Search Results (961)

Drought stress is a major abiotic factor limiting global crop productivity by disrupting cellular homeostasis, impairing photosynthesis, and restricting metabolic activity. Plant-associated microorganisms, including rhizobacteria, endophytes, and arbuscular mycorrhizal fungi, play key roles in enhancing drought resilience through molecular, biochemical, and physiological mechanisms. These beneficial microbes modulate phytohormone biosynthesis, enhance osmolyte accumulation, increase organic acid exudation, and activate ROS-scavenging antioxidant pathways. Microbe-mediated regulation of aquaporins, heat shock proteins, and root system architecture further improves water-use efficiency, hydraulic conductance, and stress acclimation. Advances in microbial genomics and systems biology have revealed the molecular drivers of plant–microbe synergism, enabling the development of tailored microbial consortia and next-generation bioinoculants. Complementarily, genetic and genome-guided modulation of drought-responsive regulatory hubs including transcription factors (DREB, NAC, MYB, bZIP), signal transducers (MAPKs, CDPKs), and protective proteins enhances adaptive plasticity under water deficit conditions. This review integrates current molecular insights into drought-induced perturbations in plants and highlights the convergence of microbial interventions and genome-guided strategies in reinforcing drought tolerance. Emphasizing mechanistic frameworks, scalable microbial technologies, and molecular breeding approaches, this work underscores their potential to improve crop resilience in increasingly water-limited environments. Full article

In this study, blood cell counts and serum C3, C4, and CH50 values at baseline and after more than 6-month drug use were measured to elucidate changes in blood cells and complements during relapse prevention therapies for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD). A total of 70 patients with AQP4+ NMOSD (87% female, median age 56 years) were enrolled. They were divided into the following treatment groups: glucocorticoids and/or immunosuppressants (GC/IS, n = 22), inebilizumab/rituximab (anti-CD19/20, n = 13), satralizumab (anti-IL-6R, n = 22), and eculizumab/ravulizumab (anti-C5, n = 13). At baseline, the blood counts and complement levels did not differ among the groups. At follow-up, the neutrophil and platelet counts in the anti-IL-6R group decreased from those at baseline (p < 0.0001 and p < 0.001, respectively). Compared with the GC/IS, anti-CD19/20, and anti-C5 groups, the anti-IL-6R group had lower levels of C3 (p < 0.0001, p < 0.01, and p < 0.05, respectively) and C4 (p < 0.0001, p < 0.01, p < 0.001, respectively). Furthermore, the anti-C5 group had significantly lower CH50 levels than the GC/IS, anti-CD19/20, and anti-IL-6R groups (p < 0.0001, p < 0.0001, p < 0.05, respectively). In addition, the anti-IL-6R group had lower CH50 levels than the GC/IS and anti-CD19/20 groups (p < 0.001 and p < 0.05, respectively). The present study demonstrated that anti-IL-6R therapy broadly and mildly suppressed the complement system and decreased the neutrophil and platelet counts. It also showed that anti-C5 therapy strongly suppressed total complement activity but did not affect the C3 and C4 levels or blood counts. These findings may have implications for the mode of action of the drugs and the risk of adverse drug reactions, including infections. Full article

Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem cell persistence, hypoxia-induced metabolic and epigenetic plasticity, adaptive oncogenic signaling, and profound immunosuppression within the tumor microenvironment. Emerging evidence shows that dysfunction of the glymphatic system, mislocalization of aquaporin-4, and increased intracranial pressure compromise cerebrospinal fluid–interstitial fluid exchange and impair antigen drainage to meningeal lymphatics, thereby weakening immunosurveillance. GBM simultaneously remodels the blood–brain barrier into a heterogeneous and permeable blood–tumor barrier that restricts uniform drug penetration yet enables tumor progression. These alterations intersect with profound immunosuppression mediated by pericytes, tumor-associated macrophages, and hypoxic niches. Advances in imaging, including DCE-MRI, DTI-ALPS, CSF-tracing PET, and elastography, now allow in vivo characterization of glymphatic function and interstitial flow. Therapeutic strategies targeting the fluid-immune interface are rapidly expanding, including convection-enhanced delivery, intrathecal and intranasal approaches, focused ultrasound, nanoparticle systems, and lymphatic-modulating immunotherapies such as VEGF-C and STING agonists. Integrating barrier modulation with immunotherapy and nanomedicine holds promise for overcoming treatment resistance. Our review synthesizes the mechanistic, microenvironmental, and translational advances that position the glymphatic–immune axis as a new frontier in glioblastoma research. Full article

