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Abstract Background Artemisiae Scopariae Herba (ASH) has been widely used as plant medicine in East Asia with remarkable antitumor activity. However, the underlying mechanisms have not been fully elucidated. Methods This study aimed to construct a multi-disciplinary approach to screen topoisomerase I (topo I) inhibitors from ASH extract, and explore the antitumor mechanisms. Bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS was used to identify chemical constitution of ASH extract as well as the topo I inhibitors, and in silico docking coupled with multiple complex networks was applied to interpret the molecular mechanisms. Results Crude ASH extract exhibited toxicogenetic and antiproliferative activities on A549 cells. A series of 34 ingredients were identified from the extract, and 6 compounds were screened as potential topo I inhibitors. Docking results showed that the formation of hydrogen bond and π-π stacking contributed most to their binding with topo I. Interrelationships among the 6 compounds, related targets and pathways were analyzed by multiple complex networks model. These networks displayed power-law degree distribution and small-world property. Statistical analysis indicated that isorhamnetin and quercetin were main active ingredients, and that chemical carcinogenesis-reactive oxygen species was the critical pathway. Electrophoretic results showed a therapeutic effect of ASH extract on the conversion of supercoiled DNA to relaxed forms, as well as potential synergistic effect of isorhamnetin and quercetin. Conclusions The results improved current understanding of Artemisiae Scopariae Herba on the treatment of tumor. Moreover, the combination of multi-disciplinary methods provided a new strategy for the study of bioactive constituents in medicinal plants.

Abstract The relation between exposure to single metal/metalloid and the risk of chronic kidney disease (CKD) remains unclear. We aimed to determine the single and mixed associations of 21 heavy metals/metalloids exposure and the risk of CKD. We performed a cross-sectional study that recruited 4055 participants. Multivariate logistic regression, linear regression and weighted quantile sum (WQS) regression were conducted to explore the possible effects of single and mixed metals/metalloids exposure on the risk of CKD, the risk of albuminuria and changes in the estimated glomerular filtration rate (eGFR). In single-metal models, Cu, Fe, and Zn were positively associated with increased risks of CKD (P-trend

The deployment of network security has become a crucial strategy for the development of modern nations, with skilled professionals serving as the core driving force behind cybersecurity efforts.Cultivating cybersecurity talents and fostering team building are essential for China's talent reserves and strategic capital accumulation.With economic globalization, 0-day vulnerabilities have constantly emerged in information systems, attack chains have become increasingly complex, threat targets were difficult to detect, and hidden viruses varied over time.Talents trained by traditional universities for network security were unable to adapt to innovative production and practical activities in the new fields, as it was confined to their training structure system.In order to break through the shackles of the internal administrative structure and traditional curriculum system of universities, and ease the contradiction between the uncertainty of cyberspace security situation and the standardization of talent cultivation, the talent cultivation models based on Bourdieu's theory were studied, the fusion meaning of cultural capital in the academic field was analyzed and three practical standards were put forward in terms of teaching content, cultivation model and teaching opportunity of cyberspace security talents in combination with the actual cases of the “Fang class”.In terms of education content, standards and open knowledge systems were established to meet the differentiated needs of students.The mentorship approach was employed to construct habitus, fostering students’ ability to adapt flexibly to problems by adopting different cognitive thinking modes.Favorable teaching opportunities were utilized by tutors in various roles to promote efficient integration of individuals and fields, helping students establish a valuable and stable mindset.By leveraging Bourdieu's theory to explore the integration path of academic fields, it has leveraged the advantages of independently cultivating high-quality talents, vigorously promoting technological innovation and the healthy ecological development of the industry.

Abstract Background Community-acquired pneumonia (CAP) is usually diagnosed in children, and the type of respiratory specimen is critical. Differences in pathogens detection between induced sputum (IS) and bronchoalveolar lavage fluid (BALF) have not been evaluated. Methods In 2018, paired sputum and BALF samples from CAP hospitalised children with indications for bronchoalveolar lavage (BAL) were subjected to multiplex PCR for the detection of 11 common respiratory pathogens. Results A total of 142 children with paired sputum and BALF were tested. The overall positivity rate was 85.9% (122/142) for sputum and 80.3% (114/142) for BALF. The two specimens presented almost perfect agreement between the detection on M. pneumoniae, influenza A, influenza B, bocavirus and RSV. In contrast, adenovirus had the lowest kappa value of 0.156, and a false negative rate (FNR) of 66.7%. Rhinovirus had the highest false positive rate (FPR) as 18.5%. The consistent rate was significantly higher in school-age children than those under 1 year old (p = .005). Bacterial co-infection in BALF specimens were observed in 14.8% (21/142). Of the 11 discordant pairs of specimens, 9 cases were sputum(+)/BALF(-) with adenovirus predominating. Conclusion Our findings suggest that the consistency of results between sputum and BALF is pathogen specific. Careful consideration needs to be given to whether sputum can be used as a substitute for BALF when children are young or co-infections with bacteria are suspected.

