Search Results (5,704)

SIDT2 is a lysosomal membrane protein that—together with LAMP2—has been implicated in a recently described process known as RNAutophagy. Mutations in LAMP2 have long been known to cause Danon disease, a rare lysosomal storage disorder that affects multiple organ systems including brain and skeletal muscle. Recently, we have shown that loss of SIDT2 function in both humans and mice causes brain dysfunction, and it has been previously observed that loss of SIDT2 in mice also leads to muscle damage and reduced muscle strength. Here, we show that changes in the skeletal muscle of Sidt2^-/- mice are reminiscent of those seen in Danon disease as evidenced by accumulation of autophagic vacuoles with sarcolemmal features, selective atrophy of fast twitch fibers, and a shared alteration in gene expression. Moreover, we find that loss of SIDT2 not only leads to impaired autophagy in skeletal muscle as previously described but also stimulates a type I interferon response and increased apoptosis. Full article

Hydrogen production from biomass and organic waste offers a route to combine renewable energy generation, residue valorization, and circular carbon management. However, the resulting H₂-containing streams are chemically complex and may contain CO, CO₂, CH₄, steam, light hydrocarbons, tars, sulfur species, and particulates, making hydrogen recovery and purification major process bottlenecks. This review critically assesses the role of H₂-selective membranes in biomass- and waste-derived hydrogen production, with particular emphasis on supported Pd-based multilayer architectures and their integration into separation units and membrane reactors. The conversion routes examined include gasification, pyrolysis-derived reforming, reforming of glycerol, bioethanol and biogas, aqueous-phase reforming, and water–gas shift conditioning of the resulting product streams. A route-specific comparison based on hydrogen partial pressure and permeation driving force indicates that direct Pd-membrane integration is most technically credible for conditioned reformate and water–gas shift streams. By contrast, gasification- and pyrolysis-derived streams generally require more extensive upstream cleaning and conditioning, whereas aqueous-phase reforming is better suited to downstream purification or hybrid separation schemes because of its comparatively low operating temperature and pressure. Across the reviewed studies, membrane performance is governed by the complete support/interlayer/selective-layer/seal/reactor assembly rather than solely by the intrinsic permeance of the Pd-based film. Architecture–process co-design, validation under realistic multicomponent mixtures, contaminant-tolerance assessment, reproducible and scalable fabrication, and integrated techno-economic and life-cycle evaluation are identified as the principal priorities for industrial deployment. Full article

Metastasis is responsible for the majority of cancer-related deaths. During metastasis, cancer cells undergo a series of biological events that allow them to invade surrounding tissues, disseminate through the bloodstream or lymphatic system, and colonize secondary sites. Cancer cells’ phenotypic plasticity facilitates this process by enabling them to adapt to diverse microenvironments. Unlike localized tumors, metastasis is more challenging to treat because it represents a systemic disease that can no longer be managed solely through surgery or radiotherapy. Additionally, specific mechanisms underlying metastasis may contribute to resistance to conventional chemotherapy. Therefore, identifying new therapeutic strategies to regulate the key processes underlying metastasis is essential. In recent years, antimicrobial peptides (AMPs) have garnered increasing interest because of their anticancer properties. AMPs are small molecules that are part of the innate immune system of virtually all living organisms and are characterized by their ability to selectively interact with the cell membranes of pathogens and cancer cells. Diverse AMPs have been shown to induce cancer cell death, inhibit proliferation, and interfere with processes associated with metastasis. This review discusses the potential of AMPs as metastasis modulators, highlighting their proposed mechanisms of action, their advantages over conventional therapeutic approaches, and the conceptual framework governing their dual pro- and anti-metastatic activities. Full article

