Search Results (19,478)

Acute Respiratory Distress Syndrome (ARDS) is a severe complication of acute lung injury (ALI) characterized by acute hypoxemic respiratory failure and diffuse alveolar damage, with a high mortality rate and a current lack of treatments beyond supportive care. Its complex pathophysiology involves immune cell activation, pro-inflammatory cytokine release, and disruption of the alveolar–capillary barrier, leading to pulmonary edema and fibrosis. This review explores the potential of small interfering RNA (siRNA) therapy as a novel pathogenetic treatment for ARDS. The mechanism of RNA interference is described, highlighting its high specificity for silencing target genes. The paper then evaluates various animal models used in ARDS preclinical research, noting the advantages of large animals (pigs) for their physiological similarity to humans and the suitability of rodents for studying long-term fibrotic stages. Finally, the review summarizes promising in vivo studies where siRNA-mediated knockdown of several genes (e.g., TIMP1, BTK, LCN2, HDAC7, CCL2, NOX4, TNFα and TLR4) significantly reduced inflammation, improved lung histology, and increased survival. The collective evidence underscores siRNA’s considerable potential for developing targeted therapies against ARDS, moving beyond symptomatic care to address the root molecular mechanisms of the disease. Full article

Cerebrovascular diseases are a leading cause of global mortality, underscoring the need for objective and quantitative 3D visualization of cerebral vasculature from dynamic imaging modalities. Conventional analysis is often labor-intensive, subjective, and prone to errors due to image noise and subtraction artifacts. This study tackles the challenge of achieving fast and accurate volumetric reconstruction from angiography sequences. We propose a multi-stage pipeline that begins with image restoration to enhance input quality, followed by neural segmentation to extract vascular structures. Camera poses and sparse geometry are estimated through Structure-from-Motion, and these reconstructions are refined by leveraging the segmentation maps to isolate vessel-specific features. The resulting data are then used to initialize and optimize a 3D Gaussian Splatting model, enabling anatomically precise representation of cerebral vasculature. The integration of deep neural segmentation priors with explicit geometric initialization yields highly detailed 3D reconstructions of cerebral angiography. The resulting models leverage the computational efficiency of 3D Gaussian Splatting, achieving near-real-time rendering performance competitive with state-of-the-art reconstruction methods. The segmentation of brain vessels using nnU-Net and our trained model achieved an accuracy of 84.21%, highlighting the improvement in the performance of the proposed approach. Overall, our pipeline significantly improves both the efficiency and accuracy of volumetric cerebral vasculature reconstruction, providing a robust foundation for quantitative clinical analysis and enhanced guidance during endovascular procedures. Full article

Background and Clinical Significance: Giant sphenoid wing meningiomas are generally viewed as skull base masses that compress frontal centers and their respective pathways gradually enough to cause a dysexecutive–apathetic syndrome, which can mimic primary neurodegenerative disease. The aim of this report is to illustrate how bedside phenotyping and multimodal imaging can disclose similar clinical presentations as surgically treatable network lesions. Case Presentation: An independent, right-handed older female developed an incremental, two-year decline of her ability to perform executive functions, extreme apathy, lack of instrumental functioning, and a frontal-based gait disturbance, culminating in a first generalized seizure and a newly acquired left-sided upper extremity pyramidal sign. Standardized neuropsychological evaluation revealed a predominant frontal-based dysexecutive profile with intact core language skills, similar to behavioral-variant frontotemporal dementia (bvFTD). MRI demonstrated a large, right fronto-temporo-basal extra-axial tumor attached to the sphenoid wing with homogeneous postcontrast enhancement, significant vasogenic edema within the frontal projection pathways, and a marked midline displacement of structures with an open venous pathway. With the use of a skull-base flattening pterional craniotomy with early devascularization followed by staged internal debulking, arachnoid preserving dissection, and conservative venous preservation, the surgeon accomplished a Simpson Grade I resection. Sequential improvements in the patient’s frontal “re-awakening” were demonstrated through postoperative improvements on standardized stroke, cognitive and functional assessment scales that correlated well with persistent decompression and symmetric ventricles on follow-up images. Conclusions: This case illustrates the possibility of a non-dominant sphenoid wing meningioma resulting in a pseudo-degenerative frontal syndrome and its potential for reversal if recognized as a network lesion and treated with tailored, venous-sparing skull-base surgery. Contrast-enhanced imaging and routine frontal testing in atypical “dementia” presentations may aid in identifying additional patients with potentially surgically remediable cases. Full article

