Oocyte quality is largely governed by metabolic cooperation between oocytes and granulosa cells (GCs). PCOS is prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenaemia, skewed gonadotropins, insulin resistance, anovulation and poor oocyte quality. We aim to unravel glucose metabolism dynamics in oocyte microenvironment in PCOS compared to healthy controls undergoing IVF using follicular fluid (FF) and GCs.

To investigate the role of CDC42 signaling in endothelial barrier dysfunction during seawater drowning-induced acute lung injury (SWD-ALI).

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause small intestinal injury and dysbiosis. Although NSAID-induced dysbiosis is well-characterized and contributes to enteropathy, the changes in host-bacterial interactions during enteropathy remain largely unexplored. Here we assessed the expression pattern of six toll-like receptors (TLRs) and three antimicrobial peptides (AMPs) over the course of indomethacin (IND)-induced enteropathy in rats, and evaluated their correlations with inflammation and dysbiosis. In addition, we assessed for the first time the effect of IND on small intestinal mucosal biofilm structure.

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage degradation and chronic inflammatory responses. Given the limited regenerative capacity of cartilage and the complexity of the inflammatory microenvironment, the treatment of OA presents significant clinical challenges. This review highlights the pivotal role of immune regulation in OA treatment and provides a comprehensive overview of the specific mechanisms and therapeutic applications of immunomodulatory cartilage tissue engineering mediated by biomaterials, bioactive additives, and cell intervention. A comparative analysis of these three approaches is conducted, clarifying their respective clinical relevance and feasibility. Furthermore, the review discusses the standardized assessment methods for immune regulation and tissue regeneration, and emphasizes the importance of establishing a unified evaluation framework for clinical translation. Finally, current challenges in immunomodulatory tissue engineering strategies for OA treatment are identified, and future directions for the development of personalized medicine are outlined in light of advancements in multi-omics technologies, generative artificial intelligence, and intelligent medical devices.

Male infertility, particularly non-obstructive azoospermia (NOA), remains a major clinical challenge. Although the testis is one of the most transcriptionally complex organs, stage-specific changes in total RNA abundance remain poorly characterized. Through total RNA staining, we identified distinct RNA content profiles across spermatogenic stages, supporting its value as a discriminative marker. Based on this, we developed RNA-DNA dual-parameter flow cytometry (RD-Cyto), a novel method that simultaneously measures RNA and DNA content at single-cell resolution for high-precision classification of testicular cells. Compared to conventional Hoechst-based cytometry, RD-Cyto offers superior resolution, enabling clear separation of pachytene (P) and diplotene (D) spermatocytes, first-time identification of metaphase I spermatocytes (MI), and subdivision of metaphase II spermatocytes (MII) into two subsets. To assess its utility in mechanistic research, we applied RD-Cyto to investigate the RNA-binding protein (RBP) DEAD-Box Helicase 17 (DDX17) and found that its deletion causes RNA accumulation in preleptotene spermatocytes and meiotic failure-demonstrating RD-Cyto's sensitivity to stage-specific regulatory disruptions. We further applied RD-Cyto to the clinical diagnosis of azoospermia. Combined with testicular fine-needle aspiration cytology (FNAC), RD-Cyto accurately evaluated spermatogenesis in all enrolled patients, showing 100 % concordance with testicular sperm retrieval outcomes. It successfully identified Sertoli cell-only syndrome (SCOS) in NOA, predicted sperm retrieval in rare NOA cases with residual spermatogenesis, and revealed spermatogenic and morphological abnormalities linked to pathogenic mutations in oligoasthenospermia (OAS). These findings establish RD-Cyto as a robust platform for both mechanistic investigation and diagnostic stratification in male infertility.

Calpastatin (CS) is an endogenous inhibitor of calpain, the Ca-activated protease. We previously reported that CS can facilitate the opening of the cardiac Ca1.2 channel. However, the pathophysiological implications of the regulatory effects of CS on Ca1.2 channels remain unclear. This study aims to investigate how CS modulates Ca1.2 channels and its role in cardiac ischemic injury.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition characterized by weight loss as a prominent feature. Non-alcoholic fatty liver disease (NAFLD), typically linked to obesity and metabolic dysregulation, is increasingly recognized as being influenced by the gut-liver axis. Notably, IBD patients exhibit a heightened susceptibility to NAFLD, although the underlying mechanisms remain poorly understood. Intestinal alkaline phosphatase (IAP), an endogenous enzyme, plays a critical role in preventing intestinal bacterial translocation. We hypothesized that IAP may serve as a potential therapeutic agent for mitigating IBD-associated NAFLD.

Post-translational modifications in the form of phosphorylation of key insulin signaling proteins are known to contribute to insulin resistance by regulating the activity and function of proteins such as IR, IRS, and Akt. However, little is known about the ubiquitination code in an insulin-resistant state. Several studies have connected the ubiquitin-proteasome system to dysfunctional insulin signaling. We aimed to investigate how reduced sensitivity to insulin affects hepatic ubiquitination in vivo.

