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Ovarian cancer (OC) remains the most lethal gynecological malignancy, primarily due to its late-stage diagnosis, frequent recurrence, and resistance to conventional chemotherapy. A critical factor contributing to OC’s aggressiveness is the tumor microenvironment (TME), particularly the presence and polarization of tumor-associated macrophages (TAMs). TAMs, often skewed toward an immunosuppressive M2-like phenotype, facilitate tumor growth, angiogenesis, metastasis, and resistance to therapy. This comprehensive review delves into the multifaceted regulation of macrophage polarization in OC, highlighting key molecular pathways such as PTEN loss, Wnt/β-catenin signaling, NF-κB, Myc, STAT3, and JNK, among others. Additionally, it explores the role of chemokines, non-coding RNAs, and various proteins in modulating TAM phenotypes. Emerging evidence underscores the significance of extracellular vesicles (EVs) and ovarian cancer stem cells (CSCs) in promoting M2 polarization, thereby enhancing tumor progression and therapy resistance. The review also identifies critical biomarkers associated with macrophage polarization, including CD163, LILRB1, MUC2, and others, which hold prognostic and therapeutic potential. Therapeutic strategies targeting TAMs are extensively discussed, encompassing oncolytic viruses, engineered EVs, immunotherapies, nanoparticles, targeted therapies, and natural products. These approaches aim to reprogram TAMs from a pro-tumorigenic M2 state to an anti-tumorigenic M1 phenotype, thereby enhancing immune responses and overcoming resistance to treatments such as chemotherapy and immune checkpoint inhibitors. Furthermore, the review addresses the interplay between macrophage polarization and therapy resistance, emphasizing the need for novel interventions to modulate the TME effectively. By synthesizing current knowledge on macrophage polarization in ovarian cancer, this study underscores the potential of targeting TAMs to improve clinical outcomes and personalize treatment strategies for OC patients. Continued research in this domain is essential to develop robust therapeutic frameworks that can mitigate the immunosuppressive TME and enhance the efficacy of existing and novel cancer therapies.

Currently, breast cancer (BC) and cardiovascular diseases (CVD), as two major diseases that seriously threaten global public health, have become major public health problems that need to be urgently solved as their morbidity and mortality rates continue to rise. In recent years, with the continuous improvement of BC diagnosis and treatment, the overall survival of patients has been significantly prolonged, but CVD has gradually become one of the major non-oncological causes of death among BC survivors. It has been pointed out that there are multiple common mechanisms between BC and CVD at the pathophysiological level, including chronic inflammation, metabolic abnormalities, hormonal dysregulation and neuroendocrine system activation. This review summarizes the potential interactions between BC and CVD, the associated cardiotoxicity induced by cancer therapies, and the application of relevant biomarkers in diagnosis and risk assessment, with the aim of providing insights and reference for the comprehensive management of patients with coexisting BC and CVD.

Background Scabies is a contagious skin infestation caused by Sarcoptes scabiei var. hominis , presenting with a wide range of clinical manifestations. Nodular scabies is an uncommon variant that typically affects the genital region. When nodules appear in atypical locations, they may resemble other dermatoses and complicate diagnosis. Case presentation A 56-year-old woman presented with persistent, pruritic nodules on the chest, buttocks, and thighs that clinically resembled papular urticaria. She had previously been treated with topical corticosteroids and antihistamines without improvement, prompting a diagnostic biopsy. Histopathological examination confirmed the presence of Sarcoptes mites in the stratum corneum. The patient and her family were treated with 10% sulfur ointment applied once daily for three consecutive days per course, with two courses administered one week apart. The nodules gradually regressed after two courses, while pruritus and intermittent wheals persisted for four weeks and resolved completely within two months. Conclusion The case emphasizes the need to consider atypical scabies in the differential diagnosis of persistent nodular eruptions occurring in uncommon anatomical sites. Clinical trial number Not applicable.

Wilson’s disease (WD) is an inherited disorder characterized by excessive accumulation of copper in the body, particularly in the liver and brain. In the central nervous system (CNS), extracellular copper accumulation triggers pathological microglial activation and subsequent neurotoxicity. Growing evidence suggests that levels of inflammatory cytokines are elevated in the brain of murine WD models. However, the mechanisms associated with copper deposition to neuroinflammation have not been completely elucidated. In this study, we investigated how the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to copper-mediated neuroinflammation in an animal model of WD. Elevated levels of interleukin-1β, interleukin-18, interleukin-6, and tumor necrosis factor-α were observed in the sera of WD patients and toxic milk (TX) mice. The protein levels of inflammasome adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cleaved caspase-1, and interleukin-1β were upregulated in the brain regions of the TX mice. The NLRP3 inflammasome was activated in the TX mice brains. Furthermore, the activation of NLRP3 inflammasome was noted in primary microglia treated with CuCl 2 , accompanied by the increased levels of cleaved caspase-1, ASC, and interleukin-1β. Blocking NLRP3 inflammasome activation with siNlrp3 or MCC950 reduced interleukin-1β and interleukin-18 production, thereby effectively mitigating cognitive decline, locomotor behavior impairment, and neurodegeneration in TX mice. Overall, our study demonstrates the contribution of copper overload-mediated activation of NLRP3 inflammasome to progressive neuropathology in the CNS of a murine model of WD. Therefore, blockade of the NLRP3 inflammasome activation could be a potential therapeutic strategy for WD.

