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Abstract Background Dirigent (DIR) genes play a key role in the development of organic products in plants. They confer conformational influence on processes that lack stereoselectivity and regioselectivity through processes that are mostly understood. They are required to produce lignans, which are a unique and widely distributed family of plant secondary metabolites with intriguing pharmacological characteristics and potential role in plant development. DIR genes are implicated in the process of lignification and protect plants from environmental stresses, including biotic and abiotic stresses. Nevertheless, no research has been performed on the DIR gene family in Solanum lycopersicum. This study provides detailed information on the DIR gene family in S. lycopersicum. Methods and results The conserved domain analysis, phylogenetic analysis, evolutionary adaptation, cis-acting elements, proteomic analysis, signal peptide detection, transmembrane potential analysis, sequence identity and similarity analysis, gene assembly, genomic localization, duplication of gene analysis, and evolutionary linkage of 31 potential DIR genes were studied. All these analyses provide a deep understanding of DIR genes in the S. lycopersicum genome that will provide a useful reference for further functional analysis of the DIR genes in S. lycopersicum. Conclusion This research provides an in-depth and comprehensive explanation of the detailed process and structural characterization of DIR genes in the genome of S. lycopersicum, laying the groundwork for future plant genetic engineering and crop development exploration. This work will provide valuable information for identifying DIR genes in higher plants and support future research on the DIR gene family.

To investigate human exposure to short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) through dermal and oral intake via hand-to-mouth contact, wipes from the face, forearm, hand, and foot of 30 volunteers were sampled. The concentration of ∑SCCPs and ∑MCCPs ranged from 0.66 to 119 and 0.71 to 565 µg/m2, respectively. Hands exhibited significantly higher ∑CPs concentrations than other skin areas, indicating that direct contact with indoor surfaces contributed considerable CP levels on this bare skin area. Gender differences in CP levels were observed in wipes from all locations, except for the hands, possibly because of the significant variability in residuals on the hands. A significant positive relationship was found between CP levels on the hands and faces, and the CP ratios of the hands/faces were related to log KOA. Bare skin showed more significant variations in CP partitioning among related congeners and between genders than skin covered by clothing, as elucidated by the linear analysis of RSD and log KOA. Although concentrations on clothing-covered areas were relatively lower than on bare skin, the median estimated dermal absorption doses of ∑SCCPs and ∑MCCPs (152 and 737 ng/kg bw/day, respectively) for the entire body were approximately 1–2 orders of magnitude higher than those for oral ingestion (1.62 and 7.94 ng/kg bw/day, respectively), emphasizing indirect dermal uptake as a significant exposure pathway for humans.

A polysaccharide (PSMP2) was isolated from Salvia miltiorrhiza, and its sulfated derivative (PSMP2-S) was synthesized. The chemical structures of PSMP2 and PSMP2-S were analyzed by various chemical analysis methods and instrumental analysis methods. The ultrastructures and thermal stability were further investigated. In addition, PSMP2 and PSMP2-S had strong immunomodulatory activity and could regulate cytokines (interleukin-2, interleukin-6 and tumor necrosis factor-α), increased the content of short chain fatty acids and effectively reduced the relative abundance of Bacteroides and increased the relative abundance of Firmicutes, significantly increase Muribaculaceae and Lactobacillaceae, and inhibit Lachnospiraceae and Ruminococcaceae, improve the composition of gut microbiota. This study showed that PSMP2 and PSMP2-S might be used as potential natural immune regulators and gut microbiota regulators, and had great development value in the field of food and medicine.

Cottonseed is a by-product of cotton industry, but its broad application in human diets has not been fully elucidated. This study aims to analyse the nutritional composition of cotton sprouts and investigate metabolic and transcriptomic differences under light and darkness. The findings revealed that the glanded ZM41 yellow cotton sprouts were rich in protein (2.8 %), vitamin E (0.443 mg/100 g), and minerals, with < 0.01 % free gossypol. Moreover, protein, aspartic acid (1,026 mg/100 g), and serine (136 mg/100 g) reached their highest levels in nine-day-old sprouts, while no significant differences were observed in the other nutrients on the 7th, 9th, or 11th day. The average quantitative values of 64 cottonseed varieties found gossypol (27.9 mg/kg), protein (3.6 %), potassium (1,487.3 mg/kg), calcium (506.2 mg/kg) and magnesium (330.2 mg/kg). Integrated metabolome and transcriptome analyses revealed that 317 out of 1,880 metabolites were differentially accumulated between light and dark conditions, wherein the downregulation of structural genes encoding CHI, F3H, FLS, DFR, F3′H, ANS, LAR and ANR resulted in decreased flavonoid levels in dark-cultivated sprouts, while the upregulation of HMGR and 2-ODD-1 enhanced the biosynthesis of gossypol. This study provides insights into the nutritional and metabolic aspects of cotton sprouts, offering a reference for potential commercial applications.

Safflower (Carthamus tinctorius L.), a member of the Asteraceae family, is widely used in traditional herbal medicine. This review summarized agronomic conditions, genetic diversity, clinical application, and phytochemicals and pharmacological properties of safflower. The genetic diversity of the plant is rich. Abundant in secondary metabolites like flavonoids, phenols, alkaloids, polysaccharides, fatty acids, polyacetylene, and other bioactive components, the medicinal plant is effective for treating cardiovascular diseases, neurodegenerative diseases, and respiratory diseases. Especially, Hydroxysafflor yellow A (HYSA) has a variety of pharmacological effects. In terms of treatment and prevention of some space sickness in space travel, safflower could be a potential therapeutic agent. Further studies are still required to support the development of safflower in medicine. Our review indicates that safflower is an important medicinal plant and research prospects regarding safflower are very broad and worthy of further investigation.

