Explore the vast range of titles available.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans , is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection. Candidalysin is a toxin secreted by Candida albicans . Although critical for pathogenesis, its intracellular targets are not well mapped. Here, Zhang et al screen for interacting proteins and identify that candidalysin can modulate the DNA damage repair pathway to promote fungal infection.

Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non–small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis.

Lung recurrence following hepatectomy is a common and clinically significant complication in patients with hepatocellular carcinoma (HCC), often leading to poor prognosis. However, the underlying mechanisms and reliable predictive biomarkers remain poorly defined. We performed cDNA microarray analysis to identify genes associated with lung recurrence after hepatectomy in HCC patients and identified lysyl oxidase (LOX) as a candidate. We further evaluated the association between LOX expression, circulating tumor cell (CTC), and microvessel density (MVD). The predictive value of serum LOX levels was assessed in both training and validation cohorts. LOX expression was significantly elevated in HCC patients who developed lung recurrence post-hepatectomy and was associated with worse prognosis. High intratumoral LOX expression correlated with increased CTC counts and elevated MVD. In vitro, LOX overexpression enhanced HCC cell migration and invasion, while LOX knockdown suppressed these phenotypes. Serum LOX levels demonstrated predictive potential for postoperative lung recurrence in both cohorts. LOX overexpression is closely associated with lung recurrence after hepatectomy in HCC patients. LOX may serve as a potential biomarker, and its serum level could be used to predict postoperative lung recurrence.

Deep brain stimulation (DBS) significantly improves tremor, rigidity, bradykinesia, and dyskinesia for patients with Parkinson's disease (PD), but gait and speech remain inconsistent. These discrepancies underscore the need for a systematic, quantitative synthesis of existing data to clarify the impact of DBS across different motor domains. To systematically evaluate the effects of DBS on motor symptoms in PD by analyzing UPDRS-III scores and conducting subgroup analyses based on stimulation target, stimulation type, and medication status. A literature search was conducted to identify relevant studies on clinical trials and observational studies reporting pre- and post-DBS motor assessments in PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Web of Science from inception to 15 December 2024. A total of 35 studies comprising 1,082 PD patients were included. The pooled analysis demonstrated a significant improvement in overall UPDRS-III scores post-DBS (WMD: = -1.09, 95% CI: -1.32 to -0.87,  < 0.05). Subgroup analyses showed consistent improvements across tremor, rigidity, akinesia, bradykinesia, dyskinesia, and axial symptoms, regardless of stimulation target or medication state. UPDRS Part IV scores also significantly improved, reflecting reduced motor complications. However, speech function remained unchanged, and UPDRS Part I scores initially showed no significant improvement, though significance emerged after removing sources of heterogeneity. DBS significantly improves overall motor function, particularly tremor, rigidity, and bradykinesia. However, its effects on gait and speech remain inconsistent, which shows the need for further research to refine patient selection and optimize stimulation parameters. These findings provide valuable insights into the therapeutic impact of DBS in PD management.

The morphology of benign and malignant solitary pulmonary lesions sometimes overlaps, making the differentiation difficult. This research aimed to create a radiomics-based prediction model using dual-phase 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) for noninvasive classification of these lesions. A total of 132 patients with solitary pulmonary lesions were included. CT, routine PET (PET 1 ), delayed PET (PET 2 ) and clinical data were acquired. Five combinations of radiomic features (CT, CT + PET 1 , CT + PET 2 , CT + PET 1  + PET 2 , CT+(PET 2 -PET 1 )/PET 1 ) were analyzed. Feature selection used eight methods, and the top ten ranked features were retained based on their weight coefficients. Seven classifiers were used to construct models. The receiver operating characteristic (ROC) curves of the five optimal radiomics models for solitary pulmonary lesions were compared. The optimal CT+(PET 2 -PET 1 )/PET 1 model achieved the highest AUC of 0.898 (95% CI: 0.828–0.968), compared to the optimal CT (0.828, 95% confidence interval [CI]: 0.754–0.902), CT + PET 1 (0.858, 95% CI: 0.785–0.931), CT + PET 2 (0.867, 95% CI: 0.796–0.938), and CT + PET 1  + PET 2 (0.868, 95% CI: 0.798–0.939) models. Based on dual-phase 18 F-FDG PET/CT for radiomic analysis, the optimal CT+(PET 2 -PET 1 )/PET 1 model demonstrated promising diagnostic efficacy and can be a clinical diagnostic tool to distinguish between benign and malignant solitary pulmonary lesions.