The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 through sensor proteins and two protein complexes named GATOR1 and GATOR2. In this study, we identify VWCE (von Willebrand factor C and EGF domains) as a negative regulator of amino acid-dependent mTORC1 signaling. Knockdown of VWCE promotes mTORC1 activity even in the absence of amino acids. VWCE interacts with the KICSTOR complex to facilitate the recruitment of GATOR1 to the lysosomes. Bioinformatic analysis reveals that expression of VWCE is reduced in prostate cancer. More importantly, overexpression of VWCE inhibits the development of prostate cancer. Therefore, VWCE may serve as a potential therapeutic target for the treatment of prostate cancers. mTORC1 adapts cellular metabolism in response to nutrient signals. Here, the authors identify VWCE as a negative regulator of amino acid-dependent mTORC1 signaling and a potential as a therapeutic target in prostate cancer treatments.

Avian influenza viral ribonucleoproteins (vRNPs) complete genome transcription and replication by interacting with host proteins, and RNA-dependent RNA polymerase (RdRp) is its major component. PB2 is a component of RdRp and plays an important role in viral RNA synthesis. Our previous mass spectrometry analysis identified PB2 interacted with avian cellular heterogeneous nuclear ribonucleoprotein AB (hnRNP AB). However, the specific mechanism of this interaction regulating viral replication needs to be further clarified. In this study, we found that avian hnRNP AB inhibited the replication of multiple subtypes of avian influenza viruses (AIVs) from different reservoirs, and the glycine-rich domain (GRD) of hnRNP AB was the function domain that inhibited AIV replication. Moreover, we demonstrated that the GRD of avian hnRNP AB interacted with the C-terminus of PB2, reducing the binding of PB1 to PB2 and interfering with RdRp assembly. Based on the previous discovery that hnRNP AB affected the nucleoplasmic distribution of PB2 mRNA, we have further explored the mechanism here. Mechanically, hnRNP AB intervened in the nuclear export of PB2 mRNA by reducing the binding ability of UAP56, and decreased PB2 expression to interfere with RdRp formation and reduce vRNA synthesis, which in turn inhibited viral replication. Collectively, this study demonstrated that the avian host protein hnRNP AB inhibited AIV replication by blocking assembly of RdRp and vRNA synthesis, in which was associated with UAP56-mediated nuclear export of PB2 mRNA, providing a potential target for antiviral intervention. Graphical Abstract

Synaptic efficacy is critical for memory formation and consolidation. Accumulating evidence suggest that synapses are impaired during Wilson’s disease (WD), contributing to neuronal dysfunction and cognitive decline. WD is a prototypical condition among the copper metabolism disorders. Cognitive impairment is a common feature of affected patients with neurological symptoms, presenting as memory deficits, decreased cognitive flexibility, and impaired learning capabilities. These cognitive deficits can significantly impact the quality of life, affecting work and academic performance. However, the mechanisms mediating the inhibitory synaptic dysfunction in WD are incompletely understood. We investigated the effects of the double-stranded RNA-dependent protein kinase/eukaryotic initiation factor 2α (PKR/eIF2α) pathway on synaptic structure and function in WD using a murine model, toxic milk (TX mice). During mouse open-field tests, we noted a substantial rise in the mobility/immobility ratio among WD model animals compared to that in WT mice. Additionally, WD mice exhibited diminished central area exploration, as evidenced by reduced travel distance. Moreover, they displayed prolonged escape latency in the Barnes maze, suggesting that chronic copper accumulation is associated with neuropsychiatric alterations and cognitive impairment. We also found a decrease in the expression of synapse-associated proteins (synapsin 1, synaptophysin, postsynaptic density protein-93 [PSD93], postsynaptic density protein-95 [PSD95]), and vesicle-associated membrane protein2 [VAMP2]) besides abnormal neurotransmitter levels (including glutamate and GABA), indicating the presence of synaptic dysfunction in TX mice. Inhibiting PKR via C16 prevented these changes, suggesting that dysfunctional cognition is associated with the PKR/eIF2α pathway. We also observed changes in synapses, vesicles, dendritic spine density, and dendritic length that were associated with the presence of cognitive dysfunction. Further investigation revealed that C16 treatment decreased the TUNEL-positive cell numbers in the hippocampus of TX mice and prevented 8-OHdG-induced synaptic dysfunction. Results suggest that PKR downregulation prevents copper-induced synaptic dysfunction in the murine WD model. Therefore, targeting PKR pharmacologically may be a potential therapeutic strategy for treating the copper-induced neuropathology of patients with WD.

