Search Results (703)

Background/Objectives: Obesity is a multifactorial metabolic disorder characterized by excessive adipose accumulation and dysregulated lipid and glucose homeostasis. Marine brown algae contain diverse bioactive compounds with potential metabolic benefits; however, the in vivo anti-obesity effects of Padina minor remain insufficiently characterized. Methods: This study evaluated the effects of P. minor ethanolic extract on adipose metabolism and metabolic parameters in obese rats induced by a high-fat diet (HFD). Male Wistar rats (n = 36) were rendered obese via HFD and treated with P. minor extract (25, 50, or 100 mg/kg BW) for 4 weeks, with orlistat (30 mg/kg BW) serving as a reference control. Body weight, food intake, Lee index, visceral fat mass, serum lipid profile, and glucose levels were assessed, alongside protein expression of PPARγ, CNR1, and ESR1 (ELISA) and gene expression of Pparγ and Adipor1 (qPCR). Phytochemical constituents were analyzed using GC–MS and LC–MS/MS. Results: P. minor extract significantly attenuated body weight gain, adiposity indices, and visceral fat accumulation compared with HFD controls (p < 0.05), and improved metabolic profiles by reducing total cholesterol, triglycerides, and glucose levels while increasing HDL-cholesterol. At the molecular level, treatment was associated with decreased PPARγ and CNR1 expression and increased Adipor1 and ESR1 expression. The highest dose (100 mg/kg BW) produced effects comparable to orlistat. Phytochemical analysis identified flavonoids and phenolic acids, including quercetin, catechin, chlorogenic acid, and p-coumaric acid. Conclusions: Padina minor ethanolic extract improves metabolic parameters and adipose tissue characteristics in HFD-induced obese rats, potentially through modulation of pathways related to adipogenesis and lipid metabolism, supporting its potential as a marine-derived nutraceutical candidate for obesity management; however, further studies are required to confirm its mechanisms and clinical relevance. Full article

Ferroptosis is an iron-dependent, lipid peroxidation–driven form of regulated cell death that has emerged as a therapeutic vulnerability in hepatocellular carcinoma (HCC), yet the contribution of lysosomes to this process remains incompletely understood. In this study, we investigated whether lysosomal ion channels regulate ferroptosis sensitivity in HCC cells, focusing on the two-pore channel 2 (TPC2) and the transient receptor potential mucolipin 1 (TRPML1). Using pharmacological modulation, genetic knockout models, flow cytometry-based cell death and lipid peroxidation assays, lipidomics, calcium measurements, and molecular analyses across multiple HCC cell lines, we examined how these channels influence ferroptotic signaling. We show that NAADP-dependent TPC2 activity is required for efficient ferroptosis induction, whereas TPC2 loss renders HCC cells resistant to ferroptosis triggered by system Xc⁻ inhibition or glutathione peroxidase 4 (GPX4)blockade. This resistance is associated with reduced lipid peroxidation, altered calcium signaling, and selective depletion of polyunsaturated phosphatidylethanolamine species linked to decreased Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) expression. In contrast, TRPML1 deficiency sensitizes cells to ferroptosis and correlates with enhanced endoplasmic reticulum stress and oxidative imbalance rather than major lipid remodeling. Collectively, these findings identify lysosomal ion channels as key modulators of ferroptosis in HCC and highlight distinct mechanisms by which TPC2 and TRPML1 regulate cellular redox balance and death susceptibility. Full article

