Design, synthesis, activity and molecular dynamics studies of 1,3,4-thiadiazole derivatives as selective allosteric inhibitors of SHP2 for the treatment of cancer.

Overexpression or gene mutation of SHP2 is closely linked with a variety of cancers and has been identified as a crucial anticancer target. In the study, we took SHP2 allosteric inhibitor SHP099 as the lead compound, and 32 1,3,4-thiadiazole derivatives were identified as selective allosteric inhibitors of SHP2. In vitro enzyme activity test showed that some compounds had high inhibition on full length SHP2, and almost no activity on homologous protein SHP1, exhibiting high selectivity.

CD207 Expression Level is a New Prognostic Marker for Condyloma Acuminatum.

Background: Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.

MRAs may have lost their cornerstone position for heart failure treatment in the age of SGLT-2 inhibitors: A meta-analysis of randomized controlled trials.

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone drug class for heart failure therapy. Several clinical studies have demonstrated its role in heart failure therapy. However, due to the recommendation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors for the treatment of heart failure, there is a lack of sufficient evidence regarding whether MRAs can continue to play a cornerstone role in heart failure treatment.

NR_103776.1 as a novel diagnostic biomarker for systemic lupus erythematosus.

Background: With the development of sequencing technologies, there is increasing evidence that long noncoding RNAs (lncRNAs) are involved in systemic lupus erythematosus (SLE). The level of NR_103776.1 expression in SLE and its clinical associations are still not well defined.

A New Predictive Nomogram for the Risk of Delayed Incision Healing After Open Posterior Lumbar Surgery: A Retrospective Study.

Study Design: This was a primary research study.

Objective: A risk nomogram was established and externally validated by exploring the related risk factors for delayed incision healing in patients undergoing open posterior lumbar surgery.

Summary Of Background Data: The use of a nomogram model to predict prognosis in patients with delayed incision healing is an evolving field given the complex presentation of patients with this condition.

FOXK2 regulates PFKFB3 in promoting glycolysis and tumorigenesis in multiple myeloma.

Forkhead box K2 (FOXK2) is a transcription factor involved in regulating the pathophysiological processes in many types of cancers. Functioning as either an oncogene or tumor suppressor, FOXK2 is involved in cell proliferation, metastasis, DNA damage, metabolism, and autophagy. However, the functions of FOXK2 in multiple myeloma (MM) are still unexplored.

Structural and energetic insights into the selective inhibition of PKMYT1 against WEE1.

Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the WEE family and responsible for the regulation of CDK1 phosphorylation, has been considered a promising therapeutic target for cancer therapy. However, the highly structural conservation of the ATP-binding sites of the WEE family poses a challenge to the design of selective inhibitors for PKMYT1. Here, molecular docking, multiple microsecond-length molecular dynamics (MD) simulations and end-point free energy calculations were performed to uncover the molecular mechanism of the binding selectivity of RP-6306 toward PKMYT1 over its highly homologous kinase WEE1.

Endovascular Stent Implantation in the Treatment of Vertebrobasilar Dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a rare disease in clinic, with an incidence of 0.06% and 5.8%.

MicroRNA-361-5p acts as a biomarker for carotid artery stenosis and promotes vascular smooth muscle cell proliferation and migration.

Background: Vascular smooth muscle cells (VSMCs) dysfunction participates in carotid artery stenosis (CAS). The study aimed to examine the expression pattern of miR-361-5p in CAS patients, and explore its role in VSMCs proliferation and migration.

Methods: qRT-PCR was performed for the detection of miR-361-5p in serum samples of 150 CAS cases and 150 healthy people.

Histone lysine demethylase 3B regulates autophagy via transcriptional regulation of in acute myeloid leukemia cells.

