Microglia specific alternative splicing alterations in multiple sclerosis.

Several aberrant alternative splicing (AS) events and their regulatory mechanisms are widely recognized in multiple sclerosis (MS). Yet the cell-type specific AS events have not been extensively examined. Here we assessed the diversity of AS events using web-based RNA-seq data of sorted CD15-CD11b+ microglia in white matter (WM) region from 10 patients with MS and 11 control subjects. The GSE111972 dataset was downloaded from GEO and ENA databases, aligned to the GRCh38 reference genome from ENSEMBL via STAR. rMATS was used to assess five types of AS events, alternative 3'SS (A3SS), alternative 5'SS (A5SS), skipped exon (SE), retained intron (RI) and mutually exclusive exons (MXE), followed by visualizing with rmats2sashimiplot and maser. Differential genes or transcripts were analyzed using the limma R package. Gene ontology (GO) analysis was performed with the clusterProfiler R package. 42,663 raw counts of AS events were identified and 132 significant AS events were retained based on the filtered criteria: 1) average coverage >10 and 2) delta percent spliced in (ΔPSI) >0.1. SE was the most common AS event (36.36%), followed by MXE events (32.58%), and RI (18.94%). Genes related to telomere maintenance and organization primarily underwent SE splicing, while genes associated with protein folding and mitochondrion organization were predominantly spliced in the MXE pattern. Conversely, genes experiencing RI were enriched in immune response and immunoglobulin production. In conclusion, we identified microglia-specific AS changes in the white matter of MS patients, which may shed light on novel pathological mechanisms underlying MS.

Revitalizing maize growth and yield in water-limited environments through silicon and zinc foliar applications.

Maize is an economically vital cereal crop. However, water deficiency can severely impact its productivity. Thus, it is necessary to implement an essential approach to increase maize yield while navigating the limitations imposed by scarce water supplies. The present study aimed to investigate whether foliar applications of silicon (Si) and zinc (Zn) could mitigate the adverse effects of water deficiency and improve maize growth and yield. Field experiments were conducted in Egypt during two growing seasons (2021-2022) under three irrigation regimes: full irrigation (ET0), moderate stress (ET1), and severe stress (ET2). The treatments comprised foliar sprays of Si, Zn, Si + Zn, and water control. Phenological, growth, physiological, chemical, and yield-related traits were assessed. Results showed that adequate irrigation (ET0) enhanced most parameters compared to water stress treatments. Under ET0, the combined silicon and zinc treatment resulted in the highest values for plant height, leaf area, chlorophyll content, grains per ear, kernel weight, ear size, and yield compared to other foliar treatments. Under drought stress (ET1, ET2), Si + Zn applications maintained superiority in mitigating yield losses. Proline accumulation was highest under severe stress (ET2) in the absence of foliar sprays, indicating greater drought impacts. Correlation analysis revealed positive associations of grain yield with ear size, leaf area, kernel weight, and biological yield. Cluster analysis separated irrigation regimes and visualized the consistently beneficial effects of Si + Zn across all water levels. Overall, the results demonstrate the synergistic potential of Si and Zn supplementation to sustain maize performance and yields under varying water availability.

Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis.

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.

A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble.

Purpose: Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Conclusion: Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

Skull and vertebral bone marrow in central nervous system inflammation.

Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system (CNS). CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory responses. Here, we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS diseases. Further, we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.

Optimizing wheat productivity through integrated management of irrigation, nutrition, and organic amendments.

Enhancing wheat productivity by implementing a comprehensive approach that combines irrigation, nutrition, and organic amendments shows potential for collectively enhancing crop performance. This study examined the individual and combined effects of using irrigation systems (IS), foliar potassium bicarbonate (PBR) application, and compost application methods (CM) on nine traits related to the growth, physiology, and yield of the Giza-171 wheat cultivar. Analysis of variance revealed significant (P ≤ 0.05) main effects of IS, PBR, and CM on wheat growth, physiology, and yield traits over the two growing seasons of the study. Drip irrigation resulted in a 16% increase in plant height, leaf area index, crop growth rate, yield components, and grain yield compared to spray irrigation. Additionally, the application of foliar PBR at a concentration of 0.08 g/L boosted these parameters by up to 22% compared to the control. Furthermore, the application of compost using the role method resulted in enhanced wheat performance compared to the treatment including mix application. Importantly, the combined analysis revealed that the three-way interaction between the three factors had a significant effect (P ≤ 0.05) on all the studied traits, with drip irrigation at 0.08 g PBR rate and role compost application method (referred as Drip_0.08g_Role) resulting in the best performance across all traits, while sprinkle irrigation without PBR and conventional mixed compost method (referred as sprinkle_CK_Mix) produced the poorest results. This highlights the potential to synergistically improve wheat performance through optimized agronomic inputs.

