Functional characterization of Varroa destructor secreted saliva reveals insights into mechanisms for parasitism of the honey bee.

Rice diseases — blast (Magnaporthe oryzae), bacterial leaf blight (Xanthomonas oryzae pv. oryzae), and sheath blight (Rhizoctonia solani)—cause annual global yield losses of 10–100%, resulting in billions of U.S. dollars in economic damage. Smallholder farmers in remote regions often lack access to agronomy experts and face difficulties using image-based diagnostic systems on low-capacity devices. This study proposes and evaluates a hybrid three-module Decision Support System (DSS) framework based on non-image tabular data to address these challenges. The framework integrates: (1) Dempster–Shafer Theory for probabilistic disease diagnosis using 48 structured clinical symptom parameters from ESforRPD2; (2) a hybrid AHP–TOPSIS module with CRITIC-based objective weight verification for multicriteria treatment ranking; and (3) an adaptive Fuzzy SAW module employing dynamic weights based on crop growth stages derived from Paddy Doctor Metadata. Experimental results show that the Dempster–Shafer module achieved 88.9% accuracy, a macro F1-score of 0.877, and a macro AUC-ROC of 0.939, outperforming Certainty Factor (82.4%), Random Forest (85.7%), and XGBoost (86.1%). The AHP model produced a valid Consistency Ratio (CR = 0.030), while CRITIC analysis revealed substantial differences between expert-assigned and data-driven weights. The adaptive Fuzzy SAW module achieved 100% agreement with agronomy expert recommendations (Spearman’s rho = 0.941), surpassing static SAW (25%, rho = 0.487) and standalone TOPSIS (0%, rho = 0.412). The framework operates without image input and provides recommendations in under two seconds, making it suitable for low-capacity devices and remote agricultural environment

Pathological cardiac hypertrophy drives heart failure progression, but the proteostatic mechanisms restraining maladaptive remodeling remain poorly defined. Here, we identify Zyg-11-related regulator 1 (ZER1) as a previously unrecognized Gly/N-degron proteostatic regulator of pressure overload-induced remodeling. Failing human hearts and mouse transverse aortic constriction (TAC) hearts show suppression of a CRL2/Gly-N-degron signature and reduced ZER1 abundance. Global and cardiomyocyte-specific Zer1 loss exacerbates TAC-induced hypertrophy, fibrosis, and systolic dysfunction. Mechanistically, ZER1 directly binds disheveled segment polarity protein 2 (DVL2) in an N-terminus-dependent manner and promotes its K48-linked polyubiquitination and proteasomal degradation, thereby limiting DVL2 accumulation and downstream CaMKII-HDAC4-MEF2C signaling. Cardiomyocyte-targeted Dvl2 knockdown abolishes the phenotypic differences between Zer1fl/fl and Zer1-cKO mice after TAC. WWP1 knockdown cannot rescue the phenotype induced by ZER1 deletion, demonstrating that ZER1 is required for Wwp1 knockdown-mediated protection against pressure overload-induced cardiac remodeling. Importantly, cardiomyocyte-selective AAV9-mediated restoration of ZER1 after TAC onset attenuates established remodeling and preserves cardiac function. Together, these findings define a ZER1-DVL2 proteostatic checkpoint that links Gly/N-degron-dependent protein quality control to pathological cardiac remodeling and highlights ZER1 as a potential therapeutic target for heart failure.

NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma.

Tomato gray mold, caused by Botrytis cinerea, causes severe global economic losses. This study evaluates the biocontrol efficacy and underlying mechanisms of Trichoderma harzianum T4 which has application potential. Results showed that T. harzianum T4 significantly promoted tomato seed germination and growth while enhancing systemic resistance. T4 exhibited high ecological fitness, maintaining growth and sporulation under salinity, acid, and nutrient stress. Notably, both volatile organic compounds and cell-free culture filtrates of T4 markedly inhibited B. cinerea by disrupting physiological homeostasis. These treatments triggered reactive oxygen species accumulation, impaired toxicant efflux transport, and induced apoptosis-like programmed cell death. Transcriptomic and RT-qPCR analyses confirmed that T4 treatments downregulated genes related to virulence, cellulolysis, and infection structure formation in B. cinerea. These findings demonstrate the multi-targeted antagonistic strategy of T. harzianum T4, providing a theoretical and technical foundation for its application as a sustainable antimicrobial agent in integrated management.

