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Abstract Background Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic. Methods To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed. Results Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH. Conclusion Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.

A thorough understanding of the ecological impacts behind the hydrologic alteration is still insufficient and hinders the watershed management. Here, we used eco-flow indicators, multiple hydrological indicators, and fluvial biodiversity to investigate the ecological flow in different temporal scales. The case study in the Han River shows a decrease in high flows contributed to the decrease in eco-surplus and increase in eco-deficit in summer and autumn, while the decrease in eco-deficit can be attributed to the change of low flow in spring. An integrated hydrologic alteration was over 48% degree and was under moderate ecological risk degree in impact period I, while DHRAM scores showed the Huangzhuang station faced a high ecological risk degree in impact period II. The decrease (increase) in total seasonal eco-surplus (eco-deficit) was identified after alteration with the change in seasonal eco-flow indicators contributions. Shannon index showed a decreasing trend, indicating the degradation of fluvial biodiversity in the Han River basin. Eco-flow indicators such as eco-surplus and eco-deficit are in strong relationships with 32 hydrological indicators and can be accepted for ecohydrological alterations at multiple temporal scales. This study deepens the understanding of ecological responses to hydrologic alteration, which may provide references for water resources management and ecological security maintenance. HIGHLIGHTS Quantitative evaluation of ecological flows considering precipitation and reservoir factors.; Unveil effects of reservoirs on flow regimes in the Han River.; Comprehensive evaluation of ecological responses to hydrological alterations.; Scientific foundation for water resources management in the Han River.;

BackgroundTuberculosis (TB), mainly caused by Mycobacterium tuberculosis (Mtb), remains a serious public health problem. Increasing evidence supports that selective evolution is an important force affecting genomic determinants of Mtb phenotypes. It is necessary to further understand the Mtb selective evolution and identify the positively selected genes that probably drive the phenotype of Mtb.MethodsThis study mainly focused on the positive selection of 807 Mtb strains from Southern Xinjiang of China using whole genome sequencing (WGS). PAML software was used for identifying the genes and sites under positive selection in 807 Mtb strains.ResultsLineage 2 (62.70%) strains were the dominant strains in this area, followed by lineage 3 (19.45%) and lineage 4 (17.84%) strains. There were 239 codons in 47 genes under positive selection, and the genes were majorly associated with the functions of transcription, defense mechanisms, and cell wall/membrane/envelope biogenesis. There were 28 codons (43 mutations) in eight genes (gyrA, rpoB, rpoC, katG, pncA, embB, gid, and cut1) under positive selection in multi-drug resistance (MDR) strains but not in drug-susceptible (DS) strains, in which 27 mutations were drug-resistant loci, 9 mutations were non-drug-resistant loci but were in drug-resistant genes, 2 mutations were compensatory mutations, and 5 mutations were in unknown drug-resistant gene of cut1. There was a codon in Rv0336 under positive selection in L3 strains but not in L2 and L4 strains. The epitopes of T and B cells were both hyper-conserved, particularly in the T-cell epitopes.ConclusionThis study revealed the ongoing selective evolution of Mtb. We found some special genes and sites under positive selection which may contribute to the advantage of MDR and L3 strains. It is necessary to further study these mutations to understand their impact on phenotypes for providing more useful information to develop new TB interventions.

Abstract Background DFR is a crucial structural gene in plant flavonoid and polyphenol metabolism, and DFR knockout (DFR-KO) plants may have increased biomass accumulation. It is uncertain whether DFR-KO has comparable effects in tobacco and what the molecular mechanism is. We employed the CRISPR/Cas9 method to generate a knockout homozygous construct and collected samples from various developmental phases for transcriptome and metabolome detection and analysis. Results DFR-KO turned tobacco blossoms white on homozygous tobacco (Nicotiana tabacum) plants with both NtDFR1 and NtDFR2 knockout. RNA-seq investigation of anthesis leaf (LF), anthesis flower (FF), mature leaf (LM), and mature root (RM) variations in wild-type (CK) and DFR-KO lines revealed 2898, 276, 311, and 101 differentially expressed genes (DEGs), respectively. DFR-KO primarily affected leaves during anthesis. According to KEGG and GSEA studies, DFR-KO lines upregulated photosynthetic pathway carbon fixation and downregulated photosystem I and II genes. DFR-KO may diminish tobacco anthesis leaf photosynthetic light reaction but boost dark reaction carbon fixation. DFR-KO lowered the expression of pathway-related genes in LF, such as oxidative phosphorylation and proteasome, while boosting those in the plant–pathogen interaction and MAPK signaling pathways, indicating that it may increase biological stress resistance. DFR-KO greatly boosted the expression of other structural genes involved in phenylpropanoid production in FF, which may account for metabolite accumulation. The metabolome showed that LF overexpressed 8 flavonoid metabolites and FF downregulated 24 flavone metabolites. In DFR-KO LF, proteasome-related genes downregulated 16 amino acid metabolites and reduced free amino acids. Furthermore, the DEG analysis on LM revealed that the impact of DFR-KO on tobacco growth may progressively diminish with time. Conclusion The broad impact of DFR-KO on different phases and organs of tobacco development was thoroughly and methodically investigated in this research. DFR-KO decreased catabolism and photosynthetic light reactions in leaves during the flowering stage while increasing carbon fixation and disease resistance pathways. However, the impact of DFR-KO on tobacco growth steadily declined as it grew and matured, and transcriptional and metabolic modifications were consistent. This work offers a fresh insight and theoretical foundation for tobacco breeding and the development of gene-edited strains.

