Neuronal depolarization activates L-type voltage-gated Ca2+ channels (LTCCs), increasing local Ca2+ concentrations to initiate excitation-transcription (E-T) coupling. We show that depolarization enhances clustering of CaV1.2 and CaV1.3 LTCCs in cultured hippocampal neurons, coinciding with increased nuclear CREB phosphorylation. LTCC clustering and LTCC-dependent CREB phosphorylation are selectively disrupted by 1,6-hexanediol, implicating biomolecular condensation. Activated CaMKIIα holoenzymes assemble complexes containing multiple CaV1.2 and/or CaV1.3 α1 subunits. Complex assembly is facilitated by co-expression of CaMKII-binding β2a subunits and Shank3 and selectively disrupted by 1,6-hexanediol. In HEK293 cells, pharmacological LTCC activation enhances clustering only when wild-type CaMKIIα is co-expressed. A CaMKII mutant that cannot bind LTCC N-terminal domains fails to support LTCC subunit complex formation in vitro and LTCC clustering in HEK293 cells. In neurons, the knockdown of CaMKII expression disrupts depolarization-induced (co-)clustering of CaV1.2 and CaV1.3. Together, these findings indicate that CaMKII-dependent clustering of plasma membrane LTCCs via biomolecular condensation is essential for initiating long-range signaling to activate gene expression following neuronal depolarization.

Genetic variation within intron 3 of the CACNA1C calcium channel gene is associated with schizophrenia and other neuropsychiatric disorders, but analysis of the causal variants and their effect is complicated by a nearby variable- number tandem repeat (VNTR). Here, we explored the structure and population variability of the CACNA1C intron 3 VNTR using 155 long- read genome assemblies from 78 diverse individuals. Based on sequence differences among repeat units, we clustered individual sequences into 7 VNTR structural alleles called Types. Three Types were related through large duplications, but the other Types diverged much earlier such that only 12 repeat units at the 5 ' end of the VNTR were shared across most Types. The most diverged Types were rare and present only in individuals with African ancestry, but a multiallelic structural polymorphism was present across populations at different frequencies, consistent with expansion of the VNTR preceding the emergence of early hominins. We demonstrated that this polymorphism was in complete linkage disequilibrium with fine- mapped schizophrenia variants from genome- wide association studies (GWAS) and that this risk haplotype was associated with decreased CACNA1C gene expression in the brain. Our work suggests that sequence variation within a human- specific VNTR affects gene expression and provides a detailed characterization of new alleles at a flagship neuropsychiatric GWAS locus.

Heavy metal pollution in agricultural soil has been tightly associated with anthropogenic emissions. Although there are many studies that focus on a regional scale, the source identification of heavy metal contamination on a field scale around industrial areas remains unclear. The average concentrations in topsoils of Hg, Cd, As, Pb, Cr, Ni, Zn, and Cu were 2.07, 0.13, 8.56, 42.3, 81.1, 37.3, 105, and 43.8 mg kg−1, respectively. The enrichment of Hg was particularly presented on topsoils, with the highest single pollution index (Pi) (9.00) and ecological risk index (Eri) (922) values. An integrated methodology was employed in source identification of heavy metals contamination, especially for Hg, including Pearson’s and PCA analysis, soil profile morphology, mathematical modeling, and Hg isotope analysis. Results revealed that the concentrations of Hg decreased as a function of depth, suggesting Hg contamination was an anthropogenic source and can be supported by Hg isotope analysis. The negative Δ199Hg values of the residual Hg (F4-Hg) and soil profile in 80–100 cm deviate from those of the soil profiles in 0–80 cm, indicating exogenous input of Hg occurred in the study area. According to the UNMIX model, the contribution of coal combustion, agricultural activities, parent material, and industrial/traffic emissions to Hg accumulation in soils were 66.2%, 16.9%, 9.81%, and 7.0%, respectively. However, the contribution rates calculated with the PMF model of mixed industrial source, traffic emissions, and parent material were 71.4%, 27.8%, and 0.8%, respectively. This study can accurately quantify and identify the factors contributing to heavy metal contamination in agricultural soil on a field scale.

