Search Results (17,108)

Genipin, a natural compound derived from Gardenia jasminoides, is widely used as an inhibitor of uncoupling protein 2 (UCP2), a protein located in the inner mitochondrial membrane (IMM) that plays a crucial role in regulating oxidative stress and cellular metabolism. Pharmacological inhibition of UCP2 has been explored as a strategy to modulate reactive oxygen species (ROS) and inflammatory responses. However, the utility of genipin is limited by its relatively low bioavailability and dose-dependent toxicity. To address these limitations, we developed mito-genipin, a mitochondria-targeted genipin derivative incorporating a triphenylphosphonium (TPP⁺) moiety, designed to enhance mitochondrial accumulation and thereby increase efficacy. In macrophages, mito-genipin induced mitochondrial hyperpolarization, elevated ROS production, and amplified pro-inflammatory cytokine expression compared with control or genipin treatment. In cells lacking UCP2, mito-genipin did not enhance ROS production. Our data identify mito-genipin as an effective modulator of oxidative stress and inflammation, supporting a putative link to UCP2 inhibition and highlighting potential implications in redox biology and immunomodulation. Full article

Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity. It affects ~10% of reproductive-aged individuals and is associated with dysmenorrhea and infertility. Although imaging modalities have improved diagnosis, laparoscopy is required in many cases, contributing to 4–11 years of diagnostic delay. Non-invasive biomarkers could improve diagnosis and clinical decision-making, yet no candidate has achieved sufficient accuracy for routine use. Galectins, a family of β-galactoside-binding lectins involved in angiogenesis, immune regulation, and fibrosis, have emerged as promising biomarkers. In this study, we measured serum Galectin-1 (Gal-1) concentrations in 80 women with endometriosis and 15 controls using ELISA at four time points. Preoperative Gal-1 levels were significantly higher in endometriosis patients, particularly in Stage III–IV disease. ROC analysis yielded a modest diagnostic performance (AUC 0.692; p = 0.011) with high sensitivity (91.3%) and excellent negative predictive value (96.8%) but low specificity (46.7%) at a study-derived threshold (>14.06 ng/mL). Longitudinally, Gal-1 levels decreased immediately after surgery and rose above baseline by one year, while no significant correlations with preoperative pain severity were observed. These findings suggest that serum Gal-1 alone is insufficient as a diagnostic test but may be useful for multi-marker strategies to improve early diagnosis. Full article

Although pastures cover nearly half of Brazil’s agricultural land and form the backbone of national livestock production, they have historically received limited attention regarding management and fertilization, resulting in widespread degradation. Sustainable intensification of these pasture-based systems is therefore essential to meet growing global demand for animal products while minimizing environmental impacts. This review highlights recent technological innovations in pasture fertilization in Brazil, with a particular focus on alternative phosphorus sources such as natural reactive phosphates, which offer slow-release nutrients at lower costs compared to conventional fertilizers. Efforts to enhance nitrogen use efficiency through nitrification and urease inhibitors show promise in reducing nutrient losses and greenhouse gas emissions, despite current cost constraints limiting adoption. The integration of grass-legume intercropping, especially with Arachis pintoi, has been shown to enhance forage quality and system persistence when appropriately managed. Moreover, plant growth-promoting microorganisms emerge as sustainable biotechnological tools for restoring degraded pastures and boosting forage productivity without adverse environmental consequences. Properly treated agro-industrial residues also present a viable nutrient source for pastures, provided environmental regulations are strictly followed to prevent pollution. Together, these innovations offer a comprehensive framework for enhancing the productivity and sustainability of Brazilian livestock systems, highlighting the pressing need for continued research and the adoption of advanced fertilization strategies. Full article

The arbuscular mycorrhizal fungi (AMF) form symbiotic, mutually beneficial relationships in the rhizosphere, and modulate phosphorus’ (P) availability to regulate plant growth, nutrient uptake, and quality. However, their roles in cut-flower species remain poorly understood. The aim of this study was to evaluate the effects of single and dual inoculation with Glomus intraradices and G. mosseae on Lisianthus (Eustoma grandiflorum) grown under three P levels (10, 20, and 40 mg kg⁻¹) in greenhouse conditions. Under intermediate P, dual-inoculated plants exhibited the greatest above-ground vigor, with increases in stem length (+31%), dry shoot weight (+67%), and highest shoot P (+54%) and N (+23%) content, compared with non-inoculated controls. Under low P, dual inoculation maximized dry root weight (+63%) and mycorrhizal colonization, whereas AMF effects diminished at high P. Principal component analysis showed that there were distinct mycorrhizal interactions (PCA2, 20.3% variance) and a close integration between vegetative growth and nutrient accumulation (PCA1, 54.3% variance). For the first time, this study demonstrates that Lisianthus exhibits a strong response to dual AMF inoculation, offering a novel strategy to enhance growth, nutrition, and ornamental quality when P fertilization is optimized. By reducing chemical fertilizer use, this dual AMF–P management offers a sustainable framework for high-quality cut-flower production. Full article