Veliparib exerts protective effects in intracerebral hemorrhage mice by inhibiting the inflammatory response and accelerating hematoma resolution.

Poly (ADP-ribose) polymerase (PARP) inhibitors have potent anti-inflammatory effects, including the suppression of brain microglial activation. Veliparib, a well-known PARP1/2 inhibitor, exhibits particularly high brain penetration, but its effects on stroke outcome is unknown. Here, the effects of veliparib on the short-term outcome of intracerebral hemorrhage (ICH), the most lethal type of stroke, were investigated. Collagenase-induced mice ICH model was applied, and the T2-weighted magnetic resonance imaging was performed to evaluate lesion volume. Motor function and hematoma volume were also measured. We further performed immunofluorescence, enzyme linked immunosorbent assay, flow cytometry, and blood-brain barrier assessment to explore the potential mechanisms. Our results demonstrated veliparib reduced the ICH lesion volume dose-dependently and at a dosage of 5 mg/kg, veliparib significantly improved mouse motor function and promoted hematoma resolution at days 3 and 7 post-ICH. Veliparib inhibited glial activation and downregulated the production of pro-inflammatory cytokines. Veliparib significantly decreased microglia counts and inhibited peripheral immune cell infiltration into the brain on day 3 after ICH. Veliparib improved blood-brain barrier integrity at day 3 after ICH. These findings demonstrate that veliparib improves ICH outcome by inhibiting inflammatory responses and may represent a promising novel therapy for ICH.

Genetic analysis and QTL mapping of seed hardness trait in a soybean (Glycine max) recombinant inbred line (RIL) population.

Seed hardness is a critical quality trait impacting both the suitability of soybeans for consumption and their processing. The primary objective of this study was to explore the genetic foundations underlying seed hardness in soybeans. A 234 recombinant inbred line (RIL) population was evaluated for seed hardness across three years (2015 in Gansu, 2016, and 2017 in Hainan). Notably, the parent varieties, Zhonghuang35 and Jindou21, displayed significant differences in seed hardness. Also, the RIL population exhibited a wide range of genetic variation in seed hardness, with coefficients of variation between 70.53 % and 94.94 %. The frequency distribution of this trait conformed to a relatively normal distribution, making it suitable for QTL analysis. Six QTLs associated with seed hardness were identified with three located on chromosome 2 and three on chromosome 16. The major QTL, qHS-2-1, consistently exhibited the highest percentage of PVE and LOD in Gansu 2015, Hainan 2016, and Hainan 2017, suggesting its central role in determining seed hardness. Further investigation revealed four genes within the qHS-2-1 interval potentially related to seed hardness. GO enrichment analysis provided insights into their functions, including factors such as Glyma.02G307000, a pectin lyase-like superfamily protein, which could influence seed hardness through its role in pectin lyase enzyme activity. Expression analysis of these candidate genes demonstrated significant differences between the two parent varieties, further highlighting their potential role in seed coat hardness. This study offers valuable insights into the genetic mechanisms governing soybean seed coat hardness, providing a foundation for future research and crop improvement efforts.

Analysis of pollutant dispersion patterns in rivers under different rainfall based on an integrated water-land model.

