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Abstract Background Bladder cancer (BLCA) is a common malignancy characterized by dysregulated transcription and a lack of effective therapeutic targets. In this study, we aimed to identify and evaluate novel targets with clinical potential essential for tumor growth in BLCA. Methods CRISPR-Cas9 screening was used to identify transcription factors essential for bladder cancer cell viability. The biological functions of KLF16 in bladder cancer were investigated both in vitro and in vivo. The regulatory mechanism between KLF16 and MYC was elucidated through a series of analyses, including RNA sequencing, quantitative polymerase chain reaction (qPCR), RNA immunoprecipitation, Western blotting, Mass spectrometry, Dual-luciferase reporter assays, Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, OptoDroplets assays, and RNA stability assay. The clinical relevance of KLF16 and MYC in bladder cancer was evaluated through analyses of public databases and immunohistochemistry. Results Krüppel-like factor 16 (KLF16) was essential for BLCA cell viability. Elevated expression of KLF16 was observed in bladder cancer tissues, and higher expression levels of KLF16 were correlated with poor progression-free survival (PFS) and cancer-specific survival (CSS) probabilities in BLCA patients. Mechanistically, KLF16 mRNA competed with the mRNA of dual-specificity phosphatase 16 (DUSP16) for binding to the RNA-binding protein, WW domain binding protein 11 (WBP11), resulting in destabilization of the DUSP16 mRNA. This, in turn, led to activation of ERK1/2, which stabilized the MYC protein. Furthermore, KLF16 interacted with MYC to form nuclear condensates, thereby enhancing MYC’s transcriptional activity. Additionally, MYC transcriptionally upregulated KLF16, creating a positive feedback loop between KLF16 and MYC that amplified their oncogenic functions. Targeting this loop with bromodomain inhibitors, such as OTX015 and ABBV-744, suppressed the transcription of both KLF16 and MYC, resulting in reduced BLCA cell viability and tumor growth, as well as increased sensitivity to chemotherapy. Conclusions Our study revealed the crucial role of the KLF16/MYC regulatory axis in modulating tumor growth and chemotherapy sensitivity in BLCA, suggesting that combining bromodomain inhibitors, such as OTX015 or ABBV-744, with DDP or gemcitabine could be a promising therapeutic intervention for BLCA patients.

Abstract Background Cervical cancer is the fourth leading cause of cancer-related death among women worldwide, and effective therapeutic strategies for its treatment are limited. Recent studies have indicated that ferroptosis, a form of regulated cell death, is a promising therapeutic strategy. KLF14 has been shown to regulate both cell proliferation and apoptosis in cervical cancer. However, its role in modulating lipid peroxidation and ferroptosis remains largely unexplored and enigmatic. Methods SiHa and HeLa cells were transduced with lentiviral vectors to overexpress KLF14. Protein levels were analyzed via western blotting and immunohistochemistry (IHC). LDH assays, calcein-AM/propidium iodide (PI) staining, and generation of cell growth curves using a real-time cell analysis (RTCA) system were used to detect cell damage and proliferation. Cellular ROS, lipid ROS, transmission electron microscopy (TEM), and Fe2+ assays and a xenograft mouse model were used to measure the level of ferroptosis. Proteomics combined with bioinformatics methods was used to screen target genes regulated by KLF14, and CUT&Tag and dual-luciferase assays confirmed the repression of GPX4 by KLF14 via direct binding to its promoter. Results KLF14 is abnormally expressed in various tumors and downregulated in cervical cancer. Overexpression of KLF14 induced ferroptosis and inhibited cell proliferation in vitro as well as xenograft tumorigenicity in vivo. Mechanistic studies revealed that KLF14 binds to the promoter of GPX4, suppressing its transcriptional activity and thereby decreasing its expression, which contributes to the induction of ferroptosis. Truncation and point mutation analyses of the GPX4 promoter revealed multiple binding sites for KLF14 within the − 1000 bp to + 35 bp region, which are responsible for its inhibitory effect on GPX4 transcription. Additionally, deletion of the zinc finger motif in KLF14 abolished its inhibitory effect on GPX4 promoter activity and cell proliferation. Conclusion Our data revealed a previously unidentified function of KLF14 in promoting ferroptosis, which results in the suppression of cell proliferation. Mechanistically, we revealed a novel regulatory mechanism by which KLF14 targets GPX4. These findings suggest a novel strategy to induce ferroptosis through the targeting of KLF14 in human cervical cancer cells.

Introduction: In the current technological era, the implementation and use of information and communication technology are crucial for productivity and organizational management in the health sector. This study aimed to investigate factors influencing staff acceptance of the Hospital Management System (HMS) using the Unified Theory of Acceptance and Use of Technology (UTAUT) in a private hospital in Selangor, Malaysia. Methods: Semi-structured interviews were conducted with 25 healthcare professionals, including doctors, nurses, and administrative staff, to explore their experiences and perceptions of the HMS. Data collection was performed through interviews and observations and analyzed using thematic analysis with ATLAS.ti. Results: The study identified five key themes influencing HMS acceptance: performance expectancy, effort expectancy, social influence, facilitating conditions, and behavioral intention. Participants emphasized the importance of system reliability, speed, and user-friendly interfaces for efficient workflow. Peer support and a technology-promoting organizational culture positively influenced system use. Comprehensive training and continuous technical support were crucial for user confidence. Despite recognizing the system's benefits, participants highlighted challenges such as inadequate system integration and the need for simultaneous digital and traditional record-keeping. Conclusion: Addressing these issues and tailoring the HMS to meet specific departmental needs can enhance user satisfaction and system effectiveness. The study underscores the importance of understanding user needs and providing robust support systems to facilitate the successful implementation and adoption of HMS in healthcare settings.

Heat moisture treatment (HMT) is a widely used method for starch modification due to its safe, green, environmentally friendly, and efficient characteristics. In this study, quinoa starch was modified by HMT with varying moisture contents (20%, 25%, and 30%) at a temperature of 120 °C for 10 hours, and its rheological properties, in vitro digestive properties, and structure were further evaluated. The steady rheology results indicated that all the samples were shear-thinning non-Newtonian fluids. After undergoing HMT, the apparent viscosity of quinoa starch decreased significantly. Additionally, the samples' apparent viscosity decreased as the moisture content of HMT increased. The results of frequency sweep showed that the storage modulus G' of quinoa starch decreased with the increase of moisture content of HMT, while the loss modulus G'', and loss factor increased with the increase of moisture content of HMT. The thixotropic results showed that the thixotropic ring area of quinoa starch decreased with the increase of the moisture content of HMT. Additionally, the results of in vitro digestion showed that the content of rapidly digestible starch in quinoa starch decreased significantly after HMT (P

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1–5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8–11), and 4 phenolic acids (12–15). Compounds 6–7 and 9–12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8–11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125–250 µg/mL.

