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Abstract Global climate change, with warming as its main feature, has altered the spatial-temporal evolution of factors such as precipitation and temperature that can cause meteorological disasters. The complex and changeable climate has led to frequent natural disasters, while the frequency and intensity of extreme climate events have also significantly increased, posing an enormous threat to societal production and human life. As the most important geoecological transitional zone of mainland China, the stability of agricultural production in China’s north–south transitional zone is crucial for ensuring food security under climate change. With the use of daily precipitation and potential evapotranspiration data from 1961 to 2018, this study focused on analysing disturbances such as extreme precipitation and drought disasters at different time scales during the winter wheat and summer maize growing seasons in the north–south transitional zone of China from an agricultural production perspective and attempted to answer the following questions: first, from an agricultural production perspective, what are the temporal and spatial distribution patterns of extreme precipitation and arid climate events in the north–south transitional zone? Second, which areas are at high risk of being disturbed by different types of meteorological disasters and require increased attention? The results indicated that (1) in terms of the overall temporal variation, the degree of extreme precipitation and drought stress faced by agricultural production in the region is decreasing. However, the temporal variation at each station in the north–south transitional zone was not completely consistent with the overall trend, and both increasing and decreasing trends were observed. The sites exhibiting an increase overlapped with typical regions of the north–south transitional zone to varying degrees, indicating that the typical regions represented not only theoretical potential risk areas under climate change but also suffered from meteorological disaster disturbances. (2) The precipitation distribution during the winter wheat growth period in the south–north transitional zone was uneven and varied significantly. High values of extreme precipitation indices during the winter wheat growth period were mainly concentrated in the southern part of the eastern section of the north‒south transitional zone. The precipitation distribution during the summer maize growth period significantly differed, with the highest amount of heavy rain and largest number of rainstorm days concentrated in the southeastern part of the north‒south transitional zone. The spatial distribution of the drought frequency in the north–south transitional zone, as indicated by the monthly standardized precipitation evapotranspiration index (SPEI1), showed that the areas with high total drought frequencies were mainly concentrated in northeast Jiangsu, southeast Henan, and north Anhui, which primarily experienced light drought. The central part of Jiangsu Province exhibited a high frequency of moderate drought, while southern Jiangsu Province and southwestern Shaanxi Province were prone to severe drought. Additionally, southeastern Hebei and eastern Henan were identified as areas with a high frequency of extreme drought. Finally, the central region of Sichuan Province was characterized by both severe and extreme drought conditions. Based on the SPEI12-derived spatial distribution of the drought frequency in the north–south transitional zone, the areas with a high total drought frequency were mainly concentrated in central and eastern Henan, southeast Shaanxi, southeast Shandong, and central Sichuan, which primarily experienced light to moderate drought. The northwestern part of Jiangsu, the southern part of Hebei, and the western part of Shandong are regions with a high frequency of severe drought, while the eastern part of Henan is an area with high frequencies of both severe and extreme drought. (3) High-value areas of extreme precipitation and drought disturbance in the north–south transitional zone overlapped with the edge of the transitional zone to varying degrees. Approximately 63.58% of the north‒south transitional zone of China was characterized by moderate or high stress levels, primarily concentrated along the southern boundary and central core area, and nearly 39.5% of all counties experienced two or more types of disaster stresses.

Abstract Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.

Abstract The single-component colistin E2, with superior antibacterial activity and lower toxicity, was being developed as the latest generation of polymyxin drugs. However, colistin E2 has not been tested quantitatively in biological matrices. In this study, based on the quantitative detection of colistin methanesulphonate (CMS) and colistin by Zhao et al., 15N-labeled colistin E2 was used as an internal standard (IS) for a more accurate quantitative detection of CMS E2 in human plasma. A rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) assay method was developed for determination of CMS E2 and colistin E2 in human plasma. After pretreatment of plasma samples by 96-well SPE Supra-Clean Weak Cation Exchange (WCX) plate, the formed colistin E2 was detected and quantified by UHPLC–MS/MS system. All plasma lots were found to be free of interferences with the analyte. The matrix has no effect on the quantitation of the analyte. No significant effect of the carryover was observed. The dilution integrity was demonstrated in plasma samples without the loss of accuracy and precision. The lower limit of quantification (LLOQ) was 0.0300 mg/L for colistin E2 in plasma with accuracy (relative error, 5.1–12.7%) and precision (relative standard deviation, − 5.7–9.3%). Stability of CMS E2 and colistin E2 was demonstrated in biological samples before and during sample treatment, and in the extract. Furthermore, this method was successfully applied to the analysis of plasma samples obtained from Chinese healthy volunteers receiving a single intravenous CMS E2 dose of 5 mg/kg. In conclusion, the detection method was characterized by speed and high accuracy, which laid a solid foundation for the subsequent development of CMS E2 drug.

