Discovery of a Novel and Potent Dual-Targeting Inhibitor of ATM and HDAC2 Through Structure-Based Virtual Screening for the Treatment of Testicular Cancer.

Purpose: Dual inhibition of ataxia telangiectasia mutated (ATM) and histone deacetylase 2 (HDAC2) may be a potential strategy to improve antitumor efficacy in testicular cancer.

Methods: A combined virtual screening protocol including pharmacophore modeling and molecular docking was used for screening potent dual-target ATM/HDAC2 inhibitors. In order to obtain the optimal lead compound, the dual ATM/HDAC2 inhibitory activity of the screened compounds was further evaluated using enzyme inhibition methods.

The gut microbiome, chronic kidney disease, and sarcopenia.

Sarcopenia is a prevalent condition in patients with chronic kidney disease (CKD), intricately linked to adverse prognoses, heightened cardiovascular risks, and increased mortality rates. Extensive studies have found a close and complex association between gut microbiota, kidney and muscle. On one front, patients with CKD manifest disturbances in gut microbiota and alterations in serum metabolites.

Association of the use of e-cigarettes, combustible cigarettes or dual use with hypertension and mortality in hypertensive individuals: Insights from NHANES 2015-2018.

Introduction: Combustible cigarettes have been shown to increase hypertension risk. Nevertheless, data on the association between electronic cigarettes (e-cigarettes), as well as dual use of e-cigarettes and combustible cigarettes, and hypertension, are limited.

Methods: This study aims to examine the association of the use of e-cigarettes, combustible cigarettes or dual use with hypertension.

Astragaloside IV alleviates septic myocardial injury through DUSP1-Prohibitin 2 mediated mitochondrial quality control and ER-autophagy.

Introduction: Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis.

Objectives: This study highlights the potential of Astragaloside IV(AS) in the treatment of septic cardiomyopathy and provides a reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction.

Methods: Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2) /DUSP1 transgenic mice (DUSP1/PHB2) were used to generate LPS-induced sepsis models.

rTM reprograms macrophages via the HIF-1α/METTL3/PFKM axis to protect mice against sepsis.

The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macrophage phenotype switching, the rate-limiting enzymes in glycolysis may be key to treating sepsis. Here, we found that, compared with other isoenzymes, the expression of 6-phosphofructokinase, muscle type (PFKM) was the most upregulated in monocytes from septic patients.

Early death prediction model for breast cancer with synchronous lung metastases: an analysis of the SEER database.

Background: Breast cancer with lung metastases (BCLM) is a serious condition that often leads to early death. This study aims to screen the risk factors of early death in BCLM patients and establish a simple and accurate nomogram prediction model. Identifying prognostic markers and developing accurate prediction models can help guide clinical decision-making.

Global research trends and prospects on immune-related therapy in ischemic stroke: a bibliometric analysis.

Background: Following ischemic stroke, non-neuronal cells within the nervous system play a crucial role in maintaining neurovascular unit functions, regulating metabolic and inflammatory processes of the nervous system. Investigating the functions and regulation of these cells, particularly immune cells, deepens our understanding of the complex mechanisms of neuroinflammation and immune modulation after ischemic stroke and provides new perspectives and methods for immune-related therapy.

Methods: The annual distribution, journals, authors, countries, institutions, and keywords of articles published between 2015 and 2024 were visualized and analyzed using CiteSpace and other bibliometric tools.

Mass-tagged self-assembled nanoprobe reveals the transport of PD-L1 from cancer cells to tumor-educated platelets.

Background: The expression level of immune checkpoint proteins detected by tissue biopsy is currently used as a predictive biomarker for immune checkpoint blockade (ICB) therapy. However, tissue biopsy is susceptible to invasive sample collection procedures, significant sampling heterogeneity, and the difficulty of repeated sampling. Therefore, liquid biopsy of blood samples is becoming an alternative choice for immune checkpoint protein detection.

NSUN5 Facilitates Hepatocellular Carcinoma Progression by Increasing SMAD3 Expression.

