Genome-wide identification of hormone biosynthetic and metabolism genes in the 2OGD family of tobacco and JOX genes silencing enhances drought tolerance in plants.

Phytohormones play crucial roles in regulation of plant growth and tolerance to abiotic stresses. The 2-oxoglutarate-dependent dioxygenase (2OGD) superfamily responds to hormone biosynthesis and metabolism in plants. However, the Nt2OGD family in tobacco has not been fully explored. In this study, we identify 126 members of the Nt2OGD family, and 60 of them are involved in hormone biosynthesis and metabolism process (Nt2OGD-Hs), including 1-aminocyclopropane-1-carboxylic acid oxidases (ACO), dioxygenases for auxin oxidation (DAO), gibberellin (GA) 20-oxidases and 3-oxidases (GA20ox and GA3ox), carbon-19 and carbon-20 GA 2-oxidases (C19-GA2ox and C20-GA2ox), lateral branching oxidoreductases (LBO), jasmonate-induced oxygenases (JOX), downy mildew resistant 6, and DMR6-like oxygenases (DMR6/DLO). Gene duplication analysis suggests the segmental duplication and whole genome duplication (WGD) might be a potential mechanism for the expansion of this family. Expression analysis reveals that most of Nt2OGD-Hs show tissue-specific expression patterns, and some of them respond to environmental conditions. Of Nt2OGD-Hs, the expression of NtJOX3 and NtJOX5, which are involved in JA metabolism, exhibits remarkable changes during drought treatments. Silencing of NtJOX3 or NtJOX5 increases tobacco tolerance to drought stress. Furthermore, knocking out OsJOX3 and OsJOX4, respectively in rice, result in high tolerance to drought. Taken together, our work comprehensively identifies the Nt2OGD family in tobacco and provides new insights into roles of the JA pathway in drought tolerance in plants.

Dynamics of phytoplankton assemblages determined by the HPLC-PIGMENTUM approach and the related environmental variables in the northern Chinese sea.

During the spring and summer of 2021, two investigations were conducted in the northern Chinese sea by using the high-performance liquid chromatography with the pigment-based chemotaxonomic tool PIGMENTUM. Results showed that the average chlorophyll a (Chl a) concentration during spring was significantly higher (p < 0.01) than that during summer. 19'-hexanoyloxyfucoxanthin-containing algae, alloxanthin-containing algae (ACA), and fucoxanthin-containing algae (FCA) were the main pigment groups in spring, whereas zeaxanthin-containing algae (ZCA) and peridinin-containing algae (PeCA) were dominated in summer. Five ecological provinces were divided, and the phytoplankton biomass (Chl a) in Province V was the lowest. Redundancy analysis showed that ACA, FCA, and PeCA were positively correlated with nutrients; in comparison, ZCA preferred high salinity. The PIGMENTUM estimates were significantly positively correlated (p < 0.01) with CHEMTAX for all phytoplankton assemblages. Nevertheless, the coefficients of determination and slope by regression analysis between two methods showed large differences for several phytoplankton groups.

Cylindrical compression of thin wires by irradiation with a Joule-class short-pulse laser.

Equation of state measurements at Jovian or stellar conditions are currently conducted by dynamic shock compression driven by multi-kilojoule multi-beam nanosecond-duration lasers. These experiments require precise design of the target and specific tailoring of the spatial and temporal laser profiles to reach the highest pressures. At the same time, the studies are limited by the low repetition rate of the lasers. Here, we show that by the irradiation of a thin wire with single-beam Joule-class short-pulse laser, a converging cylindrical shock is generated compressing the wire material to conditions relevant to the above applications. The shockwave was observed using Phase Contrast Imaging employing a hard X-ray Free Electron Laser with unprecedented temporal and spatial sensitivity. The data collected for Cu wires is in agreement with hydrodynamic simulations of an ablative shock launched by highly impulsive and transient resistive heating of the wire surface. The subsequent cylindrical shockwave travels toward the wire axis and is predicted to reach a compression factor of 9 and pressures above 800 Mbar. Simulations for astrophysical relevant materials underline the potential of this compression technique as a new tool for high energy density studies at high repetition rates.

