatohepatitis in high-fat fed mice by inhibiting ATP synthase activity.

Background And Purpose: Non-alcoholic hepatic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome in the liver and non-alcoholic steatohepatitis (NASH) represents its advanced stage. R17 derived from bouchardatine, shows benefits in the metabolic syndrome, but has not been tested in the liver. The present study examined the pharmacological effects of R17 in a model of NAFLD/NASH and its mode of action.