Purpose: The effect of the diurnal temperature range (DTR) on human health in diverse geographic areas and the potential confounding factors are not fully understood. Additionally, while a robust association has been reported between temperature and cardiomyopathy (CM), evidence of the impact of DTR is relatively limited. Here, we determined whether an association exists between DTR and CM hospitalisations in vulnerable populations.
View Article and Find Full Text PDFBackground: The "Double Reduction" policy requires schools to reduce Chinese students' extracurricular activities and homework to lessen academic stress and improve mental well-being. However, there is limited research on primary school teachers' psychological well-being within the context of the "Double Reduction" policy. This study examined self-reported burnout levels of primary school teachers and investigated the relationship between burnout and depressive symptoms in the context of the "Double Reduction" policy in China.
View Article and Find Full Text PDFPurpose: To evaluate levels of 3 tear-soluble neuropeptides in dry eye patients and to identify the correlations with clinical signs and symptoms.
Methods: A total of 16 dry eye patients and 12 healthy volunteers were enrolled. Dry eye disease (DED) diagnosis was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II).
Eur Arch Psychiatry Clin Neurosci
December 2024
Sex differences in schizophrenia have been noted across domains such as alexithymia and cognitive function; however, how they interact remains unclear. This study aimed to explore sex differences in the relationship between alexithymia and cognitive function in patients with chronic schizophrenia. A total of 695 patients (464 males and 231 females) who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study.
View Article and Find Full Text PDFKRAS is the most commonly mutated isoform in RAS-driven cancers. In the early stage, KRAS was deemed as an "undruggable" cancer target due to the lack of suitable binding pockets. With the development of KRAS inhibitors in recent years, strategies that directly suppress oncogenic KRAS have achieved significant breakthroughs.
View Article and Find Full Text PDFIntroduction: Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis.
Methods: A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS.
PD-L1 is overexpressed on the surface of tumor cells and binds to PD-1, resulting in tumor immune escape. Therapeutic strategies to target the PD-1/PD-L1 pathway involve blocking the binding. Immune checkpoint inhibitors have limited efficacy against tumors because PD-L1 is also present in the cytoplasm.
View Article and Find Full Text PDFMultiple studies have confirmed that acid sphingomyelinase (ASM) activity is associated with depression. The discovery of direct inhibitors against ASM is of great significance for exploring antidepressants and their mechanisms of action. Herein, a series of novel phenylpyrazole analogues were rationally designed and synthesized.
View Article and Find Full Text PDFSphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2.
View Article and Find Full Text PDFAs an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.
View Article and Find Full Text PDFBackground: As a Chinese medicinal formula, the Jianshen Lishui prescription has been clinically proven to be effective in treating intracerebral hemorrhage (ICH). Yet, the mechanisms involved are unknown.
Methods: (1) Network pharmacology analysis: It involved the screening of active components in the Jianshen Lishui prescription, identification of potential targets for these components, and the screening of ICH-related targets.
Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied.
Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI.
Design, Setting, And Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial.
Mitochondria are critical cellular energy resources and are central to the life of the neuron. Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis. Mature neurons are postmitotic and consume substantial energy, thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
November 2023
Two pairs of new dimeric diketopiperazine alkaloids, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2), together with seven previously reported analogues (( ±)-3, 4-6, and ( ±)-7) were obtained from a marine-derived fungus Aspergillus sp. The structures of ( ±)-1 and ( ±)-2 were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. Speculated from the biogenesis, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2) might be the key precursor of [2 + 2] diketopiperazine dimers (( ±)-3).
View Article and Find Full Text PDFTargeting sphingosine kinase 2 (SphK2) has become a novel strategy for the treatment of cancer. However, potent and selective SphK2 inhibitors are rare. In our work, a series of novel SphK2 inhibitors were innovatively designed, synthesized and screened.
View Article and Find Full Text PDFEpidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O on AMI hospitalizations.
View Article and Find Full Text PDFBackground: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that causes impairments in social communication and stereotypical behaviors, often accompanied by developmental delay or intellectual disability. A growing body of evidence suggests that ASD is highly heritable, and genetic studies have defined numerous risk genes. However, most studies have been conducted with individuals of European and Hispanic ancestry, and there is a lack of genetic analyses of ASD in the East Asian population.
View Article and Find Full Text PDFBackground: To introduce a new and simple classification and management of coronary artery involvement in aortic dissection and report results.
Methods: Coronary artery involvement was classified into two types according to the integrity of coronary intima: simple lesion (type S) and complex lesion (type C). Complex lesions were treated by CABG and simple lesions were treated by ostial repair or reimplantation.
It is well known that chronic obstructive pulmonary disease (COPD) patients are always trapped in the vicious circle of inflammation and oxidative stress, therefore anti-inflammatory and antioxidant bifunctional agents may interrupt this vicious cycle in COPD. Phosphodiesterase 4 (PDE4) inhibitors, as anti-inflammatory drugs, have been used for COPD treatment in clinical, and the PDE4 inhibitors with antioxidant properties may be a good strategy to design bifunctional agents for COPD. Sappanone A was the first PDE4 inhibitor with antioxidant properties we identified from natural products in our previous study, which was used by us as a hit compound to design new bifunctional agents for COPD in this study.
View Article and Find Full Text PDFIn order to obtain diverse S-acylation inhibitors and address the defects of existing S-acylation inhibitors, a series of novel covalent S-acylation inhibitors are designed through synthesis. According to the results of MTT assay, most compounds produce a better anti-proliferation effect on MCF-7, MGC-803 and U937 cell lines than 2-BP. Among them, 8d, 8i, 8j and 10e exert a significant inhibitory effect on MCF-7 cell, with the IC values falling below 20 μM.
View Article and Find Full Text PDFBoth topoisomerase II (Topo II) and histone deacetylase (HDAC) are important therapeutic targets for cancer. In this study, two series of novel compounds containing pyrimido[5,4-b]indole and pyrazolo[3,4-d]pyrimidine motifs were designed and synthesized as dual Topo II/HDAC inhibitors. MTT assay indicated that all the compounds displayed potential antiproliferative activity against three cancer cell lines (MGC-803, MCF-7 and U937) and low cytotoxicity on normal cell line (3T3).
View Article and Find Full Text PDFAcid sphingomyelinase (ASM), which regulates sphingolipid metabolism and lipid signaling, has been considered as a new potential target for the treatment of atherosclerosis. In this study, a series of benzene-heterocyclic-based ASM inhibitors were rationally designed, synthesized, and screened for the first time. As a result, some compounds showed favorable inhibitory activity against recombinant human ASM.
View Article and Find Full Text PDFA series of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine were designed and synthesized with improved anti-hepatocellular carcinoma (HCC) activities. The optimal compound 4d showed strong activities against HepG2, Sk-Hep-1, Huh-7 and Hep3B cells with IC values of 0.58-1.
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