Abstract Background The application of molecular targeting therapy and immunotherapy has notably prolonged the survival of patients with hepatocellular carcinoma (HCC). However, multidrug resistance and high molecular heterogeneity of HCC still prevent the further improvement of clinical benefits. Dysfunction of tumor-infiltrating natural killer (NK) cells was strongly related to HCC progression and survival benefits of HCC patients. Hence, an NK cell-related prognostic signature was built up to predict HCC patients’ prognosis and immunotherapeutic response. Methods NK cell markers were selected from scRNA-Seq data obtained from GSE162616 data set. A consensus machine learning framework including a total of 77 algorithms was developed to establish the gene signature in TCGA–LIHC data set, GSE14520 data set, GSE76427 data set and ICGC–LIRI–JP data set. Moreover, the predictive efficacy on ICI response was externally validated by GSE91061 data set and PRJEB23709 data set. Results With the highest C-index among 77 algorithms, a 11-gene signature was established by the combination of LASSO and CoxBoost algorithm, which classified patients into high- and low-risk group. The prognostic signature displayed a good predictive performance for overall survival rate, moderate to high predictive accuracy and was an independent risk factor for HCC patients’ prognosis in TCGA, GEO and ICGC cohorts. Compared with high-risk group, low-risk patients showed higher IPS–PD1 blocker, IPS–CTLA4 blocker, common immune checkpoints expression but lower TIDE score, which indicated low-risk patients might be prone to benefiting from ICI treatment. Moreover, a real-world cohort, PRJEB23709, also revealed better immunotherapeutic response in low-risk group. Conclusions Overall, the present study developed a gene signature based on NK cell-related genes, which offered a novel platform for prognosis and immunotherapeutic response evaluation of HCC patients.

Abstract Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

Abstract The FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in β cells, which secrete the only glucose-lowering hormone—insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in β cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted β-cell survival, improved insulin secretion, and upregulated β-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed β cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in β cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in β cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.

Abstract This paper proposes an adaptive fault‐tolerant control (FTC) method for hypersonic vehicle (HSV) with unexpected centroid shift, actuator fault, time‐varying full state constraints, and input saturation. The occurrence of unexpected centroid shift has three main effects on the HSV system, which are system uncertainties, eccentric moments, and variation of input matrix. In order to ensure the time‐varying state constraints, a novel attitude state constraint control strategy, to keep the safe flight of HSV, is technically proposed by a time‐varying state constraint function (TVSCF). A unified controller is designed to handle the time‐varying state constraints according to the proposed TVSCF. Then, the constrained HSV system can be transformed into a novel free‐constrained system based on the TVSCF. For the variation of system input matrix, input saturation and actuator fault, a special Nussbaum‐type function is designed to compensate for those time‐varying nonlinear terms. Additionally, the auxiliary systems is designed to compensate the constraint of system control inputs. Then, it is proved that the proposed control scheme can guarantee the boundedness of all closed‐loop signals based on the Lyapunov stability theory. At last, the simulation results are provided to demonstrate the effectiveness of the proposed fault‐tolerant control scheme.

AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.

ABSTRACTA large number of publications have incorporated deep learning in the process of remote sensing change detection. In these Deep Learning Change Detection (DLCD) publications, deep learning methods have demonstrated their superiority over conventional change detection methods. However, the theoretical underpinnings of why deep learning improves the performance of change detection remain unresolved. As of today, few in-depth reviews have investigated the mechanisms of DLCD. Without such a review, five critical questions remain unclear. Does DLCD provide improved information representation for change detection? If so, how? How to select an appropriate DLCD method and why? How much does each type of change benefits from DLCD in terms of its performance? What are the major limitations of existing DLCD methods and what are the prospects for DLCD? To address these five questions, we reviewed according to the following strategies. We grouped the DLCD information assemblages into the four unique dimensions of remote sensing: spectral, spatial, temporal, and multi-sensor. For the extraction of information in each dimension, the difference between DLCD and conventional change detection methods was compared. We proposed a taxonomy of existing DLCD methods by dividing them into two distinctive pools: separate and coupled models. Their advantages, limitations, applicability, and performance were thoroughly investigated and explicitly presented. We examined the variations in performance between DLCD and conventional change detection. We depicted two limitations of DLCD, i.e. training sample and hardware and software dilemmas. Based on these analyses, we identified directions for future developments. As a result of our review, we found that DLCD’s advantages over conventional change detection can be attributed to three factors: improved information representation; improved change detection methods; and performance enhancements. DLCD has to surpass the limitations with regard to training samples and computing infrastructure. We envision this review can boost developments of deep learning in change detection applications.

