Search Results (1,525)

Taking the Yellow River Basin (YRB) as an example, this study explores the non-stationary drought evolution features in large river basins under climate change. This study utilized precipitation and multiple climate factor data to establish the non-stationary standardized precipitation index (NSPI) through the GAMLSS model. Combined with the run theory, Copula function and a cascaded RF-LSTM machine learning model, the drought characteristics and retrospective predictive patterns were systematically assessed. The results show that: (1) The Arctic Oscillation, the Pacific Decadal Oscillation, the Southern Oscillation and the North Pacific Index are the primary climate drivers of non-stationary precipitation variation in the YRB, with the former three being selected most frequently and NPI additionally influencing April–June and September, and their effects are both different and lagging. Compared with the traditional SPI, the NSPI assigned higher drought grades and greater severity to typical drought years (e.g., the 1974 event was rated D3 with a severity of 17.935 by NSPI versus D2 with 11.733 by SPI), and thus better captured non-stationary drought evolution. (2) The duration of droughts exhibited a decreasing trend that was not statistically significant (p > 0.05), whereas drought intensity and severity decreased significantly (p < 0.05); the peak severity showed a significant upward trend (p = 0.0078). Spatially, the northwest of the Loess Plateau was a compound core area with high severity, high frequency and long duration of droughts, while the upper reaches were mainly characterized by low severity, short duration and sudden droughts. (3) The drought risk in the YRB shows a higher frequency in the lower reaches and a lower frequency in the upper reaches. The middle and lower reaches were high-risk areas, with shorter AND-type joint exceedance return periods for moderate drought (2.46–5.83 years) and severe drought (3.77–9.15 years). The upper reaches were low-risk areas, with longer return periods reaching up to 5.83 years for moderate drought and 9.15 years for severe drought. The study shows that the NSPI, considering the driving of multiple climate factors, can more effectively identify and assess non-stationary drought risks, providing a scientific basis for drought prevention and control in river basins. Full article

Grapevine downy mildew, caused by the oomycete pathogen Plasmopara viticola (P. viticola), is one of the most devastating diseases threatening the global grape industry. The pathogen invades host plants through stomata, triggering a series of highly coordinated physiological disorders and biochemical defense events. This review systematically summarizes the dynamic changes in morphological structures (stomatal characteristics), physiological functions (photosynthesis, membrane system integrity, and carbon metabolism), and multi-level biochemical defense systems (reactive oxygen species (ROS) scavenging enzyme system, phenylpropanoid metabolic pathway, pathogenesis-related proteins, and phenolic compounds) in grapevines following infection. It focuses on analyzing the differences in the timing, intensity, and metabolic reprogramming of defense responses between resistant and susceptible cultivars, pointing out that the essence of disease resistance lies in early pathogen recognition and rapid defense induction. The conflicting conclusions regarding indicators such as soluble sugars, peroxidase (POD), and superoxide dismutase (SOD) are discussed from the perspectives of experimental systems, cultivar genetic backgrounds, and pathogen physiological race differences. Furthermore, the known physiological and biochemical alterations are linked to upstream signaling pathways, including salicylic acid and jasmonic acid (SA/JA), calcium signaling, and mitogen-activated protein kinase (MAPK) cascades. Recent advances in revealing resistance mechanisms in the omics era are also introduced. Finally, future research directions are proposed, including constructing multi-indicator dynamic evaluation models, verifying key gene functions using gene editing, exploring the potential of epigenetic regulation, and developing integrated control strategies combined with microbiome research. This review aims to provide theoretical support for grapevine downy mildew resistance breeding and sustainable disease management. Full article

Ascophyllum nodosum extracts (ANE) are widely used biostimulants associated with improvements in plant growth, productivity, nutrient acquisition, and abiotic stress tolerance. However, the molecular mechanisms linking extract composition to plant signaling and physiological responses remain incompletely resolved. ANE contains a complex mixture of bioactive constituents, including polysaccharides, osmolytes, phenolic compounds, and phytohormone-like molecules. Their composition varies according to biomass source, environmental conditions, and extraction methodology, contributing to variability in biological activity. Current evidence suggests that ANE functions mainly as a signaling modulator rather than a direct nutrient source. ANE treatment has been associated with early cellular responses, including cytosolic Ca²⁺ influx, reactive oxygen species (ROS) generation, and mitogen-activated protein kinase (MAPK)-associated signaling events. However, many proposed mechanisms remain unresolved, and a considerable proportion of the available mechanistic evidence originates from studies using purified ANE-derived polysaccharides or related elicitor systems. ANE-associated responses include modulation of nutrient transport, primary metabolism, hormonal regulation, transcriptional reprogramming, and stress-responsive pathways, contributing to improved root development, nutrient acquisition, and defense-related responses. Nevertheless, limited knowledge of receptor-mediated perception mechanisms, signaling hierarchies, and extract-dependent variability continues to constrain mechanistic understanding and reproducibility. Future research should prioritize receptor identification, bioassay-guided fractionation, integrated multi-omics approaches, and improved standardization of extraction and formulation procedures. These advances will be essential for establishing robust mechanistic models and supporting the development of evidence-based ANE biostimulants for sustainable crop production. Full article