Fruit softening, an irreversible ripening process that causes postharvest losses, is mainly attributed to cell wall disassembly, rendering cell-wall-modifying genes critical targets for genetic improvement. However, the molecular mechanism by which expansins loosen the cell wall via the nonenzymatic mechanism, thereby affecting fruit softening, remains largely unknown. In this study, HSM (melting peach, MF) fruits exhibited a rapid decline in firmness, accompanied by more extensive cell wall disassembly and larger intercellular spaces compared with CN14 (non-melting peach, NMF) during the fruit development process. The expression of PpEXPA13, an expansin gene, was significantly higher in HSM than in CN14 during fruit softening. Virus-induced gene silencing in peach delayed firmness loss, while the overexpression of PpEXPA13 in tomato accelerated it. PpEXPA13-OE fruits displayed enlarged intercellular spaces and upregulated expression of multiple cell-wall-modifying genes. Furthermore, a yeast one-hybrid assay identified the transcription factor PpMYC2 as an upstream regulator of PpEXPA13. PpMYC2 specifically binds to the MYC box (CACGTG) in the PpEXPA13 promoter. These findings reveal that PpMYC2 activates PpEXPA13 expression, which might lead to cell wall disassembly and promote peach fruit softening. Full article

Aspartylglucosaminidase (AGA) is an amidohydrolase that can hydrolyze the amide bond between N-acetylglucosamine (GlcNAc) and asparagine (Asn), producing N-acetylglucosamine and aspartic acid (Asp). AGA is distributed in both eukaryotes and prokaryotes. In this study, we identified the sequence of AGA in Elizabethkingia meningoseptica (EmAGA), cloned and expressed it in Escherichia coli, and recharacterized its properties, confirming its substrates as aspartylglucosamine (Asn-GlcNAc) and Asn. Key residues affecting its enzymatic activity were predicted through molecular docking and conserved site analysis, and 10 key residues that affected enzymatic activity were verified, eight of which regulated activity by interfering with EmAGA’s autoproteolysis, indicating that autoproteolytic cleavage into α/β subunits was essential for EmAGA maturation. Molecular dynamics simulations were performed on autohydrolysis-impaired mutants, which showed a more stable conformation and lower energy. In summary, EmAGA’s functional characterization provided novel evidence for elucidating its molecular mechanism. Clinically used Asparaginase (ASNase) exerts its therapeutic effect on acute lymphoblastic leukemia (ALL) through its asparaginase activity, but it is limited by glutamine off-target side effects, while EmAGA also has asparaginase activity but no glutaminase activity, rendering its potential as a basis for novel anti-leukemic enzymatic therapeutics. Full article

Plant polysaccharides can exert immunomodulatory activities. In this study we provided chemical characterization of wheat cell culture-derived polysaccharides (WCCPS) and assessed their capacity to modulate inflammatory responses in mouse macrophages. The total sample (T-010) contained arabinogalactans, arabinans, glucans and xyloglucans. Fractionation by anion-exchange chromatography rendered a bound acidic fraction (B-010) and an unbound neutral fraction (UB-010). The B-010 fraction was enriched in arabinogalactans and arabinans, with some galactans, homogalacturonans, and arabinoxylans. The neutral UB-010 fraction was composed of glucans and xyloglucans. None of the WCCPS preparations triggered cytokine production on their own, but each potentiated different macrophage responses to bacterial lipopolysaccharide (LPS). The total WCCPS in T-010 increased LPS-induced tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 secretion, whereas the acidic arabinogalactan-rich fraction B-010 boosted IL-6 release and selectively upregulated nitric oxide synthase 2 (Nos2) and cholesterol 25-hydroxylase (Ch25h) expression in response to LPS. In contrast, the neutral UB-010 fraction enhanced IL-6 levels and induced Nos2 expression without altering Ch25h expression. These results suggest that WCCPS can modulate distinct aspects of the inflammatory response, with their effects shaped by their composition and structural features. Future research will focus on elucidating the molecular mechanisms underlying the immunomodulatory activity of WCCPS. Full article