Background: This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation of brown adipose tissue (BAT). Methods: Adenovirus particles encoding CTRP9 and green fluorescent protein were inoculated into the scapula of C57BL/6J mice and fed a high-fat diet for 8 weeks; the body weight, lipid droplet morphology, glucose tolerance, insulin tolerance, and protein expression levels were analyzed. In addition, CTRP9 adenovirus was transfected into brown preadipocytes, and differentiation was induced to identify the effect of CTRP9 overexpression on adipocyte differentiation. Results: CTRP9 overexpression significantly increased the weight gain of mice. Additionally, the CTRP9 overexpression group exhibited significantly increased adipose tissue weight and glucose clearance rates and decreased insulin sensitivity and serum triglyceride levels compared to the control group. Furthermore, CTRP9 overexpression significantly upregulated the adipose triglyceride lipase (ATGL) and perilipin 1 protein expression levels in BAT. The cell experiment results confirmed that CTRP9 overexpression significantly inhibited the adipogenesis of brown adipocytes as evidenced by the downregulation of uncoupling protein 1, beta-3 adrenergic receptor, ATGL, and hormone-sensitive lipase mRNA levels and the significant suppression of uncoupling protein 1, ATGL, and perilipin 1 protein levels in brown adipocytes. Conclusions: The finding of this study demonstrated that CTRP9 promotes lipolysis by upregulating ATGL expression in vivo and inhibits the differentiation of brown preadipocytes in vitro.

This paper addresses the challenges of data sparsity and personalization limitations inherent in current recommendation systems when processing extensive academic paper datasets. To overcome these issues, the present work introduces an innovative recommendation model that integrates the wealth of structured information from knowledge graphs and refines the amalgamation of temporal and relational data. By applying attention mechanisms and neural network technologies, the model thoroughly explores the text characteristics of papers and the evolving patterns of user behaviors. Additionally, the model elevates the accuracy and personalization of recommendations by meticulously examining citation patterns among papers and the networks of author collaboration. The experimental findings show that the present model surpasses baseline models on all evaluation metrics, thereby enhancing the precision and personalization of academic paper recommendations.

The preparation of a novel composite carrier of polydopamine-modified carbon fiber/polyurethane foam (PDA-CF/PUF) was proposed to improve cell immobilization and the fermentation of xylitol, which is an important food sweetener and multifunctional food additive. Candida tropicalis was immobilized on the composite carrier by adsorption and covalent binding. The properties and immobilization mechanism of the composite carrier and its effect on immobilized cells were investigated. It showed that the modification of PDA enhanced the loading of CF on the PUF surface and the adhesion of cells on the composite carrier surface. Also, the biocompatibility of carriers to cells was improved. In addition, the introduction of PDA increased the active groups on the surface of the carrier, enhanced the hydrophilicity, promoted the cells immobilization, and increased the xylitol yield. It was also found that expression of the related gene XYL1 in cells was significantly increased after the immobilization of the PDA-CF/PUF composite carrier during the fermentation. The PDA-CF/PUF was an immobilized carrier with the excellent biocompatibility and immobilization performance, which has great development potential in the industrial production of xylitol.

Supercritical water gasification (SCWG) technology is highly promising for its ability to cleanly and efficiently convert biomass to hydrogen. This paper developed a model for the gasification of rice straw in supercritical water (SCW) to predict the direction and limit of the reaction based on the Gibbs free energy minimization principle. The equilibrium distribution of rice straw gasification products was analyzed under a wide range of parameters including temperatures of 400–1200 °C, pressures of 20–50 MPa, and rice straw concentrations of 5–40 wt%. Coke may not be produced due to the excellent properties of supercritical water under thermodynamic constraints. Higher temperatures, lower pressures, and biomass concentrations facilitated the movement of the chemical equilibrium towards hydrogen production. The hydrogen yield was 47.17 mol/kg at a temperature of 650 °C, a pressure of 25 MPa, and a rice straw concentration of 5 wt%. Meanwhile, there is an absorptive process in the rice straw SCWG process for high-calorific value hydrogen production. Energy self-sufficiency of the SCWG process can be maintained by adding small amounts of oxygen (ER < 0.2). This work would be of great value in guiding rice straw SCWG experiments.

Sophora alopecuroides has important uses in medicine, wind breaking, and sand fixation. The CHY-zinc-finger and RING-finger (CHYR) proteins are crucial for plant growth, development, and environmental adaptation; however, genetic data regarding the CHYR family remain scarce. We aimed to investigate the CHYR gene family in S. alopecuroides and its response to abiotic stress, and identified 18 new SaCHYR genes from S. alopecuroides whole-genome data, categorized into 3 subclasses through a phylogenetic analysis. Gene structure, protein domains, and conserved motifs analyses revealed an exon–intron structure and conserved domain similarities. A chromosome localization analysis showed distribution across 12 chromosomes. A promoter analysis revealed abiotic stress-, light-, and hormone-responsive elements. An RNA-sequencing expression pattern analysis revealed positive responses of SaCHYR genes to salt, alkali, and drought stress. SaCHYR4 overexpression considerably enhanced alkali and drought tolerance in Arabidopsis thaliana. These findings shed light on SaCHYR’s function and the resistance mechanisms of S. alopecuroides, presenting new genetic resources for crop resistance breeding.

Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.5 in CD-1 mice, and measured their synaptic spine density, microglial synaptic pruning, and complement protein expression. We found reduced dendritic spine density in the somatosensory cortex starting at 3-weeks-of-age with requisite increases in microglial synaptic pruning and phagocytosis, suggesting spine density loss was caused by increased microglial synaptic pruning. Additionally, we showed dysregulation in complement protein expression persisting into adulthood. Our findings highlight disruptions in the prenatal environment leading to alterations in multiple dynamic processes through to postnatal development. This could potentially suggest developmental time points during which synaptic processes could be measured as risk factors or targeted with therapeutics for neurodevelopmental disorders.

