Search Results (1,114)

In ecologically fragile and geomorphologically complex mountainous regions, ensuring a smooth transition from poverty alleviation to multidimensional sustainable rural development remains a key issue in regional governance. Focusing on the Qinba Mountains, a typical former contiguous poverty-stricken region in China covering 18 prefecture-level cities in six provinces, this study uses 2009–2023 prefecture-level panel data to examine the spatiotemporal evolution and driving mechanisms of coordinated rural revitalization. An integrated framework of “multi-dimensional evaluation–spatiotemporal tracking–attribution diagnosis” is developed by combining the improved AHP–entropy-weight TOPSIS method, the Coupling Coordination Degree (CCD) model, spatial Markov chains, spatial autocorrelation, and the Geodetector. The results show pronounced subsystem asynchrony. Livelihood and Well-being Security (U5) improves steadily, while Level of Industrial Development (U1), Civic Virtues and Cultural Vibrancy (U3), and Rural Governance (U4) also rise but with clear spatial differentiation; by contrast, Quality of Human Settlements (U2) fluctuates in stages under ecological fragility. Overall, the coupling coordination level advances from the Verge of Imbalance to Intermediate Coordination, yet the regional pattern remains uneven, with eastern basin cities leading and western deep mountainous cities lagging. State transitions display both policy responsiveness and path dependence: the probability of retaining the original state ranges from 50.0% to 90.5%; low-level neighborhoods reduce the upward transition probability to 25%, whereas medium-to-high-level neighborhoods raise the upward transition probability of low-level cities from 36.36% to 53.33%. Spatial dependence is also evident, with Global Moran’s I increasing, with fluctuations, from 0.331 in 2009 to 0.536 in 2023; high-value clusters extend along the Guanzhong Plain–Han River Valley corridor, while low-value clusters remain relatively locked in mountainous border areas. Driving mechanisms show clear stage-wise succession. At the single-factor level, the explanatory power of Road Network Density (F6) declines from 0.639 to 0.287, whereas Terrain Relief Amplitude (F1) becomes the dominant background constraint in the later stage (q = 0.772). Multi-factor interactions are generally enhanced. In particular, the traditional infrastructure-led pathway weakens markedly, with F1 ∩ F6 = 0.055 in 2023, while the interaction between terrain and consumer market vitality becomes dominant, with F1 ∩ F7 = 0.987 in 2023. On this basis, three major pathways are identified: government fiscal intervention and transportation accessibility improvement, capital agglomeration and market demand stimulation, and human–earth system adaptation and ecological value realization. These findings provide quantitative evidence for breaking spatial lock-in and improving cross-regional resource allocation in ecologically constrained mountainous regions. Full article

Background: Sialylation, a key terminal glycosylation modification, plays a pivotal role in tumor progression and immune evasion. The sialyltransferase ST3GAL4 is implicated in individual cancers, but its pan-cancer landscape and systemic associations remain undefined. Methods: We performed an integrated multi-omics analysis using transcriptomic, proteomic, genomic, DNA methylation, and tumor microenvironment datasets from TCGA, CPTAC, GTEx, and other public resources. Immune associations were evaluated via TIMER2.0 and TISIDB. Experimental validation included immunofluorescence staining for ST3GAL4 protein in human tumor specimens. Results: ST3GAL4 exhibited pervasive, lineage-specific dysregulation across cancers. Elevated expression correlated with adverse prognosis, genomic instability, and specific RNA modification patterns. Tumor microenvironment analyses revealed significant associations: ST3GAL4 expression positively correlated with cancer-associated fibroblast and endothelial cell infiltration but was inversely associated with cytotoxic T-cell abundance. Functional enrichment implicated ST3GAL4 within glycosphingolipid metabolism and glycan biosynthetic pathways. In experimental models, its expression demonstrated context-dependent modulation following cytokine stimulation and immunotherapy. Immunofluorescence confirmed tumor-specific protein expression and its spatial co-occurrence with stromal and immune cell markers. Conclusion: This multi-omics study delineates a comprehensive pan-cancer atlas of ST3GAL4, establishing its association with aggressive tumor behavior, an immunosuppressive microenvironment, and core glycosylation pathways. These findings position ST3GAL4 as a potential cross-tumor node linking sialylation to immune evasion, providing a rationale for future mechanistic and therapeutic exploration. Full article

