Search Results (2,879)

In order to understand the dynamic interaction process among species, enzymes, and metabolites during the fermentation process of Baobaoqu, which is a representative Daqu starter for Chinese baijiu, the intimate connection between the progression of microbial communities and the diversities and activities of enzymes was examined by metagenomics, metatranscriptomics and metaproteomics. It was found that while 5211 species of microorganisms were detected by metagenomics, only 1774 active species were detected by metatranscriptomics, which indicated that only a small proportion (34.04%) were active. The metabolic routes associated with the breakdown of substrates and synthesis of metabolites were redesigned, and the special functional microorganisms for lactate, pyrazines and phenylethyl alcohol production were isolated. It was found that the progression of the microbial community was highly coupled with the components of enzymes and flavor substrates, precisely corresponding to the three stages of the Baobaoqu fermentation process, and were regulated by multiple physical factors. During the Baobaoqu-making process of the fermentation, microorganisms with different functions work together to complete metabolism in different stages. These findings will aid us in gaining a deeper and clearer understanding of the “species–enzyme–metabolite” system within the Daqu starter culture, thus offering valuable perspectives for developing artificial synthetic communities and the production of high-quality Baobaoqu. Full article

The shift to sustainable mobility is especially challenging for island regions, where limited land, densely populated corridors, and strong reliance on fossil fuels constrain transport options. This study develops a macroscale methodology to estimate reductions in energy use, greenhouse gas emissions, and traffic congestion by replacing fossil-fuel-based public and private road transport with an electric rail system supplied exclusively by dedicated renewable energy sources. Unlike conventional electrification, this approach guarantees genuine decarbonization by ensuring a fully renewable power supply for rail operations. Gran Canaria is employed as a case study, applying the methodology through an intermodal scenario that integrates the rail system with existing public transport services. Results show substantial potential to lower the carbon footprint, improve energy efficiency, and relieve congestion. The analysis focuses on the southeastern metropolitan corridor of the island, where transport demand, population, and economic activities are most concentrated. The proposed framework offers a transferable tool for supporting sustainable mobility strategies in island contexts consistent with global climate goals and policy priorities. Although the case study is specific to Gran Canaria, the methodology provides insights that may be relevant for other territories with comparable mobility and energy challenges, including isolated or weak-grid regions. Full article

Polar patterns and topological defects are ubiquitous in active matter. In this paper, we study a paradigmatic polar active dumbbell system through numerical simulations, to clarify how polar patterns and defects emerge and shape evolution. We focus on the interplay between these patterns and morphology, domain growth, irreversibility, and compressibility, tuned by dumbbell rigidity and interaction strength. Our results show that, when separated through MIPS, dumbbells with softer interactions can slide one relative to each other and compress more easily, producing blurred hexatic patterns, polarization patterns extended across entire hexatically varied domains, and stronger compression effects. Analysis of isolated domains reveals the consistent presence of inward-pointing topological defects that drive cluster compression and generate non-trivial density profiles, whose magnitude and extension are ruled by the rigidity of the pairwise potential. Investigation of entropy production reveals instead that clusters hosting an aster/spiral defect are characterized by a flat/increasing entropy profile mirroring the underlying polarization structure, thus suggesting an alternative avenue to distinguish topological defects on thermodynamical grounds. Overall, our study highlights how interaction strength and defect–compression interplay affect cluster evolution in particle-based active models, and also provides connections with recent studies of continuum polar active field models. Full article

Oxygen diffusion in (Pu_xTh_1−x)O₂ mixed oxide crystals was investigated using molecular dynamics simulation. The model systems were isolated nanocrystals of 5460 and 15,960 particles, featuring a free surface. The oxygen diffusion coefficient D increased with decreasing thorium content, in accordance with the decrease in the melting temperature of (Pu_xTh_1−x)O₂ as x varied from 0 to 1. The temperature dependences D(T) exhibited non-linearity in the Arrhenius coordinates lnD = f(1/kT). The three linear segments of the plots corresponded to the superionic state, a transitional region, and the low-temperature crystalline phase. The transitional region was characterized by maximum values of the effective diffusion activation energy E_D(PuO₂) = 3.47 eV, E_D(ThO₂) = 5.24 eV and a complex collective mechanism of oxygen migration, which involved the displacement of anions into interstitial sites. At lower temperatures, an interstitialcy mechanism of oxygen diffusion was observed. The temperature dependence of D(PuO₂) showed quantitative agreement with low-temperature experimental data. Full article