Flowering time, plays a crucial role in tobacco ecological adaptation besides its substantial influence on tobacco production and leaf quality. Meanwhile, it is sensitive to biotic or abiotic challenges. The plant hormones Gibberellins (GAs), controlling a number of metabolic processes, govern plants growth and development. In this study, we created a late flowering mutant HG14 through knocking out NtGA3ox1 by CRISPR/Cas9. It took around 13.0 and 12.1 days longer to budding and flowering compared to wild type Honghuadajinyuan. Nearly all of the evaluated agronomic characters deteriorated in HG14, showing slower growth and noticeably shorter and narrower leaves. We found that NtGA3ox was more prevalent in flowers through quantitative reverse transcription PCR analysis. Transcriptome profiling detected 4449, 2147, and 4567 differently expressed genes at the budding, flowering, and mature stages, respectively. The KEGG pathway enrichment analysis identified the plant-pathogen interaction, plant hormone signal transduction pathway, and MAPK signaling pathway are the major clusters controlled by NtGA3ox1 throughout the budding and flowering stages. Together with the abovementioned signaling pathway, biosynthesis of monobactam, metabolism of carbon, pentose, starch, and sucrose were enriched at the mature stage. Interestingly, 108 up- and 73 down- regulated DEGs, impairing sugar metabolism, diterpenoid biosynthesis, linoleic and alpha-linolenic acid metabolism pathway, were continuously detected accompanied with the development of HG14. This was further evidenced by the decreasing content of GA metabolites such as GA4 and GA7, routine chemicals, alkaloids, amino acids, and organic acids Therefore, we discovered a novel tobacco flowering time gene NtGA3ox1 and resolved its regulatory network, which will be beneficial to the improvement of tobacco varieties.

2-acetyl-1-pyrroline (2AP) is a highly effective volatile compound that gives fragrance to numerous plant species and food. Mutation(s) in the betaine aldehyde dehydrogenase 2 (BADH2) gene results in the accumulation of 2AP. However, the function of BADH genes in tobacco (Nicotiana tabacum L.) remains poorly understood. In this study, we successfully obtained four betaine aldehyde dehydrogenase (BADH) genes from tobacco. Phylogenetic analysis of the protein sequences showed that two of the four BADH genes were closely related to the wolfberry (Lycium barbarum) BADH gene (LbBADH1), so we named them NtBADH1a and NtBADH1b, respectively. The other two BADH genes were orthologues of the tomato (Solanum lycopersicum) aminoaldehyde dehydrogenase 2 (SlAMADH2) gene, and were named NtBADH2a and NtBADH2b, respectively. Expression analysis revealed that the biological functions of NtBADH1a and NtBADH1b were different from those of genes NtBADH2a and NtBADH2b. We introduced mutations into NtBADH1a, NtBADH1b, NtBADH2a and NtBADH2b in tobacco using the CRISPR/Cas9 system and identified transgenic Ntbadh mutant tobacco lines. Single mutants (Ntbadh1a, Ntbadh1b, Ntbadh2a and Ntbadh2b) and double mutants (Ntbadh1a-Ntbadh1b and Ntbadh2a-Ntbadh2b) harbored deletion or insertion of nucleotides, both of which led to the production of a frameshift, preventing protein accumulation. A popcorn-like scent was noticeable in tobacco leaves from the Ntbadh2a-Ntbadh2b double mutant, but not from any single mutant or the Ntbadh1a-Ntbadh1b double mutant or the wild type. Consistent with this observation, we only detected 2AP in fresh leaves from the Ntbadh2a-Ntbadh2b double mutant. These findings indicate that only the combined inactivation of NtBADH2a and NtBADH2b results in 2AP accumulation in tobacco, which was not related to NtBADH1.

