Search Results (1,598)

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis. Full article

Membrane bioreactors (MBRs) have been utilized for maricultural wastewater treatment, where high-salinity stress results in dramatic membrane fouling in the actual process. A microalgal–bacterial symbiotic system (MBSS) offers advantages for photosynthetic oxygen production, dynamically regulating the structure of extracellular polymeric substances (EPSs) and improving the salinity tolerance of bacteria and algae. This study centered on the mechanisms of membrane fouling mitigation via the microalgal–bacterial interactions in the MBSS, including improving the pollutant removal, optimizing the system parameters, and controlling the gel layer formation. Moreover, the contribution of electrochemistry to decreasing the inhibitory effects of high-salinity stress was investigated in the MBSS. Furthermore, patterns of shifts in microbial communities and the impacts have been explored using metagenomic technology. Finally, this review aims to offer new insights for membrane fouling mitigation in actual maricultural wastewater treatment. Full article

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 $\mathsf{\mu }$s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins. Full article

The scalability and processability of high-performance membranes remain significant challenges in membrane technology. This work focuses on optimizing the pilot-scale production of patterned polysulfone (PSf) ultrafiltration membranes using the spray-modified non-solvent-induced phase separation (s-NIPS) method on a roll-to-roll pilot line. s-NIPS has already been studied extensively at lab-scale to prepare patterned membranes for various applications including membrane bioreactors (MBR), reverse osmosis (RO) and forward osmosis (FO). Although studied at the lab scale, membranes prepared at a larger scale can significantly differ in performance; therefore, phase inversion parameters, including polymer concentration, molecular weight, and additive type (i.e., polyethylene glycol (PEG) or polyvinylpyrolidine (PVP)) and concentration, were systematically varied when casting on a roll-to-roll, 12″ wide pilot line to identify optimal conditions for achieving defect-free, high-performance, patterned PSf membranes. The membranes were characterized for their pure water permeance, BSA rejection, casting solution viscosities, and resulting morphology. s-NIPS patterned membranes exhibit 150–350% increase in water flux as compared to their reference flat membrane, thanks to very high pattern heights up to 825 µm and formation of finger-like macrovoids. This work bridges the gap between lab-scale and pilot-scale membrane preparation, while proposing an upscaled membrane with great potential for use in water treatment. Full article

Barley leaf stripe, caused by Pyrenophora graminea (Pg), significantly reduces yields across various regions globally. Understanding the resistance mechanisms of barley to Pg is crucial for advancing disease resistance breeding efforts. In this study, two barley genotypes—highly susceptible Alexis and immune Ganpi2—were inoculated with the highly pathogenic Pg isolate QWC for 7, 14, and 18 days. The number of differentially expressed genes (DEGs) in Alexis was 1350, 1898, and 2055 at 7, 14, and 18 days, respectively, while Ganpi2 exhibited 1195, 1682, and 2225 DEGs at the same time points. Gene expression pattern analysis revealed that Alexis responded more slowly to Pg infection compared to Ganpi2. A comparative analysis identified 457 DEGs associated with Ganpi2’s immunity to Pg. Functional enrichment of these DEGs highlighted the involvement of genes related to plant-pathogen interactions and kinase activity in Pg immunity. Additionally, 20 resistance genes and 24 transcription factor genes were predicted from the 457 DEGs. Twelve candidate genes were selected for qRT-PCR verification, and the results showed that the transcriptomic data was reliable. We conducted cloning of the candidate Pg resistance gene HvLRR_8-1 by the barley cultivar Ganpi2, and the sequence analysis confirmed that the HvLRR_8-1 gene contains seven leucine-rich repeat (LRR) domains and an S_TKc domain. Subcellular localization in tobacco indicates that the HvLRR_8-1 is localized on the cell membrane. Through the functional analysis using virus-induced gene silencing, it was demonstrated that HvLRR_8-1 plays a critical role in regulating barley resistance to Pg. This study represents the first comparative transcriptome analysis of barley varieties with differing responses to Pg infection, providing that HvLRR_8-1 represents a promising candidate gene for improving durable resistance against Pg in cultivated barley. Full article