Diffusion models have attracted considerable scholarly interest for their outstanding performance in generative tasks. However, current style transfer techniques based on diffusion models still rely on fine-tuning during the inference phase to optimize the generated results. This approach is not merely laborious and resource-demanding but also fails to fully harness the creative potential of expansive diffusion models. To overcome this limitation, this paper introduces an innovative solution that utilizes a pretrained diffusion model, thereby obviating the necessity for additional training steps. The scheme proposes a Feature Normalization Mapping Module with Cross-Attention Mechanism (INN-FMM) based on the dual-path diffusion model. This module employs soft attention to extract style features and integrate them with content features. Additionally, a parameter-free Similarity Attention Mechanism (SimAM) is employed within the image feature space to facilitate the transfer of style image textures and colors, while simultaneously minimizing the loss of structural content information. The fusion of these dual attention mechanisms enables us to achieve style transfer in texture and color without sacrificing content integrity. The experimental results indicate that our approach exceeds existing methods in several evaluation metrics.

Background Acute pancreatitis (AP) can be mild and self-limited, but it can also become severe acute pancreatitis (SAP) and lead to multi-organ dysfunction. It is still difficult to identify patients who may develop severe disease at an early stage. Lactate was once viewed only as a metabolic byproduct, but recent work shows that it also acts as a signaling molecule that links cellular energy status with immune control. Its role in the progression of AP is still not clear. Results Transcriptomic analysis showed clear differences in metabolism and immune features between SAP and non-severe AP (NSAP). Among lactate-related genes (LRGs), 24 were expressed at different levels. Three machine-learning methods identified CCNA2 and H2BC5 as possible diagnostic markers. Both genes had higher expression in SAP clinical samples. In vitro experiments showed that adding lactate increased CCNA2 and H2BC5 expression and raised inflammatory cytokine production. When these genes were knocked down, the inflammatory response decreased. This suggests that both genes are involved in lactate-driven inflammatory signaling. Molecular docking and simulation showed that the MDM2 inhibitor AMG-232 binds strongly to CCNA2, and the mTOR inhibitor Torin-1 binds strongly to H2BC5. Functional tests showed that Torin-1 reduced inflammation and oxidative stress in a sodium-taurocholate–induced cell model. Conclusions This study shows that CCNA2 and H2BC5 are candidate biomarkers for SAP. They are involved in important immune and metabolic pathways. AMG-232 and Torin-1 are possible therapeutic drugs. These findings give a molecular framework for early risk detection in AP and point to new options for targeted treatment.