The emergence of taxi sharing enhances urban transport efficiency and reduces carbon emissions. Using GPS tracking data from taxis in Chengdu, China, this study first outlines conditions for identifying shareable taxi orders based on their origins and destinations. We then develop a three-phase computational model to optimize matches among all potential shareable orders, calculating the shareable mileage and the proportion of original mileage that could be shared. Our comprehensive temporal and spatial analysis reveal a significant market for taxi sharing in Chengdu, with higher potential on workdays than non-workdays and four distinct demand peaks throughout the day. The morning peak on workdays and the night peak on non-workdays are particularly pronounced. Most shareable orders originate within major city districts. We find a positive correlation between the potential of taxi sharing and average traffic speed, and negative correlations with order volume, regional economic development, and population density. Functional zones related to Enterprises, Motorcycle Services, and Transportation Services exhibit significantly higher sharing potential. Compared to traditional taxi operations, taxi sharing significantly reduces total travel mileage. This quantitative analysis offers insights into the potential demand for taxi sharing among urban residents and may help government authorities optimize taxi resources for the sustainable development of urban transport.

Emerging countries usually rely on the innovation of enterprises within the regional innovation ecosystem to enhance the national innovation level. However, existing literature lacks insight into how antitrust policies might influence innovation within them. We estimate the impact of the implementation of the Anti-Monopoly Law on enterprise innovation within Zhongguancun Science and Technology Park, China's prominentregional innovation ecosystem. Using a cross-industry difference-in-difference design, we show that greater exposure to competition shock materially boosted enterprise innovation. Antitrust policy promotes enterprise innovation by increasing the R&D investment, human capital, and export. The promotion effect of antitrust is relatively strong in the sample of electronic information industry, firms with low levels of financing constraints, and those that undertake open innovation. Our findings elucidate the nexus between competition and innovation in regional innovation ecosystems and underscore the pivotal role of antitrust policies in the development of Zhongguancun Science and Technology Park.

Abstract Purpose This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients. Method This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong’s test. Results In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83–0.93), 0.90 (95% CI 0.85–0.94), and 0.88 (95% CI 0.83–0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P

Abstract After China launched the Belt and Road Initiative in 2013, the Chinese government has invested over 1200 infrastructure projects in countries along the Belt and Road, and nearly 10% of the projects have failed or been delayed. China has also concluded free trade agreements with many countries along the Belt and Road to reduce trade and investment barriers to promote economic and trade cooperation. This paper analyzes whether the signing of the free trade agreement (FTA) is conducive to promoting China's infrastructure investment projects’ success in the countries along the Belt and Road. We conclude that the signing of the FTA agreement is conducive to reducing the failure rate of China's infrastructure investment in the countries along the Belt and Road. For deeper FTAs, the effect is more pronounced. This paper further explores the investment provision of FTA and concludes that investment provision can improve the success rate of investment, especially if it includes provision of national treatment in the pre‐establishment and the dispute settlement mechanism.

Rhizoremediation is a promising remediation technology for the removal of soil persistent organic pollutants (POPs), especially benzo[a]pyrene (BaP). However, our understanding of the associations among rhizospheric soil metabolites, functional microorganisms, and POPs degradation in different plant growth stages is limited. We combined stable-isotope probing (SIP), high-throughput sequencing, and metabolomics to analyze changes in rhizospheric soil metabolites, functional microbes, and BaP biodegradation in the early growth stages (tillering, jointing) and later stage (booting) of ryegrass. Microbial community structures differed significantly among growth stages. Metabolisms such as benzenoids and carboxylic acids tended to be enriched in the early growth stage, while lipids and organic heterocyclic compounds dominated in the later stage. From SIP, eight BaP-degrading microbes were identified, and most of which such as Ilumatobacter and Singulisphaera were first linked with BaP biodegradation. Notably, the relationship between the differential metabolites and BaP degradation efficiency further suggested that BaP-degrading microbes might metabolize BaP directly to produce benzenoid metabolites (3-hydroxybenzo[a]pyrene), or utilize benzenoids (phyllodulcin) to stimulate the co-metabolism of BaP in early growth stage; some lipids and organic acids, e.g. 1-aminocyclopropane-1-carboxylic acid, might provide nutrients for the degraders to promote BaP metabolism in later stage. Accordingly, we determined that certain rhizospheric metabolites might regulate the rhizospheric microbial communities at different growth stages, and shift the composition and diversity of BaP-degrading bacteria, thereby enhancing in situ BaP degradation. Our study sheds light on POPs rhizoremediation mechanisms in petroleum-contaminated soils.

Abstract We here perform a systematic bioinformatic analysis to uncover the role of sorting nexin (SNX) family in clinical outcome of gastric cancer (GC). Comprehensive bioinformatic analysis were realized with online tools such as TCGA, GEO, String, Timer, cBioportal and Kaplan–Meier Plotter. Statistical analysis was conducted with R language or Perl, and artificial neural network (ANN) model was established using Python. Our analysis demonstrated that SNX4/5/6/7/8/10/13/14/15/16/20/22/25/27/30 were higher expressed in GC, whereas SNX1/17/21/24/33 were in the opposite expression profiles. GSE66229 was employed as verification of the differential expression analysis based on TCGA. Clustering results gave the relative transcriptional levels of 30 SNXs in tumor, and it was totally consistent to the inner relevance of SNXs at mRNA level. Protein–Protein Interaction map showed closely and complex connection among 33 SNXs. Tumor immune infiltration analysis asserted that SNX1/3/9/18/19/21/29/33, SNX1/17/18/20/21/29/31/33, SNX1/2/3/6/10/18/29/33, and SNX1/2/6/10/17/18/20/29 were strongly correlated with four kinds of survival related tumor-infiltrating immune cells, including cancer associated fibroblast, endothelial cells, macrophages and Tregs. Kaplan–Meier survival analysis based on GEO presented more satisfactory results than that based on TCGA-STAD did, and all the 29 SNXs were statistically significant, SNX23/26/28 excluded. SNXs alteration contributed to microsatellite instability (MSI) or higher level of MSI-H (hyper-mutated MSI or high level of MSI), and other malignancy encompassing mutation of TP53 and ARID1A, as well as methylation of MLH1.The multivariate cox model, visualized as a nomogram, performed excellently in patients risk classification, for those with higher risk-score suffered from shorter overall survival (OS). Compared to previous researches, our ANN models showed a predictive power at a middle-upper level, with AUC of 0.87/0.72, 0.84/0.72, 0.90/0.71 (GSE84437), 0.98/0.66, 0.86/0.70, 0.98/0.71 (GSE66229), 0.94/0.66, 0.83/0.71, 0.88/0.72 (GSE26253) corresponding to one-, three- and five-year OS and recurrence free survival (RFS) estimation, especially ANN model built with GSE66229 including exclusively SNXs as input data. The SNX family shows great value in postoperative survival evaluation of GC, and ANN models constructed using SNXs transcriptional data manifesting excellent predictive power in both OS and RFS prediction works as convincing verification to that.