Objectives: Light intensity is a critical environmental factor regulating plant growth, development, and stress adaptation. However, the physiological and molecular mechanisms underlying light responses in Aconitum kusnezoffii, a valuable alpine medicinal plant, remain poorly understood. This study aimed to elucidate the adaptive strategies of A. kusnezoffii under different light intensities through integrated physiological and transcriptomic analyses. Methods: Two-year-old A. kusnezoffii plants were exposed to three controlled light regimes (790, 620, and 450 lx). Leaf anatomical traits were assessed via histological sectioning and microscopic imaging. Antioxidant enzyme activities (CAT, POD, and SOD), membrane lipid peroxidation (MDA content), osmoregulatory substances, and carbon metabolites were quantified using standard biochemical assays. Transcriptomic profiling was conducted using Illumina RNA-seq, with differentially expressed genes (DEGs) identified through DESeq2 and functionally annotated via GO and KEGG enrichment analyses. Results: Moderate light (620 lx) promoted optimal leaf structure by enhancing palisade tissue development and epidermal thickening, while reducing membrane lipid peroxidation. Antioxidant defense capacity was elevated through higher CAT, POD, and SOD activities, alongside increased accumulation of soluble proteins, sugars, and starch. Transcriptomic analysis revealed DEGs enriched in photosynthesis, monoterpenoid biosynthesis, hormone signaling, and glutathione metabolism pathways. Key positive regulators (PHY and HY5) were upregulated, whereas negative regulators (COP1 and PIFs) were suppressed, collectively facilitating chloroplast development and photomorphogenesis. Trend analysis indicated a “down–up” gene expression pattern, with early suppression of stress-responsive genes followed by activation of photosynthetic and metabolic processes. Conclusions: A. kusnezoffii employs a coordinated, multi-level adaptation strategy under moderate light (620 lx), integrating leaf structural optimization, enhanced antioxidant defense, and dynamic transcriptomic reprogramming to maintain energy balance, redox homeostasis, and photomorphogenic flexibility. These findings provide a theoretical foundation for optimizing artificial cultivation and light management of alpine medicinal plants. Full article

Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering of the pore pattern. In this context, we propose the fabrication of a transwell-like device pursued by combining the proton beam writing (PBW) technique with wet etching onto thin layers of polydimethylsiloxane (PDMS). The resulting transwell-like device incorporates a PDMS membrane with finely controllable pore patterning that was used to study the arrangement and migration behavior of HCMEC/D3 cells, a well-established human brain microvascular endothelial cell model widely used to study vascular maturation in the brain. A comparison between commercial polycarbonate membranes and the PBW-holed membranes highlights the impact of the ordering of the pattern and porosity on cellular growth, self-organization, and transmigration by combining fluorescent microscopy and advanced digital processing. Endothelial cells were found to exhibit distinctive clustering, alignment, and migratory behavior close to the pores of the designed PBW-holed membrane. This is indicative of activation patterns associated with cytoskeletal remodeling, a critical element in the angiogenic process. This study stands up as a novel approach toward the development of more biomimetic barrier models (such as organ-on-chips). Full article

With the rapid progression of global industrialization and urbanization, emerging contaminants (ECs) have become pervasive in environmental media, posing considerable risks to ecosystems and human health. While multidisciplinary evidence continues to accumulate regarding their environmental persistence and bioaccumulative hazards, critical knowledge gaps persist in understanding their spatiotemporal distribution, cross-media migration mechanisms, and cascading ecotoxicological consequences. This review systematically investigates the global distribution patterns of ECs in aquatic environments over the past five years and evaluates their potential ecological risks. Furthermore, it examines the performance of various treatment technologies, focusing on economic cost, efficiency, and environmental sustainability. Methodologically aligned with PRISMA 2020 guidelines, this study implements dual independent screening protocols, stringent inclusion–exclusion criteria (n = 327 studies). Key findings reveal the following: (1) Occurrences of ECs show geographical clustering in highly industrialized river basins, particularly in Asia (37.05%), Europe (24.31%), and North America (14.01%), where agricultural pharmaceuticals and fluorinated compounds contribute disproportionately to environmental loading. (2) Complex transboundary pollutant transport through atmospheric deposition and oceanic currents, coupled with compound-specific partitioning behaviors across water–sediment–air interfaces. (3) Emerging hybrid treatment systems (e.g., catalytic membrane bioreactors, plasma-assisted advanced oxidation) achieve > 90% removal for recalcitrant ECs, though requiring 15–40% cost reductions for scalable implementation. This work provides actionable insights for developing adaptive regulatory frameworks and advancing green chemistry principles in environmental engineering practice. Full article

Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell–cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell–cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention. Full article