Highly interactive honeypots can form reliable connections by responding to attackers to delay and capture intranet attacks. However, current research focuses on modeling the attacker as part of the environment and defining single-step attack actions by simulation to study the interaction of honeypots. It ignores the iterative nature of the attack and defense game, which is inconsistent with the correlative and sequential nature of actions in real attacks. These limitations lead to insufficient interaction of the honeypot response strategies generated by the study, making it difficult to support effective and continuous games with attack behaviors. In this paper, we propose an autonomous attack response framework (named AARF) to enhance interaction based on multi-agent dynamic games. AARF consists of three parts: a virtual honeynet environment, attack agents, and defense agents. Attack agents are modeled to generate multi-step attack chains based on a Hidden Markov Model (HMM) combined with the generic threat framework ATT&CK (Adversarial Tactics, Techniques, and Common Knowledge). The defense agents iteratively interact with the attack behavior chain based on reinforcement learning (RL) to learn to generate honeypot optimal response strategies. Aiming at the sample utilization inefficiency problem of random uniform sampling widely used in RL, we propose the dynamic value label sampling (DVLS) method in the dynamic environment. DVLS can effectively improve the sample utilization during the experience replay phase and thus improve the learning efficiency of honeypot agents under the RL framework. We further couple it with a classic DQN to replace the traditional random uniform sampling method. Based on AARF, we instantiate different functional honeypot models for deception in intranet scenarios. In the simulation environment, honeypots collaboratively respond to multi-step intranet attack chains to defend against these attacks, which demonstrates the effectiveness of AARF. The average cumulative reward of the DQN with DVLS is beyond eight percent, and the convergence speed is improved by five percent compared to a classic DQN.

Exogenous selenium application could effectively improve the selenium absorption of crops affected by different climatic conditions due to changes in the planting environment and planting conditions. We planted maize at planting densities of 67,500 plants ha−1 (D1) and 75,000 plants ha−1 (D2). Five selenium fertilizer gradients of 0 mg m−2 (Se0), 7.5 mg m−2 (Se1), 15.0 mg m−2 (Se2), 22.5 mg m−2 (Se3), and 30.0 mg m−2 (Se4) were applied to investigate the response of the plants to selenium fertilizer application in terms of the gradient selenium absorption and substance accumulation. With the increase in the amount of selenium fertilizer applied, more of the selenium fertilizer will be absorbed and transported from the leaves to the grains, and the selenium content of the grains will gradually increase and exceed the selenium content of leaves. Under the D2 density in 2022, the selenium content of the grains under Se1, Se2, Se3, and Se4 treatments increased by 65.67%, 72.71%, and 250.53%, respectively, compared with that of Se0. A total of 260.55% of the plants showed a gradient of grain > leaf > cob > stalk from the Se2 treatment, and the overall selenium content of the plants increased first and then decreased. Under the D1 density, compared with the Se0, the dry matter mass of the Se1, Se2, Se3, and Se4 treatments significantly improved by 5.84%, 1.49%, and 14.26% in 2021, and significantly improved by 4.84%, 3.50%, and 2.85% in 2022. The 1000-grain weight under Se2, Se3, and Se4 treatments improved by 8.57%, 9.06%, and 15.56% compared to that under the Se0 treatment, and the yield per ha under the Se2, Se3, and Se4 treatments was 18.58%, 9.09%, and 21.42% higher than that under Se0 treatment, respectively. In addition, a reasonable combination of selenium application rate and density could improve the chlorophyll content and stem growth of dryland maize. This lays a foundation for the efficient application of selenium fertilizer and provides an important reference.

This study utilizes meteorological and leaf area index (LAI) data for three shared socioeconomic pathways (SSP1–2.6, SSP2–4.5, and SSP5–8.5) from four general circulation models (GCMs) of the sixth climate model intercomparison project (CMIP6) spanning from 2015 to 2099. Employing calibrated data and incorporating future land use data under three SSPs, the distributed hydrology soil vegetation model (DHSVM) is employed to simulate streamflow in the source region of the Yellow River (SRYR). The research aims to elucidate variations in streamflow across different future scenarios and to estimate extreme streamflow events and temporal distribution changes under future land use and cover change (LUCC) and climate change scenarios. The main conclusions are as follows: The grassland status in the SRYR will significantly improve from 2020 to 2099, with noticeable increases in temperature, precipitation, and longwave radiation, alongside a pronounced decrease in wind speed. The probability of flooding events increases in the future, although the magnitude of the increase diminishes over time. Both LUCC and climate change contribute to an increase in the multi-year average streamflow in the region, with respective increments of 48.8%, 24.5%, and 18.9% under SSP1–2.6, SSP2–4.5, and SSP5–8.5. Notably, the fluctuation in streamflow is most pronounced under SSP5–8.5. In SSP1–2.6, the increase in streamflow during the near future (2020–2059) exceeds that of the distant future (2059–2099). Seasonal variations in streamflow intensify across most scenarios, leading to a more uneven distribution of streamflow throughout the year and an extension of the flood season.