A Review of Safe Reinforcement Learning: Methods, Theories and Applications.

Reinforcement Learning (RL) has achieved tremendous success in many complex decision-making tasks. However, safety concerns are raised during deploying RL in real-world applications, leading to a growing demand for safe RL algorithms, such as in autonomous driving and robotics scenarios. While safe control has a long history, the study of safe RL algorithms is still in the early stages. To establish a good foundation for future safe RL research, in this paper, we provide a review of safe RL from the perspectives of methods, theories, and applications. Firstly, we review the progress of safe RL from five dimensions and come up with five crucial problems for safe RL being deployed in real-world applications, coined as "2H3W". Secondly, we analyze the algorithm and theory progress from the perspectives of answering the "2H3W" problems. Particularly, the sample complexity of safe RL algorithms is reviewed and discussed, followed by an introduction to the applications and benchmarks of safe RL algorithms. Finally, we open the discussion of the challenging problems in safe RL, hoping to inspire future research on this thread. To advance the study of safe RL algorithms, we release an open-sourced repository containing major safe RL algorithms at the link.

MNSFß promotes LPS-induced TNFα expression by increasing the localization of RC3H1 to stress granules, and the interfering peptide HEPN2 reduces TNFα production by disrupting the MNSFß-RC3H1 interaction in macrophages.

Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.

Modulation of soil nitrous oxide emissions and nitrogen leaching by hillslope hydrological processes.

Soil nitrous oxide (N2O) emissions and nitrogen (N) leaching are key pathways for soil N loss in hillslope ecosystem, with potential implications for global warming and water body eutrophication. While soil N loss in hillslope ecosystem has been extensively studied, there is limited understanding of the spatiotemporal distribution patterns and factors driving soil N2O emissions and N leaching from a hillslope hydrology perspective. This study investigated N concentrations in leachate and soil N2O fluxes and their responses to soil hydrological factors on a tea plantation (TP) hillslope and a bamboo forest (BF) hillslope. Four distinct precipitation patterns-spring rainfall (SR), plum rain (PR), summer flood rain (SF), and drought period (DR)-were identified based on precipitation intensity, duration, and cumulative precipitation. Results showed that, soil N2O flux and leachate N concentrations were 8.2 times and 18.0 times higher On TP hillslope compared to the BF hillslope. The greatest soil N2O fluxes occurred during the PR period, while the lowest were observed during the DR period. Precipitation increased soil water content (SWC) and water-filled pore space, stimulating soil N cycling for N2O production. Fertilization activities and precipitation led to peak N concentration in leachate during the SR period. Additionally, soil wetness index (SWI) shaped spatial patterns of SWC, resulting in distinct spatial patterns of N2O emissions and nitrate leaching. Locations with higher SWI exhibited greater soil N2O flux and higher nitrate concentrations in leachate. This study emphasizes the significant effect of soil hydrological processes on soil N2O emissions and N leaching in hillslope ecosystems, providing valuable insights for N management in these environments.

Research progress on the use of Salvia miltiorrhiza Bunge extracts in the treatment of pulmonary diseases.

Salvia miltiorrhiza Bunge extracts, known for their diverse biological activities, often have remarkable efficacy in treating pulmonary diseases overlooked due to their specific cardiovascular actions. With the recent outbreak of COVID-19, research into pulmonary-related diseases has garnered significant attention. Salvia miltiorrhiza Bunge extracts can be broadly categorized into lipophilic and hydrophilic components; however, a comprehensive summary of their mechanisms in treating pulmonary diseases is lacking. Therefore, this review aims to systematically summarize the therapeutic mechanisms of 10 major Salvia miltiorrhiza Bunge extracts in treating pulmonary fibrosis, lung cancer, acute lung injury, and chronic obstructive pulmonary disease, with the goal of identifying promising options for efficacious therapies.

Multi-omics reveals the phyllosphere microbial community and material transformations in cigars.