The emergence of infections caused by Scedosporium/Lomentospora and Mucorales species poses a major clinical challenge due to their intrinsic resistance to multiple antifungal drugs and the limited number of therapeutic options available. In this study, we evaluated the antifungal activity of synthetic organic compounds and characterized the mechanisms of antifungal activity. Eight compounds were initially screened against Scedosporium aurantiacum and Rhizopus oryzae. Compounds 2, 3, and 4 inhibited more than 60% of fungal growth and were selected for further characterization. Antifungal susceptibility assays revealed that compound 2 exhibited the strongest activity, with minimum inhibitory concentrations ranging from 12.5 to 25 μg/mL, whereas compounds 3 and 4 showed MIC values between 50 and 100 μg/mL. All compounds displayed fungistatic activity and significantly impaired fungal germination and biofilm development. Drug interaction analyses demonstrated additive or synergistic effects when the compounds were combined with clinically used antifungals. Investigations revealed that the compounds induced alterations in the fungal cell surface, including reductions in neutral lipids and chitin, increased membrane permeability, disruption of sterol-enriched membrane microdomains, and ultrastructural abnormalities. Exogenous ergosterol partially reversed the activity of compounds 2 and 3, suggesting interactions with membrane sterols. In silico toxicity prediction indicated generally favorable safety profiles. In summary, these findings identify synthetic organic compounds as promising scaffolds for antifungal drug discovery and highlight their potential to target fungal membrane and cell wall integrity in resistant filamentous pathogens. Full article

Background/Objectives: Phenethyl isothiocyanate (PEITC), a bioactive compound found in cruciferous vegetables, exhibits potent anti-cancer activity, but its molecular mechanisms in acute lymphoblastic leukemia (ALL) remain poorly defined. This study aimed to investigate the anti-leukemic effects of PEITC. Methods: PEITC cytotoxicity was assessed in human cancer cell lines using resazurin reduction assays. Microarray and Ingenuity Pathway Analysis (IPA) were used to investigate altered molecular signaling pathways. Functional assays were performed to assess DNA damage, cell-cycle progression, apoptosis, autophagy, mitochondrial membrane potential, microtubule organization and endothelial tube formation. Western blotting was performed to examine pathway-related proteins, and preliminary in vivo antitumor activity was evaluated using a CCRF-CEM zebrafish xenograft model. Results: PEITC exerted potent cytotoxicity against CCRF-CEM cells (IC₅₀ = 1.76 ± 0.07 µM). Microarray and IPA analyses predicted inhibition of PI3K/AKT/mTOR signaling, which was further supported by Western blot analysis. Functional assays demonstrated that PEITC induced DNA damage, cell cycle perturbation, mitochondrial dysfunction, and apoptotic and autophagic responses. PEITC also disrupted microtubule organization in GFP-tagged α-tubulin-expressing U2OS cells. Furthermore, PEITC suppressed endothelial tube formation in EA.hy926 cell lines and exhibited preliminary in vivo antitumor activity in a zebrafish xenograft model (n = 10). Conclusions: These findings provide mechanistic insights into the anti-leukemic activity of PEITC and demonstrate its effects on multiple cellular processes associated with leukemia cell survival and proliferation, supporting further investigation of its therapeutic potential in ALL. Full article

This study reports the development, optimization and mechanistic evaluation of bio-based cellulose/lignin–tannin membrane adsorbents for the removal of representative inorganic and organic water pollutants: Cr(VI), Pb²⁺, difenoconazole (DFC) and bisphenol A (BPA). Waste cellulose fibers (wCF) from cigarette-package paperboard were converted into reactive membrane constituents by amino/ester and epoxy functionalization and subsequently cross-linked with epoxy-modified kraft lignin (EpKL), with or without tannic acid (TA), yielding wCF/EpKL and wCF/EpKL/TA membranes. Response surface methodology was used to optimize formulation parameters, while structural, morphological, and physicochemical analyses supported successful functionalization, cross-linking, and formation of porous, structurally modified surfaces. At 298 K, the Langmuir adsorption capacities of wCF/EpKL/wCF/EpKL/TA reached 85.37/88.78 mg g⁻¹ for Cr(VI), 155.6/163.9 mg g⁻¹ for Pb²⁺, 51.80/84.49 mg g⁻¹ for DFC, and 194.4/195.4 mg g⁻¹ for BPA, respectively. Isotherm, kinetic, and thermodynamic analyses indicated favorable, heterogeneous, and spontaneous adsorption involving specific surface interactions and diffusion-related contributions. Spectroscopy-supported mechanistic interpretation suggested that metal species are retained mainly through complexation with amino, phenolic, and oxygen-containing groups, together with electrostatic interactions, whereas DFC and BPA adsorption involves hydrogen bonding, hydrophobic interactions, and π–π interactions with lignin/tannin aromatic domains. Fixed-bed experiments confirmed the applicability of the membranes under continuous-flow conditions, while regeneration, stabilization/degradation, and soil-burial tests supported their potential within a more sustainable water treatment cycle. Overall, the results demonstrate that waste-derived cellulose/lignin–tannin membranes are promising regenerable sorbents for the adsorption of chemically diverse inorganic and organic pollutants. Full article

