Search Results (57,680)

Limosilactobacillus fermentum SHY0006 was isolated from Miao sour soup, a traditional fermented food from Guizhou, China, and systematically evaluated for its safety, metabolic functionality, and stress adaptability using phenotypic assays combined with whole-genome sequencing. SHY0006 exhibited no hemolytic activity and harbored no detectable virulence-associated or acquired antibiotic resistance genes, supporting its safety profile. Functionally, SHY0006 improved lipid metabolism and insulin resistance in both cell and animal models. In hyperlipidemic mice, hepatic triglyceride accumulation was markedly reduced, accompanied by favorable modulation of serum lipid parameters, including LDL-C, HDL-C, and free fatty acids. In diabetic mice, the strain improved insulin tolerance test (ITT) performance, indicating enhanced systemic insulin sensitivity. Whole-genome analysis revealed complete biosynthetic pathways for riboflavin and folate, along with extensive carbohydrate utilization capacity, highlighting its metabolic versatility. In addition, SHY0006 exhibited strong tolerance to environmental stress, supporting its potential viability in food matrices and gastrointestinal conditions. Collectively, these findings suggest that SHY0006 is a safe and metabolically versatile probiotic candidate with potential applications in functional foods targeting metabolic health. Full article

Pirfenidone (PFD) shows therapeutic potential for liver fibrosis, but its molecular mechanisms are not fully elucidated. Activation of hepatic stellate cells (HSCs) is central to liver fibrosis, making their targeted elimination a prime therapeutic strategy. Since amino acid metabolism governs both HSC activation and ferroptosis, we investigated whether PFD acts by reprogramming these metabolic pathways. Analysis of primary rat HSCs revealed that their in vitro activation induced fibrotic markers, including collagen type I and α-smooth muscle actin, as well as key metabolic enzymes. Specifically, we observed upregulation of glutaminase 1, initiating glutaminolysis to produce glutamate; serine hydroxymethyltransferase 2, which generates glycine from serine; and pyrroline-5-carboxylate synthase, the rate-limiting enzyme for de novo proline synthesis. Treatment with PFD suppressed HSC activation by reducing protein levels of these enzymes, an effect consistent with PFD’s inhibition of activating transcription factor 4 nuclear accumulation. This created a dual metabolic vulnerability, limiting amino acid precursors for both collagen synthesis and the master antioxidant glutathione (GSH). Consequently, while PFD alone was not cytotoxic, GSH depletion sensitized activated HSCs to ferroptosis. Co-treatment with the ferroptosis inducer erastin triggered a synergistic increase in reactive oxygen species, labile iron, and lipid peroxidation, culminating in cell death. This synergistic lethality was abrogated by the ferroptosis inhibitor ferrostatin-1 and the antioxidant N-acetylcysteine, confirming ferroptosis as the specific cell death modality. Our study uncovers a dual anti-fibrotic mechanism for PFD: PFD inhibits collagen synthesis by limiting key amino acid precursors and depletes GSH. This compromises antioxidant defenses, creating vulnerability to ferroptosis. Our findings establish a rationale for using PFD in combination therapies designed to eliminate activated HSCs. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Its main contributors are obesity, insulin resistance, diabetes and metabolic syndrome. Liver pathogenesis exacerbates when oxidative stress, inflammation, lipid accumulation, and attenuated autophagy signals coexist together with the main determinants of the liver disease. These findings may indicate that the suppression of the disease requires multi-targeting compounds to alleviate more than one factor, resulting in improved histopathological outcomes. This review studies natural compounds, given as supplements, with antioxidant and anti-inflammatory properties. The compounds included are vitamins, carotenoids, low-molecular-weight thiol-containing compounds, fatty acids and others that have been investigated for their pleiotropic activity alone or in combination. They act at different pathways and signals, and at gene expression control, modulating oxidative stress and inflammation, such as collagen, TNF-α, NF-κB, Nrf2 and PPARs genes. Their mechanism of action and characteristics may be encouraging treatment options as multi-targeting compounds for NAFLD and other diseases whose pathophysiology is closely related to metabolic syndrome. However, extensive study on their safety, toxicity, mechanisms of action and dosage regimen is needed before their final establishment as potential treatment options. Full article