The quality of fermented plant leaves is closely related to the interleaf microorganisms and their metabolic activities. In this experiment, a multi-omics analysis was applied to investigate the link between the structural composition of the phyllosphere microbial community and the main metabolites during the fermentation process. It was found that the whole fermentation process of cigar leaves could be divided into three stages, in which the Mid-Stage was the most active period of microbial metabolic activities and occupied an important position. Staphylococcus, Brevundimonas, Acinetobacter, Brevibacterium, Pantoea, Aspergillus, Wallemia, Meyerozyma, Sampaiozyma, Adosporium and Trichomonascus played important roles in this fermentation. Staphylococcus and Aspergillus are the microorganisms that play an important role in the fermentation process. Staphylococcus were strongly correlated with lipids and amino acids, despite its low abundance, Stenotrophomonas is importantly associated with terpene and plays a significant role throughout the process. It is worth noting that Wapper exists more characteristic fungal genera than Filler and is more rapid in fermentation progress, which implies that the details of the fermentation process should be adjusted appropriately to ensure stable quality when faced with plant leaves of different genotypes. This experiment explored the relationship between metabolites and microorganisms, and provided a theoretical basis for further optimizing the fermentation process of plant leaves and developing techniques to improve product quality. Biomarker is mostly present in the pre-fermentation phase, but the mid-fermentation phase is the most important part of the process.

Development and validation of a nomogram of all-cause mortality in adult Americans with diabetes.

This study aimed to develop and validate a predictive model of all-cause mortality risk in American adults aged ≥ 18 years with diabetes. 7918 participants with diabetes were enrolled from the National Health and Nutrition Examination Survey (NHANES) 1999-2016 and followed for a median of 96 months. The primary study endpoint was the all-cause mortality. Predictors of all-cause mortality included age, Monocytes, Erythrocyte, creatinine, Nutrition Risk Index (NRI), neutrophils/lymphocytes (NLR), smoking habits, alcohol consumption, cardiovascular disease (CVD), urinary albumin excretion rate (UAE), and insulin use. The c-index was 0.790 (95% CI 0.779-0.801, P < 0.001) and 0.792 (95% CI: 0.776-0.808, P < 0.001) for the training and validation sets, respectively. The area under the ROC curve was 0.815, 0.814, 0.827 and 0.812, 0.818 and 0.829 for the training and validation sets at 3, 5, and 10 years of follow-up, respectively. Both calibration plots and DCA curves performed well. The model provides accurate predictions of the risk of death for American persons with diabetes and its scores can effectively determine the risk of death in outpatients, providing guidance for clinical decision-making and predicting prognosis for patients.

The application value of 24†h Holter monitoring indices in predicting MACEs outside the hospital within three years after PCI in patients with STEMI.

Background: Evaluating cardiovascular risk in patients experiencing acute ST-elevation myocardial infarction (STEMI) and undergoing percutaneous coronary intervention (PCI) is crucial for early intervention and improving long-term outcomes. 24 h Holter monitoring provides continuous cardiac electrophysiological data, enabling the detection of arrhythmias and autonomic dysfunction that are not captured during routine examinations. This study aimed to examine the relationship between Holter monitoring metrics and the occurrence of out-of-hospital major adverse cardiovascular events (MACEs) following PCI in patients with STEMI, offering insights into cardiovascular risk evaluation. Methods: This prospective cohort study included STEMI patients undergoing PCI. 24 h Holter monitoring data were recorded, including heart rate, heart rate variability (HRV) metrics such as SDNN and SDANN index, heart rate deceleration capacity (DC) at different time scales (DC2, DC4, DC8), and the frequency of premature ventricular contractions (PVCs). Independent correlations between these indices and MACEs, as well as cardiovascular deaths, were investigated using multifactorial logistic regression. Predictive capacities were assessed through receiver operating characteristic (ROC) curves. Results: A total of 172 participants were enrolled in this study. Over the 3-year follow-up period, MACEs were observed in 57 patients, including 20 cases of cardiac death. In logistic regression models adjusted for confounding variables, SDNN [OR: 0.980; 95% CI: (0.967, 0.994); p = 0.005] and SDANN index [OR: 0.982; 95% CI: (0.969, 0.996); p = 0.009] were negatively associated with the incidence of MACEs. Conversely, the slowest heart rate [OR: 1.075; 95% CI: (1.022, 1.131); p = 0.005] and frequent PVCs [OR: 2.685; 95% CI: (1.204, 5.987); p = 0.016] demonstrated a positive association with MACEs. Furthermore, SDNN [OR: 0.957; 95% CI: (0.933, 0.981); p = 0.001], DC [OR: 0. 702; 95% CI: (0.526, 0.938); p = 0.017]) and DC4 [OR: 0.020; 95% CI: (0.001, 0.664); p = 0.029] were negatively associated with cardiac death. The ROC analysis results indicated that SDNN was an effective predictor of both MACEs [AUC: 0.688 (95% CI: 0.601-0.776)] and cardiac death [AUC: 0.752 (95% CI: 0.625-0.879)]. Conclusion: HRV, DC metrics, and frequent PVCs obtained by 24 h Holter monitoring were associated with the risk of MACEs in STEMI patients. These metrics can help clinicians identify at-risk patients early so that timely interventions.