This study aimed to modify metabolite synthesis in Saccharomyces cerevisiae (S. cerevisiae) under simulated wine fermentation conditions by regulating the glycerol metabolic pathway. We systematically analyzed the effects of overexpressing the aquaporin gene AQY1 and co-expressing AQY1 with the glycerol-3-phosphate dehydrogenase gene GPD1 on the metabolism of ethanol, higher alcohols, and esters. Our results indicate that AQY1 overexpression increased glycerol yield by 6.58%, reduced higher alcohol content by 14.60%, and elevated ester content by 7.15%. The downregulation of related amino acid metabolism genes correlated with the observed decrease in higher alcohol levels. Notably, co-expression of AQY1 and GPD1 further enhanced glycerol yield by 10.66% while decreasing ethanol content by 6.32%. By analyzing changes in gene expression alongside metabolic mechanisms, we hypothesize that the redistribution of carbon flux and NADH toward the glycerol pathway not only decreases the precursors for ethanol synthesis but also directly inhibits the activity of aldehyde dehydrogenase (ALD2/3/4/6), thereby constraining ethanol production. In comparison to AQY1 overexpression alone, the co-expression strategy did not significantly alter glycerol accumulation; however, it reduced both ethanol and ester content by 8.38% and 8.40%, respectively, while markedly increasing higher alcohol content by 22.30%. This increase may result from enhanced glycolytic flux and pyruvate accumulation, which promote metabolic flow toward amino acid synthesis pathways. In summary, this study effectively remodeled the central carbon metabolism network by targeting glycerol metabolism, achieving diverse metabolic product synthesis and providing important references for the selection and breeding of industrial S. cerevisiae strains. Full article

Tremella mesenterica, commonly known as the yellow brain or golden jelly fungus, has been traditionally used for its medicinal properties. In this study, we elucidated the structural characteristics of T. mesenterica polysaccharide (TMP) and evaluated its potential moisturizing mechanism in vitro, comparing it to Tremella fuciformis polysaccharide (TFP) and hyaluronic acid (HA). TMP was isolated through enzyme assisted extraction and it has a molecular weight (MW) of approximately 143 kDa. We investigated the composition of mannose, xylose, glucuronic acid, and glucose as a ratio of 59.8 ± 0.3, 24.0 ± 1.2, 11.0 ± 0.8, 5.2 ± 0.0, respectively. Through methylation and GC-MS analysis, we discovered TMP was composed of a main chain of β-(1→3)-linked mannopyranoside, substituted with various side chains such as xylopyranoside, glucuronopyranoside, glucopyranoside at the C-2 or C-4 positions of the backbone. TMP upregulated the expression of key moisturizing-related factors compared to TFP and HA, such as aquaporin-3 (AQP3) with 55% and 57% at 25 and 50 μg/mL and hyaluronic acid synthase-2 (HAS2) with 22% at 25 μg/mL, as confirmed through qRT-PCR analysis. Additionally, TMP significantly enhanced the expression of filaggrin (FLG), a critical protein involved in skin barrier function, with 22% at 25 μg/mL. Immunocytochemistry (ICC) analysis further revealed that TMP achieved the highest improvement in hyaluronic acid synthase-3 (HAS3) protein levels by 475% at 50 μg/mL. While further in vivo studies are required to substantiate its functional moisturizing efficacy, these findings suggest that TMP serves as a promising moisturizing agent. The structural and functional properties of TMP provide a potential foundation for its application in diverse industries, including cosmetics, food, biopolymers, and pharmaceuticals. Full article