Abstract Background Vascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis. Results Here, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We find that the H3K9la levels are upregulated in endothelial cells in response to VEGF stimulation. Pharmacological inhibition of glycolysis decreases H3K9 lactylation and attenuates neovascularization. CUT& Tag analysis reveals that H3K9la is enriched at the promoters of a set of angiogenic genes and promotes their transcription. Interestingly, we find that hyperlactylation of H3K9 inhibits expression of the lactylation eraser HDAC2, whereas overexpression of HDAC2 decreases H3K9 lactylation and suppresses angiogenesis. Conclusions Collectively, our study illustrates that H3K9la is important for VEGF-induced angiogenesis, and interruption of the H3K9la/HDAC2 feedback loop may represent a novel therapeutic method for treating pathological neovascularization.

As the largest organic carbon input in the agroecosystems, crop residues can increase soil carbon sequestration and crop production in greenhouse vegetable fields (GVFs). However, the soil microbiological mechanisms driving straw decomposition in GVFs under different incubation temperatures and fertilization treatments are not clear. Thus, soil samples were collected from a long-term field experiment included chemical fertilizer application alone (CF), 2/4 fertilizer N+2/4 organic fertilizer N (CM), 2/4 fertilizer N+1/4 organic fertilizer N+1/4 straw N (CMS), 2/4 fertilizer N+2/4 straw N (CS), and incubated with 13C-labeled straw at different temperatures (15, 25, and 35°C) for 60 days. Organic-amended treatments (CM, CMS, and CS), especially CMS treatment, increased soil bacterial Alpha diversity before and after straw addition. Straw decomposition process was dominated by soil Proteobacteria, Actinobacteria, and Firmicutes for each treatments. The effect of incubation temperature on soil microbial community composition was higher than that of fertilization treatments. Soil Alphaproteobacteria and Actinomycetia were the most predominant class involved in straw decomposition. Gammaproteobacteria (Pseudomonas, Steroidobacter, Acidibacter, and Arenimonas) were the unique and predominant class involved in straw decomposition at medium and high temperatures as well as in the straw-amended treatments. Organic-amended treatments, especially straw-amended treatments, increased the relative abundance of glycosyl transferases (GT) and auxiliary activities (AA). Alphaproteobacteria, Actinomycetia, and Gammaproteobacteria had higher relative contribution to carbohydrase genes. In summary, the long-term organic-amended treatments altered the structure of soil microbial communities and increased soil bacterial diversity, with the CMS having a greater potential to enhance resistance to external environmental changes. Soil Alphaproteobacteria and Actinomycetia were responsible for the dominance of straw decomposition, and Gammaproteobacteria may be responsible for the acceleration of straw decomposition. Fertilization treatments promote straw decomposition by increasing the abundance of indicator bacterial groups involved in straw decomposition, which is important for isolating key microbial species involved in straw decomposition under global warming.

Purpose: This study aimed to determine the effect of postsurgical vaginal microbiome (VM) on high-risk human papillomavirus (hrHPV) infection and the risk of disease recurrence in patients surgically treated for cervical cancer (CC) or intraepithelial neoplasia (CIN). Methods: 207 women who underwent surgical treatment for CC or CIN at the Department of Gynecologic Oncology of the First Affiliated Hospital of University of Science and Technology of China from November 2016 to October 2023 were included. The patients’ clinical data, including age, surgical modality, and diagnosis at time of index surgery, were collected retrospectively and analyzed. Associations between postsurgical VM indices, hrHPV infection, cervical cytology, and recurrence were also evaluated. Results: Patient age, surgical modality (whether complete excision of the cervix was performed), and diagnosis at time of index surgery (cervical dysplasia vs. cervical carcinoma) showed no significant association with postsurgical hrHPV infection, cervical cytology, or disease recurrence. However, postsurgical VM imbalance was significantly associated with hrHPV infection status (OR = 4.640, 95 % CI = 2.085–10.460, P

Calibrating hydrological model parameters is crucial for ensuring the models' predictive accuracy, which is fundamental for informed decision-making. We provide a toolkit that can perform multi-objective automatic calibration for the parameters of a variable infiltration capacity (VIC) model, with the purpose of locating robust calibration parameters while lowering the threshold for beginners as much as possible. We mainly use the C language to establish the internal dependency relationship between the streamflow generation and routing process through direct function calls without iterative edits to soil parameter files. The Fortran language-based streamflow routing program, previously run independently, is encapsulated in the form of a shared library and then coupled to the streamflow generation module, thus simplifying the design of the calibration program. Then, we further encapsulate the coupled VIC module into a multi-objective function and embed it into the Borg multi-objective optimization algorithm to achieve loose coupling between the Borg algorithm and the VIC model. A case study shows that VIC-Borg requires no additional effort for environment configuration in the operating system and greatly simplifies the automatic calibration of multi-objective parameter optimization. At the same time, it follows the established convention of configuring the VIC streamflow generation module, routing module, and Borg algorithm, making it easier for beginners to use.

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

Abstract Retinopathy of prematurity (ROP) is a retinal neovascularization (RNV) disease that is characterized by abnormal blood vessel development in the retina. Importantly, the etiology of ROP remains understudied. We re‐analyzed previously published single‐cell data and discovered a strong correlation between microglia and RNV diseases, particularly ROP. Subsequently, we found that reactive oxygen species reduced autophagy‐dependent protein degradation of absent in melanoma 2 (AIM2) in hypoxic BV2 cells, leading to increased AIM2 protein accumulation. Furthermore, we engineered AIM2 knockout mice and observed that the RNV was significantly reduced compared to wild‐type mice. In vitro vascular function assays also demonstrated diminished angiogenic capabilities following AIM2 knockdown in hypoxic BV2 cells. Mechanistically, AIM2 enhanced the M1‐type polarization of microglia via the ASC/CASP1/IL‐1β pathway, resulting in RNV. Notably, the administration of recombinant protein IL‐1β exacerbated angiogenesis, while its inhibition ameliorated the condition. Taken together, our study provides a novel therapeutic target for ROP and offers insight into the interaction between pyroptosis and autophagy.