Growth hormone (GH) secretion is controlled by various mechanisms, including negative feedback loops mediated by either GH or insulin-like growth factor 1 (IGF-1). Previous studies suggest that GH receptor (GHR) signaling in tyrosine hydroxylase (TH)-expressing cells regulates GH secretion. However, it is still unknown whether hypothalamic TH neurons are also responsive to IGF-1 to control GH secretion. Here, we show that a subset of TH neurons in the arcuate nucleus of the hypothalamus (ARH) expresses the GH-releasing hormone (GHRH) and the IGF-1 receptor (IGF1R). Mice with IGF1R deletion in TH cells (TH mice) experienced a decline in growth during the peripubertal period - mainly in males - that was not observed after 8 or 10 weeks of age (female or male, respectively). Male TH mice also displayed reduced GH pulse frequency. Mice with both IGF1R and GHR ablated in TH-expressing cells were generated. Unlike TH mice, TH mice did not show a peripubertal reduction in body weight, lean mass, or fat mass. In summary, IGF-1 action on TH-expressing cells influences GH pulse frequency in male mice, and the absence of IGF1R signaling in these cells results in a mild, temporary impact on body growth.

Postmenopausal osteoporosis significantly increases fragility fracture risk. While menopausal estrogen decline coincides with rising follicle-stimulating hormone (FSH), the role of circulating FSH in bone loss remains unclear. This study investigates the direct function of FSH and FSH receptor (FSHR) in bone, focusing on osteocyte-mediated mechanisms.

Metastasis and recurrence are the major causes of tumor-related deaths which occur years after primary tumor treatment. This phenomenon can be partially attributed to dormant tumor cells which evade therapeutic interventions and survive in the body for decades without clinical detection. The tumor microenvironment (TME) is a critical regulator of this process, intricately controlling tumor cell dormancy through the integration of diverse cues from physical structures, soluble factors, metabolic conditions, and immune status. In this review, we systematically discuss how the TME governs the entry, maintenance, and reactivation of dormant tumor cells. By integrating recent advances and addressing current limitations, we aim to provide novel insights for both mechanistic studies and therapeutic strategies aimed at inducing persistent dormancy or eradicating dormant cells to prevent tumor recurrence and metastasis.

Nicotine addiction remains a global public health problem, with high relapse rates and limited long-term success from current treatments. This highlights the need for new therapeutic strategies that target novel mechanisms of nicotine addiction. Ifenprodil, a GluN2B-containing N-methyl-d-aspartate receptor antagonist and G protein-activated inwardly rectifying potassium inhibitor, among other actions, potentially offers a new approach. The present study investigated the efficacy of ifenprodil in reducing nicotine-induced addiction-like behaviors. We evaluated effects of systemic ifenprodil administration on nicotine-induced behaviors in mice using two experimental paradigms: a lateral hypothalamus intracranial self-stimulation (lhICSS) test using a rate-frequency procedure and a two-bottle choice preference test. Dopamine transporter (DAT) knockout (KO) and wild-type mice were used to investigate nicotine's effects on reward-related behavior. Nicotine and ifenprodil were delivered via intraperitoneal injection. In wild-type mice, acute nicotine (0.1-1.0 mg/kg) had no significant effect on lhICSS rates across stimulation frequencies, although a low dose (0.1 mg/kg) produced a modest increase. The 0.1 mg/kg dose of nicotine but not higher doses (0.3 or 1.0 mg/kg) significantly enhanced lhICSS rates in DAT-KO mice. Pretreatment with ifenprodil (1-10 mg/kg) dose-dependently reduced the nicotine-induced enhancement of reward in DAT-KO mice. In wild-type males, ifenprodil acutely decreased nicotine preference in the two-bottle choice test following chronic nicotine exposure. These findings indicate that ifenprodil suppresses nicotine-related behaviors primarily in mice on a hyperdopaminergic (DAT-KO) background. Although further validation in wild-type models is warranted to clarify the translational generalizability of these findings, ifenprodil may be a novel approach for the treatment of nicotine addiction.

To investigate the role and regulatory mechanisms of circCNN2 in endometrial cancer progression, focusing on its epitranscriptomic regulation and interaction with the miR-615-5p/MYH14 axis.

Bombesin receptor subtype 3 (BRS3) has long been an enigmatic orphan G protein-coupled receptor, but has now emerged as a key orchestrator of energy homeostasis, primarily through its actions within the hypothalamus. This review charts the journey of its characterization, synthesizing multiscale evidence from anatomical mapping to cutting-edge spatial transcriptomics to reveal a network of functionally specialized neural circuits. The discussion highlights how distinct BRS3-expressing neuronal populations within the hypothalamus and related preoptic areas govern discrete metabolic functions: those in the preoptic area drive potent thermogenic and cardiovascular responses, while others in the paraventricular hypothalamus specifically regulate food intake. This functional segregation, however, creates a critical translational dilemma. The therapeutic potential of central BRS3 modulation is tempered by significant on-target cardiovascular risks, directly linked to these circuits. In contrast, peripheral targeting offers a promising, albeit more modest, avenue with a more favorable safety profile. To resolve this, this review proposes a circuit-based rationale for a stratified therapeutic strategy: prioritizing peripherally-restricted agonists for broad metabolic disorders and reserving central interventions for highly specific indications where the benefits demonstrably outweigh the risks. Ultimately, this review argues that a precise understanding of BRS3's circuit-specific neurochemistry is paramount not only to unlock its full therapeutic potential but also to proactively navigate its inherent risks, thereby guiding the development of safer, more effective treatments for obesity and diabetes.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by intestinal epithelial damage. Although pyroptosis is implicated in the pathogenesis of UC, the key regulators of this process remain unclear. Chitinase-3-like protein 1 (CHI3L1) is upregulated in multiple inflammatory conditions and has been proposed as a fecal biomarker for endoscopic activity in inflammatory bowel disease (IBD). This study investigates the role of CHI3L1 in regulating macrophage pyroptosis in UC.