Soybean (Glycine max L.) is a major crop valued for both food and industrial applications. The genetic diversity preserved within landrace accessions serves as a critical resource for improving agronomic traits and enhancing adaptation to climatic variability. Korean landrace soybeans, shaped by long-term cultivation across diverse local environments, provide an ideal population for dissecting genetic variation underlying key traits and regional adaptation. A genome-wide association study (GWAS) was performed on 1,693 Korean landrace soybean accessions genotyped with 67,222 SNPs from the 180 K Axiom® Soya SNP array. Population structure and genetic diversity were assessed using model-based stratification (K = 15), principal component analysis (PCA), linkage disequilibrium (LD) decay analysis (r² = 0.2 at 309 kb), and FST-based differentiation. GWAS using the MLMM, FarmCPU, and BLINK models identified 38 significant SNPs associated with flowering date (FD), maturity date (MD), number of seeds per pod (NOSPP), and 100-seed weight (SW), including pleiotropic loci. Candidate genes within LD blocks were annotated and subjected to Gene Ontology (GO) enrichment, revealing biological processes such as signaling, transcriptional regulation, sterol metabolism, and cell division. Haplotype analysis supported phenotypic differentiation among allelic groups. For SNPs located outside of LD blocks, variation in allele frequencies and trait values across regions indicated evidence of local adaptation. These findings provide new insights into the genetic architecture of agronomic traits in Korean landrace soybeans. The identified loci, functionally annotated candidate genes, and region-specific alleles constitute a valuable genomic resource for breeding programs aiming to develop climate-resilient and regionally adapted soybean cultivars.

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity. In mice, the neural mechanisms underlying aversive social learning, specifically avoidance and fear after defeat, involve oxytocin signalling in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part.

The joint construction of the Silk Road Economic Belt and the 21st Century Maritime Silk Road proposed by China has brought major development opportunities for the development of countries and regions along the routes. Traditional GDP statistics based on administrative units cannot describe the spatial differences of GDP within administrative units, which has certain limitations in exploring regional economic development analysis and supporting economic development decision making. Based on NPP-VIIRS luminous remote sensing data, land use data, and statistical yearbook data, this paper analyzes the spatial–temporal evolution pattern of economic level in China’s coastal economic belt from 2012 to 2021 using the Moran index and standard deviation ellipse. An unbalanced distribution of economic development are found along China coastal area and the economic gravity center moved southwest since the Belt and Road Initiative. The results show thatthe Yangtze River Delta was extremely active , and the economic growth of the south was better than that of the north. The grided GDP map presents more details of regional economic development, and provides an opportunity for further mechanisms exploration of the development process.

AIM:To investigate the effect of sarcopenic obesity on the progression of glycaemic status in middle-aged and older adults without diabetes. MATERIALS AND METHODS:This research involved 4637 participants without diabetes from the China Health and Retirement Longitudinal Study 2011-2015. Sarcopenic obesity at baseline was evaluated based on the Asian Working Group for Sarcopenia 2019 criteria. According to the American Diabetes Association criteria, we used fasting plasma glucose and glycated haemoglobin to define glycaemic status. Cox proportional hazard models were applied to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:The mean age of included participants was 58.98 ± 8.82 years, and 45.35% were men. During 18,497 person-years of follow-up, 1743 (37.59%) cases with glycaemic status progression were identified. Compared with participants without sarcopenia and obesity, participants with sarcopenic obesity, but not sarcopenia only or obesity only, exhibited a higher risk of progression from normoglycaemia to diabetes (HR = 2.11; 95% CI: 1.10-4.04). Moreover, participants with sarcopenic obesity (HR = 1.65; 95% CI: 1.04-2.63), sarcopenia only (HR = 1.78; 95% CI: 1.11-2.86), or obesity only (HR = 2.00; 95% CI: 1.29-3.12) had increased the risk of progression from prediabetes to diabetes. CONCLUSIONS:The effect of sarcopenic obesity on the progression of glycaemic status based on fasting plasma glucose and glycated haemoglobin may be more pronounced than that of sarcopenia only or obesity only.

