The mechanisms of Pin1 as targets for cancer therapy.

Targeted therapy has considerable promise for the effective eradication of cancer at the primary tumor site prior to subsequent metastasis. Using this therapeutic approach, gaining an understanding of mechanistic cancer models is essential for facilitating the inhibition or suppression of tumor growth. Among different oncogenes and proteins, the protein interacting with never-in-mitosis kinase-1 (Pin1) is particularly important.

Transvaginal double-layer parallel in-situ suturing for early complex vesicovaginal fistula repair: Case report.

Rationale: Complex vesicovaginal fistulas (VVFs) with large defects pose significant surgical challenges. Traditional repair methods often require extensive tissue separation and multilayer suturing, risking local blood supply and healing. This study introduces a novel modified transvaginal repair technique that simplifies the procedure while preserving tissue vascularity.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

Background: It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients.

The association between lower urinary tract symptoms secondary to benign prostatic hyperplasia and multimorbidity among Chinese middle-aged and elderly males: evidence based on propensity score matching.

Background: With the aging population, patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) often face multiple chronic conditions (multimorbidity), significantly impacting their quality of life. This study aims to determine the relationship between LUTS/BPH, multimorbidity, and various chronic diseases in middle-aged and elderly Chinese populations.

Methods: This cross-sectional study utilizes data from the China Health and Retirement Longitudinal Study (CHARLS), involving 6,645 residents aged 45 and above.

Migration of an intrauterine device to the posterior urethra with stone formation: a case report.

Migration of an intrauterine device (IUD) to the posterior urethra with stone formation has not been previously reported in the literature. A 42-year-old female patient presented to the gynecology clinic with a complaint of "discovered vaginal mass for 2 years, with growth for 5 days." She was referred to urology on suspicion of IUD migration to the bladder.

Analysis of an adult diabetes mellitus caused by a rare mutation of the gene: A case report.

Background: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.

Association between Serum Phosphorus Levels and Diabetic Retinopathy: A Cross-Sectional Study.

Background And Aims: The aim of this study was to investigate the association between serum phosphate levels and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

Methods And Results: The study sample consisted of 1657 T2DM patients hospitalized between 2017 and 2019. Patients were categorized into quartiles based on their serum phosphate levels (Q1-Q4).

EMC10 modulates hepatic ER stress and steatosis in an isoform-specific manner.

Background & Aims: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis.

[Research progress of relationship in long-novel coronavirus syndrome and sarcopenia].

At present, the major public health challenges caused by novel coronavirus infection have gradually subside. However, a large number of people are still suffering from long-novel coronavirus syndrome or post-novel coronavirus syndrome. The clinical manifestations of long coronavirus syndrome are related to multiple systems, such as respiratory, circulatory, nervous, digestive and musculoskeletal systems, with various long-term persistent symptoms after novel coronavirus infection.

Broad-spectrum antiviral strategy: Host-targeting antivirals against emerging and re-emerging viruses.

Viral infections are amongst the most prevalent diseases that pose a significant threat to human health. Targeting viral proteins or host factors represents two primary strategies for the development of antiviral drugs. In contrast to virus-targeting antivirals (VTAs), host-targeting antivirals (HTAs) offer advantages in terms of overcoming drug resistance and effectively combating a wide range of viruses, including newly emerging ones.

A novel -heterocycles substituted oseltamivir derivatives as potent inhibitors of influenza virus neuraminidase: discovery, synthesis and biological evaluation.

Our previous studies have shown that the introduction of structurally diverse benzyl side chains at the C5-NH position of oseltamivir to occupy 150-cavity contributes to the binding affinity with neuraminidase and anti-influenza activity. To obtain broad-spectrum neuraminidase inhibitors, we designed and synthesised a series of novel oseltamivir derivatives bearing different N-heterocycles substituents that have been proved to induce opening of the 150-loop of group-2 neuraminidases. Among them, compound bearing 4-(()-2-methylpyrrolidin-1-yl) benzyl group exhibited antiviral activities similar to or weaker than those of oseltamivir carboxylate against H1N1, H3N2, H5N1, H5N6 and H5N1-H274Y mutant neuraminidases.