Background This study evaluated the presentation of pulmonary sclerosing pneumocytoma (PSP) in 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) with the aim of increasing awareness of the disease. Methods Retrospective analysis was performed on 46 PSP patients who had 18F‐FDG PET/CT before surgery or pathological examination from January 2011 to December 2023. The 18F‐FDG PET/CT manifestations of PSP were summarized, and the correlation between the maximum diameter of the tumor and PET metabolic parameters was analyzed, including the maximum standardized uptake value (SUVmax), the mean SUV (SUVmean), the peak SUV (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Results The 46 tumors were randomly distributed in each lobe of both lungs. The mean maximum diameter of these lesions was 2.2 cm (range: 0.6 to 6.5 cm). The mean SUVmax was 2.96 ± 1.88 (median: 2.69, range: 0–9.02). Thirty‐three cases were categorized as mild to moderate FDG uptake, eleven cases were categorized as intense FDG uptake, and no FDG uptake was observed in the remaining two cases of the lesions qualitatively evaluated. The SUVmax of the PSP showed a positive correlation with the maximum diameter of the tumors (R = 0.493, R2 = 0.258, and p < 0.001). SUVmean (R = 0.500, R2 = 0.259, p < 0.001), SUVpeak (R = 0.553, R2 = 0.324, p < 0.001), MTV (R = 0.773, R2 = 0.592, p < 0.001) and TLG (R = 0.800, R2 = 0.654, p < 0.001) were positively correlated with the maximum diameter of the tumor. Conclusion In our study, statistically significant positive correlations were found between SUVmax, SUVmean, SUVpeak, MTV, and TLG and the maximum diameter of PSP. We found that the maximum diameter of the tumor is associated with an increase in FDG uptake in PSP, reflecting a potential correlation between lesion diameter and PET metabolic parameters, indicating a link between structural features and metabolic activity. Heatmap of correlation between the maximum diameter and PET metabolic parameters.

This review systematically summarizes the pathological microenvironment characteristics of chronic subdural hematoma (CSDH) and the regenerative medicine strategies for its intervention. CSDH is no longer regarded as a simple mechanical hematoma but is recognized as a dynamic pathological process driven by chronic inflammation, abnormal angiogenesis, extracellular matrix (ECM) imbalance, and interactions among immune cells. The article focuses on key cellular and molecular mechanisms within the microenvironment and highlights regulatory strategies targeting inflammation, vascular leakage, and matrix remodeling. These strategies include immunomodulation, stem cell therapy, exosome- and nanomaterial-based delivery systems. Such innovative approaches aim to restore tissue homeostasis at the biological level, advancing CSDH treatment from traditional surgical drainage toward microenvironment remodeling and functional reconstruction. They provide a theoretical basis for achieving precise and regenerative clinical therapies.

Autism Spectrum Disorder (ASD) is a widespread neurodevelopmental disorder with no approved medications targeting its core symptoms. Based on the \"dual-hit\" hypothesis combining Maternal Immune Activation (MIA) and Maternal Separation (MS), this study investigated whether combined maternal and offspring vitamin D3 supplementation could ameliorate autism-like behaviors by modulating the VDR pathway, neuroinflammation, and metabolic homeostasis. A \"dual-hit\" ASD mouse model was established in C57BL/6 offspring by combining maternal immune activation (MIA) with maternal separation (MS). Pregnant mice were randomly allocated into three groups (n = 5 per group): Control, Model (MIA+MS), and Intervention (MIA+MS + high vitamin D diet). Offspring in the intervention group continued to receive vitamin D supplementation post-weaning (from 3 weeks of age) until 8 weeks. Offspring behavioral tests were conducted on postnatal days 42-56, with the litter serving as the unit of analysis. Serum, brain tissue, colon contents, and liver samples were subsequently collected and analyzed using ELISA, Western blot, LC-MS, and immunohistochemistry. Compared with controls, MIA+MS offspring exhibited significant social deficits, anxiety, and repetitive behaviors. Combined vitamin D supplementation markedly improved social preference (P<0.0001), reduced anxiety (P<0.001), and decreased repetitive behaviors (P < 0.05). It also upregulated VDR expression in the brain (P<0.01), reduced neurotoxic metabolites (indoxyl sulfate, 6-phosphogluconic acid, and kynurenine pathway intermediates), lowered pro-inflammatory cytokines (IL-1β (P<0.001), IL-6 (P<0.001), TNF-α (P<0.001)), and restored carnitine metabolic homeostasis by modulating TMLHE expression and function. Combined maternal and offspring vitamin D3 supplementation significantly improves autism-like behaviors in a \"dual-hit\" ASD model. The observed protective effects may involve activation of the VDR pathway, reduction of neuroinflammation and neurotoxic metabolites, and systemic restoration of immune and metabolic homeostasis. These findings suggest the potential utility of vitamin D in ASD prevention and intervention, warranting further investigation.