In the context of rapid urban expansion, the interaction between humanity and nature has become more prominent. Urban land and rivers often exist as distinct entities with limited material exchange. However, during rainfall, these two systems interconnect, resulting in the transfer of land-derived pollutants into rivers. Such transfer significantly increases river pollutant levels, adversely affecting water quality. Therefore, developing a water quality simulation and prediction model is crucial. This model should effectively illustrate pollutant movement and dispersion during rain events. This study proposes a comprehensive model that merges the Storm Water Management Model (SWMM) with the Environmental Fluid Dynamics Code (EFDC). This integrated model assesses the spread and dispersion of pollutants, including Ammonia Nitrogen (NH3-N), Total Phosphorus (TP), Total Nitrogen (TN), and Chemical Oxygen Demand (COD), within urban water cycles for various rainfall conditions, thus offering critical theoretical support for managing the water environment. The application of this model under different rainfall intensities (light, moderate and heavy) provides vital insights. During light rainfall, the river's natural purification process can sustain surface water quality at Class IV. Moderate rainfall causes accumulation of pollutants, reducing water quality to Class V. Conversely, heavy rainfall rapidly increases pollutant concentrations due to higher inflow, pushing the river to a degraded Class V status, which is beyond its natural purification capacity, necessitating engineering solutions to reattain Class IV quality. Furthermore, pollutant accumulation in downstream river sections is more influenced by flow rate than by rainfall intensity. In summary, the SWMM-EFDC integrated model proves highly effective in predicting river water quality, thereby significantly aiding urban water pollution control.

Manipulating rhizosphere microorganisms to improve crop yield in saline-alkali soil: a study on soybean growth and development.

Introduction: Rhizosphere microorganisms can effectively promote the stress resistance of plants, and some beneficial rhizosphere microorganisms can significantly promote the growth of crops under salt stress, which has the potential to develop special microbial fertilizers for increasing the yield of saline-alkali land and provides a low-cost and environmentally friendly new strategy for improving the crop yield of saline-alkali cultivated land by using agricultural microbial technology. Methods: In May 2022, a field study in a completely randomized block design was conducted at the Heilongjiang Academy of Agricultural Sciences to explore the correlation between plant rhizosphere microorganisms and soybean growth in saline-alkali soil. Two soybean cultivars (Hening 531, a salt-tolerant variety, and 20_1846, a salt-sensitive variety) were planted at two experimental sites [Daqing (normal condition) and Harbin (saline-alkali conditions)], aiming to investigate the performance of soybean in saline-alkali environments. Results: Soybeans grown in saline-alkali soil showed substantial reductions in key traits: plant height (25%), pod number (26.6%), seed yield (33%), and 100 seed weight (13%). This underscores the unsuitability of this soil type for soybean cultivation. Additionally, microbial analysis revealed 43 depleted and 56 enriched operational taxonomic units (OTUs) in the saline-alkali soil compared to normal soil. Furthermore, an analysis of ion-associated microbes identified 85 mOTUs with significant correlations with various ions. A co-occurrence network analysis revealed strong relationships between specific mOTUs and ions, such as Proteobacteria with multiple ions. In addition, the study investigated the differences in rhizosphere species between salt-tolerant and salt-sensitive soybean varieties under saline-alkali soil conditions. Redundancy analysis (RDA) indicated that mOTUs in saline-alkali soil were associated with pH and ions, while mOTUs in normal soil were correlated with Ca2+ and K+. Comparative analyses identified significant differences in mOTUs between salt-tolerant and salt-sensitive varieties under both saline-alkali and normal soil conditions. Planctomycetes, Proteobacteria, and Actinobacteria were dominant in the bacterial community of saline-alkali soil, with significant enrichment compared to normal soil. The study explored the functioning of the soybean rhizosphere key microbiome by comparing metagenomic data to four databases related to the carbon, nitrogen, phosphorus, and sulfur cycles. A total of 141 KOs (KEGG orthologues) were identified, with 66 KOs related to the carbon cycle, 16 KOs related to the nitrogen cycle, 48 KOs associated with the phosphorus cycle, and 11 KOs linked to the sulfur cycle. Significant correlations were found between specific mOTUs, functional genes, and phenotypic traits, including per mu yield (PMY), grain weight, and effective pod number per plant. Conclusion: Overall, this study provides comprehensive insights into the structure, function, and salt-related species of soil microorganisms in saline-alkali soil and their associations with salt tolerance and soybean phenotype. The identification of key microbial species and functional categories offers valuable information for understanding the mechanisms underlying plant-microbe interactions in challenging soil conditions.

