Inhibition of inducible nitric oxide synthase (iNOS) alleviates thoracic aortic aneurysm by regulating mitochondrial dynamics.

Thoracic aortic aneurysm (TAA) is life-threatening once developing to dissection (TAAD) or rupture and currently there is no effective pharmacological treatment. The abnormal activity of inducible nitric oxide synthase (iNOS) has been related with syndromic TAA, but its potential role in non-syndromic TAA is unknown. Here we identified elevations of inducible nitric oxide synthase (iNOS) and its downstream protein kinase G1 (PRKG1) in both human non-syndromic TAA and β-aminopropionitrile (BAPN)-induced mouse model of TAA.

Structural insights into polymerase-catalyzed FAD capping of hepatitis C virus RNA.

The RNA polymerase NS5B of HCV is capable of catalyzing the addition of flavin adenine dinucleotide (FAD) to its RNA as a 5' cap structure, aiding the virus in evading host immune responses. However, the exact mechanism underlying the 5'-FAD capping process of HCV RNA remains to be elucidated. Here, we determine crystal structures of the HCV NS5B de novo initiation, primed initiation and elongation complexes in presence of FAD.

NHP2 and PRPF4 are hub genes associated with the prognosis of colorectal cancer.

Background: There is an urgent need to identify more accurate and practical prognostic markers for improving the diagnosis and treatment outcomes of colorectal cancer (CRC). This study aimed to identify hub genes of CRC and to evaluate their clinical significance.

Methods: Proteomics analysis was performed on human CRC tissues and adjacent normal tissues, with bioinformatic screening applied to identify hub genes.

Semaphorin 3A protects against thoracic aortic aneurysm dissection by suppressing aortic angiogenesis.

Thoracic aortic aneurysm (TAA) is life-threatening once developing to sudden dissection (TAAD) or rupture. The pathogenesis of TAA remains poorly understood and there is no effective pharmacologic therapy. Increased aortic angiogenesis has been recognized as a key factor contributing to TAA formation, yet the regulatory mechanisms governing this process remain unclear.

Discovering new hub genes of dilated cardiomyopathy.

Aims: Dilated cardiomyopathy (DCM) has a poor prognosis and exhibits a complex and diverse aetiology and genetic profile. The genes responsible for the pathogenesis of DCM have not been fully identified. The present study aimed to explore new hub genes of DCM by mining the human DCM databases and further by experimental validation.

Structure-based discovery of dual-target inhibitors of the helicase from bagaza virus.

Bagaza virus (BAGV) is a mosquito-borne flavivirus and has caused significant avian death in many regions, and also garnered recognition as a significant human pathogen causing diseases like encephalitis. The genome of BAGV encodes ten proteins including three structural proteins and seven nonstructural proteins. The C-terminus of the BAGV NS3 helicase serves as a helicase during BAGV replication, aiding in ATP hydrolysis and unwinding of double-stranded RNA.

Elevated Bile Acids Induce Circadian Rhythm Sleep Disorders in Chronic Liver Diseases.

Background & Aims: Sleep disorders (SDs) are common in chronic liver diseases (CLDs). Some SDs arise from impaired internal clock and are, hence, circadian rhythm SDs (CRSDs). Bile acids (BAs), whose levels are increased in many CLDs, reciprocally interact with circadian rhythm.

PTBP1 crotonylation promotes colorectal cancer progression through alternative splicing-mediated upregulation of the PKM2 gene.

Background: Aerobic glycolysis is a tumor cell phenotype and a hallmark in cancer research. The alternative splicing of the pyruvate kinase M (PKM) gene regulates the expressions of PKM1/2 isoforms and the aerobic glycolysis of tumors. Polypyrimidine tract binding protein (PTBP1) is critical in this process; however, its impact and underlying mechanisms in colorectal cancer (CRC) remain unclear.

[Effect of Csn-B Combined with Imatinib on Apoptosis of Chronic Myeloid Leukemia Cells through Nur77/Pim-1/Drp1 Pathway].

Objective: To investigate the anti- chronic myelogenous leukemia (CML) activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression, and explore the potential role of its signaling pathway.

Methods: Firstly, CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B, imatinib, and their combination on the proliferation and migration of K562 cells. Furthermore, the apoptosis rate of K562 cells treated with Csn-B, imatinib, and their combination was detected by flow cytometry.

Corrigendum to "Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors" [Genes Dis 10 (2023) 389-392].

[This corrects the article DOI: 10.1016/j.gendis.

Simultaneous Preparation of Sulfides/Selenides and Sulfones via Synergistic Nickel-Catalyzed Reductive Coupling and S2 Reaction.

Sulfone compounds and thioether compounds are two highly valuable classes of compounds, but it is challenging to prepare sulfone and thioether compounds simultaneously and efficiently. Here we report that sulfides/selenides and sulfones can be obtained simultaneously using allyl bromide/benzyl bromide-activated alkyl bromides and thiosulfonates/selenosulfonates using a nickel-catalyzed reductive coupling and S2 synergistic strategy, which is characterized by excellent atom and step economy, mild reaction conditions, broad functional group compatibility, and excellent yields.

Regioselective Thiol-yne Reaction of Thiol with ((Methyl-d)sulfonyl)ethyne: Synthesis of (2-((Methyl-d)sulfonyl)vinyl)sulfides.

Herein, we have developed a new method for the synthesis of ((methyl-d)sulfonyl)ethyne, which is cost-effective and environmentally friendly and can be synthesized at the gram level. As an ideal thiol-yne reagent, it can be reacted with various types of thiols to afford ()- and ()-type vinyl sulfides under different conditions with high selectivity. In addition, it can complete the conformational transition from Z- to E-type products under suitable conditions, and can also carry out further derivatization smoothly.

Dapagliflozin Suppresses Isoprenaline-Induced Cardiac Hypertrophy Through Inhibition of Mitochondrial Fission.

Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1) and E12) which are essential for the replication of MPXV.

Histone crotonylation of peripheral blood mononuclear cells is a potential biomarker for diagnosis of colorectal cancer.

Background: Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC).

Results: Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology.

Prognostic value of summed motion score assessed by gated SPECT myocardial perfusion imaging in patients with dilated cardiomyopathy.

Background: The prognosis of patients with dilated cardiomyopathy (DCM) is poor and new indicators are urgently needed to predict lethal cardiac events. This study aimed to investigate the value of summed motion score (SMS) in predicting cardiac death of DCM patients using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

Methods And Results: Eighty-one patients with DCM who underwent Tc-MIBI gated SPECT MPI were retrospectively enrolled and were divided into cardiac death and survivor groups.

Challenges with the discovery of RNA-based therapeutics for flaviviruses.

Introduction: Flaviviruses are emerging or reemerging pathogens that have caused several outbreaks throughout the world and pose serious threats on human health and economic development. RNA-based therapeutics are developing rapidly, and hold promise in the fight against flaviviruses. However, to develop efficient and safe therapeutics for flaviviruses, many challenges remain unsolved.

Role of OAS gene family in COVID-19 induced heart failure.

Background: COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS gene family with cardiac injury and failure in COVID-19 has not been determined.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1 stem cells.

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures.

Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid β metabolism.

Dementia is the main clinical feature of Alzheimer's disease (AD). Orexin has recently been linked to AD pathogenesis, and exogenous orexin-A (OXA) aggravates spatial memory impairment in APP/PS1 mice. However, the effects of OXA on other types of cognitive deficits, especially in 3xTg-AD mice exhibiting both plaque and tangle pathologies, have not been reported.