Water-soluble fullerene derivatives such as fullerenol C₆₀(OH)₂₄ are promising candidates for nanomedicine applications, yet their effects on innate immune cells remain poorly characterized. We investigated the interaction of fullerenol with human neutrophils isolated from healthy donors, exposed to concentrations of 0.25–200 μg/mL over 24–72 h. Using multi-parameter flow cytometry, we assessed viability, apoptosis, phagocytic activity, and intracellular reactive oxygen species (ROS) production, complemented by cell-free DPPH radical scavenging assays. Fullerenol was taken up by neutrophils in a concentration- and time-dependent manner. No significant cytotoxicity was observed up to 100 μg/mL, while viability declined at 200 μg/mL. Phagocytosis of opsonized E. coli was preserved at lower concentrations, though a statistically significant negative correlation with fullerenol concentration was detected at higher doses. In cell-free assays, fullerenol scavenged DPPH radicals with an EC₅₀ of 48.90 ± 10.02 μg/mL, exhibiting slower kinetics than Trolox or ascorbic acid. Critically, fullerenol suppressed intracellular ROS production by >33% at 50 μg/mL following PMA stimulation of neutrophils. These findings demonstrate that fullerenol C₆₀(OH)₂₄ combines potent intracellular antioxidant activity with a favorable neutrophil safety profile, supporting its potential application in oxidative stress-related conditions. Full article

Preeclampsia (PE) is a leading cause of maternal and perinatal complications and is classified by early or late onset according to the gestational age. The complex pathogenesis of PE involves placental ischemia, oxidative stress, angiogenic imbalance, and inflammation, all of which contribute to impaired placentation and widespread maternal endothelial dysfunction. These mechanisms drive hypertension, multi-organ involvement, and increased long-term cardiovascular risk. Parallel research highlighted the role of the NLRP3 inflammasome, a multiprotein complex that, upon activation, increases the gene expression, processing, and release of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 pathway is markedly upregulated in placentas from pregnant women with PE, where endogenous danger signals stimulate inflammasome activation and amplify inflammation. Increasing evidence indicates that microRNAs (miRNAs) help regulate inflammatory processes, including the NLRP3 inflammasome, thereby affecting placental function and maternal adaptation. Although several immunoregulatory miRNAs may influence NLRP3 activity, their specific contribution to inflammasome regulation in PE remains insufficiently understood. Understanding these interactions could reveal new therapeutic targets for PE. In this narrative review, we explore the interconnected roles of endothelial dysfunction, inflammasome activation, and miRNA-mediated regulation in the pathogenesis of PE. Full article

This paper presents a novel dual-mode memristor-based ring oscillator designed for energy-efficient, wireless biomedical signal conditioning systems. The proposed architecture leverages a compact DTMOS memristor emulator, consisting of only two transistors and one capacitor, to replace the conventional NMOS pull-down devices in a three-stage PMOS ring oscillator. This integration enables two distinct operating modes within a single compact core: a fixed-frequency mode for stable clock generation and carrier synthesis, and a programmable chirp mode for frequency-modulated signal generation. The fixed-frequency mode achieves continuous tuning from 3.142 GHz to 4.017 GHz via varactor control, with an ultra-low power consumption of only 111 µW at 4.017 GHz. The chirp mode generates linear frequency sweeps starting from 0.8 GHz, with the sweep range independently controllable through the state capacitor value and the pulse width of the control signal (SW_Chirp). Designed in a standard 0.18 µm CMOS process, the oscillator exhibits a low phase noise of −87.82 dBc/Hz at a 1 MHz offset for the three-stage configuration, improving to −94.3 dBc/Hz for the five-stage design. The overall frequency coverage spans 0.8–4.017 GHz, representing a 133.6% fractional range. The calculated figure of merit (FoM) is −169.45 dBc/Hz. Experimental validation using a discrete CD4007 prototype confirms the oscillation principle, while comprehensive simulations demonstrate robust performance across process corners and temperature variations. With its zero-static-power memristor core, wide tunability, and dual-mode reconfigurability, the proposed oscillator is ideally suited for multi-standard wireless biomedical applications, including implantable telemetry, neural stimulation, ultra-wideband (UWB) transmitters, and non-contact vital sign monitoring. Full article