A hierarchical titanium dioxide microspheres-supported palladium catalyst (Pd/TiO2-350) was prepared and characterized using BET, XRD, XPS, SEM, EDX, and TEM analyses. An ICP-OES analysis of Pd/TiO2-350 further confirmed the successful Pd immobilization on TiO2 with a palladium loading of 0.1 mmol g−1. Pd/TiO2-350 efficiently catalyzed the Suzuki-Miyaura reaction of aryl iodides with arylboronic acids to give the corresponding biaryl derivatives in good to excellent yields. After the reaction, the catalyst was recovered by centrifugation and reused three times without significant loss of its catalytic activity. Moreover, the loading of palladium species further decreased to 0.001 mol%, and the total turnover number and turnover frequency of the catalyst reached as high as 99 000 and 0.57 s−1, respectively.

Traditional Chinese Medicine (TCM) has some advantages, such as a multi-component, multi-target, and overall action, which makes the research on the compatibility of TCM formula a key and difficult point. On the contrary, network pharmacology (NP) uses high-throughput screening, computer simulation, and network database retrieval to reveal the drug–gene–target–disease interaction network, predict the mechanism of action of drugs through network relationships, and evaluate the efficacy and adverse reactions of drugs, thereby determining drugs with high efficiency and low toxicity. Therefore, the TCM formula has its unique TCM theories, and this paper primarily introduces the status quo of TCM compound prescriptions using TCM theories and NP, namely, the treatment theory of TCM (the core of TCM treatment and the principle of compatibility of TCM), as the theoretical guidance to evaluate drug's properties, efficacy, and toxicity. In addition, this study aims to predict drug's mechanism of action, interaction relationship, and matching selection to provide a high-efficiency and low-toxicity TCM formula and new insights into the follow-up study of TCM formula.

Abstract Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

The removal of or decrease in pesticide residues in soil has attracted considerable attention, due to the serious pollution of pesticides in soil. The purpose of the study was to explore the adsorption behavior of biochar on pesticides and the impact on the degradation of pesticide residues in soil, providing a basis for the remediation of soil by biochar. Biochars were prepared via pyrolysis of rice straw at a high temperature (300 °C, 400 °C, 500 °C, 600 °C). The individual and competitive adsorption of three triazine herbicides, prometryn, atrazine, and simazine, on biochar was investigated, and the degradation of the herbicide residues in biochar-added soil was determined. The selected herbicides presented similar adsorption characteristics to rice straw biochar, and the amount of herbicides adsorbed increased with higher preparation temperature and the amount of biochar. The rice straw biochar adsorbed the studied herbicides simultaneously, and the adsorption amount decreased as follows: simazine > atrazine > prometryn. The competition adsorption of the selected herbicides on the biochar presented a lower adsorption affinity than that when they are adsorbed individually. The adsorption isotherm was best fitted by the Freundlich model. The half-lives of prometryn, atrazine, and simazine were 9.8~12.6 d, 5.2~8.1 d, and 3.7~5.6 d, respectively. Biochar addition increased the degradation of the evaluated herbicides in soil. The rice straw biochar could be the potential sorbents that can be implemented for the removal of pesticides.

Effective prediction of carbon prices matters a great deal for risk management in the carbon financial market. This article designs a blended approach incorporating secondary decomposition and nonlinear error-correction technology to predict the regional carbon price in China. Firstly, the variational mode decomposition (VMD) method is used to decompose the carbon price, and then, the time-varying filter-based empirical mode decomposition (TVFEMD) is introduced to decompose the residual term generated by VMD, and the multiple kernel-based extreme learning machine (MKELM) optimized by the sparrow search algorithm (SSA) is innovatively built to forecast the carbon subsequences. Finally, in order to mine the hidden information contained in the forecasted error, the nonlinear error-correction method based on the SSA-MKELM model is introduced to correct the initial prediction of carbon price. The empirical results show that the proposed model improves the prediction accuracy of carbon prices, with RMSE, MAE, MAPE, and DS up to 0.1363, 0.1160, 0.0015, and 0.9231 in Guangdong, respectively. In the case of the Hubei market, the model also performs best. This research innovatively expands the prediction theory and method of China’s regional carbon price.

Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze–thaw-assisted extraction (FAE) were used to extract PSPs, and their structure–activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure–activity relationship of PSPs.

In this work, from the generalized Kaup–Newell (KN) equation spectral problem, the generalized super KN equation and its bi-Hamiltonian structure are constructed based on a Lie super-algebras and the super-trace identity. Besides, a generalized super KN equation with self-consistent sources is also discussed.

BackgroundVisual impairments related to non-correctable vision loss, including blindness and low vision, have been consistently shown to lower a person's health-related quality of life. This study assessed the reliability, validity, and discrimination of the Quality of Life Scale for Children with Visual Impairments (QOLS-CVI) in China.MethodsThe Pediatric Quality of Life Inventory™ 4.0 and World Health Organization Quality of Life-Disability Scale for physical disability were selected to define conceptual frameworks and item libraries based on relevant existing studies. According to two rounds of expert consultations and group discussions, some items were modified, and the draft scale was developed. Two item selection processes based on classical test theory and item response theory were used to conduct a preliminary survey and a formal survey in special schools in Shanxi and Hebei Provinces. Finally, the reliability and validity of the quality of life scale for visually impaired children in China were verified.ResultsThe final QOLS-CVI consisted of 38 items, 10 subdomains, and 6 domains. Reliability was verified by Cronbach's alpha coefficient, split-half reliability, and test-retest reliability (Cronbach's alpha for the full scale, 0.841; split-half reliability, 0.629; and test–retest reliability, 0.888). The validity results showed that the multidimensional scale met expectations: exploratory factor analysis and confirmatory factor analysis indicated good fitting models for children with visual impairments.ConclusionsThe QOLS-CVI was determined to be reliable and valid and to have strong feasibility and effectiveness. This scale can be used as an evaluation tool to study the QOL and social-participation ability of children with visual impairments.