Water deprivation triggers coordinated physiological responses to preserve body fluid balance, yet the molecular mechanisms that regulate aquaporin-mediated water transport under dehydration remain incompletely understood. Aquaporin-4 (AQP4), the main water channel in the brain and a basolateral water pathway in the kidney collecting duct, exists in multiple isoforms, including the translational readthrough variant AQP4ex, whose regulatory role is only beginning to be defined. Here, we investigated the effects of acute water deprivation (6–12 h) on AQP4 isoform expression and phosphorylation in a mouse kidney and brain. While total AQP4 and AQP4ex protein levels remained largely unchanged in both tissues, dehydration induced a marked and divergent regulation of the phosphorylated form of AQP4ex. Levels increased in the kidney medulla, consistent with enhanced antidiuretic water transport, but decreased in the cerebral cortex, suggesting a protective reduction in perivascular water permeability. No changes were detected in the cerebellum. These findings identify phosphorylation of AQP4ex as a rapid, tissue-specific regulatory mechanism that adjusts water flux according to the physiological needs of each organ, revealing an additional layer of control in systemic water homeostasis and highlighting AQP4ex as a potential target in dehydration-related and osmotic disorders. Future studies could explore the signaling pathways regulating AQP4ex phosphorylation and investigate its potential involvement in pathological conditions, such as diabetes insipidus or cerebral edema. Full article

Background: Sudden, non-traumatic hearing loss has been associated with vascular or inflammatory disorders. Hearing loss in Neuromyelitis optica spectrum disorder (NMOSD) is a very rare presentation. Methods: In this paper, we describe the case of a 58-year-old female patient with aquaporin-4-positive NMOSD exhibiting bilateral tinnitus and right-sided deafness in the context of a relapse. The auditory brainstem responses pointed to a lesion of the right peripheral auditory pathway (cochlea and/or auditory nerve). The patient’s hearing failed to improve after high-dose intravenous steroids; however, it showed slight improvement after plasmapheresis. We also conducted a systematic literature review in databases MEDLINE and Scopus in English, searching for all reported cases of hearing loss in NMOSD. Results: We included 10 studies reporting 15 cases of NMOSD with hearing loss. The vast majority of patients were female (11 out of 15, 73.3%), with an age range of 26 to 70 years. Hearing loss, ranging from mild to severe, seems more frequent in AQP4-positive cases, and it can even be the presenting symptom. It can present isolated or in combination with tinnitus, ataxia, and/or intractable vomiting. The auditory pathway impairment in NMOSD seems to be localized either centrally, i.e., cochlear nuclei or higher brainstem levels, or peripherally, i.e., in the cochlea or cochlear nerve itself. Intravenous methylprednisolone in high doses, followed by oral tapering, was the most common treatment option, resulting in a gradual improvement. Conclusions: This paper describes a rare case of peripheral auditory pathway affection in NMOSD, which is an inflammatory astrocytopathy mainly affecting the central nervous system. Early recognition of hearing loss in the context of an NMOSD relapse and subsequent treatment have a crucial impact on the hearing outcome of NMOSD patients. This expands our knowledge of NMOSD as an autoimmune aquaporin-4 channelopathy. Full article

Background: Functional constipation (FC) represents a highly prevalent gastrointestinal disorder, affecting approximately 8.5% of the population in China. It is frequently associated with anxiety and depression, significantly impairing patients’ quality of life. Conventional microecological therapeutic approaches predominantly rely on empirical probiotic–prebiotic combinations. However, these pairings are seldom selected based on strain-specific metabolic characteristics, ultimately leading to suboptimal therapeutic synergy. Methods: The generation time (GT) of four constipation-relief strains was measured across eight oligosaccharides to identify optimal substrates for synbiotic formulation. The GT-optimized synbiotic was verified in a loperamide-induced mouse model vs. single probiotics/prebiotics. The related mechanisms of were assessed through 16S rDNA sequencing, targeted metabolomics, and qPCR. Results: The GT-optimized synbiotic significantly outperformed all single components. Specifically, the synbiotic significantly decreased the time to first black stool and increased fecal water content. Mechanistically, it restored colonic neurotransmitter balance, suppressed aquaporin expression, enriched butyrate-producing bacteria, and repaired barrier integrity. Overall, these effects work together, increasing the moisture content of the feces and accelerating intestinal peristalsis, ultimately alleviating constipation. Conclusions: We propose a GT-guided precision-pairing strategy that identifies optimal prebiotics based on strain-specific generation times, demonstrating synergistic enhancement of short-chain fatty acid (SCFA) production, enteric neurotransmitter signaling, and aquaporin-mediated water transport. This GT guided synbiotic approach shows promise in preclinical models and warrants validation in human trials. Full article