Vulnerabilities are often accompanied by cyberattacks. CVE is the largest repository of open vulnerabilities, which keeps expanding. ATT&CK models known multi-step attacks both tactically and technically and remains up to date. It is valuable to correlate the vulnerability in CVE with the corresponding tactic and technique of ATT&CK which exploit the vulnerability, for active defense. Mappings manually is not only time-consuming but also difficult to keep up-to-date. Existing language-based automated mapping methods do not utilize the information associated with attack behaviors outside of CVE and ATT&CK and are therefore ineffective. In this paper, we propose a novel framework named VTT-LLM for mapping Vulnerabilities to Tactics and Techniques based on Large Language Models, which consists of a generation model and a mapping model. In order to generate fine-tuning instructions for LLM, we create a template to extract knowledge of CWE (a standardized list of common weaknesses) and CAPEC (a standardized list of common attack patterns). We train the generation model of VTT-LLM by fine-tuning the LLM according to the above instructions. The generation model correlates vulnerability and attack through their descriptions. The mapping model transforms the descriptions of ATT&CK tactics and techniques into vectors through text embedding and further associates them with attacks through semantic matching. By leveraging the knowledge of CWE and CAPEC, VTT-LLM can eventually automate the process of linking vulnerabilities in CVE to the attack techniques and tactics of ATT&CK. Experiments on the latest public dataset, ChatGPT-VDMEval, show the effectiveness of VTT-LLM with an accuracy of 85.18%, which is 13.69% and 54.42% higher than the existing CVET and ChatGPT-based methods, respectively. In addition, compared to fine-tuning without outside knowledge, the accuracy of VTT-LLM with chain fine-tuning is 9.24% higher on average across different LLMs.

Chalcone isomerase (CHI) is an important enzyme involved in the biosynthesis of flavonoids, one that is crucial in both plant defense and human health. Although many CHI genes have been previously identified, the function of CHI-like genes in soybean remains unclear. In this study, we cloned the CHI-like genes GmCHI4A and GmCHI4B (GmCHI4s) in soybean. The real-time quantitative polymerase chain reaction showed that GmCHI4s were expressed primarily in soybean root, but were also present in other tissues, including the stem, leaf, and seed with a low expression level. Overexpression of GmCHI4s was able to significantly improve some beneficial traits of the transformed hair roots of cotyledon or composite plants under salt stress conditions. Root length, root wet weight, and the underground biomass was increased, and the elevation of MDA content was inhibited under 100 mmol L−1 or 150 mmol L−1 NaCl treatment. Leaf chlorophyll content was elevated in overexpressed GmCHI4A composite plants under 150 mmol L−1 NaCl treatment. The expression levels of salt-stress-related genes GmSOD1, GmAPX1, GmSOS1, and GmNHX1 were significantly upregulated in overexpressed GmCHI4 hairy roots compared to that in empty-vector-expressed hairy roots. The above results indicated GmCHI4s’ potential action against salt stress. Furthermore, overexpression of GmCHI4A and GmCHI4B increased the total isoflavone content by six times and three times, respectively. Glycitin and glycitein levels were significantly elevated in the overexpressed GmCHI4A hairy roots, while glycitin, genistin, daidzein, and genistein were significantly increased in overexpressed GmCHI4B hairy roots. This study identified a new function of the CHI-like gene, as well as providing a new selected gene for salt tolerance and isoflavone improvement using biotechnological approaches in soybean.

The most commonly used real-time augmentation services in China are the International GNSS Service’s (IGS) real-time service (RTS), PPP-B2b service, and Double-Frequency Multi-Constellation (DFMC) service of the BeiDou Satellite-Based Augmentation System (BDSBAS) service. However, research on the performance evaluation, comparison, and application scope of these three products is still incomplete. This article introduces methods for obtaining real-time augmentation information and real-time orbit and clock offset recovery. Based on real-time orbit and clock offset accuracy, positioning accuracy, and positioning availability, this article systematically evaluates the performance and analyzes the application fields of Centre National d’Études Spatiales (CNES), PPP-B2b, and BDSBAS augmentation information. The results of the evaluation revealed that the radial accuracy of the CNES and PPP-B2b real-time orbit product is consistent, and the Root Mean Square (RMS) is better than 5 cm. The CNES real-time orbit product can achieve centimeter-level accuracy in both along-track and cross-track components, surpassing PPP-B2b’s decimeter-level accuracy. Both services demonstrate consistent accuracy in the real-time clock offset, with PPP-B2b showing similar standard deviations (STDs) of 0.16 ns for different satellites. However, for CNES, the STD of the real-time clock offset varies, with values of 0.10 ns, 0.19 ns, and 0.60 ns, respectively, for GPS, BDS-3 Medium Earth Orbit (MEO), and BDS-3 Inclined Geosynchronous Satellite Orbit (IGSO) satellites. Centimeter-level accuracy is achieved after convergence and positioning availability exceeds 99% for CNES and PPP-B2b services. Therefore, the difference between the two services in application areas depends on the acquisition of augmentation information. However, BDSBAS, which concentrates on code observations, demonstrates inferior performance in real-time orbit, clock offset, positioning accuracy, and positioning availability when compared to the other two services. Its primary application is in the aviation and maritime domains, where there is a greater need for service integrity, continuity, and reliability.