Protected areas are widely regarded as a cornerstone of global forest conservation, yet growing mineral demand intensifies mining pressure on them. Here, we present a global assessment of mining-induced forest loss within and beyond protected areas from 2001 to 2020. We find that approximately 11% (~1372 km2) of global mining-induced forest loss occurs within protected areas, with this proportion increasing to ~19% during 2016-2020. Furthermore, ~27% (544) of mines associated with forest loss within protected areas remain active throughout the study period. Mining impacts also extend beyond protected area boundaries, where forest loss in the surrounding 10-km buffer zones (~4113 km2) is nearly three times that observed within protected areas. Temporal analyses further reveal that mining increasingly affects forests with higher biomass density over time. These findings demonstrate growing mining pressure on protected forests and highlight the need to mitigate impacts both within and beyond protected area boundaries.

Natural disasters have increasingly threatened population health, but their global impacts on fertility remain uncertain. This study aims to quantify global fertility loss attributable to natural disasters and its socioeconomic disparities. We conducted a two-stage analysis using disaster records from the Emergency Events Database (EM-DAT) and total fertility rate (TFR) and net reproductive rate (NRR) data from the Global Burden of Disease (GBD) 2021 database. First, we used country-year panel data to assess exposure-response functions. Second, we estimated spatiotemporal distributions and inequalities of global, regional, and national fertility losses attributable to natural disasters. Here we show that, globally, floods and storms contribute to annual TFR losses of 103.79 and 38.75 per 100,000 women of childbearing age. Flood-attributable TFR loss is most pronounced in South Asia, particularly in low-SDI and low-income countries, whereas storm-attributable TFR loss is greater in high-SDI and middle-income countries. For NRR, epidemics, storms, floods, and earthquakes contribute to losses of 35.26, 32.36, 31.96, and 24.53 per 100,000 women of childbearing age annually. South Asia shows the highest NRR losses attributable to floods, storms, and earthquakes, whereas Sub-Saharan Africa shows the highest epidemic-attributable NRR loss. Epidemic- and flood-attributable NRR losses are higher in low-SDI and low-income countries, whereas earthquake- and storm-attributable NRR losses are higher in middle- to high-SDI and income countries. Floods, storms, earthquakes, and epidemics contribute to significant fertility loss worldwide, with geographical and socioeconomic disparities. Regions prone to these disasters should implement local-specific reproductive health strategies to maintain sustainable demographic structures.

Driven by digitalization, infrastructure expansion, and the clean energy transition, global mining has grown rapidly over the past two decades, intensifying land-use pressure and sharpening trade-offs between resource extraction and biodiversity conservation. However, spatially explicit assessments of mining-related biodiversity impacts and the tracing of these impacts along mining supply chains remain limited. Here, we present a spatially explicit assessment framework that links local biodiversity intactness loss, expressed as mean species abundance, to global potential species loss, and we couple this framework with a multiregional input-output model to trace consumption-driven impacts along global mining supply chains. We find that biodiversity loss impacts associated with global mining land use are nearly twice as high as those of previous global estimates. Hotspots in Indonesia, New Caledonia, Australia, Brazil, and Peru account for 57% of the global mining-related biodiversity impacts. Coal, precious metals, nickel, iron, and copper extraction together contribute 82% of the total impact. Due to international trade, 77% of mining-related biodiversity footprints occur outside the countries of final consumption, with demand from China, Europe, Japan, and the United States accounting for 58% of the total footprints. Our results improve the transparency of biodiversity impacts embedded in global mining supply chains and support hotspot-oriented biodiversity conservation and supply chain governance.

Two fluffy family proteins, CgrFlbA and CgrFlbC, coordinately regulate hyphal growth, oxidative stress, asexual development, and pathogenicity in Colletotrichum graminicola.

Global crop losses caused by plant viruses, particularly tobacco mosaic virus (TMV), amount to billions of dollars per year, necessitating the urgent development of potent and environmentally friendly antiviral agents. Twelve natural products were identified from P. strobilacea seeds. Among them, (-)-Epicatechin 3-gallate (1) showed higher anti-TMV activity than ningnanmycin at 125-500 μg mL-1, with inhibition rates of 49.36-80.27%, 39.34-70.28%, 33.48-63.13%, and 32.18-65.17% in inactivation, protective, curative, and resistance-inducing assays, respectively. Compound 1 disrupted TMV particle integrity and reduced TMV-CP gene expression. Molecular docking further suggested a potential interaction between 1 and TMV-CP, with a predicted binding affinity of -7.5 kcal mol-1 through hydrogen-bonding interactions. In addition, 1 enhanced salicylic acid accumulation, increased H₂O₂ levels, activated defense enzymes including superoxide dismutase, peroxidase, and catalase, and upregulated defense-related genes including NPR1, PR1, PR2, PR5, and PAL. Lesion phenotype and relative electrical conductivity assays suggested that 1 induced a mild local HR-like response with limited membrane damage. These results suggest that (-)-Epicatechin 3-gallate (1) is a promising lead compound for further development as both a direct-acting antiviral agent and a plant immune elicitor against TMV. © 2026 Society of Chemical Industry.