Introduction: Pedestrians lying on the road—collapsed through medical emergency, intoxication, or displacement following a prior collision—represent a disproportionately lethal and underaddressed category in road traffic safety. Forensic database analyses derived from Japan’s national police records document a fatality rate of 33.0% for collisions involving pedestrians lying on the road, more than double the rate for upright pedestrian collisions. Standard Advanced Driver-Assistance Systems (ADAS) yield a True Positive Rate (TPR) of only 21.4% for detecting pedestrians lying on the road under night conditions—a classification gap of 73.3 percentage points. Methods: In simulation trials, we evaluated the Advanced Falling Object Detection System (AFODS—where “falling object” denotes the low-profile human form at road level, distinguishing the prone pedestrian from the upright postures addressed by conventional ADAS) on a composite dataset of 3200 annotated fall events and 12,000 negative samples (training/validation), with 320 independent controlled simulation trials used for performance evaluation, spanning real-world, forensic-reconstruction, and Total Human Body Model for Safety (THUMS)-validated synthetic scenarios. No physical prototype has been evaluated; all performance data are derived from simulation, and 37.5% of positive samples are synthetically generated. These simulation conditions represent a first feasibility demonstration pending real-world hardware validation. This paper introduces three original contributions absent from prior work: a three-stage quantitative injury-risk model, a formal ISO 26262 Hazard Analysis and Risk Assessment (HARA), and a medicolegal SHAP interpretability framework. The injury-risk model translated detection latency via impact velocity to Head Injury Criterion (HIC) and estimated fatal injury probability (AIS ≥ 5); these model outputs should be interpreted as exploratory estimates pending ATD validation. Reporting follows principles consistent with the TRIPOD statement. Results: Under clear daytime conditions, AFODS demonstrated a TPR of 98.2% (95% CI: 97.4–98.8%) in simulation, decreasing to 95.6% under night dry-road conditions and 89.4% under night rain. The system achieved an AUC of 0.981 and a mean end-to-end latency of 46.5 ms, representing a 76.8 percentage-point improvement in simulation over the monocular RGB baseline (p < 0.001). The injury-risk model projects a reduction in estimated fatal head injury probability from 66.2% (Monte Carlo mean) (no detection, 50 km/h full-speed impact) to 0.7% under AFODS worst-case night/rain conditions, and to ≈0% under clear daytime simulation conditions. Conclusions: A 73.3 percentage-point classification gap places pedestrians lying on the road outside the effective detection envelope of current ADAS, compounded by the systematic exclusion of non-upright postures from regulatory test protocols and benchmark datasets. AFODS supports proof-of-concept feasibility under simulation conditions. Three translational steps are required: prototype validation on real-world hardware using instrumented Anthropomorphic Test Devices (ATDs); prone-posture biomechanical injury modelling using HIC and BrIC criteria; and regulatory extension of pedestrian AEB test standards to non-upright scenarios. Full article

Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer’s disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25–35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer’s pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer’s disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders. Full article