Photoperiod sensitivity is among the most important agronomic traits of rice, as it determines local and seasonal adaptability and plays pivotal roles in determining yield and other key agronomic characteristics. By controlling the photoperiod, early-maturing rice can be cultivated to shorten the breeding cycle, thereby reducing the risk of yield losses due to unpredictable climate change. Furthermore, early-maturing and high-yielding rice needs to be developed to ensure food security for a rapidly growing population. Early-maturing and high-yielding rice should be developed to fulfill these requirements. OsCKq1 encodes the casein kinase1 protein in rice. OsCKq1 is a gene that is activated by photophosphorylation when Ghd7, which suppresses flowering under long-day conditions, is activated. This study investigates how OsCKq1 affects heading in rice. OsCKq1-GE rice was analyzed the function of OsCKq1 was investigated by comparing the expression levels of genes related to flowering regulation. The heading date of OsCKq1-GE lines was earlier (by about 3 to 5 days) than that of Ilmi (a rice cultivar, Oryza sativa spp. japonica), and the grain length, grain width, 1,000-grain weight, and yield increased compared to Ilmi. Furthermore, the culm and panicle lengths of OsCKq1-GE lines were either equal to or longer than those of Ilmi. Our research demonstrates that OsCKq1 plays a pivotal role in regulating rice yield and photoperiod sensitivity. Specifically, under long-day conditions, OsCKq1-GE rice exhibited reduced OsCKq1 mRNA levels alongside increased mRNA levels of Hd3a, Ehd1, and RFT1, genes known for promoting flowering, leading to earlier heading compared to Ilmi. Moreover, we observed an increase in seed size. These findings underscore OsCKq1 as a promising target for developing early-maturing and high-yielding rice cultivars, highlighting the potential of CRISPR/Cas9 technology in enhancing crop traits.

Amidst the challenges posed by global climate change and accelerated urbanization, the structure and distribution of land use are shifting dramatically, exacerbating ecological and land-use conflicts, particularly in China. Effective land resource management requires accurate forecasts of land use and cover change (LUCC). However, the future trajectory of LUCC, influenced by climate change and urbanization, remains uncertain. This study developed an integrated multi-scenario framework by combining system dynamics and patch-generating land use simulation models to predict future LUCC in high-density urban regions under various Shared Socioeconomic Pathway (SSP)–Representative Concentration Pathway (RCP) scenarios. The results showed the following: (1) From 2020 to 2050, cultivated land, unused land, and water are projected to decrease, while construction land is expected to increase. (2) Future land use patterns exhibit significant spatial heterogeneity across three scenarios. Construction land will expand in all districts of Hangzhou, particularly in the main urban areas. Under the SSP585 scenario, the expansion of construction land is most significant, while it is the least under the SSP126 scenario. (3) Distinct factors drive the expansion of different land use types. The digital elevation model is the predominant factor for the expansion of forest and grassland, contributing 19.25% and 30.76%, respectively. Night light contributes the most to cultivated land and construction land, at 13.94% and 20.35%, respectively. (4) The average land use intensity (LUI) in central urban districts markedly surpasses that in the surrounding suburban areas, with Xiacheng having the highest LUI and Chun’an the lowest. Under the SSP126 scenario, the area with increased LUI is significantly smaller than under the SSP245 and SSP585 scenarios. These findings offer valuable guidance for sustainable planning and built environment management in Hangzhou and similarly situated urban centers worldwide.