Effects of salt stress on soil enzyme activities and rhizosphere microbial structure in salt-tolerant and -sensitive soybean.

Salt is recognized as one of the most major factors that limits soybean yield in acidic soils. Soil enzyme activity and bacterial community have a critical function in improving the tolerance to soybean. Our aim was to assess the activities of soil enzyme, the structure of bacteria and their potential functions for salt resistance between Salt-tolerant (Salt-T) and -sensitive (Salt-S) soybean genotypes when subject to salt stress. Plant biomass, soil physicochemical properties, soil catalase, urease, sucrase, amylase, and acid phosphatase activities, and rhizosphere microbial characteristics were investigated in Salt-T and Salt-S soybean genotypes under salt stress with a pot experiment. Salt stress significantly decreased the soil enzyme activities and changed the rhizosphere microbial structure in a genotype-dependent manner. In addition, 46 ASVs which were enriched in the Salt-T geotype under the salt stress, such as ASV19 (Alicyclobacillus), ASV132 (Tumebacillus), ASV1760 (Mycobacterium) and ASV1357 (Bacillus), which may enhance the tolerance to soybean under salt stress. Moreover, the network structure of Salt-T soybean was simplified by salt stress, which may result in soil bacterial communities being susceptible to external factors. Salt stress altered the strength of soil enzyme activities and the assembly of microbial structure in Salt-T and Salt-S soybean genotypes. Na+, NO3--N, NH4+-N and Olsen-P were the most important driving factors in the structure of bacterial community in both genotypes. Salt-T genotypes enriched several microorganisms that contributed to enhance salt tolerance in soybeans, such as Alicyclobacillus, Tumebacillus, and Bacillus. Nevertheless, the simplified network structure of salt-T genotype due to salt stress may render its bacterial community structure unstable and susceptible.

CD22 blockade modulates microglia activity to suppress neuroinflammation following intracerebral hemorrhage.

Microglia are first responders to acute brain insults and initiate neuroinflammation to drive secondary tissue injury. Yet the key molecular switches in control of the inflammatory activity of microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby a hematoma is formed within the brain parenchyma and associated with high mortality. Using a mouse model of ICH, we found upregulation of CD22 that predominantly occurred in microglia. Antibody blockade of CD22 led to a reduction in neurological deficits, brain lesion and hematoma volume. This was accompanied by reduced inflammatory activity, increased expression of alternative activation markers (CD206 and IL-10) and enhanced phagocytosis activity in microglia after ICH. CD22 blockade also led to an increase of phosphorylated SYK and AKT after ICH. Notably, the benefits of CD22 blockade were ablated in ICH mice subjected to microglial depletion with a colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, the protective effects of CD22 blockade was diminished in ICH mice receiving a SYK inhibitor R406. Together, our findings highlight CD22 as a key molecular switch to control the detrimental effects of microglia after acute brain injury, and provide a novel strategy to improve the outcome of ICH injury.

Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes.

Intracerebral hemorrhage (ICH) remains the most lethal type of stroke, and effective clinical therapies that can speed up hematoma resolution after ICH are still lacking. While the beneficial effects of IL-10 on ICH recovery have been demonstrated, the clinical translation of IL-10 requires effective delivery methods by which sufficient IL-10 can be delivered to ICH-affected regions in the brain. Here we report the use of a phosphatidylserine (PS) liposome (PSL)-based nanoparticle system for microglia/macrophage-targeted delivery of IL-10 in ICH. We first prepared IL-10-conjugated PSL (PSL-IL10) and characterized their immunomodulating effects in vitro. Then we evaluated the therapeutic effects, including hematoma absorption, short-term outcomes, and neuroinflammation, of intranasally administered PSL-IL10 (3 µg IL-10 per mouse, 2 h post-ICH) in a collagenase-induced ICH mouse model. We also isolated microglia/macrophages from the mouse brains with ICH to analyze their morphology, phagocytosis ability, and polarization. Our study reveals that, 1) PSL-IL10 treatment resulted in significantly improved outcomes and accelerated hematoma resolution in the acute phase of ICH; 2) PSL-IL10 inhibited glial activation and down-regulated pro-inflammatory cytokine production; 3) PSL-IL10 induced Iba1+ cells with a stronger phagocytosis ability; 4) PSL-IL10 activated STAT3 and upregulated CD36 expression in microglia/macrophage. These findings collectively show that PSL-IL10 is a promising nanotherapeutic for effectively ameliorating ICH.