The palm family (Arecaceae), consisting of ∼ 2600 species, is the third most economically important family of plants. The African oil palm (Elaeis guineensis) is one of the most important palms. However, the genome sequences of palms that are currently available are still limited and fragmented. Here, we report a high-quality chromosome-level reference genome of an oil palm, Dura, assembled by integrating long reads with ∼ 150× genome coverage. The assembled genome was 1.7 Gb in size, covering 94.5% of the estimated genome, of which 91.6% was assigned into 16 pseudochromosomes and 73.7% was repetitive sequences. Relying on the conserved synteny with oil palm, the existing draft genome sequences of both date palm and coconut were further assembled into chromosomal level. Transposon burst, particularly long terminal repeat retrotransposons, following the last whole-genome duplication, likely explains the genome size variation across palms. Sequence analysis of the VIRESCENS gene in palms suggests that DNA variations in this gene are related to fruit colors. Recent duplications of highly tandemly repeated pathogenesis-related proteins from the same tandem arrays play an important role in defense responses to Ganoderma. Whole-genome resequencing of both ancestral African and introduced oil palms in Southeast Asia reveals that genes under putative selection are notably associated with stress responses, suggesting adaptation to stresses in the new habitat. The genomic resources and insights gained in this study could be exploited for accelerating genetic improvement and understanding the evolution of palms.

Abstract Space groups describing the symmetry of lattice structure allow the emergence of fermionic quasiparticles with various degeneracy in the band structure. Theoretical efforts have predicted many materials hosting fermions with the highest degeneracy, i.e., eightfold fermions, yet lacking experimental realization. Here, we explore the band degeneracies in TaCo2Te2 crystals. Through systematic experimental and theoretical analyses, we establish TaCo2Te2 as a nonsymmorphic crystal with negligible spin–orbit coupling (SOC) and long-range magnetic order. These critical properties guarantee the realization of practical eightfold fermions and fourfold van Hove singularity, as directly observed by photoemission spectroscopy. TaCo2Te2 serves as a topological quantum critical platform, which can be tuned into various magnetic, topologically trivial, and nontrivial phases by adding strain, magnetic field, or SOC. The latter is demonstrated by our first-principles calculations, which show that enhancing SOC in TaCo2Te2 will promote the experimental observation of bulk hourglass fermions. Our results establish TaCo2Te2 as a platform to explore the interplay between symmetry and band topology.

According to the latest 14th Five-Year Plan, China encourages the comprehensive utilization of mining resources such as associated ore, low-grade ore and tailings. Strengthening the comprehensive utilization of resources is an important means to change the extensive economic growth and realize the circular economy and green development. With the increasing demand for valuable metals such as zinc and lead and the depletion of limited high-grade zinc ore resources, it is urgent to comprehensively recover and utilize the valuable components of middle and low grade zinc oxide ore. In this paper, the existing technology principle, process flow and effect of the comprehensive utilization of low grade zinc oxide ore resources are summarized and analyzed from two aspects of roasting method and leaching method, and the problems existing in the application of each process are put forward. Secondly, the research status of comprehensive utilization of low grade zinc oxide ore and zinc containing waste by microbial hydrometallurgical technology is briefly analyzed. Finally, the prospect of the comprehensive utilization of low grade zinc oxide ore is prospected: the microbial hydrometallurgy technology, especially the microbial and chemical combined process technology, will be the focus of future research because of its characteristics of not only realizing the efficient recovery of valuable components, but also realizing the win-win of economic benefits and environmental protection.

Discovery of new phosphors with desired properties is of great significance for developing high optical quality solid-state lighting. The single-particle-diagnosis approach is an effective way to search novel phosphors by analyzing tiny single crystals screened from the fired powder mixtures. In this work, a broadband orange-emitting phosphor of Sr3Si8O4N10:Eu2+ for solid state lighting was discovered by this method. The new oxonitridosilicate crystallizes in the monoclinic space group of P21/n (No. 14) with cell parameters of a = 4.8185 Å, b = 24.2303 Å, c = 10.5611 Å, β = 90.616°, and Z = 4. The crystal structure of Sr3Si8O4N10 was determined from the single-crystal X-ray diffraction (XRD) data of a single crystal, which is made up of a three-dimensional framework consisting of vertex-sharing SiN4 and SiN3O tetrahedra. Sr2+ ions occupy five crystallographic sites and have coordination numbers between 6 and 8 with one ordered Sr and other four disordered Sr atoms. The multiple Sr sites lead to a broadband emission centered at 565–600 nm and a bandwidth of 128–138 nm. The internal and external quantum efficiencies (IQE/EQE) of the title phosphor are 48.6% and 29.1% under 450 nm excitation, respectively. To improve the accuracy and speed of distinguishing phosphor particles in fired powder mixtures, a microscopic imaging spectroscopy is developed and demonstrated to modify the single-particle-diagnosis method.