Emerging evidence suggests that the brain–gut–skin axis (BGSA) plays a critical role in the pathogenesis of inflammatory and disfiguring skin diseases. Conditions such as acne, atopic dermatitis, psoriasis, rosacea, vitiligo, and alopecia areata, once regarded as localized disorders driven mainly by cutaneous immune dysfunction, are now recognized as systemic conditions associated with neuroendocrine stress responses, gut microbial dysbiosis, and chronic low-grade inflammation. Mechanistic studies elucidate the intricate interorgan communication mediated by microbial metabolites (e.g., short-chain fatty acids and tryptophan derivatives), cytokine networks, neuropeptides, and hypothalamic–pituitary–adrenal (HPA) axis signaling. Building on these insights, therapeutic strategies are evolving rapidly. Microbiome-directed interventions (probiotics, postbiotics, dietary modification, and fecal microbiota transplantation), together with psychoneuroimmunological approaches, have shown potential to alleviate disease severity. Integrative therapies, including traditional herbal medicine, offer promising effects; however, we emphasize that mechanistic depth and robust clinical validation for these modalities are currently limited. This review integrates mechanistic findings, clinical correlations, and emerging therapeutic approaches, while critically distinguishing between correlation and causation. Future studies should emphasize longitudinal multi-omics analyses and standardized clinical trials to clarify causal pathways and guide precision, patient-centered management for systemic and cutaneous health.

Pathogenic germline mutations in the P-type copper-transporting ATPase (ATP7B) gene cause Wilson’s disease (WD), a hereditary disorder characterized by disrupted copper metabolism. The Arg778Leu (R778L) mutation in exon 8 is prevalent among individuals with WD in East Asia and is associated with more severe phenotypes. In this study, we generated a WD mouse model harboring R778L mutation (R778L mice) using CRISPR/Cas9. R778L mice exhibit a range of pathological characteristics resembling those of patients with WD and the same point mutations, including aberrant copper metabolism, pathological cellular injury, inflammation, and severe hepatic fibrosis. At 3–5 months of age, these mice started to display neurological deficits in motor coordination and cognitive dysfunction, accompanied by increased expression of inflammatory cytokines in the central nervous system. Microglia in the striatum and cortex exhibit significant activation, shorter processes, and decreased branch points. However, the Cu 2+ levels in the brain tissue of R778L mice did not differ significantly from those of wild-type mice. Notably, inhibition of hepatic inflammation with PJ34 or si Nfkb markedly alleviated the deficiencies in cognitive performance and improved locomotor activity in R778L mice. Thus, this study establishes a novel murine model to investigate the pathophysiology of WD, highlights the liver-brain crosstalk responsible for neurological manifestations in individuals with WD caused by the R778L point mutation, and demonstrates the potential of modulating liver inflammation as a therapeutic strategy for alleviating the neurological manifestations of WD.

With the trend of economic globalization, innovation and entrepreneurship have become critical strategies for national development. College students, particularly, are a primary focus for cultivating awareness of innovation and entrepreneurship, which is essential for implementing national development strategies. The institution in eastern China has developed a program aimed at fostering medical innovation and entrepreneurship through the Biodesign framework. This study aimed to evaluate the effectiveness of this training system by surveying 479 medical students using a questionnaire designed around three stages: “identify,” “invent,” and “implement”. Factor analysis, descriptive statistical analysis, and T-tests were employed to assess the effectiveness and development pathways of the Biodesign-based cultivation of medical innovation and entrepreneurship talents. The results indicate significant improvements in students’ abilities in demand identification, demand screening, concept generation, concept selection, strategic identification, and business planning ( p  < 0.001), with the most notable improvement in demand identification (t = 6.383). Additionally, students have achieved notable success in writing and publishing papers and patents, as well as securing provincial and national-level awards. Particularly remarkable were the achievements in student competitions, with the number of national-level awards rising from 32 in 2019 to 66 in 2023. In conclusion, the Biodesign-based cultivation model for medical innovation and entrepreneurship has proven effective and merits further promotion among medical students.