The market value of fragrant rice is largely defined by the presence and intensity of its aroma, which is primarily attributed to volatile compound 2-acetyl-1-pyrroline (2-AP). The biosynthesis of 2-AP is chiefly governed by recessive alleles of the badh2 gene. Nevertheless, 2-AP accumulation is also profoundly shaped by environmental factors and agronomic management. Field practices—such as balanced nitrogen and potassium fertilization, supplementation with trace elements, and application of plant growth regulators like methyl jasmonate—promote 2-AP synthesis by increasing precursor availability and enhancing the activity of key enzymes. Additionally, tillage systems, alternate wetting and drying irrigation, optimal planting density, and harvest timing significantly affect aroma quality. Abiotic stresses, including moderate drought, salinity, optimal temperatures around 25 °C, and low light during grain filling, can also stimulate 2-AP accumulation, often through shifts in proline metabolism and activation of stress-responsive pathways involving GABA and methylglyoxal. Despite the promise of these strategies, several challenges persist, such as the common trade-off between yield and aroma intensity, complex genotype-by-environment interactions, and incomplete elucidation of the molecular mechanisms involved. Moving forward, integrating multi-omics analyses with smart agriculture technologies will be essential to unravel the regulatory networks underlying aroma formation and to advance the breeding of high-yielding fragrant rice varieties with stable aroma traits under changing climate scenarios. Full article

Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. Eupatorium lindleyanum DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related activities; however, its protective mechanisms in SALI and virus-associated inflammatory lung injury remain incompletely understood. In this study, an integrated strategy combining computational prediction and experimental validation was employed to investigate the therapeutic potential and underlying mechanisms of EL. The chemical constituents of EL were characterized by UPLC–Q–TOF/MS, followed by network pharmacology, molecular docking, and molecular dynamics analyses to predict key targets and signaling pathways. A cecal ligation and puncture (CLP)-induced SALI rat model was used to evaluate lung histopathology, pulmonary edema, cytokine production, and inflammatory signaling activation. In parallel, LPS-stimulated RAW264.7 macrophages were used to assess cytokine secretion and pathway regulation in vitro. In addition, a SARS-CoV-2 pseudovirus-induced mouse model was employed to further evaluate the in vivo relevance of the representative bioactive compound hyperoside in pseudovirus-associated lung injury. A total of 32 active compounds and 697 putative targets were identified, among which 116 were associated with sepsis and COVID-19. In vivo, EL markedly alleviated lung injury, reduced the lung coefficient and wet/dry ratio, and suppressed excessive production of proinflammatory cytokines and activation of key signaling proteins. In vitro, EL dose-dependently inhibited TNF-α and IL-6 secretion and regulated the PI3K–Akt and NF-κB signaling pathways. Notably, hyperoside showed favorable predicted interactions with PI3K–Akt pathway-related targets (EGFR, PI3K, and Akt), while molecular dynamics simulations supported stable interactions with several COVID-19-related targets, including ACE2, Mpro, and RdRp. Furthermore, hyperoside significantly alleviated SARS-CoV-2 pseudovirus-associated lung injury, reduced ACE2 protein expression, and downregulated EGFR, PI3K, and Akt mRNA levels in vivo. Collectively, these findings indicate that EL exerts protective effects through multi-component, multi-target, and multi-pathway mechanisms, and support its potential value for further investigation in SALI and virus-associated inflammatory lung injury. Full article

