Search

We analyzed the characteristics of main karstic/non-karst reaches of the Lijiang River to uncover the causes behind different flood behaviors by providing a better understanding of the flood formation. Having 63 years of rainfall-runoff data and applying the HEC-HMS model, geo/hydrological features were investigated. The available reservoir capacity of karts (ARCK) was included through soil moisture accounting loss data to assess its impact. In particular, the expected instantaneous peak discharge rates/times were found largely imbalanced with generated unit hydrographs. Moreover, significant gaps among the floods’ features for different subbasins in terms of required peak modifications (2–4 times larger for mid-upstream, respectively) were mainly associated with the unique karst structure and initial condition due to various ARCK in rainy/dry seasons. Besides, notable dissimilarities between the wedge/prism storage volumes and the hydrograph’s wave traveling/receding time were observed owing to the geomorphological conditions. Although the contribution rates of drivers in karst flood formation cannot be quantitively modeled, based on our results the ARCK emerged to play a substantial role on the forecasted results, comparatively. Our results suggest that since ARCK varies, taking it into account (as initial abstraction) results in a more reliable estimation. This was underpinned by the results in which the unmodified simulations had a qualified rate of 52% accuracy on average and increased to 67.5% after the ARCK inclusion. This work adds to the body of evidence illustrating that in karst hydrology, ignoring the situational circumstances in modeling might lead to inaccuracies in flood forecasting for such dynamic watersheds. HIGHLIGHTS Hydrological models inaccurately forecast flood features in karst basins.; The seasonality of available karst reservoir capacity drives flood peaks.; Initial conditions must be considered in model calibration for karstic areas.;

Mortality rates due to lung cancer are high worldwide. Although PD‐1 and PD‐L1 immune checkpoint inhibitors boost the survival of patients with non‐small‐cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build‐up and potential lysine‐lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non‐histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi‐omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl‐APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti‐APOC2K70‐lac antibody that sensitized anti‐PD‐1 therapy in vivo is developed. This findings highlight the potential of anti lactyl‐APOC2‐K70 approach as a new combination therapy for sensitizing immunotherapeutic responses. [ABSTRACT FROM AUTHOR]

This paper presents a multi-source preventive maintenance (MPM) based precision sensitivity optimization method for parallel robotic systems. Taking a parallel mechanism as an example, the input error can be divided into finite mutually independent uncertain error sources, and the probabilistic error model is established by the Monte Carlo stochastic method. Considering that several times of maintenance can lead to an increase of the accuracy degradation factor, a generalized hierarchy maintenance yield model is established, where the cost of preventive maintenance and failure replacement maintenance are distinguished between the independent error source and the overall error source. The nonlinear relationship between the maintenance yield per unit cost and influencing factors, including the error threshold and the maintenance times is obtained, which allows to develop an optimal maintenance strategy. Preventive maintenance is introduced to avoid unintended failure of the mechanism while extending the lifetime. The high-precision parallel mechanism has demonstrated promising applications in medical, industrial and other fields, and its economic benefits can be effectively improved by incorporating the MPM method. The experiment of manufacturing human lung models using a parallel 3D printing device demonstrates that the MPM method can improve the long-term precision and reliability of the parallel device, and the optimized human lung contour tracking precision can be improved by up to 55.56%. [ABSTRACT FROM AUTHOR]

Colletotrichum boninense is the main pathogenic fungus causing leaf spot disease in Sorghum sudangrass hybrids, which seriously impairs its quality and yield. In order to find an efficient and green means of control, this study used the agar disk diffusion method to screen for a fungicide with the strongest inhibitory effect on C. boninense from among several bacteria, fungi, and chemicals. Then, the changes in the plant's antioxidant system and metabolic levels after treatment were used to compare the three means of control. The lowest inhibitory concentration of Zalfexam was 10 mg/mL, at which point C. boninense did not grow, and the inhibition rates of Bacillus velezensis (X7) and Trichoderma harzianum were 33.87–51.85% and 77.86–80.56%, respectively. Superoxide dismutase (SOD) and chitinase were up-regulated 2.43 and 1.24 folds in the Trichoderma harzianum group (M group) and SOD activity was up-regulated 2.2 folds in the Bacillus velezensis group (X7 group) compared to the control group (CK group). SOD, peroxidase (POD), and chitinase activities were elevated in the Zalfexam group (HX group). The differential metabolites in different treatment groups were mainly enriched in amino acid metabolism and production, flavonoid production, and lipid metabolism pathways. Compared with the diseased plants (ZB group), the M, X7, HX, and CK groups were co-enriched in the tryptophan metabolic pathway and glutamate–arginine metabolic pathway, and only the CK group showed a down-regulation of the metabolites in the two common pathways, while the metabolites of the common pathways were up-regulated in the M, X7, and HX groups. In addition, the salicylic acid–jasmonic acid pathway and ascorbic acid–glutathione, which were unique to the M group, played an important role in helping Sorghum sudangrass hybrids to acquire systemic resistance against stress. This study fills the gap in the control of Colletotrichum boninene, which causes leaf spot disease in Sorghum sudangrass hybrids. This paper represents the first reported case of biological control for leaf spot disease in Sorghum sudangrass hybrids and provides a reference for the control of leaf spot disease in Sorghum sudangrass hybrids as well as other crops infected with Colletotrichum boninense. [ABSTRACT FROM AUTHOR]