High exhaust temperature is an intrinsic nature of natural gas engines which underlies power de-rating and thermal aging of after-treatment system; therefore, this study integrates an organic Rankine cycle (ORC) system between engine and it's three-way catalyst (TWC) to address these challenges. ORC facilitates power output enhancement through exhaust energy recovery and alleviates thermal aging by reducing exhaust temperature. To estimate the effectiveness of this hypothesized system, a simulation-based investigation is performed. First, simulation models, including engine, TWC, and vehicle dynamic models, are built and validated by experimental data. According to the temperature characteristics of different TWCs, three scenarios, representing old, current, and prospective TWC technology, are formulated to estimate the ORC performance under Worldwide Harmonized Light Vehicles Test Cycle. Results show that ORC system can substantially alleviate the thermal damage caused by high exhaust temperature and extend TWC lifespan. It is estimated that over 98.5 % of thermal damage can be decreased by proper ORC setting, and the average TWC lifespan extension can be at least 55.4, making a reduced noble metal usage and cost of TWC. Meanwhile, with the decrease of the working temperature of TWC, ORC can recover exhaust energy under more road conditions, further improving the net power and shortening the payback period of extra ORC hardware costs. A reduction in the working temperature of TWC from 770.5 K to 618 K yields a 109 % enhancement in maximum power, coupled with a 62.30 % reduction in the payback period. These findings fully reflect the advantage of ORC-TWC coupling and indicate that ORC is supposed to be used more for the TWC with a low working temperature to maximize economic effectiveness. This study provides a novel pathway for thermal aging alleviation of TWC and a valuable reference for prospective studies on matching ORC with TWC under road conditions.

Surface coal mining in semi-arid regions has detrimental impacts on the structure and function of surface ecosystems, thereby impeding the attainment of regional sustainable development goals. Moreover, the impact of climate change on ecological restoration in semi-arid mining areas is an inevitable consideration. To elucidate the response of ecosystem services in mining areas to regional climate change, topography, soil, vegetation and socioeconomic development, this study selected six large-scale surface coal mines located in semi-arid regions of China as research objects. In this study, we aimed to assess the main ecosystem services (carbon sequestration, soil conservation, and flow regulation) provided by these mines. In addition, we analysed the spatial and temporal evolution and interrelationships of these ecosystem services. Furthermore, we explored the underlying mechanisms between ecosystem services and environmental factors. The results showed the following: (1) Geospatially, there was a gradual decrease in carbon sequestration and flow regulation from northeast to southwest in the mining areas. However, the soil conservation exhibited an upward trend. Throughout the research period, the carbon sequestration change rate in the six mining areas displayed an initial downward and subsequent upward trend, the rate of soil conservation exhibited a gradual upward trend, and the flow regulation decline rate followed a downward trend. (2) Change rate of carbon sequestration and soil conservation in the six mining areas showed a significant positive correlation (r = 0.51, p < 0.001), with the strongest correlation observed in the Shengli Mining Area (r = 0.64, p < 0.001). (3) Ecosystem service changes in the mining areas were primarily driven by initial conditions (95.0%), followed by meteorological factors (4.2%). Three ecological restoration models were proposed for the different regions based on driver analyses. The findings of this study offer scientific evidence that can be used to inform ecological management, enhance ecological security, and promote regional sustainable development in mining areas.

Approximate Bayesian computation (ABC) relaxes the need to derive explicit likelihood functions required by formal Bayesian analysis. However, the high computational cost of evaluating models limits the application of Bayesian inference in hydrological modeling. In this paper, multivariate adaptive regression splines (MARS) are used to expedite the ABC calibration process. The MARS model is trained using 6,561 runoff simulations generated by the soil and water assessment tool (SWAT) model and subsequently replaces the SWAT model to calculate the objective functions in ABC and multi-objective evolutionary algorithm (MOEA). In experiments, MARS can successfully reproduce the runoff time series simulations of the SWAT model at a low time cost, with a runoff variance determination coefficient of 0.90 as compared to the Monte Carlo method. MARS-assisted ABC can quickly and accurately estimate the parameter distributions of the SWAT model. The comparison of ABC with non-Bayesian MOEAs helps in the selection of an appropriate calibration approach. HIGHLIGHTS Approximate Bayesian computation (ABC) was used to calibrate the complex hydrological model.; Multivariate adaptive regression splines (MARS) were used to expedite the ABC process.; The ability of MARS-assisted ABC for calibration of the SWAT model was demonstrated.; The calibration results of ABC and multi-objective evolutionary algorithms were compared.; MARS-assisted ABC has the potential to extend the use of ABC in hydrological modeling.;

Vesicle-associated membrane protein (VAMP)-associated proteins (VAP27s), which are widely expressed in plants and animals, play an important role in metabolism, physiology, growth, and development, disease resistance, and immunity. While the function of this family has been elucidated in model plants like Arabidopsis thaliana and tomato, its role in grapevine remains unclear. In this present study, 12 vesicle-associated protein-membrane protein genes were identified in the grapevine genome by bioinformatics, designated as the VAP27 gene family. A phylogenetic tree, encompassing 53 genes from three model plants, Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum, revealed the subdivision of the VAP27 gene family into three subfamilies, each presumably serving different functions, besides localizing in endoplasmic reticulum, individual members also localize in nucleus. Additionally, we compared the transcriptional levels and subcellular localizations of the VvVAP27 family members across different plant tissues (flower, leaf, seed, root, fruit, tendril, and stem), indicating site-specific functionalities for different gene members. To investigate the responsiveness of the VAP27 gene family to pathogen infection, particularly Plasmopara viticola on host plants, we analyzed the expression patterns of VAP27 genes post-infection. Our findings revealed divergent expression profiles among different members at different stages of infection. The gene family responded to the infection of downy mildew on grapevine and could inhibit the spread of Phytophthora capsici lesions in Nicotiana benthamiana. These results provide an important basis for further studies delving into the functions of the VAP27 gene family in plant growth and disease resistance.

Ecological restoration policies and their implementation are influenced by ecological and socioeconomic drivers. Top-down approach-based spatial planning, emphasizing hierarchical control within government structures, and without a comprehensive consideration of social–ecological interactions may result in implementation failure and low efficiency. Although many researchers have indicated the necessity to engage social–ecological interactions between stakeholders in effective planning processes, socioeconomic drivers of ecological restoration on a large scale are difficult to quantify because of data scarcity and knowledge limitations. Here, we established a new ecological restoration planning approach linking a social–ecological system framework to large-scale ecological restoration planning. The new spatial planning approach integrates bottom-up approaches targeting stakeholder interests and provides social considerations for stakeholder behavior analysis. Based on this approach, a meta-analysis is introduced to recognize key socioeconomic and social–ecological factors influencing large-scale ecological restoration implementation, and a stochastic model is constructed to analyze the impact of socioeconomic drivers on the behavior of authorities and participants on a large scale. We used the Yangtze River Basin-based Conversion of Cropland to Forest Program (CCFP), one of the largest payments for ecosystem service programs worldwide, to quantify the socioeconomic impacts of large-scale ecological restoration programs. Current CCFP planning without socioeconomic considerations failed to achieve large-scale program goals and showed low investment efficiency, with 19.71% of the implemented area reconverting to cropland after contract expiry. In contrast, spatial matching between planned and actual restoration increased from 61.55% to 81.86% when socioeconomic drivers were included. In addition, compared to that with the current CCFP implementation, the cost effectiveness of spatial planning with social considerations improved by 46.94%. Thus, spatial optimization planning that integrates both top-down and bottom-up approaches can result in more practical and effective ecological restoration than top-down approaches alone. Our new approach incorporates socioeconomic factors into large-scale ecological restoration planning with high practicality and efficiency.