In order to provide more scientific guidance for wetland bird protection, this study addressed the dynamics of the bird community sorted by ecotypes, classifications and threat categories from 2015 to 2019, and non-metric multidimensional scaling analysis, generalized additive models and the Mantel test were used to examine the relationships between bird communities and habitat types. The results showed that: (1) The abundance of birds peaked in 2017 at 88,258 individuals and then declined. Moreover, there was an inverse trend between species richness and abundance of birds, meaning greater abundance is associated with fewer species. (2) Swimming birds were dominant ecotypes and Anseriformes possessed the highest abundance. It was noteworthy that the abundance of critically endangered birds (Aythya baeri and Grus leucogeranus) and the species richness of endangered birds increased. (3) Building land and farmland had dominant impacts on the composition of bird community. Wading birds and birds in Gruiformes were significantly impacted by building land and farmland, and near threatened species were substantially influenced by farmland. Therefore, maintaining good connectivity between protected areas and surrounding areas is one of the best ways to effectively manage biodiversity of the target area. This research may provide a broader insight for coastal wetland bird habitat management and bird diversity preservation.

In urban North China, nitrate ( ${\text{NO}}_3^ - $ ) is a primary contributor to haze formation. So far, the production processes and source apportionments of atmospheric ${\text{NO}}_3^ - $ during the heating season (i.e. the wintertime) have not yet been well understood. This study determined δ ^15 N– ${\text{NO}}_3^ - $ , δ ^18 O– ${\text{NO}}_3^ - $ , and Δ ^17 O– ${\text{NO}}_3^ - $ of aerosol samples to compare the potential sources and formation pathways of atmospheric ${\text{NO}}_3^ - $ during heating (November to March) and non-heating (April to May) seasons. Combining stable isotope composition with the MixSIAR model based on Δ ^17 O– ${\text{NO}}_3^ - $ showed that NO _3 + DMS/HC (dimethyl sulfate/hydrocarbon) pathway was the dominant process of atmospheric nitrate formation during the heating season (mean = 52.88 ± 16.11%). During the non-heating season, the contributions of NO _3 + DMS/HC (mean = 37.89 ± 13.57%) and N _2 O _5 + H _2 O (mean = 35.24 ± 3.75%) pathways were comparable. We found that Δ ^17 O– ${\text{NO}}_3^ - $ was negatively correlated with wind speed and positively correlated with relative humidity during the heating season, possibly associated with the sources and production of atmospheric ${\text{NO}}_3^ - $ . In specific, in a dust storm event, the very low Δ ^17 O– ${\text{NO}}_3^ - $ is likely associated with particles from land surface. Under the premise of considering ^15 N fractionation, the constraint-based on δ ^15 N– ${\text{NO}}_3^ - $ illustrated that coal combustion was the major source of NO _x emission during the heating season, and the relative contribution of coal combustion decreased rapidly from the heating season (mean = 42.56 ± 15.50%) to the non-heating season (mean = 21.86 ± 4.91%). Conversely, the proportion of NO _x emitted by soil microbes rose significantly from the heating (mean = 9.67 ± 5.99%) to non-heating season (mean = 24.02 ± 11.65%). This study revealed differences in the sources and formation processes of atmospheric ${\text{NO}}_3^ - $ during the heating and non-heating seasons, which are of significance to atmospheric nitrogen oxide/nitrate pollution mitigation.

Urban multimodal transportation effectively meets the diversified travel demand of residents. However, it also generates extensive development problems such as traffic congestion, exhaust emissions and low operational efficiency. Therefore, there is an urgent need in urban sustainable development to achieve the coordinated and stable development of various modes of transportation. In this study, we took 36 major cities in China as the research object; measured the comprehensive development level of urban multimodal transportation; used the coupling coordination degree model (CCDM) to research the coordinated development relationship among buses, rail transit, and taxis; and clarified the shortcomings of the coordinated development of multimodal transportation. The results show that the comprehensive development of urban multimodal transportation in China has shown a significant upward trend from 2016 to 2020, with an average annual growth rate of about 7.36%. There are significant differences in the development levels of multimodal transportation in different cities. In addition, the relationship among buses, rail transit, and taxis in the major cities in China presents a state of uncoordinated development. Therefore, the relevant departments of cities should optimize the allocation of transportation resources, in terms of infrastructure construction and operation, according to these development levels and coordination of multimodal transportation.

Organophosphate esters (OPEs) are normally used as flame retardants, plasticizers and lubricants, but have become environmental pollutants. Because OPEs are normally present alongside heavy metals in soils, the effects of interactions between OPEs and heavy metals on plant uptake of OPEs need to be determined. In this study, we investigated the effects of OPEs chemical structure, plant cultivar and copper (Cu) on the uptake and translocation of OPEs by plants. The bioaccumulation of OPEs varied among plant cultivars. They were preferentially enriched in carrot, with the lowest concentrations observed in maize. OPEs with electron-ring substituents (ER-OPEs) exhibited a higher potential for root uptake than did OPEs with open-chain substituents (OC-OPEs), which could be attributed to the higher sorption of ER-OPEs onto root charged surfaces. This was explained by the stronger noncovalent interactions with the electron-rich structure of ER-OPEs. The presence of Cu slightly reduced the distinct difference in the ability of roots to take up OC-OPEs and ER-OPEs. This was explained by the interactions of Cu ions with the electron-rich structure of ER-OPEs, which suppressed the sorption of ER-OPEs on the root surface. A negative relationship between the logarithms of the translocation factor and octanol-water partition coefficient (Kow) was observed in treatments with either OPEs only or OPEs + Cu, implying the significant role of hydrophobicity in the OPEs acropetal translocation. The results will improve our understanding of the uptake and translocation of OPEs by plant cultivars as well as how the process is affected by the chemical structure of OPEs and Cu, leading to improvements in the ecological risk assessment of OPEs in the food chain.