In 2017, the Commission Implementing Decision (European Union [EU]) 2017/1910 officially declared Italy to be enzootic bovine leukosis (EBL)-free. The Commission Delegated Regulation (EU) 2020/689 laid criteria to maintain an official disease-free status. While some infection clusters persist in restricted areas, specific measures are being implemented to eliminate pockets of viral persistence. This updated analysis of current data, concerning epidemiological trends of EBL in Italy from January 2022 to December 2024, aimed to analyze the status of infection clusters in terms of risk factors associated with bovine leukemia virus (BLV) seropositivity to evaluate the effectiveness of the eradication measures. Our findings highlighted an improvement in EBL eradication; however, the Latium region lags behind in terms of disease eradication while the situation in Apulia is being resolved. Campania, which has implemented restrictive and consistent health measures, has the lowest prevalence and incidence rates compared with previous years. Identifying and assessing risk factors that favor EBL persistence in infection clusters is essential as is implementing specific measures to eliminate such clusters, thereby enabling disease eradication and the adoption of targeted prevention strategies. Full article

Electrocatalytic conversion of CO₂ to high-energy-density multicarbon products (C₂₊) offers a sustainable route for renewable energy storage and carbon neutrality. Precisely modulating Cu-based catalysts to enhance C₂₊ selectivity remains challenging due to uncontrollable reduction of Cu^δ+ active sites. Here, an efficient and stable Ge/Cu catalyst was developed for CO₂ reduction to ethanol via Ge modification. A Cu₂O/GeO₂/Cu core–shell composite was constructed by controlling Ge doping. The structure–performance relationship was elucidated through in situ characterization and theoretical calculations. Ge⁴⁺ stabilized Cu¹⁺ active sites and regulated the surface microenvironment via electronic effects. Ge modification simultaneously altered CO intermediate adsorption to promote asymmetric CO–CHO coupling, optimized water structure at the electrode/electrolyte interface, and inhibited over-reduction of Cu^δ+. This multi-scale synergistic effect enabled a significant ethanol Faradaic efficiency enhancement (11–20%) over a wide potential range, demonstrating promising applicability for renewable energy conversion. This study provides a strategy for designing efficient ECR catalysts and offers mechanistic insights into interfacial engineering for C–C coupling in sustainable fuel production. Full article

Grasslands provide essential forage, fuel, and ecosystem services, underpinning regional livestock husbandry and ecological integrity. However, improper utilization drives structural degradation and functional decline of the vegetation–soil–microbe system, particularly on the ecologically sensitive and fragile Qinghai–Tibet Plateau (QTP). The differential impacts of diverse utilization practices on QTP grasslands remain inadequately understood, limiting scientific support for differentiated sustainable management. To address this, we conducted a comprehensive meta-analysis to clarify effects of grazing, enclosure, and mowing on QTP grasslands, integrating studies from Web of Science, Google Scholar, and CNKI. We constructed disturbance intensity indicators to quantify utilization pressure and used multiple ecological metrics to characterize heterogeneous responses of the vegetation–soil–microbe system. Moderate grazing enhanced vegetation coverage, biomass, diversity, soil total phosphorus, and organic matter; high-intensity grazing reduced vegetation traits, soil bulk density, moisture, nutrients, and microbial biomass/diversity, while increasing soil pH. Early enclosure mitigated anthropogenic disturbance to improve grassland functions, but long-term enclosure exacerbated nutrient/moisture competition, lowering vegetation biomass/diversity and degrading soil properties. Moderate mowing improved vegetation communities by suppressing dominant species overexpansion; excessive mowing caused vegetation homogenization, soil carbon loss, and microbial destabilization. Impacts showed environmental heterogeneity linked to climate, soil, vegetation type, and elevation. In humid and fertile alpine meadows, moderate grazing more effectively promoted vegetation diversity and soil nutrient cycling, while in arid and nutrient-poor desert grasslands, even light grazing led to visible declines in vegetation coverage and soil moisture. Low-elevation alpine grasslands exhibited stronger positive responses to moderate grazing, whereas high-elevation alpine desert grasslands showed high vulnerability even to light grazing. Based on these mechanisms, regionally tailored strategies integrating multiple practices are required to balance ecological conservation and livestock production, promoting QTP grassland sustainability. In future research, we will strengthen quantitative exploration of how specific environmental factors regulate the magnitude and direction of grassland ecosystem responses to grazing, enclosure, and mowing, thereby providing more precise scientific basis for differentiated grassland management. Full article