Combining organic and chemical fertilizers is a sustainable strategy for vegetable production. However, there is limited research concerning the risks associated with heavy metals (HMs) in greenhouse systems with long-term location application. A three-year investigation, conducted from 2021 to 2023, explored a fifteen-year field experiment with combinations of chemical fertilizer (CH), corn straw (SW) and pig manure (PM). Five treatments were evaluated: excessive fertilization (high CH and PM), conventional fertilization (normal CH), organic–inorganic fertilization (3/4CN + 1/4PN, 2/4CN + 2/4PN and 2/4CN + 1/4PN + 1/4SN). This study evaluated the risks associated with heavy metals (HMs) by analyzing and quantifying their concentrations in soil and cucumber fruits, as well as by calculating the bioconcentration factors (BCFs), the geo-accumulation index (Igeo), and both the non-carcinogenic and carcinogenic risks. The results indicated that excessive fertilization (CF) increased the concentrations of Cu and Zn in fruits, as well as the Igeo values of Cu, Zn, and Cd, and the non-carcinogenic Cu risk, while decreasing the BCFs of Cu and Zn. Organic–inorganic fertilization also elevated the Igeo values of Cu and Zn. Redundancy analyses confirmed a positive correlation between the soil concentrations of Cu and Zn and higher levels of available phosphorus contents (48.4%), alongside a lower pH (4.9%). The concentrations of Cu, Zn, and Cd in both soil and cucumber fruits increased linearly with the duration of application and amount of input. Although the combined application of CH with PM or SW did not significantly elevate the non-carcinogenic or carcinogenic risks associated with most heavy metals, the carcinogenic risks of Cd and As emerged as potential risk factors after 15 years of organic–inorganic fertilization. Utilizing a combination of CH with PM and SW as a fertilizer management strategy can effectively address both the control of heavy metal inputs in the facility and the safety and quality of cucumbers.

Camellia fascicularis is a valuable ornamental, edible, and medicinal plant with promising prospects for bioactivity development. We screened the bioactivity of eight fractions (Fr. A−I) obtained from the ethyl acetate phase of C. fascicularis via silica gel column chromatography. The results indicated that the anti-inflammatory, antioxidative, and antimicrobial active components were mainly found in Fr. B*, E, A, and H; Fr. A–G; and Fr. D–I, respectively. Bioactivity-guided isolation identified 18 secondary metabolites. Compounds 1, 3–5, 7, and 15–18 were isolated from the genus Camellia for the first time in this study, whereas the other compounds were also isolated from this plant for the first time. The structures of these compounds were elucidated through comprehensive spectroscopic techniques. Compounds 1, 9−11, 28, 30, and 31 demonstrated antioxidative activities comparable to those of ascorbic acid, whereas the remaining compounds exhibited diminished antioxidative activity. In terms of antimicrobial activity, compounds 7, 18, 22, and 27 exerted inhibitory potency against Pseudomonas aeruginosa, similar to tetracycline (MIC: 125 µg/mL). Other compounds showed moderate to weak inhibitory effects against Staphylococcus aureus and Escherichia coli (MIC: 250–500 µg/mL). Molecular docking revealed that compounds 2, 36, 41, and 65 showed strong binding affinity for 8ET0, whereas compounds 2, 36, 38, 40, 63, and 65 showed strong binding affinity for 3A4A. This research further increased the diversity of the secondary metabolites of C. fascicularis, laying a foundation for the subsequent development and utilization of this species.

IntroductionMatrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to β-lactams, and, if so, by what mechanism MT works.MethodsWe screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC.Results and DiscussionThe production of β-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y103D and L517R) and mrcA (A639V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of β-lactams and improving the therapeutic efficacy of Glässer’s disease.

Inter- and intra-specific variations in phenotype are common and can be associated with genomic mutations as well as epigenomic variation. Profiling both genomic and epigenomic variants is at the core of dissecting phenotypic variation. However, an efficient targeted genotyping and epigenotyping system is lacking. We describe a new multiplex targeted genotyping and epigenotyping system called improved bulked-PCR sequencing (iBP-seq). We employed iBP-seq for the detection of genotypes and methylation levels of dozens of target regions in mixed DNA samples. iBP-seq can be adapted for the construction of linkage maps, fine mapping of quantitative-trait loci, and detection of genome editing mutations at a cost as low as $0.016 per site per sample. We developed an automated bioinformatics pipeline, including primer design, a series of bioinformatic analyses for genotyping and epigenotyping, and visualization of results. iBP-seq and its bioinformatics pipeline, available at http://zeasystemsbio.hzau.edu.cn/tools/ibp/, can be adapted to a wide variety of species.

Camellia fascicularis has important ornamental, medicinal, and food values, which also have tremendous potential for exploiting bioactivities. We performed the bioactivity-guided (antioxidant and antimicrobial) screening of eight fractions obtained from the ethyl acetate phase of C. fascicularis. The antioxidant activity was measured by DPPH, ABTS, and FRAP, and the antibacterial activity was measured by the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. The results of bioactivity-guided isolation indicated that the major antioxidant compounds in the ethanolic extracts of C. fascicularis may be present in fractions (Fr.) (A–G, obtained after silica gel column chromatography). Fr. (D–I, obtained after silica gel column chromatography) is a fraction of C. fascicularis with antimicrobial activity. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 17 compounds were identified, including four phenolics (1, 3–4, and 14), a phenylpropane (2), five terpenoids (5–7, 12, and 15), four flavonoids and flavonoid glycosides (8–10 and 16), and two lignins (13 and 17). Compounds 4–7, 13–15, and 17 were isolated from the genus Camellia for first time. The remaining compounds were also isolated from C. fascicularis for first time. The evaluation of antioxidant and antimicrobial activities revealed that compounds 1, 3, 9, 11, and 17 exhibited higher antioxidant activity than the positive control drug (ascorbic acid), and compounds 4, 8, 10, and 13 showed similar activity to ascorbic acid. The other compounds had weaker or no significant antioxidant activities. The MIC of antibacterial activity for compounds 4, 7, and 11–13 against P. aeruginosa was comparable to that of the positive control drug tetracycline at 125 µg/mL, and other secondary metabolites inhibited E. coli and S. aureus at 250–500 µg/mL. This is also the first report of antioxidant and antimicrobial activities of compounds 5–7, 13–15, and 17. The results of the study enriched the variety of secondary metabolites of C. fascicularis and laid the foundation for further research on the pharmacological efficacy and biological activity of this plant.