Efficient fabrication of cellulose polymer networks via alkaline swelling strategy for wood bonding.

Existing issues with bio-based adhesives, such as complex preparation processes, high energy consumption, and production costs, still need to be addressed. In our study, APTES was grafted onto microcrystalline cellulose (MCC) to generate active aminated cellulose, and then reacted with the epoxide group in glycerol triglycidyl ether (GTE) through a swelling strategy under alkaline solvent, forming a network structure via covalent cross-linking. The adhesive exhibits superior bonding performance and water-resistant property in the bonding strength test of poplar plywood, with a dry shear strength of 2.40 MPa, a wet shear strength of 2.16 MPa after soaking in 63 °C hot water, and a wet shear strength of 1.79 MPa after soaking in boiling water. In terms of cost calculation, the theoretical production cost of AC-GTE adhesive is calculated to be 5303.7 RMB per ton, which is comparable to that of phenol-formaldehyde (PF) resin and other petrochemical-based adhesives, and significantly lower than that of isocyanate-based adhesives. These research results can provide a practical example for producing high-efficiency, aldehyde-free, and low-cost bio-based adhesives.

Genetic diversity and population structure of Plenodomus biglobosus on flixweed (Descurainia sophia) in northwestern China.

Plenodomus biglobosus (Pb), a causal agent of blackleg of rapeseed, is composed of several subspecies, including 'australensis' (Pba), 'brassicae' (Pbb) and 'canadensis' (Pbc). Besides rapeseed, Pb can infect many wild cruciferous plants (WCPs), such as flixweed (Descurainia sophia) and pennycress (Thlaspi arvense), which may become the infection source for blackleg of rapeseed. However, Pb on WCPs has not been well investigated in China. This study identified the blackleg fungi on two WCPs in Sayram Lake and Zhaosu County in Xinjiang of China: flixweed (15 isolates) and pennycress (1 isolate) as well as on rapeseed (971 isolates). They belonged to Pba (11), Pbb (18) and Pbc (958). Pba occurred on flixweed (10) and pennycress (1) only in Sayram Lake, whereas Pbb and Pbc occurred on flixweed (1 and 4 isolates, respectively) and rapeseed (17 and 954 isolates, respectively) in Zhaosu County. Then, virulence of 16 isolates from flixweed and pennycress was determined on rapeseed. Their genomes were sequenced and used to identify the mating-type idiomorphs and to analyze population genetic structure. Results showed that all of the 16 isolates were virulent to rapeseed. Only MAT1-1 was detected in 11 Pba isolates, implying that Pba may lack sexual reproduction. The 16 isolates from two WCPs were divided into four genetic groups: Group I for Pbc (4 isolates), Group II for Pbb (1 isolate), and Group III (3 isolates) and IV (8 isolates) for Pba. The findings about the single mating-type in Pba and its limited geographic distribution provided a case showing the importance of sexual reproduction in epidemics of Pb. To the best of our knowledge, this is the first report of Pba, Pbb and Pbc on flixweed, and Pba on pennycress in China.