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these processes interact synergistically to form a self-perpetuating vicious cycle, rather than operating in isolation. This review systematically elucidates the molecular mechanisms underlying this crosstalk in PTECs. Hyperglycemia induces reactive oxygen species (ROS) overproduction, advanced glycation end products (AGEs) accumulation, and endoplasmic reticulum stress (ERS), which collectively activate key inflammatory pathways (NF-κB, NLRP3, cGAS-STING). The resulting inflammatory milieu triggers apoptosis via death receptor and mitochondrial pathways, while apoptotic cells release damage-associated molecular patterns (DAMPs) that further amplify inflammation. Concurrently, fibrogenic signaling (TGF-β1/Smad, Hippo-YAP/TAZ) promotes epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Crucially, the resulting fibrotic microenvironment reciprocally exacerbates inflammation and apoptosis through mechanical stress and hypoxia. Quantitative data from preclinical and clinical studies are integrated to underscore the magnitude of these effects. Current therapeutic strategies are evolving toward multi-target interventions against this pathological network. We contrast the paradigm of monotargeted agents (e.g., Finerenone, SGLT2 inhibitors), which offer high specificity, with that of multi-targeted natural product-based formulations (e.g., Huangkui capsule, Astragaloside IV), which provide synergistic multi-pathway modulation. Emerging approaches (metabolic reprogramming, epigenetic regulation, mechanobiological signaling) hold promise for reversing fibrosis. Future directions include leveraging single-cell technologies to decipher PTEC heterogeneity and developing kidney-targeted drug delivery systems. We conclude that disrupting the inflammation–apoptosis–fibrosis vicious cycle in PTECs is central to developing next-generation therapies for DN. Full article

Background/Objectives: Primary dysmenorrhea is a prevalent condition that causes severe uterine cramps in women worldwide. The objective of this work was to synthesize and characterize a novel immediate-release system using vitexin and ZIF-8, and to evaluate its pharmacological action in a model of primary dysmenorrhea. Methods: A 2² full factorial design guided the synthesis of the system. Physicochemical characterization was performed by FT-IR, TG, DSC, SEM, XRD, and in vitro release tests. Pharmacological activity was assessed in an oxytocin-induced dysmenorrhea model in mice. In addition, in silico molecular docking and molecular dynamics simulations were conducted to explore the potential mechanism of action of vitexin. Results: Optimal yield and loading capacity were achieved at the high levels of the factorial design. Characterization analyses confirmed the successful formation of the vitexin@ZIF-8 (VIT@ZIF-8) system. The release study demonstrated a markedly enhanced dissolution rate of vitexin. Both isolated vitexin and VIT@ZIF-8 reduced abdominal writhing when administered orally at 3 and 30 mg/kg, while intraperitoneal activity was observed only at 30 mg/kg. Computational analyses revealed favorable interactions of vitexin with aldose reductase (AKR1C3), suggesting this enzyme as a potential molecular target in dysmenorrhea. Conclusions: The VIT@ZIF-8 system represents a promising strategy to improve the dissolution profile of vitexin, although pharmacological activity in this model was not superior to the isolated compound. The combined in vivo and in silico evidence supports vitexin as a potential antidysmenorrheic agent, possibly through modulation of AKR1C3. These findings open avenues for future studies addressing the molecular pathways of vitexin and for the development of novel therapeutic approaches for primary dysmenorrhea. Full article