Epilepsy is a chronic neurological disorder characterized by episodic dysfunction of central nervous system. The most basic mechanism of epilepsy falls to the imbalance between excitation and inhibition. In adults, GABAA receptor (GABAAR) is the main inhibitory receptor to prevent neurons from developing hyperexcitability, while its inhibition relies on the low intracellular chloride anion concentration ([Cl-]i). Neuronal-specific electroneutral K+-Cl- cotransporter (KCC2) can mediate chloride efflux to lower [Cl-]i for GABAAR mediated inhibition. Our previous study has revealed that the coordinated downregulation of KCC2 and GABAAR participates in epilepsy. According to a high-throughout screen for compounds that reduce [Cl-]i, CLP290 turns out to be a specific KCC2 functional modulator. In current study, we first confirmed that CLP290 could dose-dependently suppress convulsant-induced seizures in mice in vivo as well as the epileptiform burst activities in cultured hippocampal neurons in vitro. Then, we discovered that CLP290 functioned through preventing the downregulation of the KCC2 phosphorylation at Ser940 and hence the KCC2 membrane expression during convulsant stimulation, and consequently restored the GABA inhibition. In addition, while CLP290 was given in early epileptogenesis period, it also effectively decreased the spontaneous recurrent seizures. Generally, our current results demonstrated that CLP290, as a specific KCC2 modulator by enhancing KCC2 function, not only inhibits the occurrence of the ictal seizures, but also suppresses the epileptogenic process. Therefore, we believe KCC2 may be a suitable target for future anti-epileptic drug development.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored. We found that LPI transiently increased hippocampal CA3-CA1 excitatory presynaptic release probability and evoked synaptic strength in WT mice, while attenuating inhibitory postsynaptic strength by decreasing GABAARγ2 and gephyrin puncta. LPI effects at excitatory and inhibitory synapses were eliminated by CBD pre-treatment and absent after GPR55 deletion. Acute pentylenetrazole-induced seizures elevated GPR55 and LPI levels, and chronic lithium-pilocarpine-induced epileptogenesis potentiated LPI's pro-excitatory effects. We propose that CBD exerts potential anti-seizure effects by blocking LPI's synaptic effects and dampening hyperexcitability.

Excitation–transcription coupling (E–TC) links synaptic and cellular activity to nuclear gene transcription. It is generally accepted that E–TC makes a crucial contribution to learning and memory through its role in underpinning long-lasting synaptic enhancement in late-phase long-term potentiation and has more recently been linked to late-phase long-term depression: both processes require de novo gene transcription, mRNA translation and protein synthesis. E–TC begins with the activation of glutamate-gated N -methyl- d -aspartate-type receptors and voltage-gated L-type Ca 2+ channels at the membrane and culminates in the activation of transcription factors in the nucleus. These receptors and ion channels mediate E–TC through mechanisms that include long-range signalling from the synapse to the nucleus and local interactions within dendritic spines, among other possibilities. Growing experimental evidence links these E–TC mechanisms to late-phase long-term potentiation and learning and memory. These advances in our understanding of the molecular mechanisms of E–TC mean that future efforts can focus on understanding its mesoscale functions and how it regulates neuronal network activity and behaviour in physiological and pathological conditions.

•It is the first nationwide cohort study to assess the association of BPV with depressive symptoms in non-Western populations.•Participants with the highest tertile in BPV had a higher risk of depressive symptoms, independent of mean blood pressure.•Our findings suggested that there was a nonlinear dose-response relationship between BPV and the risk of depressive symptoms.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsy, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored. We found that LPI transiently increased hippocampal CA3→CA1 excitatory presynaptic release probability and evoked synaptic strength in WT mice, while attenuating inhibitory postsynaptic strength by decreasing GABA A Rγ 2 and gephyrin puncta. Effects of LPI at both excitatory and inhibitory synapses were eliminated by CBD pretreatment and absent after GPR55 deletion. Acute pentylenetrazole-induced seizures elevated levels of GPR55 and LPI, and chronic lithium pilocarpine-induced epileptogenesis potentiated the pro-excitatory effects of LPI. We propose that CBD exerts potential therapeutic effect both by blocking synaptic effects of LPI and dampening hyperexcitability.