Plant disease specimens are invaluable resources for investigating the origin and spread mechanisms of plant pathogenic microorganisms. Citrus canker, caused by Xanthomonas citri pv. citri (Xcc), is one of the most devastating bacterial diseases in citrus production. Here, we report the complete genome sequence of Xcc strain GD82, isolated from Guangdong Province during the early outbreak stage in the 1980s. Comparative analysis with modern genomes revealed key differences in structural variations, functional single-nucleotide polymorphisms (SNPs), and phage-related fragments, suggesting potential associations between insertions/deletions (InDels) and pathogenicity or environmental adaptation. This study provides critical insights into the evolutionary trajectory of Xcc and the epidemiological dynamics of citrus canker in China. Full article

Objective: The role of adjuvant chemoradiotherapy (CRT) following curative gastrectomy remains controversial, especially in the context of D2 dissection. This research evaluated survival indicators through an analysis of previous observational studies and it evaluated treatment outcomes between patients who underwent CRT and those who received CT as their sole therapy. Methods: The researchers performed a non-randomized retrospective cohort study which analyzed 206 patients who underwent R0–R1 resection for gastric adenocarcinoma and received either adjuvant CRT (n = 107) or CT alone (n = 99). A Kaplan–Meier analysis together with Cox regression methods were used to evaluate survival outcomes of patients. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline differences between groups at the beginning of the study. The median follow-up was 52.0 months. Results: The baseline characteristics differed markedly between groups, with CRT patients showing higher rates of T4 tumors (34.6% vs. 22.2%), N3 disease (47.7% vs. 26.3%), vascular invasion (72.9% vs. 50.5%), and R1 resection (10.3% vs. 1.0%). Unadjusted survival favored CT alone (median DFS 81.7 vs. 103.9 months; median OS 86.2 months vs. not reached). These differences lost significance after IPTW adjustment (DFS: HR 1.18, p = 0.428; OS: HR 1.24, p = 0.336). T3–T4 stage, N2–N3 nodal status, vascular invasion, and positive margins emerged as independent prognostic factors. Subgroup analyses revealed no treatment interactions (all p > 0.05). Conclusions: The research used a retrospective study design which showed substantial differences between treatment groups at the beginning of the study. The survival results that showed better outcomes for CT alone became attenuated after the researchers applied propensity score adjustment to adjust for confounding from treatment selection. The study established that advanced T–N stage, vascular invasion, and positive margins were identified as independent prognostic factors. The research results are hypothesis-generating and require randomized controlled trials to establish the exact difference in effectiveness between different treatments. Full article

Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC₅₀ > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action. Full article