Antimicrobial resistance has significantly compromised the therapeutic efficacy of many antibiotics, highlighting the need for new agents capable of overcoming bacterial resistance. The discovery of antibiotics in the early 20th century contributed significantly to transforming modern medicine and saved countless lives. However, the alarming increase in antibiotic resistance now threatens these achievements. The misuse and overuse of antibiotics have driven the continuous evolution and adaptation of microorganisms, contributing to this growing global health challenge. Azithromycin (AZM), a widely used macrolide antibiotic with favorable pharmacokinetic properties, is increasingly affected by resistance mechanisms. A number of researchers have therefore designed and developed AZM derivatives with promising antibacterial properties. This review summarizes advances in the structural modification of AZM, focusing on side-chain modification, heterocyclic substitution, molecular hybridization, and their associated structure–activity relationships. Selected derivatives demonstrated enhanced activity against resistant bacterial pathogens compared with AZM, although activity varies according to substituent position, linker structure, and overall molecular properties. Nevertheless, the activity of many AZM derivatives against Gram-negative organisms remains limited, with restricted outer-membrane permeability and inadequate intracellular accumulation representing important barriers to achieving effective antibacterial activity. Overall, the structural modification of AZM represents a promising strategy for developing potential antibacterial agents, but further pharmacological and in vivo studies are required to establish their therapeutic potential. Full article

Ion channels and transporters are diverse membrane proteins that regulate ion flux across biological membranes and play essential roles in cellular signaling, homeostasis, and physiological processes. Accurate classification and functional annotation of these proteins are important for characterizing membrane protein function, interpreting pathogenic mutations, and identifying therapeutic targets. However, classification of ion channels and transporters is complicated by similar fine-grained classes, hierarchical labels, and functional determinants spanning sequence motifs, domains, and structural features. We present IonFusion, which uses sequence-conditioned cross-attention to aggregate domain-derived and structure-aware representations. To model the hierarchical organization of classes of ion channels and transporters, IonFusion employs a coarse-to-fine autoregressive classifier linking five coarse-grained classes to nine fine-grained classes. For GO annotation, IonFusion combines multimodal predictions with DIAMOND homology scores. Through comprehensive benchmarks, IonFusion achieved 0.988 accuracy and 0.860 macro-F1, outperforming eight baselines. Across three GO ontologies and sequence-identity thresholds of ≤10%, ≤30%, and ≤50%, it achieved the highest Fmax in all nine settings (mean 0.732). Ablations supported contributions from each modality and both prediction components. Attention-based and targeted perturbation analyses highlighted a conserved, class-associated motif in potassium channels. IonFusion provides a multimodal computational framework for fine-grained classification of ion channels and transporters and GO annotation within the evaluated label spaces. By integrating complementary multimodal representations with hierarchical prediction and homology-based fusion, IonFusion improves the discrimination of closely related ion channel and transporter classes and enhances GO annotation performance across different sequence-identity thresholds. Full article