This study aimed to enhance flood forecasting accuracy in the Liangfeng River basin, a small karst watershed in Southern China, by incorporating the Available Reservoir Capacity of Karst (ARCK) into the HEC-HMS model. This region is often threatened by floods during the rainy season, so an accurate flood forecast can help decision-makers better manage rivers. As a crucial influencing factor on karstic runoff, ARCK is often overlooked in hydrological models. The seasonal and volatile nature of ARCK makes the direct computation of its specific values challenging. In this study, a virtual reservoir for each sub-basin (total of 17) was introduced into the model to simulate the storage and release of ARCK-induced runoff phenomena. Simulations via the enhanced model for rainfall events with significant fluctuations in water levels during 2021–2022 revealed that the Nash–Sutcliffe efficiency coefficient (NSE) of the average simulation accuracy was improved by more than 34%. Normally, rainfalls (even heavy precipitations) during the dry season either do not generate runoff or cause negligible fluctuations in flow rates due to long intervals. Conversely, relatively frequent rainfall events (even light ones) during the wet season result in substantial runoff. Based on this observation, three distinct types of karstic reservoirs with different retaining/releasing capacities were defined, reflecting variations in both the frequency and volume of runoff during both seasons. As a real-time environmental variable, ARCK exhibits higher and lower values during the dry and rainy seasons, respectively, and we can better avoid the risk of flooding according to its special effects. [ABSTRACT FROM AUTHOR]

Agricultural activities contribute significantly to the pollution of groundwater through the incomplete absorption of nitrogen (N) and phosphorus (P). Understanding the vertical migration patterns of N and P in soil solution is crucial for controlling groundwater quality. This study is based on monitoring data of soil solution nitrogen and phosphorus at different depths (30 cm, 60 cm, 100 cm) in the Huixian Wetland Experimental Area in the Li River Basin from March to December 2021. The vertical distribution patterns of nitrogen and phosphorus in soil solution in the study area are elucidated from three aspects: seasonal variations, karst types, and land use. The results indicate that the following: (1) NO3−-N is the predominant form of nitrogen, generally decreasing with increasing soil depth, while NH4+-N concentrations show slight increases and TP concentrations remain relatively stable. Overall, NO3−-N and TN concentrations tend to accumulate at 30 cm and 60 cm depths during both irrigation and non-irrigation seasons, with no distinct distribution patterns observed for NH4+-N and TP. (2) During the irrigation season, the migration distance of NO3−-N in non-karst landforms is mainly at 60 cm, while in peak forest plains, it is mainly at 100 cm, with no clear trend observed in NO3−-N concentrations in peak cluster depressions. In non-irrigation seasons, the distribution of NO3−-N content in non-karst landforms and peak cluster depressions is mainly 30 cm > 60 cm > 100 cm. The downward migration distance of NH4+-N generally follows the order of peak cluster depressions > peak forest plains > non-karst landforms. (3) During the irrigation season, NO3−-N concentrations in paddy fields remain relatively high at 100 cm, while in drylands, NO3−-N concentrations generally follow the pattern of 30 cm > 60 cm > 100 cm but may exhibit anomalous increases or decreases at 60 cm and 100 cm depths during heavy rainfall. [ABSTRACT FROM AUTHOR]

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X‐linked (IPEX) syndrome, which is a CD4+ T cell‐driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency‐induced autoimmunity, Treg‐deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme‐linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real‐time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL‐2, IFN‐γ, IL‐4, TNF‐α, and IL‐6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL‐2‐signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency‐induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL‐2‐STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL‐2‐STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome. [ABSTRACT FROM AUTHOR]

Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site–clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity of TAD boundaries. [ABSTRACT FROM AUTHOR]