Objective: To investigate the effect of β-sitosterol on endometrial cells to understand the underlying mechanism.Materials and Methods: This is a laboratory-based experimental study conducted on animals and cells. Histologicalassays were performed to determine the effect of β-sitosterol on endometrial cells. The CCK-8 assay was used toassess the inhibitory effect of β-sitosterol on the proliferation of ectopic endometrial stromal cells (hEM15A). Flowcytometry was performed to evaluate the induction of apoptosis by β-sitosterol in hEM15A cells. The transwell invasionassay was conducted to measure the suppression of hEM15A cell migration by β-sitosterol. Western blot analyseswere performed to analyze the effect of β-sitosterol on the expression of Smad family member 7 (Smad7) and theactivity of transforming growth factor-β (TGF-β1), as well as the phosphorylation of Smad2 and Smad3.Results: Histological assays showed that β-sitosterol regulates histopathology and induces apoptosis of endometrialcells in vivo. The CCK-8 assay revealed that β-sitosterol could inhibit the proliferation of hEM15A in human endometriosispatients. Flow cytometry showed that apoptosis was triggered by β-sitosterol in hEM15A. The transwell invasion assayindicated that the hEM15A migration under the β-sitosterol treatment group was suppressed. Western blot analysessuggested that β-sitosterol increased the expression of Smad7, decreased the activity of TGF-β1, and reduced thephosphorylation of Smad2 and Smad3. The effect of β-sitosterol was weakened by the silence of Smad7.Conclusion: The results suggest that β-sitosterol can inhibit the proliferation of endometrial cells and relieveendometriosis by inhibiting TGF-β-induced phosphorylation of Smads through regulation of Smad7.

Abstract Objectives The risk and beneficial factors of early discharge after thoracoscopic anatomic lung cancer surgery are unknown, and this study aims to investigate predictors and associated 30‐day readmission for early discharge. Methods We performed a single‐center retrospective analysis of 10,834 consecutive patients who underwent thoracoscopic anatomic lung cancer surgery. Two groups were determined based on discharge date: “discharged by postoperative Day 2” and “discharged after postoperative Day 2.” Univariable and multivariable analysis were conducted to identify predictors for discharge. Using propensity score matching (PSM) to compare 30‐day readmission rate between two cohorts. Results A total of 1911 patients were discharged by postoperative Day 2. Multivariable analysis identified older age (odds ratio (OR) = 1.014, p

Summary: This study focused on examining the exact role of circulating immune cells in the development of diabetic retinopathy (DR). In vitro co-culture experiments showed that peripheral blood mononuclear cells (PBMCs) from patients with type 1 DR crucially modulated the biological functions of human retinal microvascular endothelial cells (HRMECs), consequently disrupting their normal functionality. Single-cell RNA sequencing (scRNA-seq) study revealed unique differentially expressed genes and pathways in circulating immune cells among healthy controls, non-diabetic retinopathy (NDR) patients, and DR patients. Of significance was the observed upregulation of JUND in each subset of PBMCs in patients with type 1 DR. Further studies showed that downregulating JUND in DR patient-derived PBMCs led to the amelioration of HRMEC dysfunction. These findings highlighted the notable alterations in the transcriptomic patterns of circulating immune cells in type 1 DR patients and underscored the significance of JUND as a key factor for PBMCs in participating in the pathogenesis of DR.

Water use efficiency (WUE) is an important indicator in linking the carbon and water cycles of ecosystems. Previous studies performed in alpine and cold regions have contributed greatly to understanding the WUE response of single ecosystem or specific species in small-scale regions to climatic factors; however, studies focusing on differences in the WUE response among ecosystems or species are insufficient, which has limited the understanding of the climatic adaptation of WUE in alpine and cold regions. Here, based on the 134 leaf δ13C records measured for the 46 dominant species in two main ecosystems on the Qinghai-Tibetan Plateau, variation in the response of WUE among biomes was analyzed by grouped linear regression, redundancy analysis (RDA), and structural equation models (SEMs). The results showed that (1) photosynthetically active radiation (PAR0), moisture index (MI) and vapor pressure deficit (VPD) were significantly correlated with the variation in WUE; (2) compared with the WUE of alpine grasslands, alpine desert grasslands was more sensitive to climatic factors, which presenting a steeper slope that varied with modified growing degree days (MGDD0), PAR0, MI, VPD and CO2; (3) composition of genera distributions explained 32.22% of the variation in WUE, while the WUE of Stipa was more sensitive compared to other species to most climatic factors; (4) climate (composition of genera) and their joint effects explained 58.98% (63.53%) of the variation in WUE of alpine desert grasslands (alpine grasslands), while altitude indirectly controlled the WUE variation in alpine grasslands and MI directly controlled the WUE variation in alpine desert grasslands. This study quantified the driving effects of climates and biomes on the variation in WUE and contributed to the understanding of vegetation adaptation in alpine and cold regions.

Biodiversity and ecosystem services are seriously threatened by human activities, and there have been calls for the expansion of protected areas (PAs) to mitigate this situation. Currently, there is an urgent need to establish new PA cost-effectively from concentrating on biodiversity to including the provision of ecosystem services. Hence, a prefectural evaluation was conducted across the Qinghai-Tibet Plateau (QTP) to quantify endangered species habitat provision and three key ecosystem services to identify conservation priority zones (CPZs), which were then combined with low human footprint zones to determine cost–effective zones (CEZs). A scenario simulation, which contains conservative, moderate, and ambitious targets, was further proposed to conserve more CEZs for PA design. We found that biodiversity, ecosystem services, and human footprints varied significantly among the different taxonomic groups. CPZs and CEZs cover 33 and 28 % of the QTP, respectively, including almost all forest areas, and near medium and high elevations (approximately 3000 ∼ 4700 m). In comparison with existing PAs systems, the new PAs system is considering cost-effective in terms of biodiversity and ecosystem services, increasing 42–60 %, 32–46 %, and 62–69 %, and 47–62 % of the important habitats that serve mammals, birds, amphibians, and plants, respectively, and promoting 48–66 % carbon service, 37–54 % soil retention, and 22–37 % water yield. More importantly, it reduces conflict with the human footprint by up to 22 %. Moreover, the conservative, moderate, and ambitious targets conserved 44, 48, and 53 % of the QTP, respectively. These three targets were set for each prefecture and prefectural–level city with spatially specific CEZs recognized, providing some implications on prefectural PAs priorities for policymakers.