Significance Approximately 400 United States children 1 y of age and older die suddenly from unexplained causes annually. We studied whole-exome sequence data from 124 “trios” (decedent child and living parents) to identify genetic risk factors. Nonsynonymous mutations, mostly de novo (present in child but absent in both biological parents), were highly enriched in genes associated with cardiac and seizure disorders relative to controls, and contributed to 9% of deaths. We found significant overtransmission of loss-of-function or pathogenic missense variants in cardiac and seizure disorder genes. Most pathogenic variants were de novo in origin, highlighting the importance of trio studies. Many of these pathogenic de novo mutations altered a protein network regulating calcium-related excitability at submembrane junctions in cardiomyocytes and neurons.

Understanding the responses of soil nitrous oxide (N 2 O) emissions from terrestrial ecosystems to future CO 2 enrichment and warming is critical for the development of mitigation and adaptation policies. The effects of continuous increase in elevated CO 2 (EC) and elevated temperature (ET) on N 2 O emissions are not fully known. We synthesized 209 measurements from 70 published studies and carried out a meta‐analysis to examine individual and interactive effects of EC and ET on N 2 O emissions from grasslands, croplands and forests. On average, a significant increase of 23% in N 2 O emissions was observed under EC across all case studies. EC did not affect N 2 O emissions from grasslands or forests, but significantly increased N 2 O emissions in croplands by 38%. The extent of ET effects on N 2 O emissions was nonsignificant and there was no significant difference in N 2 O emission responses among these three terrestrial systems. ET only promoted N 2 O emissions in forest by about 32% when ET was less than 2°C. The interactive effect of EC and ET on N 2 O emissions was significantly synergistic, showing a greater increase than the sum of the effects caused by EC and ET alone. Our findings indicated that the combination of EC and ET substantially promoted soil N 2 O and highlighted the urgent need to explore its mechanisms to better understand N 2 O responses under future climate change.

In agro-ecosystems, fertilization practices must accomplish high and stable crop productivity, with maximum soil organic carbon (SOC) sequestration to address climate change and food security challenges. However, the impacts of these practices on SOC and crop yields are variable over the long-term duration, and an improved understanding of the factors influencing SOC sequestration and sustainable productivity is still needed to provide evidence-based management decisions. Therefore, we conducted a meta-analysis to evaluate the impact of long-term (>= 10 years) application of different fertilizer management practices adapted across China on crop productivity, yield sustainability, and SOC sequestration. Results indicated that unbalanced mineral fertilizer (UMF), balanced mineral fertilizer (BMF), organic fertilizers (OF), combined unbalanced mineral and OF, and combined balanced mineral and organic fertilizers (BMOF) significantly enhanced the grain yield, and SOC sequestration compared with control (p < .05). For UMF, the increases in SOC and grain yields were least among fertilization practices. Comparing OF, BMF mostly produced more grain yields, but with a slight increase in C sequestration. Highest SOC sequestration rate of 0.43 Mg C ha(-1)yr(-1)was recorded in BMOF, among all the treatments. The data obtained indicated that SOC sequestration is highly time-dependent. Irrespective of fertilization mode, SOC gradually increased and attained the peak of sequestration rate in the initial two decades rather than at later stages of fertilizer addition. The linear fitted model indicated that an increase in SOC sequestration benefits sustainable productivity. The available data indicate that crop yields can be improved by 143 kg ha(-1)for rice (Oryza sativa), 255 kg ha(-1)for maize (Zea mays), and 202 kg ha(-1)for wheat (Triticum aestivum) with every 1 Mg ha(-1)increase in SOC stock by fertilization in the root zone. In crux, BMOF can maintain and improve soil quality while producing high and stable crop yields.

The activity of calcium channels in the heart increases during what is called the fight-or-flight response. An investigation into the 50-year-old mystery of how this occurs has captured a previously overlooked suspect.