Digital transformation has become a central strategic priority as organizations increasingly rely on digital technologies to redesign business processes, governance structures, and value creation mechanisms in digitally evolving environments. However, existing approaches to digital transformation readiness often rely on additive maturity models or capability inventories that assume transformation capacity increases through cumulative capability development. Such approaches overlook how strategic emphasis must be distributed across transformation domains under governance and resource constraints. This study addresses this limitation by conceptualizing digital transformation readiness as a problem of strategic prioritization rather than cumulative capability accumulation. To operationalize this perspective, the study develops the Strategic Focus Index (SFI), a governance-aligned diagnostic instrument that evaluates how organizations distribute strategic attention across interdependent transformation domains. The index is constructed through a two-round Delphi study involving 53 experts from industry, academia, and the public sector, followed by statistical validation and an illustrative diagnostic application. The findings demonstrate how domain-level prioritization patterns can be systematically interpreted to identify potential imbalances in transformation efforts. By reframing readiness assessment as a prioritization-based diagnostic rather than a linear maturity measure, this study contributes a structured approach for evaluating digital transformation in digital business and platform-based environments. Full article

Although numerous studies have focused on the potential application of heterotrophic nitrification–aerobic denitrification (HNAD) bacteria in wastewater treatment, research exploring their potential in aquaculture biofloc systems remains limited. In this study, a promising HNAD strain, identified as Stutzerimonas stutzeri MJ20, was isolated from mature biofloc. This strain efficiently utilized low-cost carbon sources (e.g., glucose) and small-molecule carbon sources (e.g., sodium acetate and sodium succinate). Under conditions with glucose as the carbon source, a carbon-to-nitrogen (C/N) ratio of 15, pH 6–9, temperature 25–35 °C, salinity 0–35‰, and shaker speed of 0–150 rpm, it achieved removal rates of 95–100% for NH₄⁺-N, NO₂⁻-N, and NO₃⁻-N at initial concentrations of 100 mg/L each. Even at higher concentrations (up to 200 mg/L NH₄⁺-N and 500 mg/L for both NO₂⁻-N and NO₃⁻-N), removal rates exceeded 99%. Under mixed nitrogen sources, strain MJ20 demonstrated efficient nitrogen removal, preferentially utilizing NH₄⁺-N, with only minimal and transient accumulation of nitrite and nitrate. Genomic analysis revealed that MJ20 carries key denitrification genes, including napA, nirS, norB and nosZ, and possesses complete pathways for nitrate reduction to nitrogen gas and ammonia assimilation, although typical autotrophic nitrification genes were not detected. Combined genomic data and autotrophic culture experiments indicated that, in addition to utilizing various organic carbon sources, the strain also exhibited certain autotrophic growth capabilities. Furthermore, MJ20 showed strong flocculation ability (flocculation rate > 96% within 16 h), sensitivity to multiple common antibiotics, and no toxicity to zebrafish, demonstrating favorable biosafety. In simulated seawater aquaculture wastewater with a C/N ratio of 5, it achieved a total nitrogen removal rate exceeding 94% within 72 h. These results indicate that strain MJ20 possesses comprehensive advantages, including efficient nitrogen removal, broad carbon source adaptability, strong environmental resilience, minimal accumulation of intermediate nitrogen products, excellent flocculation ability, and high biosafety. These traits highlight its potential for application in biofloc systems and in treating aquaculture tail water with a low C/N ratio. This study provides theoretical insights and practical guidance for screening HNAD bacteria suitable for biofloc systems. Full article

This research was motivated by the urgent need to address resource shortages and high energy costs in concrete production by replacing an energy-intensive traditional curing method with a new, more sustainable solution. By exploring solar heat treatment with composite binders and THACs, the study aimed to develop sustainable, cost-effective alternatives that harness renewable energy sources and optimize natural cement hydration processes for accelerated hardening. This article explores the potential application of solar energy in the production of precast concrete products using a composite binder. The effectiveness of the composite binder in solar thermal treatment of concrete using translucent heat-accumulating coatings is tested. The results of laboratory studies are presented, and the feasibility of using concrete based on composite binder at the laboratory scale for the production of concrete and reinforced concrete products, both with steaming and with solar thermal treatment, is established. The study of the structural features and basic physical and mechanical properties of hardened concrete under various conditions indicates that, under the investigated laboratory conditions, solar-thermally treated concrete exhibits physical and mechanical properties comparable to those of normally cured concrete. Laboratory studies confirmed the effectiveness of both steaming and solar heat treatment methods under controlled experimental conditions. Within the scope of the performed laboratory tests, the structure and properties of these concretes were comparable to those of normally cured concretes and, in several aspects, superior to those obtained under conventional steam curing regimes, which indicates the effectiveness of the described method, not only from the point of view of significant savings in fuel and energy resources. When producing products based on composite binders using solar thermal treatment, the consumption of the clinker portion of the binder is reduced by 50% (composition of the composite binder itself) and the consumption of conventional fuel during heat and moisture treatment is reduced by 70–100 kg per 1 m³ of concrete (reflecting process-level comparisons), which is of significant value for external energy demand. These findings confirm the technical feasibility and environmental advantages of the proposed method at the laboratory scale and highlight its potential for broader industrial application in precast concrete production. Full article