Introduction: Low-grade oncocytic tumor (LOT) is a recently described renal neoplasm characterized by indolent clinical behavior, a small nested architecture, and distinctive immunophenotypic features. Its distinction from other eosinophilic renal tumors, such as oncocytoma, eosinophilic chromophobe renal cell carcinoma (E-chRCC), and eosinophilic vacuolated tumor (EVT), can be challenging due to overlapping features. The L1 cell adhesion molecule (L1CAM) is being increasingly recognized as a potential diagnostic marker for LOT. Aims: To evaluate the diagnostic performance of L1CAM in distinguishing LOT from morphologically and immunophenotypically similar eosinophilic renal neoplasms. Methods: A total of 54 eosinophilic renal tumors (10 LOTs, 22 oncocytomas, 18 E-chRCCs, and 4 EVTs) were retrospectively collected from five academic institutions and reclassified according to the 2022 WHO criteria. All cases underwent histopathologic review and immunohistochemical analysis for CK7, CD117, GATA3, cathepsin K, and L1CAM. Results: L1CAM showed strong membranous expression in all LOTs (100%) and was negative in oncocytoma, E-chRCC, and EVT, yielding 100% sensitivity and specificity. Traditional markers exhibited overlapping patterns among tumor types. Conclusions: Our findings confirm L1CAM as a highly sensitive and specific marker for LOT, effectively distinguishing it from other eosinophilic renal neoplasms. Incorporating L1CAM into diagnostic panels may enhance accuracy, particularly in challenging cases. Full article

The rapid evolution of pathogens and the limited genetic diversity of hosts are two major factors contributing to the plant pathogenic phenomenon known as the loss of disease resistance in maize (Zea mays L.). It has emerged as a significant biological stressor threatening the global food supplies and security. Based on previous cross-species homologous gene screening assays conducted in the laboratory, this study identified the maize disease-resistance candidate gene ZmNLR-7 to investigate the maize immune regulation mechanism against Bipolaris maydis. Subcellular localization assays confirmed that the ZmNLR-7 protein is localized in the plasma membrane and nucleus, and phylogenetic analysis revealed that it contains a conserved NB-ARC domain. Analysis of tissue expression patterns revealed that ZmNLR-7 was expressed in all maize tissues, with the highest expression level (5.11 times) exhibited in the leaves, and that its transcription level peaked at 11.92 times 48 h post Bipolaris maydis infection. Upon inoculating the ZmNLR-7 EMS mutants with Bipolaris maydis, the disease index was increased to 33.89 and 43.33, respectively, and the lesion expansion rate was higher than that in the wild type, indicating enhanced susceptibility to southern corn leaf blight. Physiological index measurements revealed a disturbance of ROS metabolism in ZmNLR-7 EMS mutants, with SOD activity decreased by approximately 30% and 55%, and POD activity decreased by 18% and 22%. Moreover, H₂O₂ content decreased, while lipid peroxide MDA accumulation increased. Transcriptomic analysis revealed a significant inhibition of the expression of the key genes NPR1 and ACS6 in the SA/ET signaling pathway and a decrease in the expression of disease-related genes ERF1 and PR1. This study established a new paradigm for the study of NLR protein-mediated plant immune mechanisms and provided target genes for molecular breeding of disease resistance in maize. Overall, these findings provide the first evidence that ZmNLR-7 confers resistance to southern corn leaf blight in maize by synergistically regulating ROS homeostasis, SA/ET signal transduction, and downstream defense gene expression networks. Full article

Potassium is the most abundant macronutrient in plants, participating in essential physiological processes such as turgor maintenance. A reduction in cell turgor is a hallmark of the ripening process associated with fruit softening. The dynamic of K⁺ fluxes in fleshy fruits is largely unknown; however, the reallocation of K⁺ into the apoplast has been proposed as a contributing factor to the decrease in fruit turgor, contributing to fruit softening. High-affinity K⁺ transporters belonging to the KUP/HT/HAK transporter family have been implicated in this process in some fruits. In this study, a comprehensive genome-wide analysis of the KUP/KT/HAK family of high-affinity K⁺ transporters in strawberry (Fragaria × ananassa Duch.) was conducted, identifying 60 putative transporter genes. The chromosomal distribution of the FaKUP gene family and phylogenetic relationship and structure of predicted proteins were thoroughly examined. Transcriptomic profiling revealed the expression of 19 FaKUP genes within the fruit receptacle, with a predominant downregulation observed during ripening, particularly in FaKUP14, 24 and 47. This pattern suggests their functional relevance in early fruit development and turgor maintenance. Mineral composition analyses confirmed that K⁺ is the most abundant macronutrient in strawberry fruits, exhibiting a slight decrease as ripening progressed. Membrane potential (E_m) and diffusion potentials (E_D) at increasing external K⁺ concentrations were measured by electrophysiology in parenchymal cells of green and white fruits. The results obtained suggest a significant diminution in cytosolic K⁺ levels in white compared to green fruits. Furthermore, the slope of change in E_D at increasing external K⁺ concentration indicated a lower K⁺ permeability of the plasma membrane in white fruits, aligning with transcriptomic data. This study provides critical insights into the regulatory mechanisms of K⁺ transport during strawberry ripening and identifies potential targets for genetic modifications aimed at enhancing fruit firmness and shelf life. Full article