Hepatocellular carcinoma (HCC) is characterized by frequent intrahepatic and distant metastases, resulting in a poor prognosis for patients. Epithelial-mesenchymal transition (EMT) plays a pivotal role in this process. However, the expression of NOP2/Sun RNA methyltransferase 5 (NSUN5) in HCC and its role in mediating EMT remain poorly understood.

Cardiovascular-Kidney-Metabolic Syndrome Among Healthcare Workers in Chinese Tertiary Hospital.

Objective: To determine the prevalence of Cardiovascular-Kidney-Metabolic (CKM) Syndrome and identify risk factors, including occupational factors, lifestyle factors and clinical measurements, and female-specific risk enhancers among healthcare workers in China.

Methods: A cross-sectional study was conducted among healthcare workers at Taizhou People's Hospital between April and May 2024. We collected data through surveys and laboratory results.

Assessing the diagnostic utility of urinary albumin-to-creatinine ratio as a potential biomarker for diabetic peripheral neuropathy in type 2 diabetes mellitus patients.

Background And Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM).

Vincristine loaded pegylated liposomal drug delivery for efficient treatment of acute lymphoblastic leukaemia.

Vincristine sulfate (VIN) is commonly employed as a cytotoxic agent in the treatment of hematological malignancies, particularly acute lymphoblastic leukaemia (ALL). However, its maximum therapeutic benefits have been hindered due to the dose-dependent neurotoxic effects it can induce, which traditionally manifest as autonomic and peripheral sensory-motor neuropathy. The innovative approach aimed to address VIN's neurotoxic limitations while preserving its therapeutic efficacy in combating hematological malignancies, including ALL.

HTS and scRNA-seq revealed that the location and RSS quality of the mammalian TRBV and TRBJ genes impact biased rearrangement.

The quality of Recombination signal sequences (RSSs), location, and genetics of mammalian V, D, and J genes synergistically affect the recombination frequency of genes; however, the specific regulatory mechanism and efficiency have not been elucidated. By taking advantage of single-cell RNA-sequencing (scRNA-seq) and high-throughput sequencing (HTS) to investigate V(D)J rearrangement characteristics in the CDR3 repertoire, we found that the distal and proximal V genes (or J genes) "to D" gene were involved in rearrangement significantly more frequently than the middle V genes (or J genes) in the TRB locus among various species, including Primates (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis). The RSS quality of the V and J genes affected their frequency in rearrangement to varying degrees, especially when the V-RSSs with recombination signal information content (RIC) score < -45 significantly reduced the recombination frequency of the V gene.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects.

Dual roles of human endogenous retroviruses in cancer progression and antitumor immune response.

Human endogenous retroviruses (HERVs) are a class of transposable elements formed by the integration of ancient retroviruses into the germline genome. They are inherited in a Mendelian manner and approximately constitute 8 % of the human genome. HERVs were considered as "junk DNA" for decades, but increasing evidence suggests that they play significant roles in pathological inflammation, neural differentiation, and oncogenesis.

Ginsenoside 20(S)-Rg3 Hinders Esophageal Squamous Cell Carcinoma Cells Malignant Behaviors by miR-210-3p/B4GALT5 Axis.

Ginsenoside 20(S)-Rg3 (20(S)-Rg3) belongs to a natural chemical with an anti-tumor function, but its potential function and underlying mechanism in esophageal squamous cell carcinoma (ESCC) are unknown. Several reports have manifested that microRNA (miRNA) miR-210-3p functions as a tumor repressor in tumors, but its biofunction in ESCC remains obscure. Herein, the role and interaction of 20(S)-Rg3 and miR-210-3p in ESCC cells were investigated.

Identification of novel genomic hotspots and tumor-relevant genes via comprehensive analysis of HPV integration in Chinese patients of cervical cancer.

Cervical cancer accounts for 10-15% of cancer-related mortality among women globally. Infection with high-risk human papillomavirus (HPV) types constitutes a significant etiological factor in the development of cervical carcinoma. The integration of HPV DNA into the host genome is considered a pivotal event in cervical carcinogenesis.