Transmembrane facilitation of substrates by channels and secondary active transporters results in a defined steady-state concentration ratio across the membrane. Evidence is accumulating that asymmetry in the structural build of the transporters, or interaction with asymmetric partner proteins, can shift the position of the transmembrane equilibrium by biased transport directionality. For instance, the bacterial lactose transporter, LacY, and two amino acid transporters, i.e., the human excitatory amino acid carrier, EAAC1, and the yeast lysine permease, Lyp1, were reported to exhibit distinct transport kinetics in the inward and outward direction by protein-intrinsic properties. A recent example is transport modulation of human monocarboxylate transporters, MCT, by shedding of the extracellular domain of an ancillary protein, basigin. Loss of the domain selectively increases export of lactate from lung cancer cells by a factor of four, contributing to the Warburg effect and malignancy. Further, intrinsic properties of monocarboxylate transporters involving asymmetric affinities of substrate binding, or biased open probabilities were shown to generate preference for one transport direction. Here, we discuss molecular mechanisms and physiological contexts of asymmetric secondary active transmembrane transport. Focus is laid on experimentally established cases, and examples are given in which putative bias in transport directionality may have been overlooked. Full article

Background and Objective: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a significant component of demyelinating diseases in pediatric populations. Recently, diagnostic criteria for MOGAD were established. This study aims to evaluate and compare the diagnostic efficacy of the fixed-cell-based assay (Fixed-CBA) and the live cell-based assay (Live-CBA) in patients who meet the 2023 clinical diagnostic criteria for MOGAD. Methods: This retrospective study included patients suspected of having MOGAD who were enrolled between June 2023 and June 2024. Patients were selected based on the “core clinical demyelinating events” outlined in the 2023 proposed criteria of the International MOGAD Panel. Patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 antibody-positive (AQP4-Abs-positive), and non-central nervous system (non-CNS) inflammatory diseases were chosen as controls. Serum samples were simultaneously tested for MOG-Abs using Fixed-CBA and Live-CBA. Results: A total of 86 patients were enrolled in the study: 52 in the suspected MOGAD group and 34 in the control group. Out of these patients studied, 16 presented with optic neuritis (ON), 5 with myelitis, 8 with acute disseminated encephalomyelitis (ADEM), and 7 with cortical encephalitis. Sixteen patients could not be classified by clinical phenotype. The highest MOG-Ab positivity rate was among patients with cortical encephalitis [85.7% (Live-CBA)/71.4% (Fixed-CBA)]. Both assays identified 22 positive samples, with Fixed-CBA and Live-CBA sensitivities at 44.2% and 55.8%, respectively, and a specificity of 97%. Of the patients suspected of having MOGAD, 19 cases were confirmed using the Fixed-CBA, while 28 cases were confirmed using the Live-CBA. This resulted in an upgrade in diagnostic classification for nine cases. This led to a diagnostic reclassification in nine cases. Conclusions: Both the Fixed-CBA and Live-CBA were associated with higher sensitivity for patients selected based on the 2023 MOGAD clinical diagnostic criteria. The Live-CBA exhibited an 11.6% increase in sensitivity, contributing to a 17.3% (9/52) enhancement in clinical diagnostic accuracy. Full article

Obesity is a systemic metabolic disorder that is known to impair various organ systems; however, its precise impact on salivary gland homeostasis remains unclear. Recent studies have implicated ferroptosis—an iron-dependent form of regulated cell death characterized by lipid peroxidation and oxidative stress—in glandular dysfunction. In this study, we used leptin-deficient (ob/ob) mice to elucidate the role of ferroptosis in obesity-associated salivary gland pathology. The protective effects of ferroptosis inhibition were evaluated by administering ferrostatin-1 (a lipid reactive oxygen species [ROS] scavenger) and deferoxamine (an iron chelator) for an 8-week period. Obese mice exhibited significantly increased body weight, food intake, and hyperglycemia. These systemic changes are accompanied by profound histological alterations in the salivary glands, including lipid droplet accumulation, acinar atrophy, and mitochondrial ultrastructural damage. These alterations correlate with the hallmarks of ferroptotic injury, including increased ROS levels (p < 0.001), elevated malondialdehyde levels (p < 0.01), suppressed glutathione peroxidase 4 activity (p < 0.01), and iron overload (p < 0.001). Salivary gland fibrosis, inflammation, and secretory dysfunction were evident, characterized by the upregulation of TGF-β (p < 0.01) and Collagen I (p < 0.05), reduced expression of aquaporin-5 and amylase, and dysregulated levels of autophagy-related markers (LC3B and p62). Treatment with either ferrostatin-1 or deferoxamine significantly mitigated these pathologies; however, the degree of efficacy varied depending on the specific parameters that were examined. Thus, our findings implicate ferroptosis as a critical contributor to salivary gland dysfunction in obesity and suggest that pharmacological inhibition of this pathway represents a viable therapeutic strategy for preserving glandular integrity under metabolic stress. Full article