Cholinergic dysfunction is a hallmark of Alzheimer’s disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting the need for compounds suitable for preventive or earlier-stage intervention. This study investigated marine phytohormones as modulators of cholinergic imbalance, using an integrative strategy encompassing enzymatic assays, QSAR and DFT calculations, molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Among them, isopentenyl adenine (IPA) and abscisic acid (ABA) showed inhibitory activity against cholinesterases. IPA inhibited both AChE and BChE through distinct mechanisms with noncompetitive inhibition of AChE and competitive inhibition of BChE, while ABA showed selective noncompetitive inhibition of AChE. DFT-based analysis revealed distinct electronic properties supporting differential reactivity. Moreover, IPA interacted with both catalytic and peripheral residues in AChE, and aligned with BChE’s active site, while ABA was bound more peripherally. MD simulations confirmed complex-specific conformational stability based on RMSD, RMSF, Rg, and hydrogen bonding analysis. Both compounds showed low off-target potential against serine proteases and favorable predicted ADMET profiles. These results support the potential of marine phytohormones as preventive modulators of cholinergic dysfunction in AD. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, with its asymptomatic progression highlighting the urgent need for early, minimally invasive biomarkers. Exosomes derived from the aqueous humor (AH) have emerged as promising candidates, as they carry proteins, nucleic acids, and lipids that reflect the physiological and pathological state of ocular tissues such as the trabecular meshwork and ciliary body. However, their low abundance, nanoscale size, and the limited volume of AH complicate detection and characterization. Conventional methods, including Western blotting, PCR or mass spectrometry, are labor-intensive, time-consuming, and often incompatible with microliter-scale samples. Electrochemical biosensors offer a highly sensitive, rapid, and low-volume alternative, enabling the detection of exosomal surface markers and internal cargos such as microRNAs, proteins, and lipids. Recent advances in nanomaterial-enhanced electrodes, microfluidic integration, enzyme- and nanozyme-mediated signal amplification, and ratiometric detection strategies have significantly improved sensitivity, selectivity, and multiplexing capabilities. While most studies focus on blood or serum, these platforms hold great potential for AH-derived exosome analysis, supporting early-stage glaucoma diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. Continued development of miniaturized, point-of-care electrochemical biosensors could facilitate clinically viable, noninvasive exosome-based diagnostics for glaucoma. Full article

Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh classification and the Model for End-Stage Liver Disease (MELD) score. This is supplemented by newer metrics, including the MELD-Na score, the albumin–bilirubin (ALBI) grade and liver stiffness measurements. These assessments are integral to tailoring treatments, ranging from curative approaches such as surgical resection and liver transplantation to locoregional options (percutaneous ablation, transarterial chemoembolisation and radioembolisation), and systemic therapies. This review explores strategies for balancing the aggressiveness of cancer therapy with the need to preserve hepatic function, particularly in patients with advanced liver dysfunction. A multidisciplinary approach, incorporating expertise from hepatology, oncology, radiology and surgery, is essential for optimising outcomes. Advanced imaging techniques and biochemical markers also improve decision-making and ensure individualised care. Full article

Background: Metabolically associated fatty liver disease (MASLD) constitutes a major burden. Glucagon-like peptide-1 agonists (GLP-1) could improve hepatic steatosis as well as weight loss. However, the effect of GLP-1 agonists on patients with and without diabetes and the effect of newer drugs (dual and triple agonists) are unclear. Objective: To investigate the effect of GLP-1 agonists, including dual and triple agonists, in patients with metabolic-associated liver steatosis and steatohepatitis, while exploring their effect on patients with and without type 2 diabetes. Methods: We searched PubMed, Scopus, and Web of Science in October 2025 for randomized parallel controlled trials that investigated the effect of GLP-1 agonists in patients with MASLD or metabolic-associated steatohepatitis (MASH). We assessed the quality of the included studies using Cochrane ROB2. We performed the analysis using RevMan 5.4. We performed subgroup analysis based on the status of diabetes, the control group, and the class of GLP-1 agonist (single, dual, or triple). Results: We included twenty studies. Compared to the control group, GLP-1 agonists were associated with a statistically significant increase in the resolution of MASH without worsening fibrosis (RR 3.03, p < 0.0001) and at least one stage of liver fibrosis without the worsening of MASH compared to the control group (RR: 1.45, p < 0.00001). GLP-1 agonists were associated with a statistically significant weight reduction (SMD −1.11, p < 0.0001), glycosylated hemoglobin (SMD −0.81, p < 0.00001), levels of aspartate aminotransferase (SMD −0.48, p = 0.008), and alanine aminotransferase (SMD −0.54, p = 0.008). However, in patients without type 2 diabetes, GLP-1 agonists had no significant effect on weight loss (SMD −0.97, p = 0.12) or improvement in fibrosis (RR 1.54, p = 0.24). There was a statistically significant increase in the overall adverse events (RR 1.10, p < 0.00001), while there was no significant difference in serious adverse events (p = 0.35). Conclusions: GLP-1 agonists improved liver fibrosis, steatohepatitis, weight loss, HbA1c, and liver enzymes in patients with MASLD or MASH. Overall, GLP-1 agonists were associated with a significantly higher risk of adverse events compared to the control, while serious adverse events were comparable between both groups. There was no significant effect on weight loss or improvement in fibrosis in patients without type 2 diabetes. However, there was a limited number of studies in this population. Thus, further research is needed before recommendations can be made for this subgroup. Full article