Abstract The purpose of this study was to explore the role of coixendide (Coix) combine with temozolomide (TMZ) in the treatment of Glioblastoma (GBM) and explore its possible mechanism. CCK-8 was used to determine the inhibitory rate of Coix group, TMZ group and drug combination group on GBM cells, and the combination index (CI) was calculated to determine whether they had synergistic effect. Then RNA was extracted from each group, transcriptome sequencing was performed, and differentially expressed genes (DEGs) were identified. The possible mechanism was analyzed by GO enrichment analysis and KEGG enrichment analysis. The CI of Coix and TMZ indicating a synergistic effect when TMZ concentration is 0.1 mg/ml and Coix concentration is 2 mg/ml. Transcriptome sequencing analysis showed that interferon (IFN) related genes were down-regulated by Coix and up-regulated by TMZ and combined drugs, however, the up-regulation induced by combined drugs was less than that of TMZ. Besides IFN related genes, cholesterol metabolism pathway were also been regulated. Coix and TMZ have synergistic effects in the treatment of GBM at certain doses. RNA-Seq results suggested that the abnormal on genetic materials caused by DNA damage induced by TMZ treatment can be sensed by IFN related genes and activates antiviral IFN signaling, causing the activation of repairing mechanism and drug resistance. Coix inhibits IFN related genes, thereby inhibits drug resistance of TMZ. In addition, the activation of ferroptosis and the regulation of DEGs in cholesterol metabolism pathway were also contributed to the synergistic effects of Coix and TMZ.

Abstract As the particularly popular green energy, geothermal resources are gradually favored by countries around the world, and the development model centered on geothermal dew point cannot meet the increasing geothermal demand. In this paper, a GIS model combining PCA and AHP is proposed, aiming to select the advantages of geothermal resources at the regional scale and analyze the main influencing indicators. Through the combination of the two methods, both data and empirical can be considered, then the geothermal advantage distribution on the area can be displayed through GIS software images. A multi-index evaluation system is established to qualitatively and quantitatively evaluate the mid-high temperature geothermal resources in Jiangxi Province, and carry out the evaluation of the dominant target areas and the analysis of geothermal impact indicators. The results show that it is divided into 7 geothermal resource potential areas and 38 geothermal advantage targets, and the determination of deep fault is the most critical index of geothermal distribution. This method is suitable for large-scale geothermal research, multi-index and multi-data model analysis and precise positioning of high-quality geothermal resource targets, which can meet the needs of geothermal research at the regional scale.

Abstract Although an increasing number of patients benefit from immunotherapy and targeted therapies, melanoma remains incurable with increasing incidence. Drug repositioning and repurposing is an alternative strategy to discover and develop novel anticancer drugs or combined therapeutic regimens. In this study, we demonstrated that albendazole (ABZ), an Food and Drug Administration (FDA)-approved broad-spectrum antiparasitic agent, significantly inhibits the proliferation of melanoma cells in vitro and in vivo. RNA sequencing and flow cytometry analysis revealed that ABZ arrests melanoma cells at the G2/M phase of the cell cycle and induces cell apoptosis. More importantly, the CDK4/6 inhibitor palbociclib, as a member of the first and only class of highly specific CDK inhibitors approved for cancer treatment to date, showed significant synergistic effects with ABZ treatment in melanoma cells and mouse models. Taken together, we revealed a previously unappreciated function of ABZ in antimelanoma proliferation by inducing cell cycle arrest and apoptosis and provided a novel combined therapeutic regimen of ABZ plus CDK4/6 inhibitor treatment in melanoma.