Alcohol-related liver disease (ALD) and ALD-related mortality are associated with hemolysis, increased erythrophagocytosis, and disturbed iron homeostasis. While macrophage-mediated erythrophagocytosis is well established, we investigated the contribution of liver sinusoidal endothelial cells (LSECs) to handling oxidatively damaged or ethanol-primed red blood cells (RBCs) in ALD. Live-cell imaging demonstrated that damaged RBCs were rapidly taken up by SK-HEP1 cells, an endothelial cell line with LSEC-like characteristics, and RBC uptake was associated with induction of heme oxygenase-1 (HO-1) and activation of its upstream regulator Nrf2. siRNA-mediated knockdown of the scavenger receptor Stabilin-1 attenuated RBC-induced HO-1 expression, supporting a role for Stabilin-1 in efferocytic signaling. Exposure of RBCs to ethanol concentrations as low as 25 mM induced phosphatidylserine externalization and rendered erythrocytes efferocytosis-competent. Lysed RBCs and free hemin elicited comparable oxidative stress responses. In murine models of hemolysis and chronic ethanol feeding, hemoglobin-derived signals were detected within sinusoidal structures showing a diffuse CD206-positive distribution pattern consistent with the sinusoidal scavenger compartment. Similar signals were observed in sinusoidal endothelial regions in human heavy drinkers with clinical signs of hemolysis. Together, these data suggest that LSECs may represent an additional component of RBC clearance in ALD, alongside macrophages and hepatocytes, with implications for hepatic iron handling. Full article

Voice disorders severely limit verbal communication, creating a need for intuitive assistive technologies. To meet this need, we present epidermal strain sensors that capture strain signals during silent speech and hand gesture. A thin electrospun nanofiber layer integrated onto commercial polyurethane films guides uniform, controlled microcrack formation in screen-printed carbon conductive paths, achieving a gauge factor up to 243 over 0–40% strain. Signals from the seven-channel strain sensor array are recognized by a hybrid neural network that combines convolutional and Transformer architectures, reaching over 98% accuracy. The recognized outputs are rendered in virtual reality (VR), enabling intuitive, real-time communication. Moreover, the approach simplifies fabrication by enabling crack-based strain sensing with only a thin electrospun surface layer on commercial polyurethane films, eliminating the need for thick freestanding electrospun substrates. This cost-effective approach addresses limitations of conventional electrospun substrates by minimizing the thickness of the electrospun layer, thereby shortening the electrospinning time. Overall, the work demonstrates a method for translating natural non-verbal expressions into speech and text in VR, with promising applications in healthcare and assistive communication. Full article

Alhagi camelorum is a dominant leguminous shrub distributed in the Taklamakan Desert, an area characterized by extreme drought and high soil salinization, which can complete its life cycle normally in salt-affected soils. However, the underlying molecular regulatory mechanism of its salt tolerance remains largely unclear. The AcABI5 gene was successfully cloned and characterized, and it encodes a typical nuclear-localized bZIP transcription factor. Functional characterization demonstrated that overexpression of AcABI5 markedly improved the salt stress tolerance of A. camelorum calli, whereas silencing of AcABI5 via virus-induced gene silencing (VIGS) rendered the plant more sensitive to salt stress. Further mechanistic investigations revealed that AcABI5 enhanced salt tolerance by regulating the expression of superoxide dismutase (SOD)- and peroxidase (POD)-related antioxidant genes. Compared with the wild type, AcABI5-overexpressing calli exhibited significantly increased SOD and POD activities and remarkably reduced malondialdehyde (MDA) content under salt treatment, whereas AcABI5-silenced lines exhibited the opposite physiological phenotypes. Furthermore, heterologous silencing of AcABI5 in Nicotiana benthamiana via virus-induced gene silencing (VIGS) produced comparable salt-sensitive phenotypes, similar to those observed in A. camelorum AcABI5-silenced lines. Collectively, these results provide insights into the molecular mechanism by which AcABI5 enhances salt tolerance in A. camelorum, and lay a solid theoretical foundation for the optimization of the A. camelorum genetic transformation system and the expansion of related salt-tolerant crop research. Full article