Though many new remote sensing technologies have been introduced to analyze forests, regional-scale species-level mapping products are still rare, especially in large mountainous areas. Tree species abundance, low spectral separability among species and huge computing demand are hindrances for obtaining an accurate stand tree species map. This study addressed these problems by synergizing regionalization, multiple feature fusion, and model fusion and proposed a new machine learning workflow. The whole area, i.e. Yunnan province in China (approximately 390,000 km2), was firstly divided into 8 distinct floristic regions according to the distributions and phylogenetic relationships of native tree species. Thereafter, with Google Earth Engine (GEE) platform, multiple data sets, including Sentinel-2 imagery, SRTM DEM, and WorldClim bioclimatic, were collected to construct a high-dimensional feature pool for each region. Thirdly, the maximum entropy model （MaxEnt）, generally used for predicting ecological niche, and three classifiers, i.e. Random Forest (RF), Support Vector Machines (SVM), and Extreme Gradient Boosting (XGBoost), were used to pre-classify environmental and remote sensing data, respectively. After that, two types of decision fusion strategies, parallel and serial ensembles, were applied to fuse pre-classification probability maps for each sub-region. Finally, the spatial distribution of 19 forest stand species over the whole Yunnan Province was obtained by mosaicking the best classification results from 8 sub-regions. Our method achieves an overall accuracy of 72.18% on the entire validation dataset. The decision fusion models significantly improve the classification accuracy, with the eight partitioned best fusion models improving the accuracy by 7.33%–25.39% on average compared to base classifiers. This study demonstrates that the spatial partitioning strategy and the decision fusion integrating a proper machine learning algorithm and ecological niche model can significantly improve the classification accuracy of forest stand species in montane forests.

Hydrological simulation has long been a challenge because of the computationally intensive and expensive nature of complex hydrological models. In this paper, a surrogate modelling (SM) framework is presented based on the Hadoop cloud for approximating complex hydrological models. The substantial model runs required by the design of the experiment (DOE) of SM were solved using the Hadoop cloud. Polynomial chaos expansion (PCE) was fitted and verified using the high-fidelity model DOE and was then used as a case study to investigate the approximation capability in a Soil and Water Assessment Tool (SWAT) surrogate model with regard to the accuracy, fidelity, and efficiency. In experiments, the Hadoop cloud reduced the computation time by approximately 86% when used in a global sensitivity analysis. PCE achieved results equivalent to those of the standard Monte Carlo approach, with a flow variance coefficient of determination of 0.92. Moreover, PCE proved to be as reliable as the Monte Carlo approach but significantly more efficient. The proposed framework greatly decreases the computational costs through cloud computing and surrogate modelling, making it ideal for complex hydrological model simulation and optimization. HIGHLIGHTS Our surrogate modelling framework reduces the computational cost of simulations.; The design of the experiment was parallelized on a Hadoop cloud.; PCE was fitted and verified using a high-fidelity model.; The approximation ability of PCE in the SWAT surrogate model was investigated.;

Vegetation primarily draws water from soil moisture (SM), with restoration in drylands often reducing SM storage (SMS). However, anomalies have been detected in the Beijing–Tianjin Sand Source Region (BTSSR) of China via the Global Land Data Assimilation System (GLDAS) and Gravity Recovery and Climate Experiment (GRACE). This study quantified the sources of increased SMS in drylands to elucidate the effects of vegetation restoration on SMS. The results indicated the following: (1) In vegetated drylands, 46.2% experienced a significant increase in SMS while 53.8% remained stable; both were positively correlated with the normalised difference vegetation index (NDVI). (2) The increase in SMS was accompanied by a decrease in groundwater storage (GWS), as indicated by the significant correlation coefficients of −0.710 and −0.569 for SMS and GWS, respectively. Furthermore, GWS served as the primary source of water for vegetation. (3) The results of the redundancy analysis (RDA) indicated that the initial vegetation, the driver of the observed trend of increased SMS and decreased GWS, accounted for 50.3% of the variability in water storage. Therefore, to sustain dryland ecosystems, we recommend that future vegetation restoration projects give due consideration to the water balance while concurrently strengthening the dynamic monitoring of SMS and GWS.

The accurate identification of forest degradation and its driving factors is a prerequisite for implementing high-quality forest management. However, distinguishing degradation patterns is often neglected in large-scale forest quality assessments. The indicators were constructed to identify typical forest degradation patterns using remote sensing indexes, followed by an analysis of the spatiotemporal dynamics of forest degradation and quantification of the contributions from various driving factors. The results indicated that the constructed indicators could effectively distinguish typical forest degradation patterns, with a fire degradation identification accuracy of 90.0% and a fitting accuracy of drought and pest degradation higher than 0.7. The cold temperate conifer forest zone had the largest proportion of fire degradation, accounting for 67.7% of the area, and totals of 99.0% of the subtropical evergreen broadleaf forest zone and 92.8% of the temperate conifer and broadleaf mixed forest zone were moderately to severely affected by drought, with long-term stability. Additionally, 0.1% of the temperate grassland region and 0.1% of the cold temperate conifer forest zone underwent severe pest infestations, with a long-term stable trend. Meteorological factors were the primary contributors to all typical degradation patterns, accounting for 81.35%, 58.70%, and 82.29%, respectively. The research developed an index for assessing forest degradation and explained the importance of natural and anthropogenic factors in forest degradation. The results are beneficial for the scientific management of forest degradation and for improving forest management efficiency.

ABSTRACT: A comparative study was performed to investigate the differences in plasma pharmacokinetics (PKs) and tissue residues of trimethoprim (TMP) between silky fowls and 817 broilers. The 2 breeds of chickens received compound sulfadiazine suspension by gavage at 20 mg/kg (measured as TMP). Blood and tissue samples were collected at predetermined time points. The concentrations of TMP in plasma and tissue samples were determined by a validated high-performance liquid chromatography (HPLC) method. The plasma concentration-time data were subjected to noncompartment analysis by WinNonlin program (Pharsight Co., Mountain View, CA). The mean plasma concentrations of TMP in silky fowls were significantly lower than those in 817 broilers at all time-points. Significant differences were also observed between silky fowls and 817 broilers in maximum concentration (Cmax), area under the curve from time 0 to 24 h (AUC0 → 24 h), apparent volume of distribution (Vd), and total body clearance (ClB). Silky fowls had significantly higher muscle TMP concentrations and longer tissue residual time than 817 broilers. The tissue concentration of TMP followed the order of leg muscle > breast muscle > liver, which was obviously different from that of 817 broilers. The half-lives of TMP in the leg muscle, breast muscle, and liver of silky fowls were 31.42, 10.78, and 0.38 d, respectively. The current withdrawal time (WDT) was not sufficient to prevent violative residues of TMP in the edible tissues of silky fowls, and a WDT much longer than 8 d might be required.