Abstract The acquisition of 2–50 Hz low-frequency vibration signals is of great significance for the monitoring researches on engineering seismology, bridges & dams, oil & gas exploration, etc. A multi-cantilever beam low-frequency FBG acceleration sensor is proposed against the low sensitivity that predominates in the low-frequency vibration measurement by FBG acceleration sensors. Structural parameters of the sensor is subjected to simulation analysis and optimization design using the ANSYS software; the real sensor is developed based on the simulation results in the following manner: Three rectangular of the cantilever beams are evenly arranged around the mass block at 120°to improve the sensitivity and alleviate the transverse crosstalk of sensor; in the end, a performance test is performed on the sensor. According to the research findings, the sensor, whose natural frequency is approximately 64 Hz, is applicable for monitoring the low-frequency vibration signals within the range 16–54 Hz. The sensor sensitivity is approximately $$87.955\,{\text{pm/m}}\;{\text{s}}^{ - 2}$$ 87.955 pm/m s - 2 , the linearity being greater than 99%, the transverse interference immunity being lower than 2.58%, and the dynamic range being up to 86 dB. The findings offer a reference for developing sensor of the same type and further improving the sensitivity of fiber optic acceleration sensor.

Abstract Mesocotyl elongation is an important trait influencing seedling emergence and establishment in rice direct-seeding cultivation and is immediately inhibited after light exposure. Detailed researches on the molecular basis and biological processes underlying light repression of mesocotyl growth could probably provide useful information for key factors controlling this trait. Here we monitored the transcriptome and endogenous phytohormone changes specifically in the elongating mesocotyl in response to light exposure with a time-course. It was revealed that 974 transcripts were significantly differentially expressed (FDR

This research delves into the transfer and loss of energy in a discrete mass when subjected to forced vibration. Using discrete element method (DEM), we analyzed the dynamic behavior of regular spherical granular assemblies and the energy distribution characteristics under different excitation frequencies and reduced accelerations. Moreover, the energy transfer and dissipation process of granular assemblies under different vibration states are studied using an experimental method. The results show that the granular assemblies will produce collision energy dissipation, thermal energy dissipation, acoustic energy dissipation and other forms of energy dissipation in the forced vibration state and the proportion of different energy dissipation under different excitation is given. The collision and friction of granular assemblies are the key to affecting other forms of energy dissipation. When the excitation increases, the energy dissipation forms are generated inside the granular assemblies, and the proportion of collision energy dissipation of the granular assemblies increases. The acoustic energy above 20 kHz occupies the main part of the acoustic energy dissipation. Thermal energy consumption always exists, which takes a long time to play a role. The granular also have other forms of energy loss, which is hard to be measured, including Rayleigh waves generated by granular collision. In this study, the relationship between the forced vibration state of the granular assemblies and the energy loss distribution is established. Various types of energy transfer and conversion distribution which further enriches the energy dissipation of discrete element calculation of the granular assemblies is discussed and provides a reference for the energy loss analysis of the granular assemblies. [ABSTRACT FROM AUTHOR]

Abstract Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3β in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3β. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3β increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3β signaling pathway.

Abstract The overcrowding of scenic spots not only threatens tourists’ safety but also affects the travel experience. Traditional methods for addressing tourist overload have involved limited access and guided evacuation. While limited access has been effective, it often results in a diminished tourist experience. Moreover, the existing guided evacuation rarely considers the impact on tourists’ experience, resulting in a low willingness to cooperate and making it difficult to estimate evacuation effort efficiency. To solve these problems, this paper proposed a tourist evacuation route recommendation algorithm based on a graph neural network considering the similarity of tourism styles (PER-GCN) and designed a visualization system to simulate and analyse evacuation efficiency. First, the interaction matrix of tourists and scenic spots was constructed using graph mining to extract the high-order interaction information. In the output layer, the similarity between scenic spots and tourism styles was calculated to further improve the accuracy of scenic spot recommendations. Second, due to route complexity and the real-time carrying capacity of scenic spots, the researchers optimized the evacuation routes. Finally, taking the West Lake spot as the case study, the effectiveness of PER-GCN was verified. Additionally, a visualization system was designed to monitor tourist flow in real time and analyse tourist portraits according to the clustering results of scenic spot styles. In addition, the evacuation efficiency of scenic spots was analysed by adjusting the parameters of tourists’ willingness to cooperate, evacuation batch, and the weight of route complexity and scenic spot carrying capacity.