Macroautophagy (hereafter referred to as autophagy) is a highly conserved self‑digestion process that is critical for maintaining homeostasis in response to various stresses. The autophagy‑related protein family, including the GABA type A receptor‑associated protein (GABARAP) and microtubule‑associated protein 1 light chain 3 subfamilies, is crucial for autophagosome biogenesis. Although the regulatory machinery of autophagy in the cytoplasm has been widely studied, its transcriptional and epigenetic regulatory mechanisms still require more targeted investigations.

LncRNA THRIL Functions as a Marker for Carotid Artery Stenosis and Affects the Biological Function of Human Aortic Endothelial Cell.

Purpose: Carotid artery restenosis (CAS) is a leading contributor to cerebrovascular diseases and one of the leading causes of death in the world. The purpose of this study was to assess the predictive efficiency of long non-coding RNA (lncRNA) TNFalpha-and hnRNP L-related immunoregulatory lncRNA (THRIL) and its association with the pathogenesis of CAS.

Patients And Methods: The expression of THRIL was determined in patients with asymptomatic CAS and human aortic endothelial cell (HAEC) models induced by oxidized low-density lipoprotein (ox-LDL).

Identification of natural product inhibitors of PTP1B based on high-throughput virtual screening strategy: In silico, in vitro and in vivo studies.

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which is a potential therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). In this study, we identified several PTP1B inhibitors with high activity by using high-throughput virtual screening and in vitro enzyme inhibition activity verification strategies. Among them, baicalin was first reported as a selective mixed inhibitor of PTP1B, with IC value of 3.

MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy.

Osteoarthritis (OA), a late-stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH-OA and its upstream regulators remain obscure.

Lesion patterns and mechanism analysis of acute contralateral ischemic stroke accompanying stenosis of unilateral extracranial internal carotid artery.

Background: Previous studies on unilateral internal carotid artery occlusive disease have focused on the mechanisms of ipsilateral hemispheric stroke, and contralateral stroke is considered to be an accidental phenomenon. Little is known about the relationship between severe stenosis (including occlusion) of the unilateral extracranial segment of the internal carotid artery and contralateral cerebral stroke, and the infarct patterns and pathogenesis require further study. The purpose of this study was to investigate the clinical characteristics and pathogenesis of contralateral acute stroke with unilateral extracranial internal carotid artery stenosis (including occlusion).

Pre-intensive care unit use of selective serotonin reuptake inhibitors and mortality in critically ill adults with mental disorders: analysis from the MIMIC-IV database.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mental disorders in critically ill patients. We performed a retrospective cohort study to investigate the association between pre-ICU use of SSRIs and mortality in critically ill adults with mental disorders. We identified critically ill adults with mental disorders based on the Medical Information Mart in Intensive Care-IV database.

Optimizing glycation control in diabetes: An integrated approach for inhibiting nonenzymatic glycation reactions of biological macromolecules.

Diabetes is a multifactorial disorder that increases mortality and disability due to its complications. A key driver of these complications is nonenzymatic glycation, which generates advanced glycation end-products (AGEs) that impair tissue function. Therefore, effective nonenzymatic glycation prevention and control strategies are urgently needed.

Vitamin B ameliorates PM-induced kidney damage by reducing endoplasmic reticulum stress and oxidative stress in pregnant mice and HK-2.

As an air pollutant, particulate matters 2.5 (PM) poses a severe risk to kidney and the mechanism involves oxidative stress and endoplasmic reticulum (ER) stress. As an essential nutrient for human health, Vitamin B performs anti-inflammatory and antioxidant functions.

Global, Regional, and National Burden of Pancreatic Cancer, 1990-2019: Results from the Global Burden of Disease Study 2019.

Aims: Pancreatic cancer (PC) is a malignant tumor with a strong invasive nature and low survival rate. We aimed to estimate the PC burden at the global, regional, and national levels in 204 countries from 1990 to 2019.

Methods: Detailed data, including the incidence, death, and disability-adjusted life years (DALYs), were analyzed from the Global Burden of Diseases Study 2019.