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The segmentation and risk grade prediction of gliomas based on preoperative multimodal magnetic resonance imaging (MRI) are crucial tasks in computer-aided diagnosis. Due to the significant heterogeneity between and within tumors, existing methods mainly rely on single-task approaches, overlooking the inherent correlation between segmentation and grading tasks. Furthermore, the limited availability of glioma grading data presents further challenges. To address these issues, we propose a deep-ensemble learning framework based on multimodal MRI and the U-Net model, which simultaneously performs glioma segmentation and risk grade prediction. We introduce asymmetric convolution and dual-domain attention in the encoder, fully integrating effective information from different modalities, enhancing the extraction of features from critical regions, and constructing a dual-branch decoder that combines spatial features and global semantic information for both segmentation and grading. In addition, we propose a weighted composite adaptive loss function to balance the optimization objectives of the two tasks. Our experimental results on the BraTS dataset demonstrate that our method outperforms state-of-the-art methods, yielding superior segmentation accuracy and precise risk grade prediction.

Podocyte injury serves as a central pathological driver in chronic kidney diseases (CKD), including diabetic kidney disease (DKD) and IgA nephropathy (IgAN). However, conventional therapies are still limited by poor targeting efficacy and systemic side effects. Nanotechnology provides transformative strategies tunable nanomedicines, which enables precise podocyte repair through targeted drug delivery, antioxidant and anti-inflammatory effects, as well as gene regulation. This review exclusively focuses on the preclinical research progress in this field. Three categories of nanomaterials: peptide-drug conjugates (PDCs), polymeric nanoparticles (PNs), and inorganic nanomaterials (INs), exhibit distinct advantages: PDCs realize ligand-receptor-mediated precise targeting, PNs combine gene silencing with favorable biocompatibility, and INs rely on nanozyme activities to maintain redox homeostasis. Despite remarkable preclinical advances, challenges remain in optimizing targeting efficiency, overcoming biological barriers, and ensuring the long-term biosafety of nanomedicines. Future directions will center on stimuli-responsive nanosystems, multimodal therapies, organ-on-a-chip models, and sustainable manufacturing, which are critical for bridging the gap between preclinical research and clinical translation. This review highlights the great potential of nanotechnology in revolutionizing podocyte-targeted therapy and provides a comprehensive preclinical basis for addressing unmet clinical needs in CKD management interdisciplinary innovation.

Background Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disorder primarily caused by the rupture of aneurysm, which results in a high mortality rate and consequently imposes a significant burden on society. The occurrence of SAH initiates an immune response that further exacerbates brain damage. The acute inflammatory reaction subsequent to SAH plays a crucial role in determining the prognosis. Th17 cells, a subset of T cells, are related to the brain injury following SAH, and it is unclear how Th17 cells are cleared in the brain. Meningeal lymphatic vessels are a newly discovered intracranial fluid transport system that has been shown to drain large molecules and immune cells to deep cervical lymph nodes. There is limited understanding of the role of the meningeal lymphatic system in SAH. The objective of this research is to explore the impact and underlying mechanism of drainage Th17 cells by meningeal lymphatics on SAH. Methods Treatments to manipulate meningeal lymphatic function and the CCR7-CCL21 pathway were administered, including laser ablation, injection of VEGF-C geneknockout, and protein injection. Mouse behavior was assessed using the balance beam experiment and the modified Garcia scoring system. Flow cytometry, enzyme-linked immunosorbent assays (ELISA), and immunofluorescence staining were used to study the impact of meningeal lymphatic on SAH drainage. Select patients with unruptured and ruptured aneurysms in our hospital as the control group and the SAH group, with 7 cases in each group. Peripheral blood and cerebrospinal fluid (CSF) samples were assessed by ELISA and flow cytometry. Results Mice with SAH showed substantial behavioral abnormalities and brain damage in which immune cells accumulated in the brain. Laser ablation of the meningeal lymphatic system or knockout of the CCR7 gene leads to Th17 cell aggregation in the meninges, resulting in a decreased neurological function score and increased levels of inflammatory factors. Injection of VEGF-C or CCL21 protein promotes Th17 cell drainage to lymph nodes, an increased neurological function score, and decreased levels of inflammatory factors. Clinical blood and CSF results showed that inflammatory factors in SAH group were significantly increased. The number of Th17 cells in the SAH group was significantly higher than the control group. Clinical results confirmed Th17 cells aggravated the level of neuroinflammation after SAH. Conclusion This study shows that improving the drainage of Th17 cells by meningeal lymphatics via the CCR7-CCL21 pathway can reduce brain damage and improve behavior in the SAH mouse model. This could lead to new treatment options for SAH.