Background:Pinellia ternata is a major medicinal herb widely utilized in traditional medicine, but is sensitive to high temperature, which often triggers a severe “sprout tumble” phenomenon. Methods: To elucidate the molecular mechanisms of heat tolerance in P. ternata, we screened two contrasting germplasms: the heat-tolerant JBX1 and the heat-sensitive XBX4. In the present study, a combined analysis of physiology, transcriptome, and metabolome was performed on JBX1 and XBX4 under heat stress at 40 °C. Results: JBX1 exhibited significantly greater leaf thickness, higher basal chlorophyll content, more stable antioxidant enzyme activities, and lower oxidative damage than XBX4 under heat stress. Transcriptomically, JBX1 maintained elevated basal expression of genes encoding key enzymes in carbon fixation, amino acid metabolism, and phenylpropanoid biosynthesis, as well as those encoding heat shock transcription factors (HSFs), heat shock proteins (HSPs), and the thermosensor Thermo-With ABA-Response 1 (TWA1). Metabolomically, JBX1 accumulated higher levels of key primary metabolites, antioxidants, and protective phenylpropanoids under both control and heat conditions. Notably, a “polarity reversal” emerged in nitrogen metabolism, where core amino acids accumulated in JBX1 but were depleted in XBX4. Integrated analysis revealed a more coordinated gene–metabolite network in JBX1 involving the phenylpropanoid, ATP-binding cassette (ABC) transporter, and glutathione pathways. Conclusions: Our findings demonstrate that JBX1 possessed stronger basal thermotolerance, which is derived from coordinated establishment of higher constitutive metabolic reserves and efficient dynamic metabolic reprogramming. This study provides insights into the molecular mechanisms of heat stress in P. ternata. Full article

The plasma membrane plays essential roles in cellular transport and signaling. One of its fundamental structural features is the asymmetric distribution of lipids between the inner and outer leaflets. This asymmetry is actively maintained by lipid transport systems, including flippases, floppases, and scramblases, and is critical for membrane integrity and signaling regulation. Accumulating evidence indicates that membrane lipid asymmetry is frequently altered in cancer cells, leading to the externalization of normally inner-leaflet phospholipids such as phosphatidylserine and phosphatidylethanolamine. These alterations can influence tumor signaling, immune interactions, and membrane-associated biological processes. Recent studies further suggest that metabolic reprogramming in cancer may play an important role in regulating membrane lipid asymmetry. Changes in cellular energy status, oxidative stress, calcium signaling, and lipid metabolism can modulate lipid transport systems and membrane organization. In addition, tumor metabolism generates diverse circulating metabolites, including lactate, lysophospholipids, and acylcarnitines, which may influence membrane properties and lipid redistribution. These observations raise the possibility that membrane lipid asymmetry functions as a metabolically responsive interface linking intracellular metabolic state to cell surface signaling and tumor–microenvironment interactions. In this review, we propose a conceptual framework in which cancer-associated metabolic reprogramming influences lipid transport systems and membrane organization, thereby reshaping phospholipid distribution across the plasma membrane. We discuss how metabolic perturbations—including changes in energy metabolism, redox balance, calcium signaling, and lipid remodeling—may regulate membrane lipid asymmetry and explore the implications of these processes for tumor signaling, immune interactions, and emerging membrane-targeted therapeutic strategies. Full article

This study, based on the characteristic that a small number of hydrocarbon-rich sub-sags control the majority of oil and gas reservoirs discovered in the HZ sag, establishes a foothold on the HZ26 sub-sag—the most prolific hydrocarbon-generating sub-sag in the HZ sag, focuses on WC formation of its peripheral structures, and discusses the hydrocarbon accumulation mechanism of WC formation in the HZ sag. Hydrocarbon charging periods were determined through an integrated analysis of homogenization temperatures of brine inclusions coexisting with hydrocarbon inclusions, stratigraphic burial and thermal history, and hydrocarbon generation stages of source rocks. A multiphase fluid charging physical simulation experiment was conducted to establish a covariant relationship between reservoir permeability and hydrocarbon charging pressure difference. Based on the residual pressure history and reservoir property evolution, a coupling relationship was established between the hydrocarbon charging driving force and resistance during hydrocarbon charging periods. The covariant relationship between reservoir permeability and hydrocarbon charging pressure difference and the coupling relationship between hydrocarbon charging driving force and resistance during hydrocarbon charging periods were then integrated to reconstruct the hydrocarbon charging process. The results reveal a mechanism for large-scale hydrocarbon charging and differential accumulation under the influence of overpressure. Full article