The rapid expansion of the Internet of Vehicles (IoV) necessitates high-capacity backhaul connectivity, yet the deployment of such networks under strict hardware and power constraints poses significant computational challenges for network optimization. To address this challenge, this paper investigates a joint transmit–receive beamforming optimization problem for narrowband wireless backhaul in IoV networks under constant-modulus constraints. Unlike ideal digital architectures, we focus on cost-effective analog phase shifters, which introduce strictly non-convex constant-modulus constraints, rendering the optimization problem mathematically intractable for standard solvers. Since the resulting problem is highly non-convex, we develop two structured numerical methods: an iterative alternating optimization (AO) method and a joint optimization (JO) method, where AO employs auxiliary WMMSE-guided alternating updates together with constant-modulus projection, while JO jointly updates both beamformers over the constant-modulus feasible set. We compare their achievable sum-rate performance with that of a CDO-based benchmark and analyze their dominant computational costs through representative Big-O complexity expressions. Furthermore, we examine the effect of SVD-based and random feasible initializations on empirical convergence behavior, runtime, and final achievable performance. Simulation results demonstrate that the proposed computational methods significantly improve achievable sum-rate performance compared with the CDO benchmark. Moreover, SVD-based initialization provides a more structured starting point and generally leads to better convergence behavior and lower runtime than random feasible initialization. The empirical timing results further show that AO exhibits faster empirical convergence and requires lower runtime, whereas JO achieves better final sum-rate performance after more iterations. Full article

Under the background of the Rural Revitalization Strategy, Zhejiang Province is promoting “Zhejiang-style Vernacular Dwellings” as a crucial measure to enhance the rural living environment and architectural appearance. However, traditional stylistic control tools, such as standardized rural housing design atlases, exhibit limitations including weak responsiveness to villagers’ individualized needs and high professional thresholds. Consequently, they struggle to address the bottlenecks in grassroots governance efficiency caused by massive and personalized housing demands. Meanwhile, when applied to architectural design, general generative AI technologies often suffer from “structural hallucinations” and the weakening of regional characteristics due to a lack of physical tectonic constraints. Oriented towards the governance requirements of the Zhejiang Provincial Rural Housing Design Guidelines, this study proposes a compliance evaluation-driven “Contour-Semantic-Image” hierarchical generative control framework. This aims to construct a visual scheme generation and pre-screening workflow that deeply adapts to the logic of rural governance. At the data level, this research aggregates multi-source materials, including official standardized atlases, government stylistic guidelines, and real-world photographs. Through expert screening and standardized processing of 596 schemes, a dataset of 333 high-quality, finely annotated structured samples is constructed. Furthermore, a human-guided, machine-segmented workflow assisted by Segment Anything Model 2 (SAM 2) is employed to establish a semantic label system comprising 4 major categories and 13 subcategories of components, thereby achieving the structural deconstruction of architectural prior knowledge. At the generation level, a two-stage model is trained based on Stable Diffusion and ControlNet: Stage I utilizes contour conditions and “layout prompts” to generate semantic label maps, aiming to strengthen component topology and layout consistency; Stage II employs the semantic label maps and “style prompts” as conditions to generate photorealistic facade images. By utilizing explicit semantic constraints to guide the model from pixel synthesis to logical generation, it achieves the controllable rendering of stylistic details and material expressions. At the evaluation level, an automated verification system featuring “clause translation–metric calculation–comprehensive scoring” is proposed. It conducts scoring, re-ranking, and diagnostic feedback on the generated variants across three dimensions: Design Rationality (Q), General Compliance (G), and Jiangnan water-town Regional Characteristics (P-J), forming a closed-loop “Generation-Evaluation-Feedback” workflow. Overall, this framework provides a “visualizable, evaluable, and explainable” pathway for scheme generation and pre-screening in the digital governance of rural architectural appearance. Full article