Organogels are excellent drug carrier for controlled release. Organogels based on amino acid derivatives has been widely used in the area of drug delivery. In this study, a series of the organogel system based on amino acid derivatives gelators was designed and prepared to investigate the structure-property correlation in organogels. To investigate the factors that influence the property of drug release, we varied the formulation in the organogels: gelator structure, gelator concentration, volume of antigelation solvent, and drug loading. Through the Box–Behnken tests, the optimum organogel formulation in vitro was obtained. The self-healing properties of the organogel have been utilised for injection of a model lipophilic risperidone in situ, and sustained release of the drug has been studied over about one week in vivo. In conclusion, the gelation ability of gelators could be adjusted by the gelator structure. Gel property is related with the whole composition of the formulation. As drug carrier, the drug release property of organogels is affected by multiple factors. Our investigation of the gel release property will play a theoretical guiding role in the application in the in situ drug delivery system.

As a mental disease in modern society, depression shows an increasing occurrence, with low cure rate and high recurrence rate. It has become the most disabling disease in the world. At present, the treatment of depression is mainly based on drug therapy combined with psychological therapy, physical therapy, and other adjuvant therapy methods. Antidepressants are primarily administered peripherally (oral and intravenous) and have a slow onset of action. Antidepressant active ingredients, such as neuropeptides, natural active ingredients, and some chemical agents, are limited by factors such as the blood–brain barrier (BBB), first-pass metabolism, and extensive adverse effects caused by systemic administration. The potential anatomical link between the non-invasive nose–brain pathway and the lesion site of depression may provide a more attractive option for the delivery of antidepressant active ingredients. The purpose of this article is to describe the specific link between intranasal administration and depression, the challenges of intranasal administration, as well as studies of intranasal administration of antidepressant active ingredients.

Most proteins given orally have low bioavailability and are easily eliminated by rapid metabolism in vivo. In order to immobilize the drug at the site of administration and delay its release, a natural, gentle release system was designed. In this study, a heteropolysaccharide (ZOP) was isolated from Zingiber officinale using an ultrasonic assisted extraction method. ZOP Ara = 1.97: 1.15: 94.33: 1.48: 1.07. The ZOP/Chitosan (CS) composite hydrogel was synthesized using epichlorohydrin (ECH) as a cross-linking agent. The structure, morphology, and water-holding capacity of the composite hydrogel were characterized. The data showed that the addition of ZOP improved the hardness and water-holding capacity of the material. A swelling ratio test showed that the prepared hydrogel was sensitive to pH and ionic strength. In addition, the degradation rate of the hydrogel in a phosphate-buffered saline (PBS) solution with a pH value of 1.2 was higher than that in PBS with pH value of 7.4. Similarly, the release kinetics of Bovine serum albumin (BSA) showed higher release in an acidic system by the hydrogel composed of ZOP/CS. The hydrogel prepared by this study provided a good microenvironment for protein delivery. In summary, this composite polysaccharide hydrogel is a promising protein-drug-delivery material.

Accurately forecasting carbon prices is key to managing associated risks in the financial market for carbon. To this end, the traditional strategy does not adequately decompose carbon prices, and the kernel extreme learning machine (KELM) with a single kernel function struggles to adapt to the nonlinearity, nonstationarity, and multiple frequencies of regional carbon prices in China. This study constructs a model, called the VMD-ICEEMDAN-RE-SSA-HKELM model, to forecast regional carbon prices in China based on the idea of ‘decomposition–reconstruction–integration’. The VMD is first used to decompose carbon prices and the ICEEMDAN is then used to decompose the residual term that contains complex information. To reduce the systematic error caused by increases in the mode components of carbon price, range entropy (RE) is used to reconstruct the results of its secondary decomposition. Following this, HKELM is optimized by the sparrow search algorithm and used to forecast each subseries of carbon prices. Finally, predictions of the price of carbon are obtained by linearly superimposing the results of the forecasts of each of its subseries. The results of experiments show that the secondary decomposition strategy proposed in this paper is superior to the traditional decomposition strategy, and the proposed model for forecasting carbon prices has significant advantages over a considered reference group of models.

In recent times, China has emphasized five major development concepts to promote high-quality development: coordination, green, innovation, openness, and sharing. As a metamorphosis of these ideas, Chinese science and technology parks (STPs) are gathering areas of high-tech industries and represent advanced productive forces. Their greenness, openness, and innovative developments herald the future development trends of China. Based on the data of 52 STPs in China from 2011 to 2018, this study analyzes the impact of foreign direct investment (FDI) quantity and quality on the low-carbon development of the STPs. We use Hansen's nonlinear panel threshold regression model with knowledge accumulation as the threshold variable. The results show the following: First, there are complex nonlinear relationships between FDI quantity, FDI quality, and the low-carbon development of the STPs. Second, FDI quantity has a significant positive impact on the low-carbon development of the STPs only when the level of knowledge accumulation is below a certain threshold. Beyond this threshold the effect is no longer significant. Third, FDI quality has a significant positive impact on the low-carbon development of STPs only when the level of knowledge accumulation is lower than a certain threshold; beyond which, the impact is no longer significant. These results can serve as a reference for China to effectively promote economic low-carbon growth of STPs and achieve green, open, and innovative development.

With the expansion of urban scale and the growth of urban population, the bicycle-sharing system has been greatly helping grease the wheels of convenience and diversity of citizens' travel. Nevertheless, there are a set of additional problems, including imbalance of supply and demand at rental stations and low utilization of system operation, which have disrupted the travel experience of consumers, the profitability of businesses, and the coordination of government. In this study, we take Nanjing as an example to measure the operating efficiency of bicycle-sharing by calculating the capacity utilization rate (CUR). Afterwards, based on the IC card data of bicycle-sharing users, we statistically analyzed the traffic inflow and outflow at rental stations. Besides, this paper discusses the factors influencing the use of bicycle-sharing, by introducing the method of sampling stepwise regression into the study of rental situation and geographical environment. The results are as follows: (1) demand for bicycle-sharing is higher on weekdays than on weekends, especially during the morning and evening rush hours. (2) The daily average capacity utilization rate of bicycle-sharing is less than 0.08, indicating that the system is not efficient enough. During morning and evening rush hours, only less than 10% of rental stations have high inflow and outflow, and there is an imbalance of inflow and outflow for the same rental station at different times of the day. (3) The stepwise regression results show that the inflow and outflow of bicycle-sharing rental stations are mainly affected by the distribution of traffic, education, entertainment, medical, and other functional zones near the stations. These findings could provide relevant government departments and enterprises with strategies and suggestions for the efficient and healthy operation of the urban bicycle-sharing system.