This study analyzes the impact of China’s smart city pilot policy (CSCP) on green total factor energy efficiency (GTFEE) using panel data from 245 cities (2006–2021). Applying the multi-period difference-in-differences (DID) method, results show that CSCP significantly promotes GTFEE. CSCP improves urban GTFEE by about 6.18%. Meanwhile, CSCP contributes to the enhancement of GTFEE by stimulating green technological innovation and improving the efficiency of resource allocation. These impacts are particularly evident in cities characterized by higher levels of digitalization, peripherality, and being non-resource-based. The findings provide a framework for advancing urban green transitions and integrating smart and green development strategies, highlighting the importance of technology innovation in global energy governance. Full article

Feedback is an integral part of the learning process. However, delivering feedback effectively remains challenging, particularly within massified higher education systems that are characterised by large cohorts and increasingly diverse student populations. The emergence of generative artificial intelligence (GenAI) enables new ways of embedding feedback into educational offerings, some of which may be highly beneficial. In this paper, we introduce Abundant Feedback as a conceptual lens for examining the new capabilities that may be enabled by GenAI. We present a four-dimensional framework identifying the dimensions of GenAI feedback as abundance of Volume, of Availability, of Relevance and of Character. Through a systematic literature search, we describe how these dimensions manifest in recent empirical studies, and identify two educational domains, Computer Programming and Foreign Languages, as early adopters of AI-generated feedback. Beyond merely digitising existing scarce feedback processes, we discuss the emergence of new learner-driven feedback practices that are enabled by abundance, that both stimulate and demand student feedback literacy. Our multi-dimension abundance framework provides a lens, as well as the vocabulary and conceptual tools, to guide the implementation of GenAI feedback in ways that help realise the potential of artificial intelligence to enhance student learning. Full article

Compost-based biostimulants (CBB) have emerged as a promising tool in sustainable agriculture, offering an eco-friendly approach to improving soil health, crop productivity, and environmental resilience. Derived from the controlled biodegradation of organic waste, CBB contains a diverse array of beneficial microorganisms, humic substances, and bioactive compounds that act synergistically to stimulate plant growth and soil biological activity. Mechanistically, CBB enhances nutrient acquisition by increasing plant-available nitrogen and phosphate solubility, promoting root development through phytohormone synthesis, and improving stress tolerance by modulating plant defense pathways and antioxidant activity. Additionally, their application enhances soil structure, microbial diversity, and carbon sequestration, making them integral to climate-smart agriculture. Despite their growing relevance, several challenges impede the widespread adoption of CBB. Variability in compost quality, lack of standardized production protocols, limited field-scale validation, and inconsistent regulatory frameworks hinder reproducibility and commercialization. Addressing these gaps requires interdisciplinary research that integrates microbiology, biochemistry, agronomy, and data science to better understand how microbial metabolites interact and optimize formulation strategies. Future research should prioritize the standardization of composting methods, long-term multi-crop field evaluations, and integration with precision agriculture tools for real-time soil monitoring. Policy harmonization, quality assurance frameworks, and farmer education are also vital for ensuring safe and effective use of CBB. Full article