Abstract Sensing and recognizing invisible ultraviolet (UV) light is vital for exploiting advanced artificial visual perception system. However, due to the uncertainty of the natural environment, the UV signal is very hard to be detected and perceived. Here, inspired by the tetrachromatic visual system, we report a controllable UV-ultrasensitive neuromorphic vision sensor (NeuVS) that uses organic phototransistors (OPTs) as the working unit to integrate sensing, memory and processing functions. Benefiting from asymmetric molecular structure and unique UV absorption of the active layer, the as fabricated UV-ultrasensitive NeuVS can detect 370 nm UV-light with the illumination intensity as low as 31 nW cm−2, exhibiting one of the best optical figures of merit in UV-sensitive neuromorphic vision sensors. Furthermore, the NeuVS array exbibits good image sensing and memorization capability due to its ultrasensitive optical detection and large density of charge trapping states. In addition, the wavelength-selective response and multi-level optical memory properties are utilized to construct an artificial neural network for extract and identify the invisible UV information. The NeuVS array can perform static and dynamic image recognition from the original color image by filtering red, green and blue noise, and significantly improve the recognition accuracy from 46 to 90%.

Hepatitis B, a global health concern caused by the hepatitis B virus (HBV), infects nearly 2 billion individuals worldwide, as reported by the World Health Organization (WHO). HBV, a hepatotropic DNA virus, predominantly targets and replicates within hepatocytes. Those carrying the virus are at increased risk of liver cirrhosis and hepatocellular carcinoma, resulting in nearly 900,000 fatalities annually. The HBV X protein (HBx), encoded by the virus’s open reading frame x, plays a key role in its virulence. This protein is integral to viral replication, immune modulation, and liver cancer progression. Despite its significance, the precise molecular mechanisms underlying HBx remain elusive. This review investigates the HBx protein’s roles in HBV replication, interferon signaling regulation, and hepatocellular carcinoma progression. By understanding the complex interactions between the virus and its host mediated by HBx, we aim to establish a solid foundation for future research and the development of HBx-targeted therapeutics.

ABSTRACTApproximately 10% of individuals diagnosed with Clostridium difficile infection (CDI) show the resistance to fecal microbiota transplantation (FMT), with the underlying mechanisms remaining elusive. Deciphering the intricate microbiome profile within this particular subset of FMT-refractory patients via clinical FMT investigations assumes paramount importance, as it holds the key to designing targeted therapeutic interventions tailored for CDI, particularly recurrent CDI (rCDI). A cohort of twenty-three patients afflicted with rCDI, exhibiting congruent clinical baselines, was meticulously selected for FMT. Rigorous screening of thousands of healthy individuals identified ten FMT donors who met stringent health standards, while a total of 171 stool samples were collected to serve as healthy controls. To assess the influence of microbiome dynamics on FMT efficacy, fecal samples were collected from four donors over a continuous period of twenty-five weeks. After FMT treatment, seven individuals exhibited an inadequate response to FMT. These non-remission patients displayed a significant reduction in α-diversity indexes. Meanwhile, prior to FMT, the abundance of key butyrate-producing Firmicutes bacteria, including Christensenellaceae_R_7_group, Ruminococcaceae_unclassified, Coprococcus_2, Fusicatenibacter, Oscillospira, and Roseburia, were depleted in non-remission patients. Moreover, Burkholderiales_unclassified, Coprococcus_2, and Oscillospira failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of Veillonella prior to treatment, whereas its depletion was commonly observed in non-remission individuals. Genera interactions in lower effectiveness FMT donors were more similar to those in non-remission patients, and Burkholderiales_unclassified, Coprococcus_2, and Oscillospira were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of Veillonella, consistent with their poor prognosis after FMT. FMT non-remission rCDI patients exhibited distinct characteristics that hindered the colonization of beneficial butyrate-producing Firmicutes microbes. These findings hold promise in advancing the precision of FMT therapy for rCDI patients.

ABSTRACTArtificial synaptic devices are the cornerstone of neuromorphic electronics. The development of new artificial synaptic devices and the simulation of biological synaptic computational functions are important tasks in the field of neuromorphic electronics. Although two-terminal memristors and three-terminal synaptic transistors have exhibited significant capabilities in the artificial synapse, more stable devices and simpler integration are needed in practical applications. Combining the configuration advantages of memristors and transistors, a novel pseudo-transistor is proposed. Here, recent advances in the development of pseudo-transistor-based neuromorphic electronics in recent years are reviewed. The working mechanisms, device structures and materials of three typical pseudo-transistors, including tunneling random access memory (TRAM), memflash and memtransistor, are comprehensively discussed. Finally, the future development and challenges in this field are emphasized.

Adequate vascularization is crucial for the repair of bone defects. Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote H-type vessel formation, a specialized blood vessel, strongly positive for CD31 and endomucin, coupling angiogenesis and osteogenesis. However, the lack of a controllable growth factor delivery limits its clinical application, causing certain complications associated with PDGF-BB administration. This study developed an injectable heparin-conjugated hydrogel (GHH) for controlled delivery to facilitate the effective binding of PDGF-BB and rapid vascularized bone regeneration. Herein, in vitro experiments involving the controlled release of PDGF-BB showed that the PDGF-BB-loaded GHH (GHHP) hydrogel demonstrated excellent cytocompatibility and osteogenic properties. The subcutaneous implantation model in rats revealed that the GHHP hydrogel has the potential to induce the formation of H-type blood vessels in vivo. Furthermore, the healing of distal femoral condyle defects in rat models in vivo demonstrated that GHHP could substantially promote H-type angiogenesis and effectively repair bone defects. Our injectable heparin-conjugated sustained-release PDGF-BB hydrogel has excellent angiogenic and osteogenic properties, thus providing a novel and promising solution for bone defect repair.