Abstract Grazing intensity, characterized by high spatial heterogeneity, is a vital parameter to accurately depict human disturbance and its effects on grassland ecosystems. Grazing census data provide useful county-scale information; however, they do not accurately delineate spatial heterogeneity within counties, and a high-resolution dataset is urgently needed. Therefore, we built a methodological framework combining the cross-scale feature extraction method and a random forest model to spatialize census data after fully considering four features affecting grazing, and produced a high-resolution gridded grazing dataset on the Qinghai–Tibet Plateau in 1982–2015. The proposed method (R2 = 0.80) exhibited 35.59% higher accuracy than the traditional method. Our dataset were highly consistent with census data (R2 of spatial accuracy = 0.96, NSE of temporal accuracy = 0.96) and field data (R2 of spatial accuracy = 0.77). Compared with public datasets, our dataset featured a higher temporal resolution (1982–2015) and spatial resolution (over two times higher). Thus, it has the potential to elucidate the spatiotemporal variation in human activities and guide the sustainable management of grassland ecosystem.

Background NeiyiKangfu tablets (NYKF) are widely used clinically for the treatment of endometriosis (EMS), whose mechanism of action has been extensively studied. Researchers have found that NYKF may control the development of ectopic lesions by inhibiting angiogenesis and inflammatory cytokine secretion. Nevertheless, NYKF’s mechanism of action remains unclear.Methods In the present study, the function of NYKF in the progression of EMS and the associated underlying mechanism was investigated by in vivo and in vitro experiments. EMS model mice were treated with NYKF and the pro-inflammatory factors and apoptosis of ectopic endometrium as well as RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling activation were assessed. In addition, human endometriosis-derived immortalized entopic stromal (hEM15A) cells transfected with or without RAF kinase inhibitor protein (RKIP)-small-interfering RNA (siRNA) were also treated with NYKF and the proliferation, migration, apoptosis, and RAF/MEK/ERK signaling activation were measured by Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, and western blot, respectively.Results Results showed that NYKF increased the expression of RKIP, inhibited RAF/MEK/ERK signaling activation, and induced apoptosis while inhibiting proliferation and migration both in EMS mice and hEM15A cells. RKIP knockdown could inhibit the effect of NYKF treatment, leading to the activation of RAF/MEK/ERK signaling and the proliferation and migration of hEM15A cells.Conclusions In conclusion, these results suggest that NYKF treatment promotes apoptosis and inhibits proliferation and migration in EMS by inhibiting the RAF/MEK/ERK signaling pathway by targeting RKIP.

Abstract The underlying mechanisms that determine gene expression and chromatin accessibility in retinogenesis are poorly understood. Herein, single‐cell RNA sequencing and single‐cell assay for transposase‐accessible chromatin sequencing are performed on human embryonic eye samples obtained 9–26 weeks after conception to explore the heterogeneity of retinal progenitor cells (RPCs) and neurogenic RPCs. The differentiation trajectory from RPCs to 7 major types of retinal cells are verified. Subsequently, diverse lineage‐determining transcription factors are identified and their gene regulatory networks are refined at the transcriptomic and epigenomic levels. Treatment of retinospheres, with the inhibitor of RE1 silencing transcription factor, X5050, induces more neurogenesis with the regular arrangement, and a decrease in Müller glial cells. The signatures of major retinal cells and their correlation with pathogenic genes associated with multiple ocular diseases, including uveitis and age‐related macular degeneration are also described. A framework for the integrated exploration of single‐cell developmental dynamics of the human primary retina is provided.

Our prior studies have confirmed that long-term colonization of Porphyromonas gingivalis (Pg) and overexpression of the inflammatory factor glycogen synthase kinase 3β (GSK3β) promote the malignant evolution of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the functional mechanism by which Pg could promote ESCC malignancy and chemo-resistance through GSK3β-mediated mitochondrial oxidative phosphorylation (mtOXPHOS), and the clinical implications. The effects of Pg and GSK3β on mtOXPHOS, malignant behaviors and response to paclitaxel and cisplatin treatment of ESCC cells were evaluated by in vitro and in vivo studies. The results showed that Pg induced high expression of the GSK3β protein in ESCC cells and promoted the progression and chemo-resistance via GSK3β-mediated mtOXPHOS in human ESCC. Then, Pg infection and the expression of GSK3β, SIRT1 and MRPS5 in ESCC tissues were detected, and the correlations between each index and postoperative survival of ESCC patients were analysed. The results showed that Pg-positive ESCC patients with high-expression of GSK3β, SIRT1 and MRPS5 have significant short postoperative survival. In conclusion, we demonstrated that the effective removal of Pg and inhibition of its promotion of GSK3β-mediated mtOXPHOS may provide a new strategy for ESCC treatment and new insights into the aetiology of ESCC.

Neuromorphic computing (NC), considered as a promising candidate for future computer architecture, can facilitate more biomimetic intelligence while reducing energy consumption. Neuron is one of the critical building blocks of NC systems. Researchers have been engaged in promoting neuron devices with better electrical properties and more biomimetic functions. Two-dimensional (2D) materials, with ultrathin layers, diverse band structures, featuring excellent electronic properties and various sensing abilities, are promised to realize these requirements. Here, the progress of artificial neurons brought by 2D materials is reviewed, from the perspective of electrical performance of neuron devices, from stability, tunability to power consumption and on/off ratio. Rose up to system-level applications, algorithms and hardware implementation of spiking neural network, stochastic neural network and artificial perception system based on 2D materials are reviewed. 2D materials not only facilitate the realization of NC systems but also increase the integration density. Finally, current challenges and perspectives on developing 2D material-based neurons and NC systems are systematically analyzed, from the bottom 2D materials fabrication to novel neural devices, more brain-like computational algorithms and systems.