Background: Advanced liver fibrosis (LF) is a major determinant of prognosis across chronic liver diseases. Current biomarkers are often etiology-specific and lack cross-cohort robustness. Shared molecular drivers across etiologies remain incompletely defined, and effective anti-fibrotic therapies are limited. Methods: We developed a multi-algorithm consensus machine-learning framework to derive a robust LF progression signature. In the training non-alcoholic fatty liver disease (NAFLD) cohort GSE213621 (n = 368), samples were formulated as a binary classification task (mild fibrosis, F0–F2; advanced fibrosis, F3–F4). Candidate genes were screened in parallel using Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), random forest, and eXtreme Gradient Boosting (XGBoost). Genes selected by at least two algorithms were defined as a high-consensus pool, and genes consistently selected by all four algorithms were prioritized to construct a core signature. Model performance was evaluated by stratified cross-validation in the training cohort and externally validated in four independent cohorts of different etiologies (GSE49541, GSE84044, GSE130970, and GSE276114). Cellular sources of signature genes were characterized using single-cell RNA sequencing (scRNA-seq) datasets GSE136103 (human) and GSE172492 (mouse). For therapeutic discovery, the high-consensus expression profile was queried against the Connectivity Map (CMap) to prioritize compounds predicted to reverse the fibrotic transcriptional program. Withaferin A (WFA) was selected for experimental validation in a carbon tetrachloride (CCl₄)-induced mouse LF model and in the transforming growth factor-β1 (TGF-β1)-stimulated human hepatic stellate cell line LX-2. Bulk liver RNA-seq profiling was performed to interrogate WFA-associated molecular changes in vivo. Results: We identified a six-gene signature (CLEC4M, COL25A1, ITGBL1, NALCN, PAPPA, and PEG3) that discriminated advanced from mild fibrosis, achieving a mean AUC of 0.890 in internal cross-validation and an average AUC of 0.864 across external validation cohorts. scRNA-seq analysis revealed cell-type-specific expression with prominent enrichment in fibroblast populations. In vivo, WFA markedly attenuated CCl₄-induced fibrosis (p < 0.05) and reversed 1314 fibrosis-associated differentially expressed genes (adjusted p < 0.05), which were enriched in fatty acid metabolism and PPAR signaling, as well as extracellular matrix (ECM)–receptor interaction and focal adhesion (adjusted p < 0.05). In vitro, WFA suppressed TGF-β1-induced LX-2 activation, reducing α-SMA and Fibronectin expression (p < 0.05). Conclusions: We report a six-gene signature that robustly predicts advanced LF across etiologies, define its cellular context using single-cell atlases, and validate the anti-fibrotic activity of WFA in both in vivo and in vitro models. Bulk liver RNA-seq and cellular evidence further suggest that WFA-associated effects are linked to lipid metabolic programs, ECM remodeling, and attenuation of hepatic stellate cell activation. Full article

Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) as an alternative viral vector boost vaccine. Methods: A recombinant VSV-GP vector co-expressing HBV surface and core antigens (VSV-GP-HBs/c) was generated and characterized for antigen expression. Its immunogenicity, antiviral efficacy, and durability were assessed in HBV-naïve and HBV-carrier mice, using protein primed, viral vector-primed, and multi-viral vector boost regimens. Results: VSV-GP-HBs/c efficiently expressed both HBV antigens in vitro. A single immunization with VSV-GP-HBs/c induced only weak HBV-specific immune responses in vivo. Replacing protein priming with VSV-GP-HBs/c resulted in modest immune activation and limited antiviral effects in HBV-carrier mice. In contrast, substituting the modified vaccinia virus Ankara (MVA)-HBs/c boost in the TherVacB regimen with VSV-GP-HBs/c elicited robust HBV-specific antibody responses and strong CD4 and CD8 T-cell immunity, assessed by intracellular IFN-γ staining after peptide stimulation. This regimen achieved a substantial reduction in serum HBsAg levels, numbers of HBV-positive hepatocytes, and intrahepatic HBV-DNA, with antiviral efficacy comparable to that of the classical TherVacB regimen. Notably, a second viral vector boost did not enhance HBV-specific immunity or antiviral efficacy; instead, it promoted dominant vector-specific CD8 T-cell responses. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. Conclusions: These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity. Full article