Background: Large-scale production of poultry viral vaccines increasingly requires robust suspension cell platforms. However, most avian cell lines, including DF-1, are strictly anchorage-dependent, limiting scalability. Aquaporin-1 (AQP1) regulates cell–cell adhesion and membrane dynamics, making it a potential target for engineering suspension growth. This study aimed to generate a stable DF-1 suspension cell line via AQP1 disruption and evaluate its potential for enhanced infectious bursal disease virus (IBDV) production. Methodology: DF-1 cells were engineered using a CRISPR/Cas9 ribonucleoprotein system to create a truncated AQP1 gene. DF-1/AQP1⁻ cells were assessed for morphology, tumorigenicity in nude mice, and genetic stability across 20 passages. Suspension growth, cell density, and viability were measured. Cells were infected with IBDV strain BJQ902, and viral titers were compared with wild-type DF-1 and monolayer DF-1/AQP1⁻ cells. Results: DF-1/AQP1⁻ cells maintained normal morphology, were non-tumorigenic, and retained stable AQP1 mutations. They grew as true suspension cultures without adaptation, reaching 4.0 × 10⁶ cells/mL with >95% viability. Suspension DF-1/AQP1⁻ cells cells produced significantly higher viral titers (9.0 log TCID₅₀/mL; 8.63 log EID₅₀/mL) than both monolayer DF-1/AQP1⁻ and wild-type DF-1 cells. Virus production time was shortened in suspension cultures. Conclusions: Targeted AQP1 disruption converts DF-1 cells into a stable, non-tumorigenic suspension cell line with markedly enhanced IBDV production, providing a scalable platform for next-generation avian vaccine manufacturing. Full article

Entomopathogenic nematodes (EPNs), including Steinernema and Heterorhabditis, are obligate insect parasites widely used in biological pest control. However, their efficacy is often limited by susceptibility to environmental stresses like desiccation. Aquaporins (AQPs), channel proteins facilitating water and solute movement across membranes, are hypothesized to play a key role in the osmotic stress response of EPNs. This study identified and cloned three AQP genes (L596_g7661, L596_g18121, and XLOC_007750) from four strains of Steinernema carpocapsae. Bioinformatic analysis confirmed that these AQPs belong to the aquaglyceroporin subfamily and share high sequence homology across strains. Functional characterization in Xenopus oocytes demonstrated that AQP L596_g7661 facilitates glycerol transport. Expression patterns under osmotic dehydration revealed significant upregulation of L596_g7661 and XLOC_007750 in all strains, while L596_g18121 expression remained unchanged. These findings indicate that specific AQPs are involved in the molecular response of S. carpocapsae to osmotic stress, providing crucial insights for breeding resilient EPN strains and enhancing their field application. Full article

Efficient water recycling in the hydrometallurgical industry requires the dewatering of hypersaline Na₂SO₄ or similar brines via non-evaporative methods. Unfortunately, many non-evaporative methods require the use of specific solutes and are not compatible with complex hydrometallurgical effluents. Forward Osmosis (FO) uses a draw solution to link known non-evaporative water recycling methods with feed solutions that are otherwise incompatible. There is minimal experimental data on the dewatering performance of today’s available commercial FO membranes, especially with hypersaline concentrations (>70,000 mg/L total dissolved solids). This study tests the commercially available Aquaporin HFFO2 hollow fibre FO membrane module with hypersaline Na₂SO₄ or NaCl feed solutions versus a MgCl₂ draw solution. It identifies a key requirement to maintain water flux above a certain threshold to prevent a decrease in Na Rejection or an increase in Mg reverse flux. It also defines a minimum osmotic differential that can be used to parameterize water flux, similar to the temperature of approach in heat exchangers, but to determine the extent of water removal in FO. We demonstrate that even under mildly acidic conditions, existing FO membranes can concentrate Na₂SO₄ to saturation, paving the way for their use in the hydrometallurgical industry. Full article