As an auxin-responsive gene, Gretchen Hagen 3 (GH3) maintains hormonal homeostasis by conjugating excess auxin with amino acids in plant stress-related signaling pathways. GH3 genes have been characterized in many plant species, but the characteristics of pepper (Capsicum annuum L.) GH3 (CaGH3) gene family members in response to multiple stimulants are largely unknown. In this study, we systematically identified the CaGH3 gene family at the genome level and identified eight members on four chromosomes in pepper. CaGH3s were divided into two groups (I and III) and shared conserved motifs, domains, and gene structures. Moreover, CaGH3s had close evolutionary relationships with tomato (Solanum lycopersicum L.), and the promoters of most CaGH3 genes contained hormone and abiotic stress response elements. A protein interaction prediction analysis demonstrated that the CaGH3-3/3-6/3-7/3-8 proteins were possibly core members of the CaGH3 family interaction. In addition, qRT-PCR results showed that CaGH3 genes were differentially expressed in pepper tissues and could be induced by phytohormones (IAA, ABA, and MeJA) and abiotic stresses (salt, low temperature, and drought) with different patterns. In addition, CaGH3-5 and CaGH3-7 were cloned, and the sequences showed a high degree of conservation. Moreover, the results of subcellular localization indicated that they were located in the membrane and chloroplast. Notably, after overexpressing CaGH3-7 in tomato, RNA-seq was performed on wild-type and transgenic lines, and the differentially expressed genes were mainly enriched in response to external stimuli. This study not only lays the foundation for a comprehensive understanding of the function of the CaGH3 gene family during plant growth and stress responses but also provides potential genetic resources for pepper resistance breeding. Full article

The transition toward a circular water economy addresses accelerating water scarcity and pollution. A PRISMA-2020 systematic review of 50 peer-reviewed articles (January 2018–April 2024) mapped current technologies and management strategies, seeking patterns, barriers, and critical bottlenecks. Bibliometric analysis revealed the following three dominant patterns: (i) rapid diffusion of membrane bioreactors, constructed wetlands, and advanced oxidation processes; (ii) research geographically concentrated in Asia and the European Union; (iii) industry’s marked preference for by-product valorization. Key barriers—high energy costs, fragmented regulatory frameworks, and low social acceptance—converge as critical constraints during scale-up. The following three practical action lines emerge: (1) adopt progressive tariffs and targeted tax credits that internalize environmental externalities; (2) harmonize water-reuse regulations with comparable circularity metrics; (3) create multi-actor platforms that co-design projects, boosting local legitimacy. These findings provide policymakers and water-sector practitioners with a clear roadmap for accelerating Sustainable Development Goals 6, 9, and 12 through circular, inclusive, low-carbon water systems. Full article

Background/Objectives: We examined the in vivo effects of successive treatments with the histone deacetylase (HDAC) inhibitor romidepsin in patients with cutaneous T-cell lymphoma (CTCL), using changes in gene expression in peripheral blood mononuclear cells (PBMCs). Methods: Exploiting data from a highly responsive CTCL patient through 12 months of treatment, we identified a malignant cell predictor (MCP), a gene signature associated with the diminishing numbers of circulating malignant cells. Results: The MCP was successfully validated in the patient’s relapse sample 9 months after treatment was terminated and via an independent set of CTCL patient samples. Conclusions: The MCP set of genes contained novel CTCL markers, including membrane-associated proteins not normally expressed in lymphocytes. A subclass of those markers was also detectable in residual malignant cells undetected by flow cytometry in remission samples from a patient who relapsed 10 months later. We identified a subset of transcriptional regulators, miRNAs and methylation patterns associated with the effect of progressive treatments revealing potential mechanisms of transcriptional dysregulation and functional effects in the malignant cells. We demonstrate a role for transcriptional activator HLF, over-expressed in malignant cells, and downregulated transcriptional-suppressor and immune-modulator NFIL3, as regulators of CTCL-specific genes. Full article