Background: Aquaculture, a vital component of global food security, faces sustainability challenges due to intensive farming practices, including water pollution, disease outbreaks, and antibiotic overuse. Probiotics, prebiotics, and synbiotics have emerged as eco-friendly alternatives to antibiotics. However, research results remain heterogeneous across aquatic species and intervention strategies. Methods: Following PRISMA 2020, we searched two databases (up to January 2026) for in vivo trials. Two reviewers screened and extracted data, and 177 eligible studies were ultimately included, covering single-/multi-strain probiotics (SSP/MSP), live/inactivated microbial preparations, and diverse synbiotic formulations. Results: Among 177 studies, Bacillus spp. were the most widely reported and effective probiotic strains. MSP and synbiotics exhibited superior efficacy in boosting aquatic animal growth performance and disease resistance over SSP in 68% of the included trials. Probiotics act through the competitive exclusion of pathogens, immune modulation, and enhanced digestive enzyme activity; prebiotics selectively stimulate beneficial gut microbiota, improving nutrient absorption and immune function through metabolites such as short-chain fatty acids; synbiotics combine the advantages of both, exerting synergistic effects. Furthermore, as water additives or fermented feed ingredients, probiotics reduce nitrogenous waste and organic pollutants, contributing to bioremediation. Conclusions: All three additives are effective. Standardized application protocols and long-term trials are needed for sustainable aquaculture. This review provides a unified evidence-based foundation for the rational use of these additives in aquaculture. Full article

The application of multi-cycle steam stimulation in heavy oil reservoirs frequently alters reservoir properties, influencing the effectiveness of the stimulation and subsequent development strategies. The inherent heterogeneity of strata, characterized by distinct sedimentary facies rhythms, leads to differential patterns of property evolution. Therefore, understanding facies-controlled property variations during steam stimulation is essential for optimizing recovery strategies. This study integrates 1D core experiments with 3D geological modeling to dynamically simulate the stimulation process, enabling a comprehensive multi-scale analysis. The results show the following: (1) Both sedimentary rhythms exhibit progressive increases in porosity and permeability with successive cycles until reaching stabilization plateaus, with the uniform rhythm stabilizing earlier than the coarsening-upward rhythm. (2) 3D simulations reveal a predominant increasing trend in porosity and permeability after multi-cycle stimulation, albeit with localized reduction zones. (3) Multi-scale analysis indicates that, during the early stage (cycles 1–9), the underwater distributary channel microfacies undergoes more rapid property changes and achieves a greater cumulative increase in porosity and permeability. Conversely, during the later stage (cycles 10–30), the mouth bar microfacies demonstrates faster property alterations and a larger cumulative enhancement. This facies-specific, time-dependent understanding provides critical insights for tailoring steam stimulation strategies in heterogeneous heavy oil reservoirs. Full article

Background: Chronic cocaine exposure is increasingly associated with persistent brain alterations, yet it remains unclear whether these changes reflect reversible neuroadaptation, accelerated brain ageing, or a degeneration-like trajectory in a vulnerable subgroup. This Perspective proposes a neuroprogressive vulnerability framework—referred to as cocaine-specific encephalopathy/cerebropathy only in a heuristic sense—to organise heterogeneous evidence without implying a distinct neurodegenerative disease entity. Methods: We conducted a structured, critical synthesis of peer-reviewed human and preclinical literature (PubMed, Scopus, Web of Science; inception to December 2025), integrating neuroimaging (MRI/DTI/fMRI/PET/SPECT), neuropathology/post-mortem findings, neurochemical and molecular mechanisms, and neuropsychological outcomes, with explicit attention to confounders (polysubstance use, psychiatric and medical comorbidity, HIV, vascular risk, abstinence duration). Results: Convergent evidence supports a multi-hit vulnerability model in which chronic stimulant exposure may weaken neural resilience through dopaminergic dysregulation, oxidative stress, mitochondrial dysfunction, neuroinflammatory signalling, and putative α-synuclein–related mechanisms. Human imaging studies consistently implicate fronto–striato–limbic circuits and suggest possible cerebellar involvement, but findings are heterogeneous and often cross-sectional; direct evidence of progressive neuronal loss or disease-defining proteinopathies attributable to cocaine remains limited. Conclusions: Rather than asserting cocaine-induced classic neurodegeneration, we outline an exploratory framework in which chronic cocaine exposure may increase susceptibility to neuroprogressive impairment in a subset of biologically vulnerable individuals. Longitudinal multimodal studies combining advanced imaging, biomarkers, and phenotypic stratification are needed to clarify causality, temporal progression, and reversibility with sustained abstinence. Full article