Stage-Resolved Phosphoproteomic Landscape of Mouse Spermiogenesis Reveals Key Kinase Signaling in Sperm Morphogenesis.

Spermiogenesis is the committed step of sperm production, during which spermatid cells undergo dramatic morphological transformations and transcriptional silencing. Post-translational modifications (PTMs), including phosphorylation, provide a level of protein function flexibility and play important roles in spermiogenesis. Dynamic protein phosphorylation profiles of spermatids are characterized across four different developing steps, and identified phosphorylation regulation of key proteins in spermiogenesis.

The N-terminal region of HASPIN regulates phosphorylation of AURKA and meiotic progression in spermatocytes.

Protein phosphorylation is an important post-translational modification that plays a critical regulatory role in meiosis. HASPIN, a kinase highly conserved from yeast to mammals, is required for male fertility. In this study, we found that the intrinsically disordered N-terminal domain of HASPIN is also required for this function.

Functional Analysis of NPC2 in Alarm Pheromone Recognition by the Red Imported Fire Ant, (Formicidae: ).

The red imported fire ant () is a dangerous invasive insect. These ants rely on releasing an alarm pheromone, mainly composed of 2-ethyl-3,6-dimethylptrazine (EDMP), to warn nestmates of danger and trigger group defense or escape behaviors. This study found two NPC2 proteins in the ant antennae: SinvNPC2a and SinvNPC2b.

Correction: Organoids in cancer therapies: a comprehensive review.

[This corrects the article DOI: 10.3389/fbioe.2025.

A robust method for assessing mitochondrial function in healthy and diseased frozen cardiac tissue.

Cardiovascular diseases are often associated with impairment in mitochondrial function. However, existing respirometry measuring mitochondrial function are limited by the necessity of fresh tissue samples. This study develops a method with tailored substrate-inhibitor titration (TSIT) of mitochondrial electron transport complexes (ETC) to measure mitochondrial function in frozen cardiac samples using high-resolution respirometry.

Computational nanobody design through deep generative modeling and epitope landscape profiling.

Nanobodies, one-tenth the size of conventional antibodies, have gained attention as therapeutic agents for autoimmune diseases, cancer, and viral infections. However, traditional methods for nanobody discovery are often time-consuming and labor-intensive. In this study, we present a computational design framework that integrates deep generative modeling with epitope profiling.

Epigenetic modulation with nanosatellite triggers tumoricidal immunity for hepatocellular carcinoma treatment.

Epi-immunotherapy appears promising for hepatocellular carcinoma (HCC) treatment, but immunosuppressive macrophages limit the capacity of epigenetic regulation to activate T cell-mediated tumoricidal immunity. Here we report an epi-immune nanosatellite (stEiNS) that co-delivers siRNA targeting the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) alongside the histone deacetylase IIa inhibitor TMP195, enabling epigenetic reprogramming of HCC tumor cells and M2 macrophages to enhance the immunotherapeutic response. stEiNS assembles size-mismatched nanoparticles via dynamic locks in a satellite-like structure, enabling deep tissue penetration.

Ultrasound targeted microbubbles for theranostic applications in liver diseases: from molecular imaging to targeted therapy.

Liver diseases, particularly chronic conditions leading to cirrhosis and hepatocellular carcinoma, represent a major global health burden with high mortality rates, necessitating innovative diagnostic and therapeutic approaches. Ultrasound-targeted microbubble destruction (UTMD) technology has emerged as a promising theranostic platform, combining enhanced contrast imaging with targeted drug/gene delivery capabilities. When activated by ultrasound, these microbubbles exhibit unique biophysical behaviors that significantly improve drug penetration, tissue perfusion, and site-specific delivery.

Organoids in cancer therapies: a comprehensive review.

Organoid technology has significantly advanced biomedical research, offering deep insights into tumor biology and therapeutic efficacy. While existing publications have covered organoid applications, this review uniquely stresses their transformative role in cancer research. We highlight their importance in studying intratumoral heterogeneity and microenvironment interactions.

Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging.

Reproductive longevity is essential for female fertility and healthy aging; however, the role of stress response, especially stress granule accumulation, in ovarian aging remains elusive and interventions are lacking. Here, we identified deleterious mutations and decreased expression of NCOA7, a stress-response protein related to granulosa cell senescence in women with physiological and pathological ovarian aging. NCOA7 deletion accelerates oxidative stress-related cellular senescence, ovarian aging and fecundity decline in mice.

A Comparative Study of ChatGPT-4o and DeepSeek Responses to Mandibular Angle Osteotomy Questions.

Background: Mandibular angle osteotomy (MAO) is one of the most effective ways to correct square facial contours. With the development of Artificial Intelligence (AI) technology, particularly in medicine, more patients are seeking medical queries from online websites. This study compared the performance of 2 AI platforms, ChatGPT-4o and DeepSeek in answering questions about MAO.

Synthetic efferocytic receptor microglia enhances anti-inflammatory clearance of amyloid-β for AD treatment in mice.

Monoclonal antibody immunotherapy targeting the clearance of amyloid-β (Aβ) has shown promise in Alzheimer's disease (AD). However, current antibody treatments trigger Fc receptors and induce proinflammatory responses, in turn exacerbating neuronal damage. Here, we report a synthetic efferocytic receptor (SER) integrating Aβ-targeting scFv, efferocytosis receptor backbone based on TIM4 and downstream signal for microglia (MG) reprogramming, which enabled selective elimination of Aβ without inducing an inflammatory response.

Human urine-derived stem cells from different donor sources ameliorate diabetic nephropathy in mice by activating autophagy and restoring mitochondrial function of podocyte.

Background: Human urine-derived stem cells (hUSCs) are a novel type of mesenchymal stem cells (MSCs) originating from the kidney, with promising potential for personalized therapies. However, it remains unclear whether hUSCs can be successfully isolated from individuals of different ages and disease states-including healthy young individuals, healthy elderly individuals, and patients with diabetic nephropathy (DN), as well as their therapeutic potential and mechanism in DN.

Methods: hUSCs were isolated from healthy young men (hUSC-HY), healthy elderly men (hUSC-HE), and male DN patients (hUSC-DN), and their biological characteristics were systematically evaluated.

Association between seropositivity and the hemoglobin A1c/high-density lipoprotein cholesterol ratio in U.S. adults: evidence from NHANES.

Background: () infection is associated with insulin resistance and metabolic syndrome. This study investigates the association between seropositivity and the newly proposed hemoglobin A1c/high-density lipoprotein cholesterol ratio (HbA1c/HDL-C ratio) in a nationally representative U.S.

Multilayered Nanoarchitectonics of Poly(ethylene glycol) Nanoparticles with Tunable Stiffness Modulate Bio-Nano Interactions and Targeted Drug Delivery.

Stiffness, as a crucial physicochemical property of nanoparticles (NPs), has demonstrated a significant impact on bio-nano interactions, including blood circulation, biodistribution, tumor accumulation, and cellular uptake. However, the potential role of NP stiffness in modulating bio-nano interactions to potentiate drug delivery efficacy remains largely unexplored. In this study, poly(ethylene glycol) (PEG) NPs are engineered by the sophisticated layer-by-layer (LbL) assembly approach, and the Young's moduli of NPs in the range of 2-31 kPa are tuned by control over the bilayer numbers.

Effect of nebulised inhalation of antibiotics on preventing ventilator-associated pneumonia in critically ill patients: a systematic review and meta-analysis.

Objective: To investigate whether prophylactic nebulised antibiotic inhalation reduces the incidence of ventilator-associated pneumonia (VAP) in critically ill adults undergoing mechanical ventilation.

Study Design: Systematic review and meta-analysis of randomised controlled trials.

Data Sources: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to 1 January 2024 without language restrictions.

Neddylation status determines the therapeutic sensitivity of tyrosine kinase inhibitors in chronic myeloid leukemia.

BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) dominate the treatment of chronic myeloid leukemia (CML) over the past decades. In this study, we reported an unexpected role of neddylation inhibitors in desensitizing the therapeutic efficacy of BCR::ABL1-targeting TKIs in CML. Unlike their function in reducing drug resistance in many solid tumors, we revealed that neddylation inhibitors counteracted the cytotoxicity of TKIs against CML cells, both in cellular experiments and in animal model.

Enhancing medical staff participation in blood donation: Insights into willingness, motivations and policy expectations.

Medical staff hold dual roles as advocates and potential blood donors, yet systemic barriers within high-pressure clinical environments hinder their participation. Understanding their motivations and challenges is critical for strengthening blood supply systems. This cross-sectional study aimed to identify determinants of donation willingness and policy expectations among medical staff to inform evidence-based interventions.

The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancer cases globally. HCC patients have a poor prognosis because of tumor metastasis and medication resistance; thus, novel therapy targets and techniques are needed. By using the Kaplan-Meier plotter database, we identified a strong association between midkine (MDK) and HCC mortality and validated its high expression in numerous HCC cell lines.

Profiling of lincRNAs and differential regulatory mechanisms in response to nanoplastic toxicity at environmentally relevant concentrations in Caenorhabditis elegans.

Polystyrene nanoplastics (PS-NPs) at environmentally relevant concentrations have been shown to be toxic to living organisms, but the role of long noncoding RNAs (lncRNAs) in their toxicity regulation is not yet clear. Using Caenorhabditis elegans (C. elegans) as a model organism, we investigate the mechanisms and roles of lncRNAs in PS-NPs toxicity at environmentally relevant concentrations.

An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma.

Chimeric antigen receptor macrophage (CAR-M) therapy has shown great promise in solid malignancies; however, the phenotypic re-domestication of CAR-Ms in the immunosuppressive tumor niche restricts their antitumor immunity. We here report an in situ engineered chimeric interleukin (IL)-2 signaling receptor (CSR) for controllably manipulating the proinflammatory phenotype of CAR-Ms, augmenting their sustained tumoricidal immunity. Specifically, our in-house-customized lipid nanoparticles efficiently introduce dual circular RNAs into macrophages to generate CSR-functionalized CAR-Ms.

Legumain In Situ Engineering Promotes Efferocytosis of CAR Macrophage to Treat Cardiac Fibrosis.

Uncontrolled and excessive cardiac fibrosis after myocardial infarction (MI) is a primary contributor to mortality by heart failure. Chimeric antigen receptor macrophage (CAR-MΦ) therapy shows great promise in cardiac fibrosis, however, the overwhelming apoptotic cells after MI results in an overburdened efferocytosis in CAR-MΦ, which compromises their antifibrotic potency. This work here reports an in situ engineered legumain (Lgmn) to elevate the cargo degradation of phagolysosome for promoting the efferocytosis of CAR-MΦs, restoring their antifibrotic capability.

A continuous kinematic calibration method for accuracy maintenance of industrial robot based on recursive least squares algorithm.

Industrial robots have become more and more important in the advanced manufacturing industry. There is still a degradation problem in the accuracy performance of industrial robots after being calibrated. To maintain the accuracy performance of robots timely, a continuous kinematic calibration method is proposed.

The potential application of digital PCR in detecting different SARS-CoV-2 viral loads.

Rapid, effective, and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial. It is essential to control the spread of the virus and ensure accurate treatment for the disease. In the study, a total of 170 clinical specimens from 164 patients were collected and analyzed through digital PCR (dPCR) and real time quantitative reverse transcription PCR (RT-qPCR).

Clinical features and genetic analysis of nine Chinese children with Dent disease and identification of three novel and variants.

Objective: This study aims to elucidate the genetic and phenotypic characteristics of pediatric patients with potential Dent disease (DD).

Methods: High-throughput sequencing was conducted on 11 pediatric patients with potential cases of DD. We also analyzed clinical phenotype and treatment regimens.