Toxic heavy metals and metalloids in agricultural ecosystems are crucial factors that limit global crop productivity and food safety. Industrial toxic heavy metals and metalloids such as cadmium, lead, and arsenic have contaminated large areas of arable land in the world and their accumulation in the edible parts of crops is causing serious health risks to humans and animals. Plants have co-evolved with various concentrations of these toxic metals and metalloids in soil and water. Some green plant species have significant innovations in key genes for the adaptation of abiotic stress tolerance pathways that are able to tolerate heavy metals and metalloids. Increasing evidence has demonstrated that phytohormone abscisic acid (ABA) plays a vital role in the alleviation of heavy metal and metalloid stresses in plants. Here, we trace the evolutionary origins of the key gene families connecting ABA signaling with tolerance to heavy metals and metalloids in green plants. We also summarize the molecular and physiological aspects of ABA in the uptake, root-to-shoot translocation, chelation, sequestration, reutilization, and accumulation of key heavy metals and metalloids in plants. The molecular evolution and interaction between the ABA signaling pathway and mechanisms for heavy metal and metalloid tolerance are highlighted in this review. Therefore, we propose that it is promising to manipulate ABA signaling in plant tissues to reduce the uptake and accumulation of toxic heavy metals and metalloids in crops through the application of ABA-producing bacteria or ABA analogues. This may lead to improvements in tolerance of major crops to heavy metals and metalloids.

Talents are not only an important strategic resource for promoting regional development but also a core element for maintaining competitiveness. We organize the evaluation index system of regional talent attraction into the following four aspects: regional development, industry development, income and regional environment. Combined with the talent possession of 31 provinces (cities) from 2010 to 2018, we establish a regression equation of the relationship between the evaluation index and talent possession by using a stepwise regression and the Bayesian prior function. Simultaneously, we apply the spatial autocorrelation analysis method to measure the correlation and agglomeration degree of the talent attraction level of provinces and municipalities in China. The results reveal the following. (1) From 2010 to 2018, the talent attractiveness level of China's provinces shows a steady upward trend with an average annual growth rate of 5.804%. The regional environment has the highest score, and the income level has the lowest score. (2) The level of talent attraction in China shows a decreasing trend from east to west, and the ranking in 2018 was "East Coast > North Coast > Southern Coast > Middle Yangtze River > Middle Yellow River > Southwest > Northeast > Greater Northwest". The trend of spatial agglomeration is apparent and gradually increases over the years. The numbers of hot and cold spots are relatively large and concentrated in the eastern coast and western region, respectively. (3) The level of economic development, quality of people's life, and level of the development of the tertiary industry have a great impact on the attractiveness of talents. Talents also pay more attention to regional medical, education and transportation indicators. These research results can provide some guidance and references for the formulation of talent introduction policies in various provinces and municipalities.

We propose a model of the fiber coupling efficiency for a partially coherent collimating laser beam propagating through turbulent biological tissue to fiber. By studying the influence of link parameters on fiber coupling efficiency, we find that there are optimal focal length and transmitting beam radius for specific turbulent tissue. We also find that a larger characteristic length and small length-scale factor, or smaller fractal dimension and strength coefficient of refractive-index fluctuation will lead to larger fiber coupling efficiency. In order to improve the fiber coupling efficiency, we recommend select the optimum focal length, moderate transmitting beam radius, lower aperture diameter of the coupling lens, longer wavelength and higher coherent degree of light source. 2000 MSC: 41A05, 41A10, 65D05, Keywords: Fiber coupling efficiency, Biological tissue, Turbulence, Optimum parameter, Laser beam

The distribution of high-quality customers (hereafter HQC) for taxis (including ride-hailing cars) has a significant impact on drivers’ revenue and taxis’ operation efficiency. Based on the taxi global positioning system data, we construct an evaluation model of passengers to discuss the imbalance of consumption in taxi market. The profit margin for each taxi order is calculated, and then a grid-based method is used to distinguish the HQC and the regions with potential higher benefits. We analyze the HQC’s distribution of taxis (including ride-hailing cars) in different areas and in different time periods. We find that the HQC are distributed mainly on the periphery of the main urban area, which indicates that traffic condition is even worse in the urban center because of factors such as congestion. The HQC are more concentrated on workdays and more scattered on nonworkdays, which implies that the public have different travel habits and demands on workdays and nonworkdays. The proportion of HQC in each administrative district or functional zone is not always positively correlated to either the proportion of total orders or the total HQC. This indicates that the distribution of HQC in each administrative district or functional zone is imbalanced. The proportion of orders and that of HQC are roughly the same in the temporal dimension, being higher in the morning and evening rush hours. Compared with the distribution of the HQC of ride-hailing, that of taxis is more imbalanced in the temporal dimension. Relevant departments should further coordinate taxi pricing, strengthen market control, and promote sustainable development in the taxi and ride-hailing markets.

Nowadays, ride-hailing services have been established as a part of the urban transportation. Their arrival has remade the profit structure and resulted in the unbalance of interest in taxi market. Here, we establish the service models of taxis, carpooling, and car-hailing under "Internet +" from the perspective of profit margins, to perform a comparative analysis among the different services. RESULTS:First, Profit margins are generally higher for short trips than for long trips, though empty cruise fee to a certain degree make up for the driver's decreased profit margins. Second, the profit margin for carpooling is roughly 1.85 times that of ride-hailing, and 1.75 times that of taxis. This shows that the sharing economy has a certain advantage. Third, Profit margins are higher and fluctuations are lower on non-work days than on work days. At last, Profit margins are roughly 1.3 times higher on non-congested roads than on congested roads. The reduced profitability on congested roads makes it even harder to catch a ride during rush hours and on congested roads. We suggest that the relevant departments make appropriate efforts to make it more attractive for drivers to take on passengers during rush hours and on congested roads, and promote the sharing in the taxi market.