Cultivation model and deficit irrigation strategy for reducing leakage of bundle sheath cells to CO2, improve 13C carbon isotope, photosynthesis and soybean yield in semi-arid areas.

A better understanding of the photosynthesis and soil water storage regulation of soybean production will be helpful to develop a water conservation strategy under a rain-fed farming system. Reducing the leakage of CO2 bundle sheath cells and improving the photosynthesis capacity and gas exchange characteristics of soybean leaves will contribute to increase yield under the dryland agricultural system and provide a scientific basis. Therefore, during 2019 and 2020, soybean exposed to different cultivation modes to analyze the response curves of photosynthesis and CO2 under different deficit irrigation strategies. In this study, we used two cultivation models: RB: ridge covered with biodegradable film and furrow area not covered; CF: conventional flat land planting under four deficit irrigation modes (R: rainwater irrigation; IB: branch stage irrigation (220 mm); IP: Irrigation during podding (220 mm); IBP: branch stage irrigation (110 mm), podding stage irrigation (110 mm). Compared with CF-IBP treatment, RB-IBP had significant effects on rainwater collection, SWS, and soybean yield. Photo-response curve analysis showed that RB-IBP treatment a significant increase in Pn, Gs, Ci, Tr, leaf WUE, and chlorophyll ab content. Under different irrigation strategies, maximum net photosynthetic rate (Pnmax), light saturation point (LSP), and apparent quantum efficiency under RB-IBP treatment (α), Pn under respiration rate and CO2 response curve were significantly higher than that under CF cultivation mode. Compared with RB culture mode under different irrigation strategies, CF cultivation mode significantly increases Δ13C and CO2 sheath cell leakage (Փ); it also led to a significant decline in the ratio of Ci/Ca concentration. This study shows that RB-IBP treatment is the best water-saving strategy because it means reducing the leakage of CO2 from the bundle sheath, thus significantly increasing soil water storage, photosynthetic capacity, and soybean yield.

ZmG6PDH1 in glucose-6-phosphate dehydrogenase family enhances cold stress tolerance in maize.

Glucose-6-phosphate dehydrogenase (G6PDH) is a key enzyme in the pentose phosphate pathway responsible for the generation of nicotinamide adenine dinucleotide phosphate (NADPH), thereby playing a central role in facilitating cellular responses to stress and maintaining redox homeostasis. This study aimed to characterize five G6PDH gene family members in maize. The classification of these ZmG6PDHs into plastidic and cytosolic isoforms was enabled by phylogenetic and transit peptide predictive analyses and confirmed by subcellular localization imaging analyses using maize mesophyll protoplasts. These ZmG6PDH genes exhibited distinctive expression patterns across tissues and developmental stages. Exposure to stressors, including cold, osmotic stress, salinity, and alkaline conditions, also significantly affected the expression and activity of the ZmG6PDHs, with particularly high expression of a cytosolic isoform (ZmG6PDH1) in response to cold stress and closely correlated with G6PDH enzymatic activity, suggesting that it may play a central role in shaping responses to cold conditions. CRISPR/Cas9-mediated knockout of ZmG6PDH1 on the B73 background led to enhanced cold stress sensitivity. Significant changes in the redox status of the NADPH, ascorbic acid (ASA), and glutathione (GSH) pools were observed after exposure of the zmg6pdh1 mutants to cold stress, with this disrupted redox balance contributing to increased production of reactive oxygen species and resultant cellular damage and death. Overall, these results highlight the importance of cytosolic ZmG6PDH1 in supporting maize resistance to cold stress, at least in part by producing NADPH that can be used by the ASA-GSH cycle to mitigate cold-induced oxidative damage.

Research on the Optimal Regulation of Sudden Water Pollution.

