GYY4137 protects against type 2 diabetes mellitus-associated myocardial autophagy by suppressing FOXO1 signal pathway.

Diabetic cardiomyopathy (DCM) is a major complication of type 2 diabetes mellitus (T2DM), but its effective prevention and treatment are still limited. We investigated the effects of GYY4137, a slow-releasing hydrogen sulfide donor, and its downstream mediator forkhead box protein O1 (FOXO1) on T2DM-associated DCM. , T2DM mice were induced by a high-fat diet coupled with streptozotocin injection.

Metal-Free Synthesis of Functionalized Indolizines via a Cascade Michael/S2/Aromatization Reaction of 2-Alkylazaarene Derivatives with Bromonitroolefins.

A transition metal-free domino Michael/S2/aromatization annulation of 2-pyridylacetates with bromonitroolefins has been developed. A wide range of substrates containing various substituted groups was compatible with the present methodology and afforded functionalized indolizines with moderate to excellent yield (up to 99% yield). In addition, the potential practicality of the method stood out through scale-up reactions and further transformations to other valuable compounds.

Synthesis of Novel Chromene Derivatives Bearing Hydrazide/Thiazol/Oxazol/Oxime Moieties as Potential Antifungal Agents.

Four series of novel hydrazide/thiazol/oxazol/oxime ester hybrids of chromene derivatives were designed and synthesized to explore natural-product-based fungicide candidates. Preliminary antifungal activity assay results demonstrated that hydrazide-chromene and thiazol-chromene derivatives exhibited excellent and broad-spectrum inhibitory activity against ten phytopathogenic fungi. Among them, six compounds , , , , , and displayed the most remarkable antifungal effects.

Design and synthesis of some novel structurally diverse thiochroman derivatives as fungicides against phytopathogenic fungi.

Background: Plant diseases infected by pathogenic fungi have a devastating effect on global agricultural and food industry yields. The development of novel, environmentally friendly, and efficient fungicides is an important technique for preventing and combatting phytopathogenic fungi.

Results: Herein, 99 thiochroman-based derivatives containing hydroxyl, sulfoxide, sulfone, carbonyl, double bond, amino, imine, oxime, oxime ester, and amide moieties were synthesized.

A global dataset of terrestrial evapotranspiration and soil moisture dynamics from 1982 to 2020.

Quantifying terrestrial evapotranspiration (ET) and soil moisture dynamics accurately is crucial for understanding the global water cycle and surface energy balance. We present a novel, long-term dataset of global ET and soil moisture derived from the newly developed Simple Terrestrial Hydrosphere model, version 2 (SiTHv2). This ecohydrological model, driven by multi-source satellite observations and hydrometeorological variables from reanalysis data, provides daily global ET-related estimates (e.

The self-designed reactor to achieve efficient degradation of polyvinyl alcohol under high-pressure and high-temperature conditions.

A huge amount of polyvinyl alcohol (PVA) fabric is abandoned from nuclear power plants every year, the traditional treatment process will occupy land resources and pollute the environment; therefore, a lot of research has been carried out on the chemical treatment of PVA fabric. Herein, the performance of degradation of polyvinyl alcohol under high-pressure and high-temperature conditions is investigated. The effects of the initial pH value, reaction temperature, molar ratio of HO/Fe, and HO dosage on PVA degradation were evaluated.

Exploring the ecological meanings of temperature sensitivity of ecosystem respiration from different methods.

Temperature sensitivity (Q) of ecosystem respiration (R) is a critical parameter for predicting global terrestrial carbon dynamics and its response to climate warming. However, the determination of Q has been controversial. In this study, we scrutinized the underpinnings of three mainstream methods to reveal their relationships in estimating Q for R in the Heihe River Basin, northwest China.

Design and Synthesis of Novel Phthalide Derivatives containing 1,3,4-Oxadiazole/1,2,4-Triazole Units as Potential Antifungal Agents.

Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a, 4 b, 4 m, 5 b, 5 f, 5 h, and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V.

Cemiplimab combined with chemotherapy chemotherapy in advanced non-small cell lung cancer: an updated EMPOWER-Lung 3 trial-based cost-effectiveness analysis.

Objective: Cemiplimab combined with chemotherapy has emerged as a promising treatment option for advanced non-small cell lung cancer (NSCLC). Accordingly, this study has been conducted to evaluate the cost-effectiveness of this combination therapy in comparison to chemotherapy alone from the perspective of the United States healthcare system.

Methods: The present study is based on a partitioned survival model developed from clinical data obtained during the 2-year follow-up of the phase III EMPOWER-Lung 3 part 2 trial.

-Cresol-Enabled Nickel-Catalyzed Intermolecular Redox-Economical Coupling of Allyl Alcohols with Alkynes through oxa-Nickelacycle.