This study aimed to determine sediment contamination in the Beidagang Wetland Nature Reserve to describe atmospheric deposition of trace metals. We analyzed Hg, Cd, Pb, TOC, TN, TP, δ13C, and δ15N, and studied their variations in surface sediments and in the vertical profiles of sediment cores collected from the reserve. Evaluation of environmental trace metal contamination using sediment quality guidelines and geochemical background values indicated that the risk of metal pollution in the reserve sediments was relatively low. Concentrations of Hg, Cd, and Pb in the sediments were much lower than concentrations in sediment samples from Bohai Bay and polluted rivers in Tianjin. Enrichment factors indicate that samples are moderately contaminated with Hg, Cd, and Pb; whereas the geo-accumulation index results classify the sediments as uncontaminated to moderately contaminated with Hg, Cd, and Pb. The distribution patterns of trace metal concentrations in the three core samples were uniform. δ13C and δ15N were used to track the sources of TOC and TN in sediments. Results show that TOC mainly originated from the residue and decaying matter of aquatic plants (e.g., algae, reeds, and Typha), while TN was derived from soil N and elevated atmospheric N deposition. Because domestic and industrial waste is not discharged into the Beidagang Wetland Nature Reserve, trace metals found in sediments mainly originate from atmospheric deposition. The results provide baseline data for analysis of trace metal accumulation in Beijing-Tianjin-Hebei, a region subject to atmospheric deposition in northern China.

The detection of fluorescent signal in chromatographic chip is the key of disease diagnosis by immunochromatographic assay. We propose a new algorithm for the automatic identification of fluorescent signal. Based on the features of chromatographic chips, mathematic morphology in RGB color space is used to filter and enhance the images, pyramid connection is used to segment the areas of fluorescent signal and then the method of Gaussian Mixture Model is available to detect the fluorescent signal. At last we calculate the average fluorescence intensity in obtained fluorescent areas. It can be proved that the algorithm has a good effect to segment the fluorescent areas and it can detect the fluorescent signal quickly and accurately to achieve the quantitative detection of chromatographic chip through experimental data analysis.

Abstract Objective To investigate the distribution of pathogens and epidemiological changes in children hospitalized with community-acquired pneumonia (CAP) during and after the COVID-19 pandemic public health restrictive measures. aiming to provide a foundation for clinical diagnosis, treatment, and policy formulation. Methods This multicenter retrospective study spanned January 2019 to December 2023. The study included 78,256 children hospitalized for CAP in four hospitals in Henan, China, among which 27,580 cases (35.2%) were tested for pathogens using multiplex real-time fluorescent polymerase chain reaction (PCR). The pathogens detected include Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), respiratory syncytial virus (RSV), influenza A virus (Flu A), influenza B virus (Flu B), and Mycoplasma pneumoniae (MP). Results Pathogens were identified in 18,690 of the 27,580 children, resulting in a 67.8% positive detection rate. Of these cases, 15,105 (54.8%) were single pathogen infections and 3,585 (13%) were mixed pathogen infections. The pathogen positivity rate was lowest in the first year of the COVID-19 pandemic (2020), at 54.7%, and peaked at 79.1% in 2023, after public health restrictions were lifted. During the COVID-19 pandemic (2020–2022), seasonal variation in pathogen prevalence was disrupted. Post-restriction, there was a significant increase in RSV and MP cases. SP remained the leading bacterial cause of CAP, especially in young children. RSV was the predominant viral pathogen, particularly affecting infants. MP showed a rising trend with age, yet it also affected younger individuals. Conclusion The COVID-19 pandemic altered the epidemiological characteristics of pathogens in children with CAP. This impact is likely to persist, necessitating enhanced surveillance of CAP pathogens to mitigate the healthcare burden in children. Clinical trial number Not applicable.

Acanthotomicus suncei is a newly discovered bark beetle in China that significantly threatens the American sweetgum Liquidambar styraciflua. In recent years, this pest has spread from its original habitat to many surrounding cities, causing substantial economic and ecological losses. Considering the wide global distribution of its host, Liquidambar styraciflua, this pest is likely to continue to spread and expand. Once the pest colonizes a new climatically suitable area, the consequences could be severe. Therefore, we employed the CLIMEX and Random Forests model to predict the potential suitable distribution of A. suncei globally. The results showed that A. suncei was mainly distributed in Southern China, in South Hokkaido in Japan, Southern USA, the La Plata Plain in South America, southeastern Australia, and the northern Mediterranean; these areas are located in subtropical monsoon, monsoonal humid climates, or Mediterranean climate zones. Seasonal rainfall, especially in winter, is a key environmental factor that affects the suitable distribution of A. suncei. Under future climates, the total suitable area of A. suncei is projected to decrease to a certain extent. However, changes in its original habitat require serious attention. We found that A. suncei exhibited a spreading trend in Southwest, Central, and Northeast China. Suitable areas in some countries in Southeast and South Asia bordering China are also expected to show an increased distribution. The outward spread of this pest via sea transportation cannot be ignored. Hence, quarantine efforts should be concentrated in high-suitability regions determined in this study to protect against the occurrence of hosts that may contain A. suncei, thereby avoiding its long-distance spread. Long-term sentinel surveillance and control measures should be carried out as soon as A. suncei is detected, especially in regions with high suitability. Thus, our findings establish a theoretical foundation for quarantine and control measures targeting A. suncei.

BackgroundAdolescents are vulnerable to mental disorders due to physiological, psychosocial, and cognitive changes during this critical developmental stage. Depression, in particular, can lead to high-risk behaviors such as self-injury (SI) and suicide. This study aims to estimate the pooled prevalence of SI behaviors among adolescents with depression.Materials and methodsWe systematically searched databases including EMBASE, Scopus, PubMed, and Web of Sciences for relevant articles published on adolescents with depression from January 1, 2000, to January 1, 2024. The quality assessment of the studies was conducted using the Joanna Briggs Institute (JBI) criteria. The global prevalence of SI was calculated based on a random effects model using Stata software version 17.ResultsOur analysis included 29 studies involving 12,934 adolescents. The lifetime prevalence of SI was 52% (95% Confidence Interval [CI]: 41–64), while the period prevalence was 57% (95% CI: 49–64). Notably, a significant relationship was observed between the prevalence of SI and the year of publication of articles (p = 0.002). Furthermore, publication bias was not significant for both lifetime prevalence (p = 0.281) and period prevalence (0.358).ConclusionThe prevalence of self-injurious behaviors in adolescents with depression is alarmingly high, with more than half of adolescents having engaged in these high-risk behaviors during their lifetime or within the last year. Given the associated risk of suicide, it is crucial to identify individuals at risk and provide timely interventions.