Oil crop expansion threatens global biodiversity, yet its supply chain impacts remain poorly quantified. Here we analyse biodiversity impacts along oil crop supply chains from 1995 to 2020 using spatially explicit assessments, a hybridized multi-regional input-output framework, enhanced supply chain mapping and structural decomposition analysis. By 2020, oil crop cultivation caused the potential long-term loss of 1.5% of global species (plants and terrestrial vertebrates), with oil palm, coconuts and soybeans responsible for three-quarters of this effect. Tropical regions, occupying just under half of harvested area, bear almost four-fifths of impacts. More than half of this loss was outsourced through international trade, as major importers displace biodiversity burdens to tropical regions. Biodiversity impacts increased by four-fifths since 1995, statistically attributed primarily to rising per capita consumption. Our findings identify production hotspots and consumption-side contributions, supporting targeted interventions to mitigate biodiversity impacts along oil crop supply chains.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant global loss and social disruption. Although large-scale vaccination campaigns and naturally acquired immunity have reduced viral transmission, the rapid evolution of the viral genome-driven by the lack of proofreading during replication-continues to pose a major public health threat. The current SARS-CoV-2 main protease inhibitor (Mpro), Paxlovid, substantially lowers hospitalization rates but is associated with adverse effects and drug-drug interactions with many medications. To discover more effective and safer treatments, we conducted a large-scale virtual screening to identify novel structural scaffolds targeting viral Mpro. This effort yielded a series of spiropyrrolidinoxindole derivative hits with promising low-micromolar inhibitory activity. Through preliminary analysis of the structure-activity relationship and proposed binding conformations, our findings provide a basis for rational structural optimization and may facilitate the development of potent, safer spiropyrrolidinoxindole-based therapeutics against severe COVID-19.

Pantoea ananatis is a widely distributed bacterium and is one of the causal agents of onion center rot, a disease responsible for significant global yield losses. While the environmental isolate P. ananatis SK-1, recovered from the Shirakawa River, Japan, is known to induce tissue necrosis in onion, the genetic basis of its pathogenicity remained uncharacterized. In this study, we generated a high-quality hybrid genome assembly of SK-1 using Oxford Nanopore and Illumina sequencing, yielding a 5.0 Mb genome across three contigs with 100% completeness as determined by CheckM. Genomic analysis identified a highly conserved HiVir (high virulence) cluster, a known pathogenicity gene cluster in onion-pathogenic Pantoea spp. However, the alt (allicin tolerance) cluster, which is responsible for imparting tolerance to thiosulfinates in onion tissue, was absent. Functional assays demonstrated that deletion of pepM, a key gene in the HiVir cluster, abolished necrosis in onion tissues, while complementation restored pathogenesis. In contrast, SK-1 exhibited reduced growth in onion juice, consistent with increased sensitivity to thiosulfinates that supports the lack of alt cluster in the bacterium. These findings indicate that although SK-1 possesses onion-pathogenic potential, it lacked the ability to proliferate in onion tissue, suggesting a limited capacity to rot onion.

Under the dual pressures of rapid urban expansion and global climate change, ecological degradation and biodiversity loss have become major constraints on regional sustainable development. Focusing on the Jinsha River Basin, this study addresses these challenges by constructing an ecological security network and assessing its resilience. Specifically, using the InVEST model, we quantified four key ecosystem services for the period 2000–2023. We then applied the OWA multi-criteria decision-making model to develop seven risk scenarios, balance trade-offs among ecosystem services, identify integrated ecosystem service patterns, and determine priority conservation areas. Furthermore, based on circuit theory, we constructed resistance surfaces to identify ecological corridors and strategic nodes, thereby establishing a regional ecological network. Finally, complex network theory was used to simulate changes in connectivity robustness and vulnerability robustness under both targeted and random attack scenarios. The results show that: (1) From 2000 to 2023, construction land in the Jinsha River Basin expanded continuously, while forest and grassland areas increased significantly, contributing to improved ecological functions in the northern region. Habitat quality, carbon storage, and soil conservation capacity all showed upward trends, whereas water yield remained relatively stable, with only minor fluctuations driven by precipitation patterns. (2) Scenario 5 was identified as the optimal conservation scenario because it achieved the highest average conservation efficiency (1.6779) while maintaining a high level of trade-off coordination, thereby supporting the synergistic conservation of multiple ecosystem services. Under this scenario, the area of ecological source regions increased from 63,554.94 km² in 2000 to 69,436.25 km² in 2023, the number of ecological corridors rose from 306 to 380, and the network structure evolved from a locally fragmented pattern into a stable and fully connected system. (3) The ecological network of the Jinsha River Basin showed strong topological resilience to random attacks but remained highly vulnerable to targeted attacks, as the failure of core nodes could potentially lead to significant declines in network connectivity, approaching structural collapse. Although topological network resilience improved between 2000 and 2023, the system still depended heavily on a limited number of core hub patches. Overall, this study improved the identification of ecological sources through the OWA model, constructed an ecological network based on circuit theory, and evaluated its resilience using complex network theory. These efforts provide a scientific basis for ecological conservation and restoration in the Jinsha River Basin. Future research should further refine the parameter settings of the OWA model and incorporate a broader range of risk scenarios and external factors to enhance the scientific rigor and practical applicability of ecological network construction.