Silicosis is an irreversible and progressive pulmonary fibrotic disease caused by the long-term inhalation of silica dust. The precise molecular mechanisms underlying the disease remain incompletely understood, and effective early diagnostic biomarkers are still lacking. In this study, we used a silicosis mouse model and transcriptomic sequencing to identify 2950 mRNAs, 461 lncRNAs, 81 miRNAs, and 44 circRNAs that were differentially expressed in lung tissue. Enrichment analysis revealed that these differentially expressed genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. The constructed competing endogenous RNA (ceRNA) network highlighted extensive regulatory interactions among lncRNAs/circRNAs, miRNAs, and mRNAs. Human validation showed that the expression levels of hsa-miR-215-5p and hsa-miR-146b-5p were significantly upregulated in the peripheral blood of early-stage pneumoconiosis patients, while hsa-miR-485-5p was downregulated. Logistic regression analysis revealed that hsa-miR-215-5p (OR = 1.966, 95% CI: 1.6938–2.2796, p < 0.001) and hsa-miR-146b-5p (OR = 1.9367, 95% CI: 1.697–2.201, p < 0.001) were independent risk factors for pneumoconiosis (p < 0.001). ROC curve analysis showed that both miRNAs demonstrated good diagnostic efficacy for pneumoconiosis, with AUC values of 0.9563 and 0.8876, respectively. These results provide novel insights into the complex ceRNA regulatory network involved in silicosis pathogenesis and suggest potential early, non-invasive diagnostic biomarkers. Full article

Background/Objectives: Matrix metalloproteinase-7 (MMP-7) has been implicated in colorectal cancer (CRC) progression; however, its relationship to disease stage and its suitability as a circulating biomarker remain unclear. This study aimed to determine whether MMP-7 expression and activity differ between benign and malignant colorectal conditions and whether serum MMP-7 levels reflect disease progression. Methods: mRNA MMP-7 expression data and MMP-7 levels have been collected from Gepia, Protein Atlas and UALCAN databases. For the study of patient samples, ELISA, Western blot, and zymography were used. The study included 30 patients with benign findings and 60 patients with colorectal cancer. The Gepia database reported significantly higher MMP-7 levels in patients with CRC. Results: The Protein Atlas and UALCAN highlight a notable difference between benign and malignant colon adenocarcinoma patients. The MMP-7 level in tissue samples from the malignant group, evaluated by Western blot, was approximately 4.5 times higher than in the benign group, and almost 3 times higher in serum samples. Using zymography, patients in the malignant group had MMP-7 activity more than 4x higher than that of patients in the benign group. The ELISA results supported this increase in MMP-7 levels. The average MMP-7 level in the malignant group was 1.2-fold that in benign tissue samples and approximately 3-fold that in serum samples. Notably, significant sex-related differences in serum MMP-7 concentrations were observed, indicating that gender may influence the interpretation of this biomarker. Conclusions: The discordance between stable MMP7 mRNA expression and declining serum MMP-7 protein levels in advanced CRC suggests complex post-transcriptional and post-translational regulation of MMP-7 during disease progression. Although this finding contrasts with much of the existing literature, it should be regarded as novel and hypothesis-generating. These results indicate that serum MMP-7 may reflect early tumor-associated processes rather than late-stage tumor burden, warranting further investigation in larger, stage-stratified and longitudinal cohorts. Full article