Introduction: High-risk multiple myeloma (HRMM) is primarily defined by adverse cytogenetic abnormalities that are associated with inferior outcomes despite contemporary treatment with novel induction agents and autologous stem cell transplantation (ASCT). While the accumulation of high-risk lesions has been proposed to further stratify prognosis, the relative impact of single-hit versus double-hit HRMM on post-transplant outcomes in real-world clinical practice remains incompletely characterized. Methods: We conducted a multicenter retrospective cohort study of transplant-eligible adults with HRMM undergoing upfront ASCT between 2009 and 2024 at three U.S. academic centers. Patients were categorized as single-hit HRMM or double-hit HRMM based on the number of high-risk cytogenetic abnormalities at diagnosis. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between groups using standard statistical methods. Results: A total of 154 patients were included, of whom 63 had SH-HRMM, and 91 had DH-HRMM. Following induction therapy, overall response rates (ORR) were high and comparable between groups. After ASCT, ORR was significantly higher in SH-HRMM compared with DH-HRMM (97% vs. 82%, p = 0.006), although depth of response did not differ significantly. With a median follow-up of 150 months, median OS was 103 months in SH-HRMM and 94 months in DH-HRMM (p = 0.40). Median PFS was 36 months and 31 months, respectively (p = 0.20). Restricted mean survival time analyses similarly demonstrated no significant differences in OS or PFS between groups. Although ORR differed, depth of response and long-term survival did not. Conclusions: In this real-world cohort of transplant-treated HRMM, single-hit disease was associated with a higher likelihood of achieving post-ASCT response; however, no significant differences in long-term survival outcomes were observed between single-hit and double-hit HRMM. These findings suggest that cytogenetic hit burden alone may be insufficient to predict post-transplant survival, highlighting the need for refined risk stratification incorporating additional biological and response-based markers. Full article

Background: Glioblastoma (GBM) exhibits marked cellular heterogeneity and resistance to therapy. Calcium (Ca²⁺) signaling at endoplasmic reticulum (ER)–mitochondria contact sites has emerged as a key regulator of mitochondrial function and cell fate; however, its lineage-specific role and therapeutic relevance in GBM remain unclear. Methods: ITPR1 expression was analyzed using single-cell and bulk RNA sequencing (RNA-seq) datasets and validated by immunohistochemistry and survival analyses. Functional studies were conducted using genetic silencing or CRISPR-mediated activation of ITPR1, combined with DRP1 knockdown, Ca²⁺ imaging, transmission electron microscopy, co-immunoprecipitation, mitochondrial fractionation, and mitochondrial functional assays. Therapeutic efficacy was evaluated in orthotopic GBM xenograft models treated with 2-aminoethoxydiphenyl borate (2-APB), temozolomide (TMZ), or their combination. Results: ITPR1 was enriched in mesenchymal-like malignant cell states and associated with higher tumor grade, recurrence, and poor prognosis. ITPR1 knockdown suppressed GBM cell proliferation and tumor growth while promoting intrinsic apoptosis. Mechanistically, loss of ITPR1 impaired ER-to-mitochondria Ca²⁺ transfer, disrupted ER–mitochondria contacts, and altered mitochondrial ultrastructure. This was accompanied by reduced DRP1 Ser616 phosphorylation and mitochondrial recruitment, as well as decreased autophagy and mitophagy activity. Consequently, ITPR1 knockdown led to mitochondrial depolarization, increased mitochondrial reactive oxygen species (ROS) accumulation, and activation of mitochondria-dependent apoptosis. Conversely, DRP1 knockdown attenuated the mitochondrial and pro-survival effects induced by ITPR1 overexpression. In vivo, combined treatment with 2-APB and TMZ resulted in greater tumor suppression and prolonged survival compared with either treatment alone, accompanied by increased apoptosis and reduced proliferation in tumor tissues. Conclusions: ITPR1 promotes GBM progression by sustaining ER–mitochondria Ca²⁺ coupling and DRP1-dependent mitochondrial quality control, thereby maintaining mitochondrial homeostasis and cell survival. Targeting inositol 1,4,5-trisphosphate receptor (IP₃R)-mediated Ca²⁺ signaling with 2-APB enhances the therapeutic efficacy of TMZ, suggesting that ITPR1-centered Ca²⁺ signaling may represent a potential therapeutic vulnerability in aggressive GBM. Full article