Cardiomyopathies represent a heterogeneous group of myocardial disorders with distinct phenotypes and outcomes, yet their cell-type-specific mechanisms and differences remain incompletely defined. Here, we present the Cardiac Cell Atlas, a large-scale single-nucleus transcriptomic atlas of 525 cardiac tissue samples (20 newly generated and 505 publicly available) spanning dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular non-compaction (LVNC), and non-failing controls, integrating > 2million nuclei. This resource delineates both shared remodeling signatures and divergent trajectories across cardiomyopathies. We identified a previously unrecognized fibroblast (FB) subpopulation expressing cardiomyopathy genes (TNNT2, RYR2, MYBPC3), positioned between fibroblasts and ventricular cardiomyocytes (VCM) and segregating into FB-like (SORBS2-) and ventricular VCM-like (SORBS2+) states, the latter with reparative potential. Notably, HCM was dominated by compensatory hypertrophic remodeling, whereas DCM showed progressive cardiomyocyte loss and maladaptive FB expansion, consistent with their distinct clinical outcomes. Left ventricular ejection fraction (LVEF)-associated pseudotime staging revealed dynamic remodeling: early HCM showed enriched VCM-FB-endothelial(EC) signaling and effective compensation, while early DCM lacked EC involvement, predisposing to dysfunction. At mid-stage, signaling declined in HCM but intensified in DCM as ECs became active remodelers, whereas late-stage disease in both subtypes exhibited global signaling loss, with residual maladaptive extracellular matrix(ECM)-receptor activity persisting in DCM. Together, the Cardiac Cell Atlas provides a comprehensive reference for human cardiac cell states and interactions, advancing mechanistic understanding and informing clinical strategies for risk stratification, stage-specific intervention, and improved outcomes in HCM and DCM. The web portal of Cardiac Cell Atlas together with all the datasets are publicly available at http://113.54.15.143:8000/app/index/.

Quantifying the drivers of tree cover loss globally provides a synoptic understanding of pressures on the world's forests. Existing information about tree cover loss drivers relies on maps of coarse spatial and thematic resolution. In this study, we quantified the global extent of tree cover loss in 2018 at the scale of individual disturbances and provided a comprehensive accounting of land use outcomes using a global probability sample of 600 5 × 5-kilometer blocks mapped with high-resolution (3- to 10-meter) satellite data. Out of 277 thousand square kilometers of estimated global tree cover loss, nearly a third (29.0%) was due to long-term conversion of tree cover to other land uses, including conversion of natural tree cover to pasture (15.0%), cropland (6.4%), and nontimber tree plantations (3.8%).