Background/Objectives: Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury and delayed graft function after kidney transplantation. Oxidative stress, mitochondrial dysfunction, and tubular epithelial cell apoptosis are central events in renal IRI. Sophocarpine (SOP), a quinolizidine alkaloid derived from Sophora species, has reported antioxidant and anti-apoptotic activities, but its effects in renal IRI remain unclear. This study investigated the role and function of SOP in renal IRI. Methods: A bilateral renal IRI mouse model and a hypoxia/reoxygenation (H/R) model in HK-2 human proximal tubular epithelial cells were used. Renal function, histological injury, apoptosis, reactive oxygen species, malondialdehyde, superoxide dismutase activity, glutathione, mitochondrial morphology, mitochondrial membrane potential, and mitochondrial dynamics-related proteins were evaluated. SIRT1 dependency was examined using Sirt1 small interfering RNA in HK-2 cells and EX527-mediated SIRT1 inhibition in mice. Results: SOP pretreatment reduced serum creatinine and blood urea nitrogen levels, attenuated tubular injury and apoptosis, decreased oxidative stress, and preserved mitochondrial morphology and function after renal IRI. Similar protective effects were observed in HK-2 cells exposed to H/R. SOP increased SIRT1 and PGC-1α expression, whereas Sirt1 knockdown or pharmacological SIRT1 inhibition weakened the antioxidant and mitochondrial protective effects of SOP. Conclusions: SOP attenuates renal IRI-associated oxidative stress and mitochondrial dysfunction, at least in part through the SIRT1/PGC-1α axis. These findings support further investigation of SOP as a candidate renoprotective compound for ischemic kidney injury. Full article

Human-induced climate change has rendered urban areas highly vulnerable to extreme events such as heatwaves, droughts, and floods. This study conducts a scoping review of extreme and compound climate hazards in Iranian urban areas under global warming conditions. Mapping the available literature, 92 authoritative scientific works published between 1999 and 2025 were analyzed. The review synthesizes evidence on the spatiotemporal patterns of heatwaves, drought, torrential rainfall, sea-level rise, and compound hazards across Iran. The results indicate that central, northwestern, eastern, and southern Iran experience the highest heatwave intensity and frequency, with short-duration heatwaves being more common than prolonged ones. Western Iran faces a high risk of torrential rainfall, but urbanization amplifies flood consequences by expanding impervious surfaces and accelerating surface runoff. Coastal areas show high vulnerability to compound flooding due to sea-level rise and storms. The review further reveals that Iran is experiencing hydroclimate whiplash (abrupt transitions between drought and flood) driven by global warming. The study concludes by presenting management suggestions and future research directions for integrated compound hazard management in Iran. Full article

The M_w7.7 Pazarcık–Kahramanmaraş and M_w7.5 Elbistan–Kahramanmaraş earthquakes on 6 February 2023 caused the collapse of 11 buildings in Adana’s city centre—predominantly 15-storey RC structures in a narrow zone—despite peak ground accelerations of only 0.05 g; most collapses occurred during the M_w7.7 event. Two-dimensional seismic site response analyses at the site of interest with bedrock input from station TK0118 yielded topographic amplification factors of 2.37 (EW) and 2.09 (NS) for homogeneous conditions; with stratigraphic heterogeneity, NS increased to 2.66 and EW remained at 2.27, reaching above 3.0 at the slope crest. Spectral amplification factors reached 4.53 (NS, T = 0.90 s) and 3.21 (EW, T = 0.68 s), indicating amplification in the short-to-intermediate period range. These amplified records were applied to idealised 15-storey RC models—from code-compliant to deliberately deficient—with C16 and C8 concrete classes through nonlinear performance analyses. Under unamplified TK0118 records, no model reached collapse-level damage. Under amplified records, only the most deficient model exhibited widespread shear and strain failures in the lower storeys. A detected velocity pulse (T_p = 13.496 s) was excluded as a collapse mechanism, as its period far exceeds structural periods (1.2–1.9 s). The collapses are attributable to the compounding of topographic and stratigraphic amplification with pre-existing structural deficiencies. Full article

Identification of ligands targeting essential enzymes in Mycobacterium species remains an important strategy for anti-tuberculosis drug discovery. Here, a native mass spectrometry approach was employed using pooled 100-compound mixtures, enabling the direct detection of intact HPPK–ligand complexes in solution. Dual-mode MS acquisitions (low collision energy for complex detection and high collision energy for ligand confirmation), combined with an automated data analysis workflow, ensured robust identification of binding events from these complex samples. This strategy led to the identification of several HPPK-binding small molecules, all belonging to the dammarane triterpene glycoside (ginsenoside) class. Subsequent analysis of the hits revealed clear structure–affinity relationships, highlighting how specific aglycone modifications and glycosylation patterns influence binding to HPPK. Our findings expand the known chemical space of HPPK ligands and demonstrate the utility of native MS-based screening coupled with automated data analysis to uncover new ligand scaffolds for challenging enzyme targets. Full article