An intermolecular redox-economical coupling reaction of allyl alcohols with alkynes, catalyzed by Ni-Brønsted acid cocatalysis, has been developed. This method allows for the synthesis of a diverse range of γ,δ-unsaturated ketones with yields ranging from 40% to 94%, while maintaining excellent compatibility with various functional groups. The transformation of the resulting product demonstrates the significant practical value of this method.

The autophagy machinery interacts with EBV capsids during viral envelope release.

Autophagy serves as a defense mechanism against intracellular pathogens, but several microorganisms exploit it for their own benefit. Accordingly, certain herpesviruses include autophagic membranes into their infectious virus particles. In this study, we analyzed the composition of purified virions of the Epstein-Barr virus (EBV), a common oncogenic γ-herpesvirus.

Development of the "hidden" multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease.

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aβ aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized.

Type I Interferonopathy due to a Homozygous Loss-of-Inhibitory Function Mutation in STAT2.

Purpose: STAT2 is both an effector and negative regulator of type I interferon (IFN-I) signalling. We describe the characterization of a novel homozygous missense STAT2 substitution in a patient with a type I interferonopathy.

Methods: Whole-genome sequencing (WGS) was used to identify the genetic basis of disease in a patient with features of enhanced IFN-I signalling.

Downregulation of TNFAIP1 alleviates OGD/R‑induced neuronal damage by suppressing Nrf2/GPX4‑mediated ferroptosis.

TNFα-induced protein 1 (TNFAIP1) serve a role in neurovascular disease. However, the potential role and molecular mechanism of TNFAIP1 in cerebral ischemia-reperfusion (I/R) remains elusive. In the present study, reverse transcription-quantitative PCR and western blotting were used to assess TNFAIP1 mRNA and protein expression levels in PC12 cells.

Synthesis of Novel 3-Butylphthalide Derivatives Containing Isopentenylphenol Moiety as Potential Antiplatelet Agents for the Treatment of Ischemic Stroke.

In order to find novel antiplatelet drugs for the treatment of ischemic stroke, a series of 3-butylphthalide derivatives containing isopentenylphenol moiety were designed, synthesized and characterized with spectroscopic analyses. The in vitro antiplatelet activity results indicated that compound 3 better inhibited the arachidonic acid (AA) induced platelet aggregation than aspirin (ASP) and 3-butylphthalide (NBP). Additionally, compared with precursor NBP, compound 3 possessed outstanding antithrombotic activity in the animal experiment model, which could effectively alleviate the formation of tail thrombus and carotid artery thrombus in mice.

Design, synthesis and biological evaluation of cajanonic acid A analogues as potent PPAR γ antagonists.

Peroxisome proliferator-activated receptor γ (PPAR γ) antagonists are a key instrument of insulin sensitizers since they have the ability to sensitize insulin and can avoid adverse reactions caused by receptor agonist. In this paper, two series of 28 novel Cajanonic acid A (CAA) derivatives were designed and synthesized. The biological activity showed that a novel CAA derivative 9f was identified as a potential PPAR γ antagonist by medicinal chemistry efforts.

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

Ethnopharmacological Relevance: The fruit of Ginkgo biloba L. (Ginkgo nuts) has been used for a long time as a critical Chinese medicine material to treat cough and asthma, as well as a disinfectant. Similar records were written in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese) and Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese).

Icariin and Competing Endogenous RNA Network: A Potential Protective Strategy Against Contrast-Induced Acute Kidney Injury.

Background: Icariin presents protective effect in several kidney diseases. However, the role of icariin in contrast-induced acute kidney injury (CIAKI) is still unclear. This study aimed to investigate the effect of icariin in CIAKI, as well as exploring the underlying mechanism from the aspect of interaction between protein-coding genes and non-coding RNAs.

Cobalt-promoted synthesis of sulfurated oxindoles radical annulation of -arylacrylamides with disulfides.

An efficient radical annulation of -arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr as both an initiator and a promoter for the first time and (NH)SO as the oxidant. By controlling the CoBr/(NH)SO ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields.

Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies.

Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy.

Design, synthesis, and evaluation of novel -alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease.

Herein, a series of novel -alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities showed that compounds , , , , and indicated significantly selective MAO-B inhibitory potency (IC = 0.32, 0.

Simple preparation of a CuO@γ-AlO Fenton-like catalyst and its photocatalytic degradation function.

We designed a photocatalyst and developed sustainable wastewater purification technology, which have significant advantages in effectively solving the global problem of drinking water shortage. In this study, a new nanocomposite was reported and shown to be a catalyst with excellent performance; CuO was coated successively onto functionalized nano γ-AlO, and this novel structure could provide abundant active sites. We evaluated the performance of the CuO@γ-AlO nanocomposite catalyst for polyvinyl alcohol (PVA) degradation under visible light irradiation.

Development of naringenin--alkylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of naringenin--alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The biological activity results revealed that compounds and showed good antioxidant activity with ORAC values of 2.3 and 1.