Background: The mechanisms underlying the proliferation and apoptosis of glioma cells remain unelucidated. A recent study has revealed that microRNA-92b (miR-92b) inhibits apoptosis of glioma cells via downregulating DKK3. Notably, long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is predicted to have a possible interaction with miR-92b. Objective: This study aimed to identify whether NEAT1 affects glioma cell proliferation and apoptosis via regulating miR-92b. Methods: The expression of NEAT1 was compared between glioma tissues and adjacent tissues as well as between glioma cells and normal astrocytes using quantitative real-time polymerase chain reaction. Glioma cell proliferation was determined by using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and glioma cell apoptosis was determined by using the flow cytometry. Results: The expression of NEAT1 was low in glioma tissues and cells compared to the normal ones. Overexpression of NEAT1 inhibited proliferation and promoted apoptosis of glioma cell lines (U-87 MG and U251). The interaction between NEAT1 and miR-92b was confirmed using RNA immunoprecipitation, RNA pull-down assay, and luciferase reporter assay. Importantly, the tumor suppressor function of overexpressing NEAT1 was achieved by downregulating miR-92b and subsequently upregulating DKK3. Conclusion: Our findings indicated that NEAT1 acts as a tumor suppressor in glioma cells, which provides a novel target in overcoming glioma growth.

Neurological diseases such as stroke and Alzheimer's disease pose increasing challenges to global public health. Salvianolic Acid B (SalB), a major active component of , has garnered attention due to its anti-inflammatory, antioxidant, neuroprotective, and pro-angiogenic properties in neurological disease treatment. This paper aims to review the mechanisms and effects of SalB in the treatment of neurological diseases, exploring its role in improving neurological function, mitigating neuroinflammation, and reducing oxidative stress. SalB demonstrates multifaceted mechanisms in neurological disease management. In animal models of cerebral ischemia/reperfusion injury, SalB reduces infarct size and enhances neurological recovery via anti-inflammatory, anti-oxidative stress, and angiogenic pathways. It protects the blood-brain barrier and inhibits neuronal apoptosis in stroke models. In spinal cord injury models, SalB alleviates edema and promotes motor function recovery. In Alzheimer's disease models, SalB suppresses amyloid-beta formation and neuroinflammation. Additionally, SalB exhibits antidepressant and analgesic effects in pain-depression comorbidity models. These effects are mediated through the regulation of signaling pathways, including NF-κB, AMPK, PI3K/Akt, and Nrf2, highlighting SalB's broad therapeutic potential in neurological diseases. SalB exhibits promising prospects in the treatment of neurological diseases. However, its clinical application faces challenges such as chemical stability and bioavailability. Further research on the mechanisms of SalB and innovative drug delivery strategies is needed to advance its application in neurological disease therapy.

Renal cell carcinoma (RCC) poses significant challenges to precision oncology due to its pronounced molecular heterogeneity and complex tumor microenvironment (TME). Traditional two-dimensional (2D) cultures and animal models fall short in capturing patient-specific tumor biology, limiting their translational relevance. In contrast, three-dimensional (3D) organoid platforms offer structurally and functionally representative models that retain key pathological and pharmacological features of RCC. Notably, RCC organoids enable pharmacokinetic assessment, including drug penetration, metabolic activation, and off-target toxicity in a spatially organized context. This review outlines current strategies for RCC organoid construction-including patient-derived organoids (PDOs), air–liquid interface (ALI) cultures, scaffold-based matrices, and microfluidic systems-and evaluates their applications in drug screening, resistance modeling, and immunotherapy prediction. We further discuss technical and biological limitations such as phenotypic drift, inter-sample variability, and TME reconstruction, alongside emerging solutions in synthetic scaffolds, immune co-cultures, and multi-omics integration. In conclusion, RCC organoids are rapidly evolving into clinically actionable platforms, offering a scalable and predictive approach to personalized therapy in renal oncology.