Caffeine alleviate lipopolysaccharide-induced neuroinflammation and depression through regulating p-AKT and NF-κB.

Caffeine, a nonselective adenosine receptor antagonist, is the major component of coffee and the most consumed psychostimulant at nontoxic doses in the world. It has been identified that caffeine consumption reduces the risk of several neurological diseases. However, the mechanisms by which it impacts the pathophysiology of neurological diseases remain to be elucidated. In this study, we investigated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation and depression in vivo and explored the potential mechanism of caffeine through LPS-induced brain injury. Adult male Sprague-Dawley (SD) rats were intraperitoneal injected with various concentrations of LPS to induce the neuroinflammation and depressive-like behavior. Then SD rats were treated with caffeine in the presence or absence of LPS. Open-filed and closed-field tests were applied to detect the behaviors of SD rats, while western blot was performed to measure the phosphorylation level of protein kinase B (p-AKT) and nuclear factor κB (NF-κB) in the cortex after caffeine was orally administered. Our findings indicated that caffeine markedly improved the neuroinflammation and depressive-like behavior of LPS-treated SD rats. Mechanistic investigations demonstrated that caffeine down-regulated the expression of p-AKT and NF-κB in LPS-induced SD rats cortex. Taken together, these results indicated that caffeine, a potential agent for preventing inflammatory diseases, may suppress LPS-induced inflammatory and depressive responses by regulating AKT phosphorylation and NF-κB.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Constraints on the subsecond modulation of striatal dynamics by physiological dopamine signaling.

Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions.

Normal Reorientation for Scene Consistency.

With the remarkable progress of 3D scanning technique, the captured indoor scenes appear increasingly in last decade. Generating orientation-consistent normals for indoor point clouds is a fundamental and important task. The existing orientation rectification methods pay more attention to object-level targets with connected surface. However, it is challenging to compute consistent surface orientation for real scanned indoor point clouds. In this paper, we analyze the causes of this difficulty and propose a new normal reorienting framework for indoor scene consistency, namely NRSC. It first estimates normals for an indoor point cloud and extracts all the connected regions. We then design and construct an abstract orientation bridging tree (OBT) to organize the extracted regions in a hierarchical way. For all node regions, NRSC iteratively implements a set of orientation propagations to generate locally orientation-consistent regions. Moreover, we define an auxiliary viewpoint set for each pairwise parent-child node regions and introduce a voting mechanism to rectify the region orientation of child node according to its parent. After processing all the child node regions along OBT, we finally eliminate the orientation inconsistencies between related regions. Multi-groups of experimental results on both fused indoor scenes and single-view-scenes show that our method generates globally consistent orientation for indoor point clouds.

Microbial Community Shifts in Tea Plant Rhizosphere under Seawater Stress: Enrichment of Beneficial Taxa.

Seawater intrusion has a significant impact on the irrigation quality of agricultural water, thereby posing a threat to plant growth and development. We hypothesized that the rhizosphere of tea plants harbors beneficial microorganisms, which may improve the tolerance of tea plants to seawater stress. This study utilized 16s and ITS techniques to analyze microbial community shifts in the tea plant rhizosphere and non-rhizosphere under seawater stress conditions. The findings suggest that seawater stress leads to a reduction in microbial diversity, although the rhizosphere microbial diversity in stressed soils showed a relatively higher level. Moreover, the rhizosphere of the tea plant under seawater stress exhibited an enrichment of plant growth-promoting rhizobacteria alongside a higher presence of pathogenic fungi. Network analysis revealed that seawater stress resulted in the construction of a more complex and stable rhizosphere microbial network compared to normal conditions. Predictions of bacterial potential functions highlighted a greater diversity of functional groups, enhancing resource utilization efficiency. In general, the rhizosphere microorganisms of tea plants are jointly selected by seawater and the host. The microorganisms closely related to the rhizosphere of tea plants are retained and, at the same time, attract beneficial microorganisms that may alleviate stress. These findings provide new insights into plant responses to saline stress and have significant implications for leveraging vegetation to enhance the resilience of coastal saline soils and contribute to economic progress.