Phenolic compounds, essential for grape quality, are affected by environmental factors, including abiotic stressors such as hail. This study examined the impact of varying levels of natural hail damage on the physicochemical parameters, phenolic composition, and antioxidant capacity of Thompson seedless grapevines (Vitis vinifera L.) under Mediterranean climatic conditions. The research was carried out in a commercial vineyard in Greece during the 2015 growing season, following a major hailstorm. Three treatments were implemented: control (undamaged), moderate hail damage, and total hail damage. The results showed that pH levels and specific physiological parameters, including proline concentration, were significantly influenced across treatments. Detailed analysis revealed that the concentrations of phenolic compounds generally increased with greater hail damage, indicating enhanced antioxidant capacity and metabolic adaptation to natural hail-induced mechanical stress. Additionally, individual phenolic compounds, such as flavanols, hydroxybenzoic acids, and stilbenes, responded differently to hail damage, demonstrating complex regulatory mechanisms in grape metabolism. These findings underscore the importance of understanding grapevine biochemical responses to extreme weather events in the context of climate change, as changes in phenolic composition can directly affect grape quality. Full article

This study investigates the influence of organic matter properties in surface waters on the efficiency of single- and two-stage coagulation processes in drinking water treatment plants. The research was conducted at three treatment plants supplied by different surface water sources over a 15-month monitoring period. The analyzed parameters included total and dissolved organic carbon (TOC and DOC), biodegradable dissolved organic carbon (BDOC), water color, UV absorbance, zeta potential, and molecular weight distribution of organic substances. The results showed that coagulation efficiency depends strongly on both the concentration and the molecular characteristics of organic matter. The highest removal efficiency was observed for high-molecular-weight fractions (>2.0 kDa), mainly humic substances, whereas low-molecular-weight compounds were removed less effectively. The study also demonstrated that surrogate spectrophotometric parameters, particularly UV₂₅₄ absorbance and color at 410 nm, can be used to monitor and optimize the coagulation process. Given the increasing frequency of extreme climate events and rapid shifts in raw water quality, optimizing single- and two-stage coagulation configurations has become an urgent operational necessity. This work provides a novel direct linkage between simple spectrophotometric indexes and precise chromatographic molecular ranges, delivering an immediate, high-impact predictive tool for real-time dosage optimization in water treatment engineering. Full article

Compound extreme climate events have become increasingly frequent under climate change and may alter terrestrial carbon cycling through different atmospheric and soil pathways. Focusing on the Dongting Lake Eco-Economic Zone, this study identified three types of compound extreme events during 2003–2024: atmospheric compound hot–dry events (ACHDs), soil compound hot–dry events (SCHDs), and drought-to-rewetting events (DRWs). We then examined their associations with monthly anomalies of net primary production (NPP), heterotrophic respiration (RH), and net ecosystem exchange (NEE) under different land cover backgrounds. The results showed that ACHDs and SCHDs both increased significantly, whereas DRWs exhibited a slight decreasing trend and a more scattered spatial distribution. During the same period, regional NPP increased significantly, RH decreased slightly, and NEE became more negative, indicating an overall strengthening of net carbon uptake. Different event types were associated with contrasting carbon flux response pathways: ACHDs were mainly associated with reduced NPP and slightly increased RH, thereby shifting NEE toward more positive values and weakening regional net carbon uptake, whereas SCHDs and DRWs were more strongly associated with reduced RH and more negative NEE. In addition, the event–carbon relationships differed among land cover types, with cropland, built-up land, and sparsely vegetated surfaces showing higher sensitivity to ACHDs, whereas the responses to SCHDs and DRWs varied markedly among forest, grassland, wetland, and open water classes. These results highlight that compound atmospheric and soil extremes influence regional carbon cycling through distinct component-specific pathways, and that land use background is an important factor associated with differences in carbon flux sensitivity in humid lake–floodplain systems. Full article