Abstract Lawsonia intracellularis, the etiologic agent of proliferative enteropathy (PE), is an obligate intracellular Gram-negative bacterium possessing a type III secretion system (T3SS), which enables the pathogen to translocate effector proteins into targeted host cells to modulate their functions. T3SS is a syringe-like apparatus consisting of a base, an extracellular needle, a tip, and a translocon. The translocon proteins assembled by two hydrophobic membrane proteins can form pores in the host-cell membrane, and therefore play an essential role in the function of T3SS. To date, little is known about the T3SS and translocon proteins of L. intracellularis. In this study, we first analyzed the conservation of the T3S apparatus between L. intracellularis and Yersinia, and characterized the putative T3S hydrophobic major translocon protein LI1158 and minor translocon protein LI1159 in the L. intracellularis genome. Then, by using Yersinia pseudotuberculosis as a surrogate system, we found that the full-length LI1158 and LI1159 proteins, but not the putative class II chaperone LI1157, were secreted in a − Ca2+ and T3SS-dependent manner and the secretion signal was located at the N terminus (aa 1–40). Furthermore, yeast-two hybrid experiments revealed that LI1158 and LI1159 could self-interact, and LI1159 could interact with LI1157. However, unlike CPn0809 and YopB, which are the major hydrophobic translocon proteins of the T3SS of C. pneumoniae and Yersinia, respectively, full-length LI1158 was non-toxic to both yeast and Escherichia coli cells, but full-length LI1159 showed certain toxicity to E. coli cells. Taken together, despite some differences from the findings in other bacteria, our results demonstrate that LI1158 and LI1159 may be the translocon proteins of L. intracellularis T3SS, and probably play important roles in the translocation of effector proteins at the early pathogen infection stage.

Background To explore the direct effect of core self-evaluation and the indirect effects of positive and negative coping styles on school adaptation of high school students after their return to school during the COVID-19 pandemic. Methods The Core Self-Evaluation Scale, Simple Coping Style Scale, and School Adaptation Questionnaire were used for the psychometric analysis of 500 high school students (229 males and 271 females) one month after their return to school. The bootstrap method was applied for mediation analysis. Results A positive correlation was noted between core self-evaluation and school adaptation (r = 0.56), and the predictive effect was significant (β = 0.43). Core self-evaluation positively predicted positive coping styles, which positively predicted school adaptation, while core self-evaluation negatively predicted negative coping styles, which negatively predicted school adaptation. Positive and negative coping styles played a significant mediating role between core self-evaluation and school adaptation. The mediating effect included the indirect effects generated by two pathways: core self-evaluation → positive coping style → school adaptation (95% CI [0.08–0.19]) and core self-evaluation → negative coping style → school adaptation (95% CI [0.03–0.11]). Conclusion There is a positive association between the core self-evaluation and school adaptation of high school students after their return to school during the COVID-19 pandemic. It may directly or indirectly affect the school adaptation of high school students after their return to school through positive or negative coping styles. After returning to school, educators should guide students to view themselves positively, cultivate healthy core self-evaluation, and enable them to have good school adaptation.

Abstract Background Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. Methods We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. Results We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52+ NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. Conclusions We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system.

Breast cancer cells are known to metastasize to the bone but why the cells should migrate and metastasize to this particular organ is not clearly understood. Here, the authors show that EZH2 activates an integrin B1 and FAK signaling pathway in breast cancer cells, which activates TGFB signaling to drive metastasis in the bone.

IntroductionThis study explored the effects of coping style and two potential intermediately factors (cognitive reappraisal and psychological resilience) on the mental health of middle school students during the normalization of epidemic prevention and control in China.MethodsAnswers on questionnaires designed to assess coping style, cognitive reappraisal, psychological resilience, and mental health among 743 middle school students (386 boys, 357 girls, 241 first graders, 235 second graders, and 267 third graders) were analyzed using structural equation modeling.ResultsThe results showed that coping style, cognitive reappraisal, and psychological resilience directly predicted mental health. The negative effect of a negative coping style on mental health was significantly stronger than the positive effect of a positive coping style. Coping style affected mental health through the independent mediating effects of cognitive reappraisal and psychological resilience and through their chain mediation.DiscussionThe use of positive coping styles by most students led to greater cognitive reappraisal, strengthened psychological resilience, and thus few mental health problems. These findings provide empirical evidence and may guide educators in the prevention and intervention of mental health problems among middle school students.

Accurate prediction of drug response is a crucial step in personalized medicine. Recently, deep learning techniques have been witnessed with significant breakthroughs in a variety of areas including biomedical research and chemogenomic applications. This motivated us to develop a novel deep learning platform to accurately and reliably predict the response of cancer cells to different drug treatments. In the present work, we describe a Java-based implementation of deep neural network method, termed JavaDL, to predict cancer responses to drugs solely based on their chemical features. To this end, we devised a novel cost function and added a regularization term which suppresses overfitting. We also adopted an early stopping strategy to further reduce overfit and improve the accuracy and robustness of our models. To evaluate our method, we compared with several popular machine learning and deep neural network programs and observed that JavaDL either outperformed those methods in model building or obtained comparable predictions. Finally, JavaDL was employed to predict drug responses of several aggressive breast cancer cell lines, and the results showed robust and accurate predictions with r2 as high as 0.81.

Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM).Methods: Low and high doses of water extract of PM were given to mice by gavage for 8 weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression.Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1.Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.

Abstract Background Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear. Results Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4+ T cells and CD8+ T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2. Conclusions Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.

Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5′ nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.

Abstract We develop PIRCh-seq, a method which enables a comprehensive survey of chromatin-associated RNAs in a histone modification-specific manner. We identify hundreds of chromatin-associated RNAs in several cell types with substantially less contamination by nascent transcripts. Non-coding RNAs are found enriched on chromatin and are classified into functional groups based on the patterns of their association with specific histone modifications. We find single-stranded RNA bases are more chromatin-associated, and we discover hundreds of allele-specific RNA-chromatin interactions. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interactions.