Prostate cancer (PCa) is a common malignancy in men with limited therapeutic options at advanced stages. Statins, widely prescribed lipid-lowering agents, have demonstrated antitumor activity in PCa, but underlying mechanisms are not fully understood. Studies suggested that tumor progression is facilitated upon activation of mevalonate (MVA) pathway, while it is reduced via MVA pathway inhibition-induced ferroptosis. Therefore, this study aimed to determine whether lovastatin suppresses prostate cancer progression by inducing ferroptosis through inhibition of the MVA pathway. Five clinically used statins were screened in prostate cancer cell lines to identify the most effective compound. Cell proliferation, migration, and invasion were assessed. Ferroptosis was evaluated by measuring intracellular Fe2+ and reactive oxygen species (ROS) levels, mitochondrial membrane potential, ferroptosis-related protein expression, and ultrastructural mitochondrial alterations. Rescue experiments were performed using the ferroptosis inhibitor deferoxamine and MVA supplementation. Lovastatin exhibited the strongest inhibitory effect, significantly reducing proliferation, migration, and invasion. Lovastatin significantly suppressing PCa cell aggressiveness and inducing ferroptosis, as evidenced by typical biochemical and morphological markers, all of which were reversed by deferoxamine. MVA supplementation restored cell viability, normalized oxidative stress and iron levels, and reversed alterations in MVA pathway enzymes and ferroptosis-associated proteins. Lovastatin suppresses prostate cancer cell growth and invasiveness by inhibiting the MVA pathway and inducing ferroptosis, highlighting the MVA-ferroptosis axis as a potential therapeutic target for PCa.

Objective Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. Methods This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). Results A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P <  0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors. Conclusion Female patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus.

In recent years, interventional surgery has become a treatment for ischemic stroke due to its low risk of injury. However, the occurrence of restenosis hinders the long-term effectiveness and safety of stent implantation. At present, drug-eluting stents mainly prevent the stenosis of drug-eluting stents by inhibiting the proliferation of smooth muscle cells (SMCs). However, these drugs cause damage to endothelial cells (ECs), prevent timely re endothelialization of blood vessels, and increase the risk of late thrombosis and late restenosis. EPS-15-interacting protein 1 (Epsin1)- EPS-15-interacting protein 2 (Epsin2)-shrna coated stents have the potential to promote early endothelialization and inhibit restenosis, which contributes to the candidate development of novel drug coated stents. We found that the expression of Epsin was elevated in the mouse carotid artery ligation model, and the intimal hyperplasia(IH) could be reduced by intervening Epsin. Epsin in cultured endothelial cells was interfered to study proliferation and migration functions, and its role in cocultured endothelial cells and smooth muscle cells was evaluated. In addition, we explored the potential therapeutic benefits of inhibiting Epsin in a porcine model using scaffolds coated with plasmids containing Epsin short hairpin RNA (shRNA). Our study showed that the expression of Epsin1 and Epsin2 was elevated in the proliferative intima of mice, and the inhibition of Epsin reduced the proliferation of neointima in mice. The inhibition of Epsin led to enhanced proliferation and migration of endothelial cells, and maintained a healthy cell membrane potential. In cocultured cells, inhibition of Epsin resulted in reduced proliferation and migration of smooth muscle cells. In a porcine carotid artery model, Epsin shRNA coated scaffolds promoted early re endothelialization and reduced IH. These results suggest that Epsin plays a crucial role in endothelial and smooth muscle cell proliferation and migration functions, and its inhibition may be a potentially effective therapeutic strategy to prevent in stent stenosis.

Objective The potential roles and mechanisms of pericytes in maintaining blood–brain barrier (BBB) integrity, which would be helpful for the development of therapeutic strategies for subarachnoid hemorrhage (SAH), remain unclear. We sought to provide evidence on the potential role of pericytes in BBB disruption and possible involvement and mechanism of CypA signaling in both cultured pericytes and SAH models. Methods Three hundred fifty-three adult male C57B6J mice weighing 22 to 30 g, 29 CypA −/− mice, 30 CypA +/+ (flox/flox) mice, and 30 male neonatal C57B6J mice were used to investigate the time course of CypA expression in pericytes after SAH, the intrinsic function and mechanism of CypA in pericytes, and whether the known receptor CD147 mediates these effects. Results Our data demonstrated both intracellular CypA and CypA secretion increased after SAH and could activate CD147 receptor and downstream NF-κB pathway to induce MMP9 expression and proteolytic functions for degradation of endothelium tight junction proteins and basal membranes. CypA served as autocrine or paracrine ligand for its receptor, CD147. Although CypA could be endocytosed by pericytes, specific endocytosis inhibitor chlorpromazine did not have any effect on MMP9 activation. However, specific knockdown of CD147 could reverse the harmful effects of CypA expression in pericytes on the BBB integrity after SAH. Conclusions This study demonstrated for the first time that CypA mediated the harmful effects of pericytes on BBB disruption after SAH, which potentially mediated by CD147/NF-κB/MMP9 signal, and junction protein degradation in the brain. By targeting CypA and pericytes, this study may provide new insights on the management of SAH patients.