Ischemia-reperfusion injury (IRI) determines early and delayed graft function and long-term allograft survival in solid organ transplantation and is one determinant of outcome that remains modifiable in the operating room. Cell-free heme, a Danger-Associated Molecular Pattern (DAMP), is liberated from hemoproteins as a result of IRI, and overwhelms the haptoglobin, hemopexin scavenging systems. As such, it then intercalates into cell membranes, drives Fenton chemistry, and acts as a DAMP that engages TLR4/MD2, precipitating cell death. Heme also triggers its own clearance through NRF2 and BACH1, which regulate expression of heme oxygenase-1 (HO-1, Hmox1), that degrades heme into the bioactive molecules, carbon monoxide (CO), biliverdin and ferrous iron. CO modulates inflammation, inhibits cell death pathways and preserves the microcirculation. Biliverdin and bilirubin act as potent antioxidants, and ferritin sequesters labile, highly reactive iron. The role of heme and HO-1 has been well-studied in models of kidney transplantation where HO-1 induction and, independently, exogenous CO treatment have been shown to attenuate transplant-induced IRI and chronic rejection. Importantly, human HO-1 is a critical component of the multi-transgenic donor pig organs that are being tested in ongoing clinical trials. This review discusses the current state of HO-1 in transplantation, including mechanisms of action, preclinical modeling, and clinical applications. Full article

S-palmitoylation is a reversible lipid modification that can alter protein localization, stability, interactions and signaling, but detection of a modified cysteine does not establish its functional importance. Post-translational Modification-Palmoylation Pipeline(PTM-PAL) is a web-accessible workflow for prioritizing candidate S-palmitoylation sites and modification configurations for functional follow-up. It integrates site-specific evolutionary context and UniProt annotation, paired wild-type and palmitoylated structural models, local protein-body solvent-accessible surface-area remodeling, and membrane-embedding descriptors. The workflow takes site metadata, full-length sequences and paired WT/PAL structural models as input and returns dimension-resolved outputs together with a within-protein score on a 0–10 scale. Single-site and dual-site configurations can be examined separately, while the underlying measurements remain available for inspection. PTM-PAL is intended to organize heterogeneous biochemical, structural and membrane-related evidence into testable priorities; the score is not a calibrated probability and does not replace biochemical or functional validation. Full article

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants with high ecotoxicity and bioaccumulation potential, and plant-microbe-assisted remediation is a promising green strategy for their removal. This study investigated Sphingobium abikonense GHP1, a phenanthrene-degrading bacterium isolated from a municipal solid waste incineration site, to elucidate its potential remediation mechanism using untargeted metabolomics and root endophytic bacterial community analysis. GHP1 completely degraded phenanthrene (50 mg L⁻¹) within 3 days using it as the sole carbon source. During degradation, aromatic intermediates, including 1-hydroxy-2-naphthoic acid, salicylic acid, and hydroxybenzoic acid derivatives, accumulated, while central carbon metabolism, 2-oxocarboxylic acid metabolism, aromatic compound degradation, and benzoate degradation pathways were activated. Increased levels of NAD, purine metabolites, phosphatidylcholine, and phosphatidylethanolamine suggested enhanced redox regulation, energy metabolism, and membrane homeostasis under phenanthrene stress. In lettuce, GHP1 inoculation promoted plant growth, increased biomass and chlorophyll content, and reduced phenanthrene residues in roots and leaves. Moreover, GHP1 increased the richness of the root endophytic bacterial community and enriched Actinobacteriota, Firmicutes, and other bacterial taxa. These findings demonstrate that GHP1 enhances phenanthrene remediation through coordinated pollutant degradation, metabolic regulation, and plant-microbe interactions, providing a promising microbial resource for the remediation of PAH-contaminated environments. Full article

