Recent advances in developing targeted protein degraders.

Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited to proteolysis targeting chimeras (PROTACs), molecular glues, hydrophobic tag tethering degraders (HyTTD), and lysosome-targeted chimeras (LYTACs). Central to TPD are small molecule ligands, which play a critical role in mediating the degradation of target proteins. This review summarizes the current landscape of small molecule ligands for TPD molecules.

Differential Response to Cisplatin between Co-cultured Cells and Pure Cultured Cells Based on Single-cell RNA Sequencing of Three-dimensional-cultured Breast Cancer Cells.

Objective: The current study aimed to develop an experimental approach for the direct co-culture of three-dimensional breast cancer cells using single-cell RNA sequencing (scRNA-seq).

Methods: The following four cell culture groups were established in the Matrigel matrix: the untreated Michigan Cancer Foundation (MCF)-7 cell culture group, the MCF-7 cell culture plus cisplatin group, the untreated co-culture group, and the cell co-culture plus cisplatin group. For cell co-culture, MCF-7 cells, human mammary fibroblasts, and human umbilical vein endothelial cells were mixed at a ratio of 1:1:1.

Application of Macrophage Subtype Analysis in Acute Lung Injury/Acute Respiratory Distress Syndrome.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common critical illness. Supportive therapy is still the main strategy for ALI/ARDS. Macrophages are the predominant immune cells in the lungs and play a pivotal role in maintaining homeostasis, regulating metabolism, and facilitating tissue repair.

Astragalus Polysaccharide Mitigates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of M1 Macrophage Polarization and the cGAS-STING Pathway.

Purpose: This study aimed to examine the impact of APS on acute kidney injury induced by rhabdomyolysis (RIAKI), exploring its association with macrophage M1 polarization and elucidating the underlying mechanisms.

Methods: C57BL/6J mice were randomly assigned to one of three groups: a normal control group, a RIAKI model group, and an APS treatment group. Techniques such as flow cytometry and immunofluorescence were employed to demonstrate that APS can inhibit the transition of renal macrophages to the M1 phenotype in RIAKI.

Family Functioning, Anxiety and Depression in Chinese Higher Vocational School Students: A Network Analysis.

Purpose: Network analysis is a statistical method that explores the complex interrelationships among variables by representing them as nodes and edges in a network structure. This study aimed to examine the interconnections between family functioning, anxiety, and depression among vocational school students through network analysis approach.

Participants And Methods: A sample of 2728 higher vocational school students participated in a survey utilizing the Family APGAR Index Questionnaire (APGAR), Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire (PHQ-9).

Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple-Negative Breast Cancer: A Comprehensive Analysis.

Triple-negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear.

Postoperative adjuvant immunotherapy for pathological stage II-IVa esophageal squamous cell carcinoma after radical surgery does not improve disease-free recurrence rates.

Background/objectives: Postoperative adjuvant therapy for esophageal squamous cell carcinoma (ESCC) primarily includes chemotherapy and chemoradiotherapy. The survival benefits of postoperative adjuvant therapy for R0-resected ESCC remain controversial. Immunotherapy is being gradually applied perioperatively for esophageal cancer, but the efficacy of postoperative immunotherapy in ESCC is unclear.

Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3.

Background: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

Methods: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases.

Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer.

Objective: Small cell lung cancer (SCLC) is commonly recognized as the most fatal lung cancer type. Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers, their benefits are limited to a minority of patients with SCLC. In the present study, novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.

A Preliminary Study on Transcriptional Regulation of SNP Site C-1888T in the Promoter Region of Human PLUNC Gene and Nasopharyngeal Carcinoma Susceptibility.

The transcriptional regulatory factors binding to the polymorphic site C-1888T in the promoter region of the palate, lung, and nasal epithelium clone (PLUNC) gene were identified to investigate whether the C-1888T polymorphic site affects the transcriptional regulation and function of PLUNC gene. Three genotypes of C-1888T polymorphic locus were screened from established nasopharyngeal carcinoma (NPC) cells, and the mRNA expression levels of PLUNC gene in different genotypes were detected. The respective transcription factors that were more likely to bind with A or G in SNP were predicted by biological information and preliminarily verified in vitro by gel electrophoresis migration rate analysis.

Development and validation of a novel immune-related prognostic model and the potential metastatic mechanism in synovial sarcoma.

Background: Several clinical trials have shown that immunotherapy plays a pivotal role in the treatment of patients with metastatic synovial sarcoma. Immune-related genes (IRGs) have been demonstrated to predict the immunotherapy response in certain malignant tumours. However, the clinical significance of IRGs in patients with synovial sarcoma (SS) is still unclear.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status: 5-year follow-up of a prospective cohort study.

Objective: We investigated the relation between man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test.

Methods: 4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test.

TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.

Background: Tumor-derived exosomes are involved in tumor progression and immune invasion and might function as promising noninvasive approaches for clinical management. However, there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma (ccRCC).

Methods: The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC patients were correspondingly deregulated in ccRCC tissues.