Contrasting nitrogen transport patterns in subtropical basins revealed by combined multiple isotopic analyzes and hydrological simulations.

Although enhancing the knowledge of nitrogen (N) dynamics in aquatic systems is crucial for basin N management, there is still a lack of theories on the patterns of basin N sources and transport because of the intricate influence of human activities, climatic conditions, landscape patterns, and topography on the trajectory of basin N. To shed new light on the patterns of basin N sources and transport in the Chinese subtropical monsoon region, this study provides a comprehensive approach combining multiple isotopes and hydrological model based on monthly records of hydro-chemistry and isotopes (18O-NO3- /15N-NO-3 and 18O-H2O /2H-H2O) for river water, groundwater and rainfall in three basins over multiple years. Our observations of hydro-chemistry showed that fluvial N levels in highly urbanized basins (3.05 ± 1.42 mg·L-1) were the highest and were characterized by higher levels in the dry season. In the agricultural basin, fluvial N levels in February and March were approximately 1.9 times higher than those in the other months. The fluvial N load was higher in agricultural basins (0.624-0.728 T N km -2 y -1) than in urban basins (0.558 T N km -2 y -1), primarily because of variations in sewage treatment rates and fertilizer application. In highly urbanized basin, manure and sewage (46.9 %) were the dominant sources of fluvial N, which were discharged into rivers after treatment. In the plain agricultural basin, a substantial portion of diffused residential sewage leaches into aquifers and is stored. In the hilly agro-forest mixed basin, the high baseflow coefficient (75.8 %) and the key role of groundwater N, mainly from soil N (27.3 %), chemical fertilizers (20.2 %), manure and sewage (46.6 %), to fluvial N (26.5 %) indicated that a high proportion of the N sources leached into the aquifer and were then transported to rivers. For the first time, this study integrated multiple methods to substantiate the proposed typical patterns of N sources and transport within the basins. These findings have significant implications for tailored basin-specific N management strategies.

UBXN3B is crucial for B lymphopoiesis.

BACKGROUND: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. METHODS: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. FINDINGS: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. INTERPRETATION: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. FUNDING: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Nicotinamide improves the impaired extravillous trophoblast cell invasion induced by PM2.5 exposure-associated increase of TNFα secretion through the ROS/NF-κB/FLT1 pathway.

It has been well acknowledged that maternal exposure to fine particulate matters (PM2.5) might lead to poor pregnancy outcomes including the intrauterine growth restriction (IUGR) by interfering with the placental development. Our previous studies have demonstrated that maternal PM2.5 exposure induces IUGR, accompanied with increased maternal circulating TNFα level and impaired extravillous trophoblast cells (EVTs) invasion in mice. In this study, HTR8/SVneo cells, the immortalized human EVTs line, were used to assess effects and the underlying molecular mechanisms of nicotinamide on the impaired EVTs invasion. Our results showed that, the placental FLT1 protein level was significantly increased whereas maternal serum nicotinamide concentration was remarkably decreased in PM2.5-exposured pregnant mice at GD17.5 (vaginal plug day=GD0.5), compared to that in normal GD17.5 pregnant mice. FLT1 expression in HTR8/SVneo cells was significantly up-regulated by TNFα treatment, and the down-regulated FLT1 expression effectively abated the inhibitory effects of TNFα on HTR8/SVneo cells migration and invasion. Meanwhile, TNFα promoted reactive oxygen species (ROS) production and NF-κB signaling pathway activation in HTR8/SVneo cells in a dose-dependent manner. Nicotinamide treatment significantly reversed the effects of TNFα on cell migration and invasion, as well as the FLT1 expression, ROS production and NF-κB pathway activation. In summary, increased TNFα induced by PM2.5 exposure inhibits EVTs invasion by activating the ROS/NF-κB/FLT1 signaling pathway, and this adverse effect could be attenuated by nicotinamide treatment, suggesting a potential application in the clinical intervention of PM2.5-induced IUGR.