In the context of China’s rural revitalization strategy, improving the livability and sustainability of traditional dwellings in border regions has become a critical priority. This study examines Chinese–Korean houses in border villages, where field investigations and quantitative analysis reveal persistent challenges: poor indoor thermal comfort and high energy consumption due to outdated building envelopes and inefficient heating systems. To address these issues, we propose an integrated retrofitting solution that combines building-integrated photovoltaics (BIPV) and ground-source heat pump (GSHP) technologies. Unlike previous studies focusing on isolated applications, our approach emphasizes the synergistic integration of active energy generation and high-efficiency thermal regulation, while preserving the architectural and cultural identity of traditional dwellings. Pilot results demonstrate significant improvements in PMV (Predicted Mean Vote) and economic viability, and achieve a high level of esthetic and cultural compatibility. Modular BIPV integration provides on-site renewable electricity without altering roof forms, while GSHP ensures stable, efficient heating and cooling year-round. This solution offers a replicable, regionally adaptive model for low-carbon rural housing transformation. By aligning technological innovation with cultural preservation and socioeconomic feasibility, the study contributes to a new paradigm of rural development, supporting ecological sustainability, ethnic unity, and border stability. Full article

Mancozeb is a broad-spectrum fungicide used extensively in agriculture to protect crops against a wide range of plant diseases. Although its capacity to induce oxidative stress is well documented, the cytotoxic effects of mancozeb on red blood cells (RBCs) remain poorly characterized. The present study aimed to investigate the cytotoxic effects of mancozeb on isolated RBCs, with particular focus on oxidative stress-induced cellular and molecular alterations. Human RBCs were exposed to mancozeb (0.5–100 µM) for 24 h. No hemolytic activity was observed across the tested concentrations. However, 10 and 100 µM mancozeb induced a significant increase in intracellular reactive oxygen species (ROS), leading to lipid and protein oxidation and impaired Na⁺/K⁺-ATPase and anion exchanger 1 (AE1) function. These changes resulted in altered RBC morphology, reduced deformability, and increased methemoglobin levels. Alterations in glycophorin A distribution, anion exchanger 1 (AE1) clustering and phosphorylation, and α/β-spectrin and band 4.1 re-arrangement indicated disrupted membrane–cytoskeleton interactions. A release of extracellular vesicles (EVs) positive for glycophorin A and annexin-V was also observed, consistent with plasma membrane remodeling. Despite increased intracellular calcium, eryptosis remained minimal, possibly due to activation of protective estrogen receptor (ER)-mediated pathways involving ERK1/2 and AKT signaling. Activation of the cellular antioxidant system and the glutathione redox system (GSH/GSSG) occurred, with catalase (CAT) playing a predominant role, while superoxide dismutase (SOD) activity remained largely unchanged. These findings offer mechanistic insights regarding the potential health impact of oxidative stress induced by pesticide exposure. Full article

Arsenic (As) toxicity drives the evolution of resistance mechanisms in environmental microorganisms. Bacteria of the Bacillus genus are frequently identified in isolates from arsenic-contaminated sites, highlighting the importance of understanding the molecular mechanisms related to this bacterial genus. Bacillus subtilis, a soil microorganism and Gram-positive model paradigm, employs multiple strategies to counteract As toxicity, including biosorption, redox transformation, active efflux, and inducible genetic regulation. This review provides a comprehensive analysis of the physiological and molecular mechanisms involved in arsenic response in B. subtilis and related species, focusing on the ars and ase operons. The ars operon, located within the mobile SKIN element, encodes a reductase (ArsC), an Acr3-type efflux pump (ArsB), a carbon–arsenic lyase (ArsI/YqcK), and a transcriptional repressor (ArsR), all co-regulated in response to arsenic. In turn, the ase operon contributes to resistance via an ArsB-type efflux system (AseA) and its own regulatory protein (AseR) but lacks an arsenate reductase. Additionally, genes such as aioAB, arrAB, and arsD are discussed, along with evidence for extracellular detoxification and cell surface immobilization of As. Studies on environmental Bacillus species are examined, pointing out the evolutionary implications of As resistance and the biotechnological potential for remediation of contaminated sites. Full article