Abstract As the water source for the middle route of the South-to-North Water Transfer Project, the Han River in China plays a role of the world’s largest inter-basin water transfer project. However, this human-interfered area has suffered from over-standard pollution emission and water blooms in recent years, which necessitates urgent awareness at both national and provincial scales. To perform a comprehensive analysis of the water quality condition of this study area, we apply both the water quality index (WQI) and minimal WQI (WQImin) methods to investigate the spatiotemporal variation characteristics of water quality. The results show that 8 parameters consisting of permanganate index (PI), chemical oxygen demand (COD), total phosphorus (TP), fluoride (F-), arsenic (As), plumbum (Pb), copper (Cu), and zinc (Zn) have significant discrepancy in spatial scales, and the study basin also has a seasonal variation pattern with the lowest WQI values in summer and autumn. Moreover, compared to the traditional WQI, the WQImin model, with the assistance of stepwise linear regression analysis, could exhibit more accurate explanation with the coefficient of determination (R2) and percentage error (PE) values being 0.895 and 5.515%, respectively. The proposed framework is of great importance to improve the spatiotemporal recognition of water quality patterns and further helps develop efficient water management strategies at a reduced cost.

Tobacco belongs to the family Solanaceae, which easily forms continuous cropping obstacles. Continuous cropping exacerbates the accumulation of autotoxins in tobacco rhizospheric soil, affects the normal metabolism and growth of plants, changes soil microecology, and severely reduces the yield and quality of tobacco. In this study, the types and composition of tobacco autotoxins under continuous cropping systems are summarized, and a model is proposed, suggesting that autotoxins can cause toxicity to tobacco plants at the cell level, plant-growth level, and physiological process level, negatively affecting soil microbial life activities, population number, and community structure and disrupting soil microecology. A combined strategy for managing tobacco autotoxicity is proposed based on the breeding of superior varieties, and this approach can be combined with adjustments to cropping systems, the induction of plant immunity, and the optimization of cultivation and biological control measures. Additionally, future research directions are suggested and challenges associated with autotoxicity are provided. This study aims to serve as a reference and provide inspirations needed to develop green and sustainable strategies and alleviate the continuous cropping obstacles of tobacco. It also acts as a reference for resolving continuous cropping challenges in other crops.

Abstract The hydrological cycle, affected by climate change and rapid urbanization in recent decades, has been altered to some extent and further poses great challenges to three key factors of water resources allocation (i.e., efficiency, equity and sustainability). However, previous studies usually focused on one or two aspects without considering their underlying interconnections, which are insufficient for interaction cognition between hydrology and social systems. This study aims at reinforcing water management by considering all factors simultaneously. The efficiency represents the total economic interests of domesticity, industry and agriculture sectors, and the Gini coefficient is introduced to measure the allocation equity. A multi-objective water resources allocation model was developed for efficiency and equity optimization, with sustainability (the river ecological flow) as a constraint. The Non-dominated sorting genetic algorithm II (NSGA-II) was employed to derive the Pareto front of such a water resources allocation system, which enabled decision-makers to make a scientific and practical policy in water resources planning and management. The proposed model was demonstrated in the middle and lower Han River basin, China. The results indicate that the Pareto front can reflect the conflicting relationship of efficiency and equity in water resources allocation, and the best alternative chosen by cost performance method may provide rich information as references in integrated water resources planning and management.

Abstract Global warming and anthropogenic changes can result in the heterogeneity of water availability in the spatiotemporal scale, which will further affect the allocation of water resources. A lot of researches have been devoted to examining the responses of water availability to global warming while neglected future anthropogenic changes. What’s more, only a few studies have investigated the response of optimal allocation of water resources to the projected climate and anthropogenic changes. In this study, a cascade model chain is developed to evaluate the impacts of projected climate change and human activities on optimal allocation of water resources. Firstly, a large set of global climate models (GCMs) associated with the Daily Bias Correction (DBC) method are employed to project future climate scenarios, while the Cellular Automaton–Markov (CA–Markov) model is used to project future Land Use/Cover Change (LUCC) scenarios. Then the runoff simulation is based on the Soil and Water Assessment Tool (SWAT) hydrological model with necessary inputs under the future conditions. Finally, the optimal water resources allocation model is established based on the evaluation of water supply and water demand. The Han River basin in China was selected as a case study. The results show that: (1) the annual runoff indicates an increasing trend in the future in contrast with the base period, while the ascending rate of the basin under RCP 4.5 is 4.47%; (2) a nonlinear relationship has been identified between the optimal allocation of water resources and water availability, while a linear association exists between the former and water demand; (3) increased water supply are needed in the water donor area, the middle and lower reaches should be supplemented with 4.495 billion m3 water in 2030. This study provides an example of a management template for guiding the allocation of water resources, and improves understandings of the assessments of water availability and demand at a regional or national scale.