This paper presents a proposed LSTM-based vertical-gradient prediction combined with three-dimensional kriging that enables reconstruction of greenhouse 3D temperature fields under sparse-sensor deployments while capturing temporal dynamics and spatial correlations. In northern China, winter solar greenhouses rely on standardized structures and passive climate-control strategies, which often lead to non-uniform thermal conditions that complicate precise regulation. To address this challenge, 24 sensors were deployed, and their time-series data were used to train a long short-term memory (LSTM) model for vertical temperature-gradient prediction. The predicted values at multiple heights were fused with in situ observations, and three-dimensional ordinary kriging (3D-OK) was applied to reconstruct the spatiotemporal temperature field. Compared with conventional 2D monitoring and computationally intensive CFD, the proposed approach balances accuracy, efficiency, and deployability. LSTM–Kriging validation showed Trend + Residual Kriging had the lowest RMSE (0.45558 °C) and bias (−0.03148 °C) (p < 0.01), outperforming Trend-only RMSE (3.59 °C) and Kriging-only RMSE (0.48 °C); the 3D model effectively distinguished sunny and rainy dynamics. This cost-effective framework balances accuracy, efficiency, and deployability, overcoming limitations of 2D monitoring and CFD. It provides critical support for adaptive greenhouse climate regulation and digital-twin development, directly advancing precision management and yield stability in CEA. Full article

Traditionally used to combat infections, systemic effects of antibiotics are increasingly recognized in the context of absorption through unconventional routes. One such as the ocular surface. This review tackles the bidirectional liver–eye axis, highlighting how trace antibiotic residues from environmental and therapeutic sources affect the tear film, disturb ocular microbiota, and impact liver metabolism. It engages in anatomical pathways, microbial regulation, pharmacokinetics, and systemic immune responses. Additionally, this review discusses forensic uses and new therapeutic strategies, stressing the importance of integrated environmental monitoring and precision medicine to tackle nonmedicinal antibiotic exposure. Due to the absence of results from a systematic literature review, a narrative literature review was undertaken instead. More than 100 studies discussing mechanistic, clinical, and experimental insights were reviewed, with 98 of those studies being documented as source literature. The findings demonstrate that antibiotics may penetrate and be absorbed through the ocular surface, cause modifications of the hepatic first-pass metabolism, and change the activity of cytochrome P450. Correlations were documented between the various liver function biomarkers and the ocular tear film, as well as the thickness of the retinal pigment epithelium. The dysbiosis of eye microbiota may be an indicator of systemic inflammation associated with immune dysregulation. Restoring microbial homeostasis and addressing systemic dysregulation are novel therapeutic approaches, including the use of probiotics, nanoparticle scavengers, and CRISPR. The eye is a sensory organ and a metabolically active organ. Systemically, the eye can affect the liver through the ocular surface and the antibiotics through the liver–eye axis. To protect the systemic health of the individual and the lensed metabolically active eye, the eye and liver must be viewed as a sentinel of systemic balance. Novel therapies will be necessary with the added need for environmental monitoring. Full article

In vehicle routing problems, long-distance transportation poses a significant challenge to the optimization of transportation costs while adhering to regulations. This study investigates a special type of logistics problem that focuses on liquid transportation systems involving full truckload delivery and the rest–break–drive periods of truck drivers over long distances according to the regulations of the United States. Based on an exact solution algorithm, this work combines a long-distance full truckload fluid transportation problem with the concept of truck driver schedules for the first time. The goal is to optimize transportation expenses while managing challenges related to the rest–break–drive periods of truck drivers, time windows, trailer varieties, customer segments, food and non-food products, a diverse fleet, starting locations, and the diverse tasks of vehicles. In order to reach optimality, a construction heuristic and the column generation method were employed, supplemented by several acceleration strategies. Performance analysis, carried out with artificial input sets mirroring real-life scenarios, indicates that low optimality gaps can be obtained in an appropriate amount of time for large-scale long-haul liquid transportation. Full article

Late spring frosts represent a major threat to grapevine (Vitis vinifera L.), a risk increasingly exacerbated by climate change-driven shifts in phenology. To explore sustainable strategies for frost mitigation, this study investigated the effect of a natural polysaccharide-based biogel, derived from carob (Ceratonia siliqua L.), on the molecular response of grapevine buds exposed to severe cold stress. To this aim, a preliminary RNA-Seq analysis was carried out to compare the transcriptomes of biogel-treated frozen buds (BIOGEL), untreated frozen buds (NTF), and unstressed controls (TNT). The transcriptomic analysis revealed extensive reprogramming of gene expression under freezing stress, highlighting the involvement of pathways related to membrane stabilization, osmotic adjustment, and metabolic regulation. Interestingly, the biogel treatment appeared to attenuate the modulation of several cold-responsive genes, particularly those associated with membrane functionality. Based on these preliminary transcriptomic data, twelve candidate genes, representative of the functional classes affected by biogel treatment, were selected for qRT-PCR validation. The expression patterns confirmed the RNA-Seq trends, further suggesting that biogel application might mitigate the typical transcriptional activation induced by frost, while supporting genes involved in cellular protection and integrity maintenance. The overall analyses suggest that the biogel may act through a dual mechanism: (i) providing a physical barrier that reduces cold-induced cellular damage and stress perception, and (ii) promoting a selective adjustment of gene expression that restrains excessive defense activation while enhancing membrane stability. Although further field validation is required, this natural and biodegradable formulation represents a promising and sustainable tool for mitigating late frost injuries in viticulture. 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