Impaired wound healing is a major cause of morbidity among patients with diabetes. Human α1-antitrypsin (hAAT) promotes the resolution of injured tissues. In hyperglycemic conditions, circulating hAAT is likely to undergo glycation, yet it is unknown whether its reparative properties are preserved. We hypothesized that clinical-grade hAAT treatment, but not deliberately glycated hAAT (gly-hAAT), would promote wound repair under hyperglycemic conditions. Mice were rendered hyperglycemic, excisional wounding was performed, and wounds were treated with topical albumin or hAAT every three days. The wound area was assessed, and samples were collected for histology and gene expression analysis. Gly-hAAT was generated from clinical-grade hAAT, after which in vitro RAW 264.7 macrophage responses and re-epithelialization of A549 cells were assessed. Gap closure was further assessed using sera from a human cohort (prospective samples from 10 patients with poorly controlled diabetes at Soroka University Medical Center, Beer-Sheva, Israel, 2018). Group comparisons were performed using one-way ANOVA with Tukey’s post hoc test. hAAT accelerated in vivo wound closure and in vitro A549 cell gap closure, accompanied by an anti-inflammatory IL-1Ra/IL-1β gene expression profile. In contrast, gly-hAAT inhibited normoglycemic mouse wound closure, evoked an inflammatory response in macrophages, and interfered with A549 cell gap closure; concomitant hAAT treatment improved gap closure. Similarly, patient serum inhibited A549 gap closure, and concomitant hAAT treatment improved gap closure. Importantly, inferential statistical analysis was not performed on this outcome due to the small and heterogeneous human cohort. In conclusion, hAAT accelerated wound closure in hyperglycemic mice and in A549 cells, whereas gly-hAAT promoted inflammatory responses and impaired wound closure, a trend reversed by native hAAT. These findings support the concept that glycation undermines the beneficial functions of circulating hAAT and provides a mechanistic insight into the pathophysiology of diabetic wound healing. Further studies are warranted to evaluate clinical-grade hAAT as a potential therapeutic for hyperglycemia-associated impaired wound healing. Full article

Naked oat (Avena nuda L.) is an important dual-purpose crop for grain and forage in cold regions; however, its high fatty acid content renders seeds prone to deterioration during storage. This study aimed to investigate the protective effects of zinc oxide nanoparticles (ZnO NPs) on artificially aged naked oat seeds and elucidate the underlying molecular mechanisms. Non-aged seeds (Naged) were subjected to artificial aging at 45 °C and 100% relative humidity for 24 h (Aged), followed by priming with 30 mg L⁻¹ ZnO NPs for 6 h (Daged). Antioxidant enzyme activities were determined spectrophotometrically, and transcriptome sequencing was performed on an Illumina platform to identify differentially expressed genes (DEGs) and enriched pathways. We found that ZnO NPs increased catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activities by 3–4-fold, restored germination rate from 75% to 98%, and enhanced seed vigor index. A total of 21,403 DEGs were detected, with 15,841 stably expressed in response to nano-priming. Reactive oxygen species (ROS) burst rapidly induced up-regulation of AP2/EREBP transcription factor family members, which subsequently activated antioxidant enzyme genes to maintain cellular redox homeostasis. Metabolic pathway analysis demonstrated that the phenylpropanoid pathway was reprogrammed, characterized by down-regulated lignin biosynthesis and up-regulated flavonoid production, thereby enhancing ROS scavenging capacity. Additionally, the pentose phosphate pathway was activated to provide additional NADPH for antioxidant defense, and up-regulated ADP-glucose pyrophosphorylase (AGPase) facilitated starch accumulation. Notably, the 40S ribosomal protein S13 exhibited the highest connectivity in protein–protein interaction networks, was up-regulated 2.1-fold, and was enriched in post-translational modification processes. These findings suggest that nano-priming with ZnO NPs represents a promising biotechnological strategy for enhancing seed vigor and storability in naked oat, with potential applications in sustainable agriculture and the seed industry. Full article

Reconstructing photorealistic and animatable whole-body avatars from monocular videos is a hot topic in computer vision and computer graphics. However, existing methods still face challenges due to the limited frequency response of single-scale geometry encodings and the instability of appearance modeling without an explicit surface anchor. In this paper, we present H²Avatar, a real-time framework that builds on a mesh-embedded 3D Gaussian representation guided by SMPL-X and disentangles geometry and appearance into hierarchical and hybrid components. For geometry, we propose a semantic-aware hierarchical encoding based on a multi-scale tri-plane pyramid, where features at different resolutions capture both global structure and high-frequency surface details such as clothing wrinkles. For appearance, we introduce a hybrid rendering strategy that anchors canonical colors using a learnable UV texture map, and complements it with a neural residual color branch conditioned on tri-plane features, pose embedding, and surface normals to model pose- and view-dependent shading variations. This design improves temporal stability and preserves identity details while enhancing photorealism under complex motions. Experiments on the NeuMan dataset demonstrate that H²Avatar consistently outperforms representative baselines across multiple sequences, outperforming ExAvatar by up to 0.66 dB in PSNR and reducing LPIPS by up to 16.3%. These results validate the effectiveness of hierarchical geometry encoding and texture-anchored hybrid appearance modeling. Full article