Development of chalcone-like derivatives and their biological and mechanistic investigations as novel influenza nuclear export inhibitors.

Concerning the emergence of resistance to current anti-influenza drugs, our previous phenotypic-based screening study identified the compound A9 as a promising lead compound. This chalcone analog, containing a 2,6-dimethoxyphenyl moiety, exhibited significant inhibitory activity against oseltamivir-resistant strains (H1N1 pdm09), with an EC value of 1.34 μM.

Design, synthesis, and mechanistic study of 2-piperazineone-bearing peptidomimetics as novel HIV capsid modulators.

HIV-1 capsid (CA) is an attractive target for its indispensable roles in the viral life cycle. We report the design, synthesis, and mechanistic study of a novel series of 2-piperazineone peptidomimetics as HIV capsid modulators by mimicking the structure of host factors binding to CA. F-Id-3o was the most potent compound from the synthesized series, with an anti-HIV-1 EC value of 6.

Discovery of N-substituted oseltamivir derivatives as novel neuraminidase inhibitors with improved drug resistance profiles and favorable drug-like properties.

To yield potent neuraminidase inhibitors with improved drug resistance and favorable drug-like properties, two series of novel oseltamivir derivatives targeting the 150-cavity of neuraminidase were designed, synthesized, and biologically evaluated. Among the synthesized compounds, the most potent compound 43b bearing 3-floro-4-cyclopentenylphenzyl moiety exhibited weaker or slightly improved inhibitory activity against wild-type neuraminidases (NAs) of H1N1, H5N1, and H5N8 compared to oseltamivir carboxylate (OSC). Encouragingly, 43b displayed 62.

Progesterone levels associated with proteinuria in male diabetes mellitus patients: A cross-sectional retrospective study.

Introduction: The relationship between progesterone (P) and diabetic nephropathy (DKD) is unclear. Herein, we investigated the relationship between progesterone and DKD in men and postmenopausal women with type 2 diabetes mellitus. MATERIALS AND METHODS: We recruited 3,556 male and postmenopausal female patients and obtained the dominance ratio (OR) and corresponding 95% confidence intervals (CIs) associated with progesterone by logistic regression analysis after adjusting for potentially confounding variants.

The risk of nonalcoholic fatty liver disease in gout patients with frequent flares: a retrospective cohort study.

Objective: Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that is related to high serum uric acid; however, the association between the frequency of gout flares and NAFLD risk remains unclear. This study aimed to investigate whether frequent gout flares were associated with incident NAFLD and analyze the interaction of frequency of gout flares and Adipo-IR on NAFLD in the gout Chinese population.

Methods: A total of 350 cases of gout patients were enrolled in this retrospective cohort study.

Circadian secretion rhythm of GLP-1 and its influencing factors.

Circadian rhythm is an inherent endogenous biological rhythm in living organisms. However, with the improvement of modern living standards, many factors such as prolonged artificial lighting, sedentarism, short sleep duration, intestinal flora and high-calorie food intake have disturbed circadian rhythm regulation on various metabolic processes, including GLP-1 secretion, which plays an essential role in the development of various metabolic diseases. Herein, we focused on GLP-1 and its circadian rhythm to explore the factors affecting GLP-1 circadian rhythm and its potential mechanisms and propose some feasible suggestions to improve GLP-1 secretion.

Immunosenescence is a therapeutic target for frailty in older adults: a narrative review.

Background And Objective: Aging refers to a progressive decrease in functional performance, leading to increased mortality risk. At present, life expectancy is increasing worldwide and is expected to exceed 80 years by 2040. However, this increase in life expectancy also indicates a rise in the incidence and prevalence of diseases, such as cardiovascular, neurological, musculoskeletal, and oncological diseases, which are associated with aging.