Abstract The association between red blood cell distribution width (RDW) and in-hospital mortality in intensive care patients with acute pancreatitis (AP) is inconclusive. We extracted the baseline data, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, Sequential Organ Failure Assessment (SOFA) score, and in-hospital prognosis of intensive care patients with AP from the Medical Information Mart for Intensive Care IV database. Performing binary logistic regression analysis to determine whether RDW is an independent risk factor for in-hospital mortality. By drawing receiver operating characteristic (ROC) curves and comparing the areas under the ROC curves (AUC) to determine the predictive value of RDW for in-hospital mortality, and by conducting survival analysis to evaluate the impact of RDW on survival time in hospital. Before and after the propensity score matching (PSM) analysis, RDW was always a risk factor for in-hospital mortality in patients with AP. The AUC of RDW was comparable to BISAP, while the AUCs of combining RDW and BISAP or SOFA were greater than that of BISAP or SOFA alone. The median survival time of the high-RDW group (RDW > 15.37%, before PSM; RDW > 15.35%, after PSM) was shorter than that of the low-RDW group. Compared with the low-RDW group, the hazard ratios of the high-RDW group were 3.0708 (before PSM) and 1.4197 (after PSM). RDW is an independent risk factor for in-hospital mortality in patients with AP. The predictive value of RDW for in-hospital mortality of patients with AP is comparable to BISAP, and the combination of RDW and BISAP or SOFA scoring system can improve the predictive performance to a certain extent.

Abstract Few studies have addressed radiomics based differentiation of Glioblastoma (GBM) and intracranial metastatic disease (IMD). However, the effect of different tumor masks, comparison of single versus multiparametric MRI (mp-MRI) or select combination of sequences remains undefined. We cross-compared multiple radiomics based machine learning (ML) models using mp-MRI to determine optimized configurations. Our retrospective study included 60 GBM and 60 IMD patients. Forty-five combinations of ML models and feature reduction strategies were assessed for features extracted from whole tumor and edema masks using mp-MRI [T1W, T2W, T1-contrast enhanced (T1-CE), ADC, FLAIR], individual MRI sequences and combined T1-CE and FLAIR sequences. Model performance was assessed using receiver operating characteristic curve. For mp-MRI, the best model was LASSO model fit using full feature set (AUC 0.953). FLAIR was the best individual sequence (LASSO-full feature set, AUC 0.951). For combined T1-CE/FLAIR sequence, adaBoost-full feature set was the best performer (AUC 0.951). No significant difference was seen between top models across all scenarios, including models using FLAIR only, mp-MRI and combined T1-CE/FLAIR sequence. Top features were extracted from both the whole tumor and edema masks. Shape sphericity is an important discriminating feature.

Abstract GTP cyclohydrolase 1 (GCH1) and its product tetrahydrobiopterin play crucial roles in cardiovascular health and disease, yet the exact regulation and role of GCH1 in adverse cardiac remodeling after myocardial infarction are still enigmatic. Here we report that cardiac GCH1 is degraded in remodeled hearts after myocardial infarction, concomitant with increases in the thickness of interventricular septum, interstitial fibrosis, and phosphorylated p38 mitogen-activated protein kinase and decreases in left ventricular anterior wall thickness, cardiac contractility, tetrahydrobiopterin, the dimers of nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and the expression of sarcoplasmic reticulum Ca2+ handling proteins. Intriguingly, transgenic overexpression of GCH1 in cardiomyocytes reduces the thickness of interventricular septum and interstitial fibrosis and increases anterior wall thickness and cardiac contractility after infarction. Moreover, we show that GCH1 overexpression decreases phosphorylated p38 mitogen-activated protein kinase and elevates tetrahydrobiopterin levels, the dimerization and phosphorylation of neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and sarcoplasmic reticulum Ca2+ handling proteins in post-infarction remodeled hearts. Our results indicate that the pivotal role of GCH1 overexpression in post-infarction cardiac remodeling is attributable to preservation of neuronal nitric oxide synthase and sarcoplasmic reticulum Ca2+ handling proteins, and identify a new therapeutic target for cardiac remodeling after infarction.

Abstract Owing to the rapid development of urbanisation and industrialisation, heavy metal pollution has become a widespread environmental problem. Maize planted on mercury (Hg)-polluted soil can absorb and accumulate Hg in its edible parts, posing a potential threat to human health. To understand the genetic mechanism of Hg accumulation in maize, we performed a genome-wide association study using a mixed linear model on an association population consisting of 230 maize inbred lines with abundant genetic variation. The order of relative Hg concentrations in different maize tissues was as follows: leaves > bracts > stems > axes > kernels. Combined two locations, a total of 37 significant single-nucleotide polymorphisms (SNPs) associated with kernels, 12 with axes, 13 with stems, 27 with bracts and 23 with leaves were detected with p