Machine learning (ML) is transforming gas-separation membrane research, yet high retrospective accuracy does not necessarily translate into experimentally viable or process-relevant materials. This review reframes the field around the evidence chain required to convert a membrane record into a defensible discovery decision. Across polymers, metal–organic and covalent organic frameworks, mixed-matrix membranes, carbon molecular sieves, and two-dimensional systems, we critically examine data curation, physics-aligned representation, multitask and multi-fidelity learning, uncertainty quantification, inverse design, and prospective validation. We introduce a five-level evidence framework spanning retrospective interpolation, domain-disjoint generalization, physics or simulation confirmation, prospective membrane validation, and deployment-relevant testing. We further propose a contextualized observation unit that binds chemical identity to membrane state, fabrication history, feed composition, operating conditions, time, protocol, and provenance, thereby exposing leakage and structural uncertainty hidden by conventional datasets. Our analysis shows that ML has demonstrably accelerated data completion, simulation, and candidate prioritization, whereas evidence for routinely discovering manufacturable, durable, mixed-gas-performing membranes remains limited and concentrated in polymer studies. To close this gap, we develop a constrained, uncertainty-aware closed-loop architecture that treats feasibility and fabrication failures as learnable outcomes, couples acquisition to multiscale process utility, and advances candidates through staged experimental fidelities. A minimum reporting standard and measurable research priorities are provided. Together, these contributions propose “decision-grade ML” as an emerging framework for evaluating machine learning in membrane science: models should know their applicability domain, preserve physical context, propose feasible experiments, quantify uncertainty under domain shift, and demonstrate value under the conditions of intended membrane use rather than merely reproduce familiar labels or idealized proxies. Full article

The assembly of mitochondrial oxidative phosphorylation (OXPHOS) supercomplexes determines electron flux and ATP synthesis. Although several techniques have been developed to isolate these supercomplexes, their native assembly states within the inner mitochondrial membrane have remained unclear. Here, we developed a separation technique based on saponins from Sapindus saponaria pericarps that enables the isolation of megacomplexes from mitochondria. Using size-exclusion chromatography (SEC) coupled with Western blot, we found that these megacomplexes may represent the predominant assembly state of the mitochondrial OXPHOS system. Furthermore, co-immunoprecipitation followed by Western blot assays revealed a megacomplex comprising respiratory chain complexes I–IV and ATP synthase. Notably, these supercomplexes remained intact under both fasting and a 24-h high-fat diet, underscoring their stability in vitro. Collectively, this study defines the primary architectural organization of OXPHOS system and establishes the saponin-based method as a mild alternative for extracting membrane protein supercomplexes. Full article

Forward osmosis (FO) membrane performance is commonly described through water flux J_w, reverse-solute flux J_s, and the specific reverse-solute ratio R_J = J_s/J_w. These observables provide a low-dimensional projection of a coupled transport system where selective-layer permeability, support resistance, concentration polarization, and defect-mediated leakage interact, producing non-unique links between membrane organization and measured performance. The objective of this study is to determine to what extent the commonly reported FO observables J_w, J_s, and R_J can constrain the underlying transport mechanisms, and to quantify the residual ambiguity when different combinations of selective-layer permeability, support resistance, concentration polarization, and defect-mediated leakage remain compatible with the same measured response. To address this objective, the study develops an admissible-inference framework in the experimentally accessible (J_w, R_J) plane, where published FO measurements are analyzed through observable-space mapping, concentration-polarization amplification, covariance-rank analysis, Fisher/SVD sensitivity diagnostics, and admissible-volume mapping. The resulting framework determines which transport interpretations remain compatible with the observations and which mechanistic directions require additional independent measurements to be resolved. Full article

Anion exchange membrane water electrolysis (AEMWE) is a promising route to low-cost, noble-metal-free green hydrogen production, but its performance remains limited by the sluggish kinetics of the anodic oxygen evolution reaction (OER) and by the poor intrinsic electrical conductivity of many candidate catalyst supports. Covalent organic frameworks (COFs) offer crystalline, highly porous, and chemically tunable platforms for anchoring transition-metal and single-atom active sites, but pristine COFs are electrically insulating. This review summarizes recent progress in conductive COF-based hybrid anodes for AEMWE, covering the fundamentals of AEMWE operation, COF chemistry and synthesis, strategies for engineering electrical conductivity (hybridization with MXene, graphene, carbon nanotubes, heteroatom doping, metal coordination, defect and interface engineering), the OER mechanism on COF-based active sites, electrochemical performance metrics, comparative benchmarking against commercial and other non-precious-metal catalysts, computational and machine-learning-assisted design approaches, and the remaining challenges in stability, scalability, and cost that must be addressed before commercialization. Full article