Uncovering novel therapeutic clues for hypercoagulable active ulcerative colitis: novel findings from old data.

Background: Hypercoagulability has been shown to act as an important component of ulcerative colitis (UC) pathogenesis and disease activity, and is strongly correlated with the occurrence of venous thromboembolism (VTE). This study aimed at providing novel therapeutic clues for hypercoagulable active UC.

Methods: The coagulation score model was developed using VTE cohorts, and the predictive performance of this model was evaluated by coagulation subtypes of UC patients, which were clustered by the unsupervised method.

Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.

Resveratrol-Loaded Versatile Nanovesicle for Alopecia Therapy via Comprehensive Strategies.

Introduction: Alopecia is a systemic disease with multiple contributing factors. Effective treatment is challenging when only hair growth mechanisms are targeted while ignoring the role of maintaining hair follicle microenvironment homeostasis, which is crucial for cell growth and angiogenesis. Oxidative stress and inflammation are major disruptors of this microenvironment, leading to inhibited cell proliferation and compromised hair follicle circulation.

Injectable Polyhydroxyalkanoate-Nano-Clay Microcarriers Loaded with r-BMSCs Enhance the Repair of Cranial Defects in Rats.

Purpose: Successful regeneration of cranial defects necessitates the use of porous bone fillers to facilitate cell proliferation and nutrient diffusion. Open porous microspheres, characterized by their high specific surface area and osteo-inductive properties, offer an optimal microenvironment for cell ingrowth and efficient ossification, potentially accelerating bone regeneration.

Materials And Methods: An in vitro investigation was conducted to assess the physicochemical properties, porosity, and biocompatibility of PHA-nano-clay open porous microspheres.

The Genetic and Epigenetic Toxicity of Silica Nanoparticles: An Updated Review.

Silica nanoparticles (SiNPs) are widely used in biomedical fields, such as drug delivery, disease diagnosis, and molecular imaging. An increasing number of consumer products containing SiNPs are being used without supervision, and the toxicity of SiNPs to the human body is becoming a major problem. SiNPs contact the human body in various ways and cause damage to the structure and function of genetic material, potentially leading to carcinogenesis, teratogenicity and infertility.

Study protocol: A national cross-sectional study on psychology and behavior investigation of Chinese residents in 2023.

Introduction: This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population. It aims to establish a consistent database of Chinese residents' psychological and behavioral surveys through multi-center and large-sample cross-sectional surveys to provide robust data support for developing research in related fields. It will track the public's physical and psychological health more comprehensively and systematically.

Alterations of the paired maternal vaginal microbiome and neonatal meconium microbiome in vulvovaginal candidiasis positive pregnant women.

Background: Women with vulvovaginal candidiasis (VVC) are known to experience vaginal microbial dysbiosis. However, the dynamic alterations of the vaginal microbiome in pregnant women with VVC and its effect on neonatal gut microbiome remain unclear. This study aims to characterize the vaginal microbiome in pregnant women with VVC and its impact on their offspring's meconium microbiome.

Association between cardiometabolic index and the incidence of stroke: a prospective nationwide cohort study in China.

Objectives: Cardiometabolic index (CMI), based on triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and waist-to-height ratio (WHtR), has been recognized as a novel and practical marker for the assessment of cardiometabolic risk. However, the relationship between CMI and the incidence of stroke remains to be elucidated. This investigation aimed to explore the association between CMI and stroke incidence.

Immunogenicity of Short-Course, High-Dose Hepatitis B Vaccination in Patients with Chronic Kidney Disease - Shanxi Province, China, 2019-2020.

What Is Already Known About This Topic?: As one of the populations at high risk of hepatitis B virus (HBV) infection, patients with chronic kidney disease (CKD) require rapid and effective development of hepatitis B surface antibodies (anti-HBs).

What Is Added By This Report?: The short-course, high-dose regimen of hepatitis B vaccination rapidly induced comparable immunological responses to the routine regimen, achieving a seroconversion rate of 88.5%, a high-response rate of 64.

From the microspheres to scaffolds: advances in polymer microsphere scaffolds for bone regeneration applications.

The treatment and repair of bone tissue damage and loss due to infection, tumours, and trauma are major challenges in clinical practice. Artificial bone scaffolds offer a safer, simpler, and more feasible alternative to bone transplantation, serving to fill bone defects and promote bone tissue regeneration. Ideally, these scaffolds should possess osteoconductive, osteoinductive, and osseointegrative properties.

Design of upper limb muscle strength assessment system based on surface electromyography signals and joint motion.

Purpose: This study aims to develop a assessment system for evaluating shoulder joint muscle strength in patients with varying degrees of upper limb injuries post-stroke, using surface electromyographic (sEMG) signals and joint motion data.

Methods: The assessment system includes modules for acquiring muscle electromyography (EMG) signals and joint motion data. The EMG signals from the anterior, middle, and posterior deltoid muscles were collected, filtered, and denoised to extract time-domain features.