Cytotoxic CD8 T lymphocytes are crucial in antiviral immune responses. However, their recruitment to infection sites renders them at risk of viral infection, which could affect their effector activity. CD8 T lymphocytes express RIG-I, which detects cytosolic viral RNA and subsequently induces antiviral gene expression. We investigated how Influenza A virus infection and synthetic triphosphorylated double-stranded RNA, a specific RIG-I ligand, influence TCR-dependent effector responses in primary human CD8 T cells. Cells were isolated from healthy donors and either infected with the reassortant virus RG-PR8-Brazil78 (H1N1) or transfected with the synthetic RNA. Proliferation, degranulation, and cytokine production upon anti-CD3/CD28 stimulation were assessed using flow cytometry and intracellular cytokine staining. Type I IFN production and downstream signaling were measured using IFN-I reporter assay and Western blotting. CRISPR/Cas9 gene editing was employed to knock out RIG-I and STAT2 to evaluate their roles in antiviral responses. Influenza A virus infection of CD8 T cells stimulated RIG-I and activated downstream pathways, including TBK1 and NF-κB, resulting in type-I interferon secretion. Transfection of cytotoxic CD8 T lymphocytes with synthetic RIG-I ligands not only stimulated these pathways but also enhanced the proliferation of CD8 T cells in vitro and protected them from influenza A virus infection. In line with a positive effect on CD8 effector function, both influenza A virus infection and RIG-I ligand transfection enhanced CD8 T cell degranulation and cytokine secretion. Conversely, activation of CD8 T lymphocytes via CD3/CD28 crosslinking increased their susceptibility to influenza A virus infection. We demonstrated that RIG-I stimulation by virus infection or RIG-I ligand transfection promotes intrinsic antiviral pathways and enhances CD8 T-cell effector functions and proliferation. This suggests that RIG-I agonists could enhance and prolong the effector function of cytotoxic CD8 T lymphocytes in immunotherapy. Full article

Antimicrobial resistance has renewed interest in bacteriophage therapy, yet bacterial evolution frequently undermines treatment efficacy. Combination phage therapy is commonly implemented as simultaneous phage cocktails, but whether this is optimal remains in question. Here, we experimentally compared simultaneous versus sequential administration of two phages, an evolved λ called ‘λtrn’ and T2, on Escherichia coli K-12 under controlled laboratory conditions. Across replicated experiments, treatment outcome depended strongly on delivery strategy, dosing order, and timing. Contrary to expectations, sequential delivery consistently achieved greater and more sustained bacterial suppression than simultaneous cocktails, although only when T2 initiated the sequence. Phenotypic assays revealed that treatment differences were driven by the accessibility and timing of cross-resistance evolution. λ-first treatments rapidly selected for cross-resistant bacteria prior to exposure to the second phage, rendering subsequent treatment ineffective. In contrast, T2-first sequential treatments delayed or limited cross-resistance and frequently produced single-phage resistance or collateral sensitivity. Cocktail treatments showed intermediate dynamics, with cross-resistance evolving more slowly but consistently. Whole genome sequencing identified distinct genetic routes to cross-resistance, including regulatory mutations in envZ affecting expression of the phage receptor OmpF, as well as envelope-modifying, mucoidy-associated mutations. Engineering envZ mutations into unevolved backgrounds confirmed the mutation’s sufficiency to confer low-cost cross-resistance. Together, these results demonstrated that phage therapy efficacy depended not only on phage composition but on how selection pressures were ordered in time, highlighting evolutionary steering as a powerful principle for multi-phage therapy design. Full article