Invasive species are recognised as a major driver of global biodiversity loss. In marine ecosystems, blooms of non-native jellyfish species are widely perceived to be increasing globally, with impacts on food webs, ecosystem services, biogeochemical cycles, and coastal livelihoods. Pelagia noctiluca (Forsskål, 1775) is a jellyfish native to the Mediterranean Sea and the northeastern Atlantic Ocean, but has been increasingly associated with recurrent bloom events in non-native regions, which cause adverse ecological and socio-economic impacts. Here, we use an ensemble species distribution modelling framework implemented in the biomod2 package in R to assess the global habitat suitability of P. noctiluca, and to evaluate its present-day and future invasion potential across non-native marine ecosystems. Based on species occurrence records and eight environmental variables, our results indicate that P. noctiluca exhibits high habitat suitability in temperate and subtropical coastal waters, driven primarily by salinity, primary productivity, and sea surface temperature. Ultimately, by projecting a substantial future habitat contraction, our findings strongly contradict the general perception that jellyfish blooms and distribution will universally increase under global climate change.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally expressed UBE3A gene. Epilepsy and abnormal electroencephalographic (EEG) rhythms are key features, but their mechanisms and treatment remain unclear. Previous work showed that extrasynaptic γ-aminobutyric acid type A (GABAA) receptor-mediated tonic inhibition is reduced in cerebellar granule cells of AS model mice, contributing to motor deficits. Here, we evaluated tonic inhibition across brain regions and tested whether its dysregulation drives epilepsy, EEG abnormalities, and behavioral deficits in AS. Tonic inhibition was measured in principal neurons of the neocortex, hippocampus, and thalamus in maternal Ube3a knockout mice. We examined the effects of MP-III-022, an α5-containing GABAA receptor-selective positive allosteric modulator, and gaboxadol, a δ-containing GABAA receptor agonist, on EEG, seizure threshold, and anxiety-like behavior. Tonic inhibition was reduced in cortical layer 5 and hippocampal CA1 pyramidal neurons but preserved in thalamic relay neurons. This reduction correlated with elevated GAT1 expression in the cortex and hippocampus but not the thalamus. MP-III-022 reduced abnormal slow-wave EEG activity, increased seizure thresholds, and improved anxiety-like behavior. In contrast, gaboxadol enhanced slow-wave activity and lowered seizure thresholds. Deficits in tonic inhibition in AS mice are region-specific. These region-dependent differences in tonic inhibition, rather than a global loss, likely underlie EEG abnormalities and heightened seizure susceptibility. α5-containing GABAA receptors may offer a promising therapeutic target for adjunctive AS treatment.

Climate change and land-use changes are key drivers of global biodiversity loss. Many species are shifting to higher elevations or latitudes in response to global warming, often encountering unfavorable land-use conditions during the shift. These changes can lead to reduced range size and increased extinction risks, particularly for mountain species that are often confined to narrow high-altitude habitats. Predicting future distributions of mountain species requires accounting for their bioclimatic responses, topographical distribution, land-use preferences, and ability to colonize new areas via dispersal. We projected the future distribution of 34 mountain mammal and 361 nonmigratory mountain bird species in 2050 under different emission scenarios. Using species distribution models (SDMs) that incorporated topography, climate, and land-use data, we assessed the impacts of global change on species' ranges across mountain regions worldwide and compared different emission scenarios to clarify the contributions of climate, land-use change, and dispersal to shaping future distributions. Species were projected to experience greater range loss under the high-emissions scenario than under the low-emissions scenario (16% higher on average). Dispersal played a key role in range shifts: when dispersal was included in the model, the number of birds that shifted their range increased by 144%. The most severe range losses were projected for species located in Central and South America and Oceania, whereas European mountains showed fewer losses, highlighting substantial regional differences in vulnerability. When land use was also considered, range dynamics remained stable, showing climate as the primary driver of mountain species distribution change. Our findings emphasize the importance of considering dispersal capacity when assessing climatic biodiversity risks in mountains. Our results highlight the urgency of applying regional strategies to establish ecological corridors, improve connectivity, and manage habitats to conserve the unique biodiversity of mountains.

Several somatic diseases have been consistently linked with an increased dementia risk. However, the underlying neuropathological substrates remain poorly characterized. This narrative review aims to summarize evidence on the association between common age-related somatic conditions (i.e., heart diseases, type 2 diabetes, kidney disease, liver diseases, lung disease, and anemia) and neuropathological findings, encompassing both Alzheimer's disease (AD)-related pathology (amyloid and tau deposition) and non-AD co-pathologies (i.e., neuronal loss, neuroinflammation, cerebrovascular lesions, and non-AD proteinopathies). We conducted a PubMed search for human studies examining these associations using postmortem data, brain imaging, or cerebrospinal fluid biomarkers. Evidence was qualitatively synthesized and graded according to its strength. Strong and consistent associations were observed between most examined somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, evidence associating these conditions with amyloid and tau pathology was limited and inconsistent. No studies systematically examined neuroinflammation or non-AD proteinopathies in relation to somatic diseases. Together, the available evidence suggests that somatic diseases are unlikely to primarily drive AD pathology but instead contribute to brain damage through a combination of non-AD processes, particularly cerebrovascular injury and diffuse neuronal loss. These findings highlight the need to increase our knowledge of "mixed dementia" and move beyond a purely brain-centric view of dementia, especially in older adults with complex clinical profiles.