For the needs of the whole region's emergency regulation of the nullah sudden water pollution event, the emergency regulation strategy of the accident section and upstream and downstream of the sudden water pollution event is studied. For the accident section, the duration of the whole emergency event is calculated using the parameter quantification method; for the upstream of the accident section, the NSGA-II is used to adjust the gate opening to ensure the water level stability of the upstream pools; for the downstream section, the optimized partition method is used to identify the unfavorable pools and close the unfavorable pool to extend the water supply time. Based on the example of an emergency event in the section of the Liyanghe gate-Guyunhe gate of the middle line project, the research results are as follows: the accident section is identified as the Xiaohe gate-Hutuohe gate, the upstream of the accident section is the Liyanghe gate-Xiaohe gate, and the downstream of the accident section is the Hutuohe gate-Gangtou Tunnel gate. The duration of the emergency event in the accident section is 7.9 h; the maximum average water level deviation before the gate upstream of the accident section is 0.05 m; two unfavorable canal pools are identified in the stream of the accident section, and the water supply time of the unfavorable pools is extended by 6.13 and 5.61 d.

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat.

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome. Here we develop NeuronChat, a method and package for the inference, visualization and analysis of neural-specific communication networks among pre-defined cell groups using single-cell expression data. We incorporate a manually curated molecular interaction database of neural signaling for both human and mouse, and benchmark NeuronChat on several published datasets to validate its ability in predicting neural connectivity. Then, we apply NeuronChat to three different neural tissue datasets to illustrate its functionalities in identifying interneural communication networks, revealing conserved or context-specific interactions across different biological contexts, and predicting communication pattern changes in diseased brains with autism spectrum disorder. Finally, we demonstrate NeuronChat can utilize spatial transcriptomics data to infer and visualize neural-specific cell-cell communication.

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat.

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome. Here we develop NeuronChat, a method and package for the inference, visualization and analysis of neural-specific communication networks among pre-defined cell groups using single-cell expression data. We incorporate a manually curated molecular interaction database of neural signaling for both human and mouse, and benchmark NeuronChat on several published datasets to validate its ability in predicting neural connectivity. Then, we apply NeuronChat to three different neural tissue datasets to illustrate its functionalities in identifying interneural communication networks, revealing conserved or context-specific interactions across different biological contexts, and predicting communication pattern changes in diseased brains with autism spectrum disorder. Finally, we demonstrate NeuronChat can utilize spatial transcriptomics data to infer and visualize neural-specific cell-cell communication.

A Study of Strength Parameter Evolution and a Statistical Damage Constitutive Model of Cemented Sand and Gravel.

Cemented sand and gravel (CSG) has a wide range of applications in dam construction, and its properties are between rockfill and roller compacted concrete (RCC). A difference in gel content will result in a variance in CSG's structure and mechanical properties. To investigate the intricate structural mechanical properties of CSG, this study conducted a series of laboratory tests and associated discrete element analyses. Accordingly, the evolution law of the strength parameters of CSG is explored and a statistical damage constitutive model suitable for CSG is established. The main contributions of this study are as follows: (1) The failure mechanism of the CSG was described from the microscopic level, and the evolution law of the strength parameter cohesion and friction angle of the CSG was analyzed and summarized. (2) Based on the particle flow model, the energy development law and the spatiotemporal distribution law of acoustic emission (AE) provide illustrations of the strain hardening-softening transition features and the interaction between cohesion and friction of CSG. (3) The evolution function between the strength parameter and the strain softening parameter was built, and the critical strain softening parameter was determined by the microcrack evolution law of the particle flow model. (4) The accuracy of the evolution curve was confirmed by comparing it to experimental results. (5) Based on the relationship between cohesion loss and material damage, a statistical damage constitutive model was developed using the improved Mohr-Coulomb strength criterion as the micro strength function. The constitutive model can accurately describe the stress-strain curves of CSG with different gel content. Furthermore, the model reflects the strain hardening-softening properties of CSG and reveals the relationship between the weakening of cohesion and material damage at the microscopic level. These findings provide valuable guidelines for investigating the damage laws and microcosmic failure features of CSG and other relevant materials.

A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum.

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.