Abstract Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

The dataset contains reservoir characteristic parameters, streamflow series of reservoirs in the upper Yangtze River, the standard operating rules (SORs) and the seasonal top of buffer pools (seasonal TBPs) for these reservoirs, which were provided by the Yangtze River Commission. Moreover, annual hydropower of these reservoirs is tested to evaluate operation performance. These research materials are related to the research article in Advances in Water Resources, entitled ‘Optimal impoundment operation for cascade reservoirs coupling parallel dynamic programming with importance sampling and successive approximation’ (He et al., 2019). The dataset could be used to derive optimal operating rules to explore the potential benefits of water resources via our proposed algorithm (importance sampling – parallel dynamic programming, IS-PDP) in different runoff scenarios. It can also be further applied for water resources management and other potential users. Keywords: Cascade reservoirs, Impoundment operation, Yangtze river basin, Streamflow observation, Parallel dynamic programming, Importance sampling, Seasonal top of buffer pools

Water environmental capacity (WEC) is an essential indicator for effective environmental management. The designed low water flow condition is a prerequisite to determine WEC and is often based on the stationarity assumption of low water flow series. As the low water flow series has been remarkably disturbed by climate change as well as reservoirs operation and water acquisition, the stationarity assumption might bring risk for WEC planning. As the reservoir operation and water acquisition under climate change can be simulated by a water resources allocation model, the low water flow series outputted from the model are the simulations of the disturbances and often show nonstationary conditions. After estimating the designed low water flow through nonstationary frequency analysis from these low water flow series, the WEC under the nonstationary conditions can be determined. Thus, the impacts of water resources allocation on WEC under climate change can be quantitatively assessed. The mid-lower reaches of the Hanjiang River basin in China were taken as a case study due to the intensive reservoir operation and water acquisition under the climate change. A representative concentration pathway scenario (RCP4.5) was employed to project future climate, and a Soil and Water Assessment Tool (SWAT) model was employed to simulate water availability for driving the Interactive River-Aquifer Simulation (IRAS) model for allocating water. Water demand in 2016 and 2030 were selected as baseline and future planning years, respectively. The results show that water resources allocation can increase the amount of WEC due to amplifying the designed low water flow through reservoir operation. Larger regulating capacities of water projects can result in fewer differences of WEC under varied water availability and water demand conditions. The increasing local water demand will decrease WEC, with less regulating capacity of the water projects. Even the total available water resources will increase over the study area under RCP4.5. More water deficit will be found due to the uneven temporal-spatial distribution as well as the increasing water demand in the future, and low water flow will decrease, which further leads to cut down WEC. Therefore, the proposed method for determining the WEC can quantify the risk of the impacts of water supply and climate change on WEC to help water environmental management.

As one of the most crucial indices of sustainable development and water security, water resources carrying capacity (WRCC) has been a pivotal and hot-button issue in water resources planning and management. Quantifying WRCC can provide useful references on optimizing water resources allocation and guiding sustainable development. In this study, the WRCCs in both current and future periods were systematically quantified using set pair analysis (SPA), which was formulated to represent carrying grade and explore carrying mechanism. The Soil and Water Assessment Tool (SWAT) model, along with water resources development and utilization model, was employed to project future water resources scenarios. The proposed framework was tested on a case study of China’s Han River basin. A comprehensive evaluation index system across water resources, social economy, and ecological environment was established to assess the WRCC. During the current period, the WRCC first decreased and then increased, and the water resources subsystem performed best, while the eco-environment subsystem achieved inferior WRCC. The SWAT model projected that the amount of the total water resources will reach about 56.9 billion m3 in 2035s, and the water resources development and utilization model projected a rise of water consumption. The declining WRCC implies that the water resources are unable to support or satisfy the demand of ecological and socioeconomic development in 2035s. The study furnishes abundant and valuable information for guiding water resources planning, and the core idea of this model can be extended for the assessment, prediction, and regulation of other systems.