As the largest organic carbon input to agroecosystems, crop straw can solve the problem of soil quality degradation in greenhouse vegetable fields, harmonize the balance between soil nutrients and energy, and improve soil quality to maintain the sustainable production of greenhouse vegetables. However, the microbial mechanism of the straw decomposition process under different temperatures and fertilization treatments in greenhouse vegetable soils has not been clarified. Soil samples were used to investigate the biology of straw decomposition in the soil at three incubation temperatures (15, 25, and 35 °C) through a soil incubation experiment (60 d) under different fertilization treatments. Fertilization treatments for this long-term field experiment included chemical fertilizer (CF), substitution of half of the chemical N fertilizer with manure (CM), straw (CS), or combined manure and straw (CMS). The results showed that soil hydrolase activities tended to decrease with increasing temperature during straw decomposition. Compared with the CF, organic substitutions (CM, CMS, and CS) increased soil β-glucosidase, β-cellobiosidase, N-acetyl-glucosaminidase, and β-xylosidase activities during straw decomposition. Soil CO2 emission rates were the highest at each incubation temperature on the first day, rapidly declining at 25 °C and 35 °C and slowly declining at 15 °C. The soil CO2 cumulative emissions tended to increase with increasing temperature under different fertilization treatments. PCA showed that the responses of soil enzyme activities to temperature at 7, 15, and 30 d of straw decomposition were stronger than those of fertilization. In summary, both fertilization treatment and incubation temperature could influence soil CO2 emissions by affecting soil physicochemical properties and enzyme activities during straw decomposition, whereas incubation temperature had a stronger effect on straw decomposition than fertilization, as indicated by PLS-PM and three-way ANOVA. Considering the influence for fertilization on the straw decomposition process at different incubation temperatures, the straw applications (CMS and CS) were more suitable to temperature changes.

Abstract Chinese first-born children need to learn how to get along with their siblings after the implementation of the universal two-child policy in 2016. We investigated the relationships between temperament, parenting style, and psychological adjustment among firstborns. The current study employed a questionnaire survey conducted in four regions in China. A total of 524 Chinese two-child families participated in the study; the firstborns were between 3 and 8 years old and their younger siblings were between 1 month and 5 years old. The results indicated that (1) children’s temperament subscales were significantly related to parenting style subscales and psychological adaptation. Moreover, the parenting style subscales were significantly related to psychological adaptation, and (2) authoritarian parenting partially mediated the relationship between approach or withdrawal and psychological adjustment.

The treatment outcome of breast cancer is closely related to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Triple-negative breast cancer (TNBC) lacking ER, PR, and HER2 expression has limited treatment options and a poor prognosis. Tumor-infiltrating lymphocytes (TILs) play a role in promoting or resisting tumors by affecting the tumor microenvironment and are known as key regulators in breast cancer progression. However, treatments for TNBC (e.g., surgery, chemotherapy and radiotherapy) have non-satisfaction’s curative effect so far. This article reviews the role of different types of TILs in TNBC and the research progress of adoptive cell therapy, aiming to provide new therapeutic approaches for TNBC.

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders.

In the context of global climate change, temperate forests in climate-sensitive areas are inevitably affected. To deepen the understanding of the impact on precipitation changes into the relationship between key ecosystem services (ESs), this study selected net primary productivity (NPP), soil conservation (SC) and water yield (WY) of temperate forest in northern China as objects, and the Spearman correlation test and redundancy analysis were applied to analyze the response of ESs relationship to precipitation gradient. The results show that precipitation is the meteorological factor with the greatest impact (contribution 21.2%, p

Oilseed crops are rich in plant lipids that not only provide essential fatty acids for the human diet but also play important roles as major sources of biofuels and indispensable raw materials for the chemical industry. The regulation of lipid metabolism genes is a major factor affecting oil production. In this review, we systematically summarize the metabolic pathways related to lipid production and storage in plants and highlight key research advances in characterizing the genes and regulatory factors influencing lipid anabolic metabolism. In addition, we integrate the latest results from multi-omics studies on lipid metabolism to provide a reference to better understand the molecular mechanisms underlying oil anabolism in oilseed crops.

Seedlessness in grapes is much appreciated by consumers and especially in cultivars consumed either as table grapes or as raisins. In many parts of the world, low temperature is the main environmental stress limiting grape production. In this study, stenospermocarpic (seed abortion) cultivars were selected as the female parents while seeded cold-resistant cultivars were selected as the male parents to develop new cold-resistant seedless grapes using embryo rescue technology, which has previously been shown to be a highly efficient way of breeding seedless grapes. Here, we report optima in genotype, sampling time, and culture medium for the embryo rescue of 14 hybrid combinations. Our results indicate that the embryo development rate (39.9%) and the seedlings rate (21.5%) were highest among the 14 crosses when ‘Ruby Seedless’ was used as the female parent and ‘Beibinghong’ was used as the male parent. The best sampling times for ‘Yuehong Wuhe’, ‘Ruby Seedless’, and ‘Melissa seedless’ were 37, 55, and 52 days after flowering, respectively. Embryo rescue efficiency was highest when the sucrose concentration for seedlings was maintained at about 1.0%. Using molecular markers, we detected 91 hybrids with seedless traits and 18 hybrids with cold resistance traits.

Abstract Stem cell therapy is a promising strategy to rescue visual impairment caused by retinal degeneration. Previous studies have proposed controversial theories about whether in situ retinal stem cells (RSCs) are present in adult human eye tissue. Single‐cell RNA sequencing (scRNA‐seq) has emerged as one of the most powerful tools to reveal the heterogeneity of tissue cells. By using scRNA‐seq, we explored the cell heterogeneity of different subregions of adult human eyes, including pars plicata, pars plana, retinal pigment epithelium (RPE), iris, and neural retina (NR). We identified one subpopulation expressing SRY‐box transcription factor 2 (SOX2) as RSCs, which were present in the pars plicata of the adult human eye. Further analysis showed the identified subpopulation of RSCs expressed specific markers aquaporin 1 (AQP1) and tetraspanin 12 (TSPAN12). We, therefore, isolated this subpopulation using these two markers by flow sorting and found that the isolated RSCs could proliferate and differentiate into some retinal cell types, including photoreceptors, neurons, RPE cells, microglia, astrocytes, horizontal cells, bipolar cells, and ganglion cells; whereas, AQP1− TSPAN12− cells did not have this differentiation potential. In conclusion, our results showed that SOX2‐positive RSCs are present in the pars plicata and may be valuable for treating human retinal diseases due to their proliferation and differentiation potential.

Vectorized isosurface mapping is critical for conducting scientific research in computational fluid dynamics (CFD). We provide a Python-based tool for the vectorized isosurface mapping of scalar field information in CFD simulation results, with the goal of reducing file size while ensuring file editability and graphical presentation independent of resolution. The ideal interpolation angle is first determined by spatially rotating the target region, which reduces the invalid interpolation range. Second, because it uses the spatial clipping approach, it offers a graphics processing method for particular geometric structures such as “islands” or “masks”. Finally, the data size is decreased using Geobuf’s space-compressed storage format. The application case, which visualizes the spatiotemporal evolution of the EFDC (Environmental Fluid Dynamics Code) concentration field, demonstrates that the spatial rotation and clipping strategies improve both the spatial interpolation and isosurface tracking effectiveness, and make the analysis results conform better to the actual situation. The spatial compression strategy substantially promotes network propagation and the retrieval of contour maps, supporting multi-scenario analysis web applications based on the isosurface spatiotemporal evolution animation method.