Gene regulatory networks (GRN) govern cellular identity and function through precise control of gene transcription. Single-cell technologies have provided powerful means to dissect regulatory mechanisms within specific cellular states. However, existing computational approaches for modeling single-cell RNA sequencing (scRNA-seq) data often infer local regulatory interactions independently, which limits their ability to resolve regulatory mechanisms from a global perspective. Here, we propose a deep learning framework (Planet) based on diffusion models for constructing cell-specific GRN, thereby providing a systems-level view of how protein regulators orchestrate transcriptional programs. Planet jointly optimizes local network structures in conjunction with gene expression profiles, thereby enhancing the structural consistency of the resulting networks at the global level. Specifically, Planet decomposes GRN generation into a series of Markovian evolution steps and introduces a Triple Hybrid-Attention Transformer to capture long-range regulatory dependencies across diffusion time-steps. Benchmarks on multiple scRNA-seq datasets demonstrate that Planet achieves competitive performance against state-of-the-art methods and yields only a slight improvement over DigNet under comparable conditions. Compared with conventional diffusion models that rely on fixed sampling schedules, Planet employs a fast-sampling strategy that accelerates inference with only minimal accuracy trade-off. When applied to mouse-lung Cd8⁺Gzmk⁺ T cells, Planet successfully reconstructs a cell-type-specific GRN, recovers both established and previously uncharacterized regulators, and delineates the dynamic immunoregulatory changes that accompany ageing. Overall, Planet provides a practical framework for constructing cell-specific GRNs with improved global consistency, offering a complementary perspective to existing methods and new insights into regulatory dynamics in health and disease. Full article

Autoclaved lightweight concrete (ALC) exhibits considerable potential as a wall material in prefabricated structures, but its high water absorption and limited mechanical properties limit its widespread application. Ultra-high-performance concrete (UHPC), which possesses superior mechanical strength and durability, presents a promising reinforcement strategy. This study proposes the development of a UHPC-ALC composite wall material to enhance structural performance. The effects of shrinkage-reducing agent (SRA) content and expansive agent (EA) dosage on UHPC properties were systematically investigated. Results indicate that increasing SRA content improves the fluidity of UHPC and significantly reduces early autogenous shrinkage while the optimal EA dosage enhances both its mechanical properties and volume stability. Furthermore, an interfacial agent was employed to enhance the bonding performance between UHPC and ALC resulting in an average bonding strength of 0.93 MPa which represents a 675% increase compared with the untreated group. Finite element simulations and mechanical tests revealed that the composite material demonstrates a compressive strength of 11.2 MPa and a flexural strength of 6.8 MPa which corresponds to increases of 111.3% and 325%, respectively, relative to monolithic ALC. The composite demonstrated ductile failure and the experimental damage modes were consistent with those of the simulation results. This study offers guidance for optimizing UHPC-based composite wall materials via the multi-scale regulation of shrinkage behavior, interfacial properties, and structural design. Full article

Natural killer (NK) cells are the main cytotoxic lymphocytes of the natural immune system, which play an important role in tumor immune surveillance and anti-viral response. The surface receptor NKG2D can recognize NKG2D ligands on the surface of tumor or metabolism-stressed cells, thereby activating immune responses and mediating cytotoxicity and anti-tumor activity of NK cells. However, NKG2D-positive NK cells are regulated by metabolites, and play a negative role in metabolic diseases. Various metabolites, including lipids, reactive oxygen species (ROS), glucose and amino acids, regulate NKG2D expression and NK cell activity and decide the immune microenvironment of pathological tissue. Thus, targeted therapies based on NKG2D-positive NK cell have entirely different strategies in the treatment of tumor or metabolic diseases. This article focuses on the metabolic regulation of NKG2D-positive NK cells and their opposite roles in disease progression, including of cancer and metabolic disease. In the future, in-depth studies of the regulatory mechanisms of the NKG2D signaling pathway by metabolites and the optimization of the safety and efficacy of targeted therapeutic strategies will lead to new breakthroughs in the treatment of tumors and metabolic diseases, providing patients with more effective treatment options. Full article