The pathogenesis of atopic dermatitis (AD) involves a complex immune regulatory network between dendritic cells (DCs) and keratinocytes (KCs). Recent studies have found that N6-methyladenosine (mA) RNA modification modulates immune regulation and skin barrier homeostasis, but it is unclear whether it participates in AD through the DCs-KCs interaction crosstalk. This study aimed to investigate whether mA modification contributes to the pathological features of atopic dermatitis by regulating ALOX15 expression in dendritic cells.

The release of neutrophil extracellular traps (NETs) - web-like structures composed of extracellular DNA and antimicrobial proteins - is a key innate immune response mechanism against different pathogens, including fungi like Histoplasma capsulatum, the primary etiological agent of histoplasmosis.

Obesity and metabolic syndrome are linked to chronic inflammation and insulin resistance (IR) in adipose tissue (AT), contributing to type 2 diabetes (T2D). Regulatory T cells expressing RORγt and Foxp3 (Tr17 cells) have immunosuppressive functions, but the role of IL-6 in their differentiation and in obesity-induced T2D is unclear. This study investigated whether recombinant Lactococcus lactis expressing IL-6 (L. lactis-R) could elicite Tr17 cells in the gut and improve metabolic dysfunction. The contribution of interleukin-10 (IL-10), which promotes anti-inflammatory M2 macrophages, was also examined. In vitro, IL-6 generates CD4Foxp3 T cells from Foxp3 mice into Tr17 cells positive for CCR6 receptor expression. In C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks, L. lactis-R supplementation did not affect body weight or AT mass, but reduced fasting blood glucose, improved insulin sensitivity, restored intestinal barrier integrity, and significantly decreased bacterial translocation. L. lactis-R supplementation also increased Tr17 cells in the colon and caused their accumulation in visceral AT, associated with a higher proportion of anti-inflammatory M2 macrophages. Furthermore, adoptive transfer of Tr17 cells into IL-10-deficient mice improved insulin sensitivity, reinforced the epithelial barrier, and increased adiponectin levels, demonstrating their protective role against obesity-induced T2D. In conclusion, L. lactis-R supplementation attenuates bacterial translocation, reduces metainflammation, and improves insulin resistance in T2D. These findings highlight the critical role of IL-10-producing Tr17 cells in maintaining intestinal and metabolic homeostasis and suggest that targeting this pathway may represent a promising therapeutic strategy for obesity-associated metabolic disorders such as T2D.

Mitochondrial dysfunction plays a critical role in cardiovascular aging and is a key player in the development of cardiovascular diseases (CVDs) such as hypertension, arteriosclerosis, aneurysms, and heart failure. Aging disrupts mitochondrial function through impaired oxidative phosphorylation, excessive reactive oxygen species generation, mitochondrial DNA mutations, endoplasmic reticulum stress, mitochondrial enzyme dysregulation, and impaired calcium homeostasis. These alterations drive endothelial dysfunction, arterial stiffening, cardiac remodeling, and ultimately exacerbate age-related cardiovascular decline. Despite extensive research, the precise mechanisms by which mitochondrial aging impairs the function of endothelial cells, vascular smooth muscle cells, and cardiomyocytes remain poorly understood. Therefore, this review synthesizes current evidence on how aging-associated mitochondrial dysfunction contributes to endothelial dysfunction, arterial stiffening and remodeling, and cardiac dysfunction. It also outlines emerging pathophysiological mechanisms linking mitochondrial dysfunction to age-related CVDs, offering insights into potential therapeutic targets to promote cardiovascular health in aging populations. This review highlights key biomarkers of declining mitochondrial function to facilitate early diagnosis of CVD-related mitochondrial dysfunction. We show that aging disrupts key regulators of mitochondrial dynamics and quality control in the vasculature and heart across human studies and preclinical models of aging. Recent evidence indicates that impaired mitochondrial function in aging cardiomyocytes results in valvular degeneration, left ventricular hypertrophy, diastolic dysfunction, atrial fibrillation, and diminished exercise capacity. Therefore, understanding the pathophysiological mechanisms linking mitochondrial dysfunction to cardiovascular aging may guide the development of new therapeutic strategies for mitigating age-related cardiovascular decline in older adults.