Background and Objectives: Among CNS malignancies arising in infancy, ATRT stands out as the most frequently diagnosed in children younger than six months. Disruption of the SMARCB1 gene underlies the overwhelming majority of cases. Progress toward effective treatment has been hampered by two persistent challenges. Current mouse models, while informative, fall short of reproducing the full clinical and biological picture of human ATRT, and their ability to predict therapeutic outcomes in patients remains uncertain. Compounding this, the rarity of the disease makes it difficult to assemble patient cohorts of sufficient size for meaningful clinical trials. At the molecular level, germline loss of SMARCB1 exons 4 and 5 has emerged as a particularly penetrant predisposing event, with affected individuals presenting at an earlier age than those harboring other mutation types. The porcine SMARCB1 gene offers a compelling basis for translational modeling as its protein product is identical to the human ortholog at every amino acid position across isoforms, a degree of conservation that exceeds what is seen in the mouse. Methods: Thus, we hypothesized that germline deletion of exons 4 and 5 would predispose heterozygote swine to ATRT development. In this manuscript, we describe the creation of an ATRT porcine model through a CRISPR/Cas9 mediated gene-editing approach. Results: 15 piglets were produced, two of which had confirmed SMARCB1 targeted excisions. However, none developed tumors. To induce further tumorigenicity, one pig with confirmed exons 4 and 5 excision was crossed with a pig with TP53 exon 2 truncation. In total, 11 piglets were born, of which one contained the original excision without a TP53 mutation. This piglet developed a spinal mass at the T1 level. Conclusion: To our knowledge, this is the first ATRT porcine model ever developed and provides proof-of-concept feasibility for large animal modeling of SMARCB1-deficient rhabdoid tumors. These findings support the continued development of porcine RTPS-1 models toward preclinical application. Full article

Glacial lake outburst floods (GLOFs) are a major cryosphere-related hazard in High Mountain Asia (HMA), where glacier mass loss and changing hydroclimatic conditions are reshaping glacial-lake systems and increasing the prevalence of potentially unstable lake–dam configurations. However, current knowledge remains fragmented across HMA. Therefore, this review synthesizes historical evidence, future changes, and risk-reduction strategies of GLOFs across HMA from a remote-sensing perspective. Historical evidence derived from satellite archives, multi-temporal lake inventories, geomorphological analyses, and documented event records indicate that reported GLOFs in HMA are strongly clustered by sub-region and dam type, with moraine-dammed lakes representing the dominant source of documented events, while ice-dammed lakes remain important in several mountain belts. The compiled record also shows that GLOFs have caused severe human, economic, geomorphic, and ecological losses. Future projections based on glacier evolution, glacial-lake expansion, and climate-sensitive hazard assessments indicate continued glacial-lake growth under global warming. However, reliable prediction of future GLOF event timing, magnitude, and frequency remains constrained by uncertainties in glacier evolution, dam stability, and triggering processes. This review further shows that effective GLOF risk reduction in HMA requires integrated systems that combine hazard and risk mapping, early warning, structural interventions, and non-structural measures. It also highlights the need to better link remote sensing with monitoring, assessment, and implementation frameworks, and proposes an integrated management cycle to support practical risk reduction. It concludes that the most urgent research priorities are harmonized multi-temporal lake inventories, targeted field observations, explicit consideration of heatwaves and compound extremes, transparent uncertainty propagation, and stronger operationalization of monitoring and warning systems to support durable climate adaptation and disaster risk reduction across HMA. Full article

PM2.5 and near-surface O₃ compound pollution is a major challenge for further air quality improvement in the Yangtze River Delta (YRD). Despite research on the chemical coupling mechanisms and concentration co-variation between PM2.5 and O₃, the directional linkages of compound pollution events among cities and the network mechanisms underlying their formation remain unclear. Here, we identified PM2.5–O₃ compound pollution events for 41 YRD cities from 2015 to 2024 using city-year-specific P80 dual-threshold criteria. We then constructed annual directed synchronization networks based on event-leading relationships and used temporal exponential random graph models to identify the formation mechanisms of significant leading ties. PM2.5–O₃ compound pollution events in the YRD generally decreased during 2015–2024, with characteristics shifting from high frequency, persistence, and strong intercity linkage in the early stage to lower frequency, weaker intensity, and continued episodic fluctuations. Directed event networks exhibited a clear stage-dependent evolution: network density, total edge weight, reciprocity, and local closure were relatively high during 2015–2018, networks became markedly sparse during 2020–2022, and a partial rebound occurred after 2023. Spatial backbone analysis indicated reorganization of the dominant linkage structure, shifting from the Shanghai–southern Jiangsu–northern Zhejiang coastal core toward the northern Jiangsu, Anhui, and interprovincial corridors. Key node analysis further revealed a clear functional differentiation among cities, with some cities acting as potential leading sources, some as receiving nodes, and several non-traditional core cities serving as cross-regional bridges. Significant leading ties were jointly shaped by reciprocity, local closures, temporal memory, economic development, industrial structure, and digital governance. Therefore, as well as a problem of co-occurrence, PM2.5–O₃ compound pollution in the YRD is a cross-city event-network process characterized by directionality, stage-dependent evolution, and differentiated urban roles. This study provides empirical evidence for dynamic joint prevention and control based on event linkages, urban roles, and cross-city coordination. Full article