This study investigates the selective synthesis of α- and γ-alumina nanoparticles using plasma-induced microbubbles. Although plasma-induced bubbles provide an effective reaction environment for the synthesis of nanomaterials, precise phase control remains challenging. Herein, we demonstrate that the modulation of the pulse off time regulates the thermal environment within the bubbles. Optical emission spectroscopy revealed that a shorter off time maintains a high electron temperature, indicating substantial heat accumulation. This high-energy state promotes the atomization of the precursor mist and the subsequent growth of molten droplets, providing sufficient activation energy for the formation of the thermodynamically stable α-phase. In contrast, a longer off time leads to the formation of a metastable γ-phase because of insufficient heating and rapid quenching. These findings prove that alumina nanoparticles with desired crystal phase and size can be synthesized by controlling the thermal energy inside the plasma-induced microbubbles. Full article

Intensive horticultural management modifies soil physicochemical conditions, yet its effects on microbial community assembly and functional organization remain poorly resolved. This study examined bulk soil (BS) and rhizosphere soil (Rh) bacterial communities associated with tomato plants grown in two contrasting commercial horticultural establishments: a long-term intensive monoculture (>10 years; MC) and a recently established system (FC). Total bacterial abundance and community structure were characterized using qPCR and 16S rRNA gene amplicon sequencing, respectively; the abundance and diversity of functional plant-growth-promoting (PGP) genes—nifH, phoD, and acdS—were assessed by qPCR and DGGE profiling. The MC system, associated with increased salinity, nutrient accumulation, and organic matter content, supported higher bacterial abundance, whereas the FC system showed a higher relative abundance of PGP genes. Amplicon sequencing revealed significant differentiation between BS and Rh, identifying microhabitat in tomato-associated soil as the primary driver of taxonomic structure, while site effects were weaker. In contrast, DGGE profiling supported differences in functional gene composition between management systems, whereas predicted pathway profiles inferred from 16S data were comparatively similar across samples. Overall, these results indicate that horticultural intensification is associated with shifts in predicted functional potential that are not paralleled by major changes in taxonomic structure. Full article

Astragalin (AST), a natural flavonoid found in various plants, possesses antioxidant and anti-inflammatory properties. However, its protective efficacy against ultraviolet B (UVB)-induced cutaneous damage remains unclear. This study investigated the photoprotective effects of AST against UVB-induced photodamage using HaCaT keratinocytes and Kunming mice. In vitro, AST mitigated UVB-induced cytotoxicity and apoptosis in HaCaT cells. In vivo, topical application of AST attenuated UVB-induced erythema, epidermal hyperplasia, and collagen degradation in mouse skin. Additionally, AST reduced reactive oxygen species accumulation and enhanced antioxidant enzyme activity via activation of the Keap1/Nrf2 pathway. Furthermore, AST suppressed the expression of proinflammatory cytokines by inhibiting the TLR4/NF-κB signaling pathway. These findings demonstrate the photoprotective properties of AST and support its potential as a natural therapeutic agent for preventing UVB-induced skin damage. Full article

Accurate regional wind speed forecasting is critical yet challenging due to inherent spatiotemporal correlations and data non-stationarity. This paper proposes a hybrid framework combining Principal Component Analysis (PCA), Variational Mode Decomposition (VMD), and Long Short-Term Memory (LSTM) networks. First, PCA extracts dominant spatial features from a regional wind field (9 × 9 grid), retaining 99.5% of the information to reduce redundancy. Next, an adaptive VMD strategy, optimized by the Sparrow Search Algorithm (SSA), decomposes these components to mitigate temporal non-stationarity. High-correlation sub-signals are then fed into the LSTM predictor. Experimental results demonstrate that the framework achieves an average coefficient of determination (R²) of approximately 0.41 in the first forecasting step. Crucially, it significantly mitigates error accumulation in multi-step forecasting, maintaining a stable R² of 0.39 in the third step. Conversely, complex spatiotemporal models like ConvLSTM achieve high initial accuracy but suffer severe degradation (R² dropping from 0.70 to 0.24) alongside significantly higher computational overhead. The proposed strategy effectively prevents overfitting to high-frequency noise, ensuring a computationally efficient and robust solution for multi-step regional wind forecasting. Full article