Hyperkalemia is a major complication of chronic kidney disease (CKD). However, owing to the absence of specific symptoms in its early stages, hyperkalemia frequently remains undiagnosed. This study aimed to develop a machine learning model for predicting the risk of early hyperkalemia in patients with CKD. By conducting a comparative analysis of six machine learning methods, CatBoost demonstrated superiority across various evaluation metrics. Further evaluation using confusion matrix and decision curve analysis (DCA) confirmed its high classification accuracy and substantial clinical utility. Meanwhile, through multiple interpretability analyses based on SHAP and Local Interpretable Model-agnostic Explanations (LIME) techniques, we precisely quantify the contributions and positive or negative effects of risk factors for hyperkalemia. Full article

Background/Objectives: Periodontal disease is a prevalent chronic inflammatory condition that often progresses to irreversible tissue destruction. This study aimed to evaluate the clinical efficacy of a combined minimally invasive periodontal therapeutic protocol scaling and root planing (SRP) with injectable platelet-rich fibrin (i-PRF) and microneedling (MN) compared to conventional SRP with i-PRF alone in patients with stage II–III periodontitis. Methods: A prospective split-mouth clinical study was conducted on 54 patients diagnosed according to the 2018 EFP/AAP classification. Each participant received SRP + i-PRF in the upper arch (control) and SRP + i-PRF + MN in the lower arch (test). Periodontal parameters clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) were measured at baseline, 1, 3, and 6 months. Data were analyzed using Friedman and Wilcoxon tests with Bonferroni correction. Results: Both treatment protocols produced significant longitudinal improvements in CAL, BOP, and PI (p < 0.001). The most pronounced BOP reduction occurred within the first month, while CAL improvement was progressive and stabilized after six months. The Combined protocol achieved slightly greater CAL gain at 6 months (mean difference ≈ 0.46 mm; p = 0.0013), indicating a modest yet statistically significant advantage in attachment recovery. Correlation analyses confirmed a coherent healing trajectory characterized by early inflammation resolution, plaque control, and later tissue stabilization. Conclusions: Both i-PRF-based regenerative approaches significantly improved periodontal parameters. The addition of MN enhanced CAL recovery and may favor early vascularization and collagen remodeling. Although the clinical difference was limited, the biological plausibility and sustained improvement suggest that MN could represent a valuable adjunct to non-surgical regenerative periodontal therapy. Longer-term studies are warranted to assess the durability of these effects. Full article

The study investigates the use of silver nanoparticles (AgNPs) in agriculture, focusing on their potential to enhance the immune response of potato (Solanum tuberosum L.) plants against phytopathogenic attacks. The research highlights how AgNPs, stabilized by biologically active polymers polyhexamethylene biguanide and tallow amphopolycarboxyglycinate, can induce oxidative stress. Triple foliar application of 0.1–9.0 g/ha silver nanoparticles at the budding and later stages demonstrated significant efficacy in suppressing diseases caused by Phytophthora infestans and Alternaria solani (over 60%). This effect was linked to the increased activity of peroxidase—over 30–50%—and the decreased catalase activity, indicative of a well-coordinated oxidative stress response to the invasion of P. infestans and A. solani. The results suggest that AgNPs in low concentrations can prime the plant’s innate immune system, enhancing its resistance without detrimental effects on growth parameters, thus contributing to the improved crop yield. These findings underscore the potential of AgNPs not as traditional biocides, but as intelligent elicitors of plant-induced resistance, positioning them as next-generation tools for sustainable crop protection and yield optimization, which can be applied at extremely low doses (less than 10 g/ha of active substance). Full article