Abstract Environmental filtering is deemed to play a predominant role in regulating the abundance and distribution of animals during the urbanization process. However, the current knowledge about the effects of urbanization on the population densities of terrestrial mammals is limited. In this study, we compared two invasive mammals (dogs Canis lupus familiaris and cats Felis silvestris) and three indigenous mammals (Siberian weasels Mustela sibirica, Amur hedgehogs Erinaceus amurensis, and Tolai hares Lepus tolai) in response to urbanization using camera trap distance sampling (CTDS) in the rural–urban landscape of Tianjin, China. We used generalized additive mixed models (GAMMs) to test the specific responses of their densities to levels of urbanization. Invasive dogs (2.63 individuals/km2, 95% CI: 0.91–7.62) exhibited similar density estimations to cats (2.15 individuals/km2, 95% CI: 1.31–3.50). Amur hedgehogs were the most abundant species (6.73 individuals/km2, 95% CI: 3.15–14.38), followed by Tolai hares (2.22 individuals/km2, 95% CI: 0.87–5.68) and Siberian weasels (2.15 individuals/km2, 95% CI: 1.06–4.36). The densities of cats, Siberian weasels, and Amur hedgehogs increased with the level of urbanization. The population densities of dogs and cats were only influenced by urban‐related variables, while the densities of Siberian weasels and Amur hedgehogs were influenced by both urban‐related variables and nature‐related variables. Our findings highlight that the CTDS is a suitable and promising method for wildlife surveys in rural–urban landscapes, and urban wildlife management needs to consider the integrated repercussions of urban‐ and nature‐related factors, especially the critical impacts of green space habitats at finer scales.

Background: Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome regulates IBD and alters gut microbiota. Methods: Here, the NLRP3 expression was evaluated in the colon of IBD subjects. Then, we investigated the effects of NLRP3 inhibition by MCC950 on the gut microbiota and IBD-like symptoms induced by dextran sulfate sodium (DSS). Results: Firstly, NLRP3 and IL-1β levels were increased in patients with IBD as compared with healthy individuals. Then, the animal experiment showed that NLRP3 inhibition by MCC950 significantly attenuated IBD-like symptoms such as diarrhea and colonic inflammation in DSS-induced mice. In addition, NLRP3 inhibition inhibited NLRP3/ASC/caspase-1/IL-1β signaling pathway in the colon, which was over-activated by DSS. Furthermore, MCC950 increased the abundance of phylum Firmicutes, decreased the abundance of phylum Bacteroidetes, and increased the Firmicutes/Bacteroidetes ratio, indicating that the inhibition of NLRP3 inflammasome could regulate the abundance of intestinal flora. According to correlation analysis, NLRP3 might produce its functional role in the regulation of oxidation indicators by changing the gut microbiota composition, especially the phylum Bacteroidota, genus Lactobacillus and species Lactobacillus reuteri. Conclusions: This study suggests that NLRP3 inflammasome inhibition attenuates IBD-like symptoms by regulating gut microbiota, and provides a basis for the clinical application of NLRP3 as a target for the treatment of IBD.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu2+)-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu2+ release in the acidic infection microenvironment. The release Cu2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.

Large herbivores are particularly susceptible to changes in quantity and quality of forage resources, in turn constraining populations of large and threatened carnivores. Key prey species for Amur tigers (Panthera tigris altaica) and leopards (P. pardus orientalis), Siberian roe deer (Capreolus pygargus) have a spatial distribution which is greatly influenced by habitat quality across topographic regions. In this study, we used 138 camera-trap stations to record the abundance and distribution of Siberian roe deer in the mountains (n = 88) and valleys (n = 50) of the Northeast China Tiger and Leopard National Park, and we examined the impact of overstory structure and understory food resources on the relative abundance index (RAI) of the deer. We use generalized linear mixed models (GLMM) with negative binomial distributions, with the response variable of RAI of either of deer on the mountain or in the valley. We included canopy cover (CC), tree richness (TR) and basal area (BA) from overstory structure and mass of shrub layer (SM), mass of grasses and sedges (GM), forbs mass (FoM), ferns mass (FeM) and understory mass (UM) from understory food as fixed effects. We found that RAI of roe deer was significantly higher for the mountain than the valley. For the mountain, BA, TR and FoM were found to have a significant positive effect on roe deer, while CC showed a negative effect. In the valley, BA had a significant positive effect on roe deer, while SM showed a negative effect. Roe deer appeared to trade-off overstory structure with understory food resources, especially BA and FoM, which may lead them to prefer mountains over valleys in the national park. These findings will assist in understanding the distribution of roe deer populations in Northeast China Tiger and Leopard National Park, and may suggest more effective conservation and management strategies for the forest ecosystems of Northeast China.