Background/Objectives: Human papillomavirus (HPV) is the main causative agent of cervical cancer and contributes to a significant proportion of other anogenital and oropharyngeal malignancies. The need for better biomarkers and therapeutic approaches in HPV-associated cancers has drawn attention to exosomes, small extracellular vesicles known for their stability, biomolecule transport capabilities, and role in cell-to-cell communication. Methods: This review comprehensively evaluates recent literature on the diagnostic, prognostic, and therapeutic applications of small extracellular vesicles, particularly exosomes, in HPV-related cancers. It analyzes findings on exosomal nucleic acids, proteins, and long non-coding RNAs, as well as engineered exosome-based therapies. Results: Exosomal miRNAs (e.g., miR-204-5p, miR-99a-5p, miR-21), proteins (e.g., glycolytic enzymes, HSP90), and lncRNAs (e.g., HOTAIR, DLEU1) have emerged as promising biomarkers for disease detection and monitoring. Exosomal cargo actively participates in HPV-related tumor progression. For example, miRNAs such as miR-21 and miR-146a modulate immune cell polarization and inflammatory signaling, while lncRNAs like HOTAIR promote oncogenic transcriptional programs. Exosomal proteins including HSP90 and ANXA1 facilitate extracellular matrix remodeling and immune evasion, thereby influencing tumor growth and metastasis. In HPV-positive head and neck and cervical cancers, exosomal cargo reflects HPV status, tumor progression, and treatment response. Therapeutic studies demonstrate the utility of exosomes in vaccine delivery, immune modulation, and drug delivery systems, including the use of PROTACs. However, clinical translation faces barriers including isolation protocol standardization, biomarker validation, and scalable production. Conclusions: Exosomes hold great promise for integration into diagnostic and therapeutic workflows for HPV-related cancers. Future research should focus on resolving standardization issues, validating biomarkers in diverse cohorts, and optimizing engineered exosome platforms for targeted therapy. Full article

Skin hyperpigmentation disorders represent a major dermatological challenge, and safe alternatives to conventional depigmenting agents remain scarce. Probiotics and their postbiotic derivatives have emerged as promising natural candidates; however, only a few bacterial strains have been investigated for melanogenesis-inhibitory activity, and their true potential remains largely unexplored. Here, we report for the first time the biosafety profile and anti-melanogenic activity of Lactobacillus salivarius BGHO-1 and Lactobacillus paracasei BGSJ2-8, and assess their possible use in the treatment of skin hyperpigmentation. Two complementary zebrafish-based approaches were employed: (i) image-assisted analysis of pigmentation patterns, melanocyte morphology, and melanocytotoxicity, and (ii) quantitative melanin analysis, enabling integrated safety and efficacy evaluation. We investigated both native and heat-inactivated preparations, including whole cultures, cell-free supernatants, isolated cells, and separated cell walls/membranes and cytoplasmic fractions. While several fractions demonstrated the ability to inhibit melanogenesis, the cell wall/membrane fraction was the most potent, reducing melanin content by 64% compared to untreated embryos, while causing no systemic side effects and preserving melanocyte structure. Furthermore, this fraction did not elicit inflammatory responses or neutropenia, underscoring its favorable safety profile at anti-melanogenic doses. Collectively, this study identifies specific postbiotics as effective and safe modulators of melanogenesis and highlights their translational potential in developing novel approaches for treating skin hyperpigmentation. Full article

Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD). However, its exact targets remain to be elucidated. In this study, we used a mouse intestinal organoid–macrophage co-culture model to investigate the anti-inflammatory effects and immune effects of BBR. Our findings demonstrated that lipopolysaccharide (LPS) induced more robust inflammatory responses and epithelium damage in the co-culture system compared to the organoid alone. BBR effectively attenuated inflammation and restored epithelial barrier integrity by suppressing M1 macrophage polarisation and infiltration, alongside upregulating the expression and organisation of tight junction protein zonula occludens-1 (ZO-1). RNA sequencing and proteomic analysis revealed that BBR disrupted organoid–macrophage interaction by inhibiting chemokine (e.g., C-X-C motif chemokine ligand 1 (CXCL1) and macrophage migration inhibitory factor (MIF)) release from epithelial cells, thereby reducing macrophage recruitment. Collectively, our study establishes the organoid–macrophage co-culture system as a more physiologically relevant model for studying epithelial–immune interactions and elucidates the multi-target mechanism of BBR, which concurrently modulates epithelial cells, macrophages, and their crosstalk. These findings lay the foundation for further exploration of the therapeutic potential of BBR in inflammatory bowel disease and the development of targeted therapies that regulate cell interactions. Full article

Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and affordable alternatives. Mangifera indica L. (mango), a widely cultivated fruit tree deeply rooted in traditional medicine, has long been used to treat conditions symptomatic of parasitic diseases, including fever, diarrhea, and dysentery. Phytochemical investigations have revealed a rich spectrum of bioactive compounds, notably mangiferin, phenolic compounds and terpenoids, which exhibit antimicrobial, antioxidant, and immunomodulatory activities. This review critically synthesizes evidence on the antiparasitic potential of M. indica against protozoa, such as Plasmodium, Leishmania, Trypanosoma, Toxoplasma gondii, Entamoeba histolytica, and free-living amoebae, as well as helminths. Strongest evidence exists for malaria and helminth infections, where both crude extracts and isolated compounds demonstrated significant activity in vitro and in vivo. Encouraging but limited findings are available for leishmaniasis and trypanosomiasis, while data on toxoplasmosis and amoebiasis remain largely speculative. Variations in efficacy across studies are influenced by plant parts and extraction methods, with ethanolic extracts and mangiferin often showing superior results. Despite promising findings, mechanistic studies, standardized methodologies, toxicological evaluations, and clinical trials are scarce. Future research should focus on elucidating molecular mechanisms, exploring synergistic interactions with existing drugs, and leveraging advanced delivery systems to enhance bioavailability. Full article

This paper proposes a local sliding mode control (SMC) strategy for frequency regulation and active power sharing in islanded microgrids (MGs). Unlike advanced strategies, either droop-based or droop-free, that rely on inter-inverter communication, the proposed method operates in a fully decentralized manner, using only measurements available at each inverter. In addition, it adopts a minimalist structure that avoids adaptive laws and consensus mechanisms, which simplifies implementation. A discontinuous control law is derived to enforce sliding dynamics on a frequency-based surface, ensuring robust behavior in the face of disturbances, such as clock drifts, sudden load variations, and topological reconfigurations. A formal Lyapunov-based analysis is conducted to establish the stability of the closed-loop system under the proposed control law. The method guarantees that steady-state frequency deviations remain bounded and predictable as a function of the controller parameters. Simulation results demonstrate that the proposed controller achieves rapid frequency convergence, equitable active power sharing, and sustained stability. Owing to its communication-free design, the proposed strategy is particularly well-suited for MGs operating in rural, isolated, or resource-constrained environments. A comparative evaluation against both conventional droop and communication-based droop-free SMC approaches further highlights the method’s strengths in terms of resilience, implementation simplicity, and practical deployability. Full article

This paper addresses the suppression of multi-frequency line spectrum vibrations during the operation of indoor substations through the development of an active vibration isolation scheme based on a piezoelectric stack inertial actuator. Based on the finite element modal analysis, the excitation frequencies that strongly influence structural response were identified, and the excitation points and sensor layout strategies were determined under a collocated control configuration. Subsequently, the actuator’s structural design and system integration were carried out. Experimental results demonstrate vibration amplitude reductions of 18.75 dB at 100 Hz, 46.02 dB at 200 Hz, and 32.04 dB at 300 Hz, respectively, validating the effectiveness of the proposed method in controlling line spectrum vibrations at multiple frequencies. The study shows that the coordinated optimization of modal matching and the dynamic response capability of inertial actuators provides experimental evidence and technical guidelines for active vibration isolation in large plate-shell structures. Full article