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Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are m⁶A readers that stabilize target mRNAs by recognizing the GG(m⁶A)C sequence. While previous studies have explored the biological mechanisms of IGF2BPs in lung cancer, their prognostic value remains unclear. This study investigated the expression, molecular mechanisms, and prognostic significance of IGF2BPs in lung adenocarcinoma (LUAD) using TCGA and GEO datasets. IGF2BP1/2/3 were found to be highly expressed in LUAD, with high mRNA stability scores (RS) associated with shorter overall survival (OS) and linked to hypoxia, EMT, IL2-STAT5 signaling, immune suppression, and decreased gefitinib sensitivity. In cell-based experiments, siRNA knockdown of IGF2BPs in LUAD cell lines reduced TGF-β signaling pathway-related genes and inhibited cell proliferation. Our findings suggest that the IGF2BPs gene signature is a prognostic biomarker in LUAD, contributing to tumor progression, immune escape, and poor prognosis by activating specific pathways., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The manuscript has been read by all participating authors, all of whom agreed to its submission for publication. Competing interests: The authors declare no competing interests. Code sharing statement: If readers have any questions regarding the specific R packages or functions used, they are welcome to contact the corresponding author., (© 2025. The Author(s).)

Climate change and environmental degradation are critical global challenges, and the G-20 nations play a pivotal role in addressing these issues due to their substantial contributions to global GDP and carbon emissions. Transitioning toward renewable energy sources is imperative for mitigating CO2 emissions and achieving sustainable development. This study investigates the impact of technological innovation, gross domestic product (GDP), renewable energy consumption, economic freedom, and financial advancement on renewable energy use and environmental pollution levels in G-20 countries from 1995 to 2022. Utilizing the PMG-ARDL dynamic panel method, the research analyzes both long-term and short-term relationships among the variables. The findings reveal that technological innovation significantly boosts renewable energy adoption, with a 1% increase in technological innovation leading to a 0.33% rise in renewable energy use in the long run and a 0.17% increase in the short run. Additionally, increased renewable energy consumption is strongly associated with reductions in CO2 emissions, highlighting its critical role in promoting environmental sustainability. The study emphasizes the importance of policies designed to enhance technological innovation to foster renewable energy usage and reduce environmental pollution. It recommends expanding and reforming the technological sector to align international and local resources with renewable energy initiatives, providing a workable framework for supporting the green growth of institutions and achieving a more sustainable future for G-20 nations. This research contributes to understanding the intricate dynamics of renewable energy transitions, offering actionable insights for policymakers and stakeholders in addressing global environmental challenges., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Acute rejection (AR) is a significant complication in liver transplantation, impacting graft function and patient survival. Kupffer cells (KCs), liver-specific macrophages, can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, both of which critically influence AR outcomes. Angiopoietin-like 4 (ANGPTL4), a secretory protein, is recognized for its function in regulating inflammation and macrophage polarization. This study investigates the effects of ANGPTL4 on KC polarization through cellular interactions between hepatocytes (HCs) and KCs. Using a rat orthotopic liver transplantation model, we observed reduced ANGPTL4 expression during AR, whereas increased ANGPTL4 levels were linked to immune tolerance. Administration of ANGPTL4 recombinant protein improved liver function, suppressed inflammation, and promoted M2 polarization of KCs. Co-culture experiments demonstrated that hepatocyte-derived ANGPTL4 significantly modulates KC polarization and inflammatory responses, mainly by inhibiting the NF-κB signaling pathway. The results emphasize the promise of ANGPTL4 as a therapeutic target to reduce AR and improve liver transplant outcomes by influencing hepatocyte-KC interactions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional review board statement: The study protocol was reviewed and approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (IACUC-CQMU-2024-0609). Informed consent: No human subjects were used in this study., (© 2025. The Author(s).)

Coastal populations are susceptible to relative sea-level (RSL) rise and accurate local projections are necessary for coastal adaptation. Local RSL rise may deviate from global mean sea-level rise because of processes such as geoid change, glacial isostatic adjustment (GIA), and vertical land motion (VLM). Amongst all factors, the VLM is often inadequately estimated. Here, we estimated the VLM for the Oka estuary, northern Spain and compared it to the VLM component of sea-level projections in the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report (AR6) and the Spanish National Climate Change Adaptation Plan (NCCAP). To estimate VLM, we updated Holocene RSL data from the Atlantic coast of Europe and compared it with two 3D GIA models. Both models fit well with RSL data except in the Oka estuary. We derived a VLM rate of - 0.88 ± 0.03 mm/yr for the Oka estuary using the residuals of GIA misfits. Comparable VLM rates of - 0.85 ± 0.14 mm/yr and - 0.80 ± 0.32 mm/yr are estimated based on a nearby Global Navigation Satellite Systems station and differenced altimetry-tide gauge technique, respectively. Incorporating the updated late Holocene estimate of VLM in IPCC AR6 RSL projections under a moderate emissions scenario increased the rate of RSL rise by 15% by 2030, 11% by 2050, and 9% by 2150 compared to the original IPCC AR6 projections, and also increased the magnitude of RSL rise by over 40% by 2035 and 2090 compared with projections from the Spanish NCCAP. Our study demonstrates the importance of accurate VLM estimates for local sea-level projections., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The dimensional optimization based on kinematic and dynamic performance indices is proven significant for improving the operational performance of parallel robots. As the pose-dependent performances vary with the dimensional parameters, there are still many challenges in the optimal design of parallel robots, such as the possible conflict amongst different performance indices and computational expensiveness. By considering a 4-DOF high-speed parallel robot as an illustrative example, this paper presents a framework for the optimal design of parallel robots by integrating skeleton modeling, CAD-CAE integration and multi-objective optimization techniques. In this approach, the models for kinematic and elasto-dynamic performance evaluation are first developed using the CAD and CAE techniques, respectively. After evaluating the performance distributions over the task workspace, several reference poses representative of multiple neighboring sample poses are determined to formulate corresponding local performance indices by using the Hard C-Means (HCM) clustering analysis algorithm. This consideration leads to the determination of the optimal dimensions by investigating the Pareto-optimal solutions of a multi-objective optimization problem, allowing the conflict amongst different performance indices to be appropriately handled and the computational time to be saved significantly. The results of the case study show that the proposed approach can significantly enhance the elastic dynamic performance while ensuring that the kinematic performance is not excessively compromised, when compared to the performance of existing physical prototype of the robot. A software package has been developed using the proposed framework, providing a highly accessible way for designing various types of parallel/hybrid robots based on CAD and CAE techniques., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammation, is crucial in the progression of cardiovascular diseases (CVD). Its predictive value for all-cause and cardiovascular mortality in CVD patients with diabetes or pre-diabetes remains unclear. We analyzed 3,780 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (2001-2018). Kaplan-Meier survival curves, weighted Cox proportional hazards models, and restricted cubic spline (RCS) analyses were used to assess the relationship between NLR and mortality risk. RCS revealed a U-shaped association between NLR and all-cause mortality, with an inflection point at 1.776. For NLR < 1.776, the risk of all-cause mortality decreased by 13% per unit increase in NLR (HR: 0.87, 95% CI: 0.76-0.98). For NLR ≥ 1.776, the risk increased by 15% per unit increase (HR: 1.15, 95% CI: 1.10-1.26). A positive linear association was found between NLR and cardiovascular mortality, with a 17% increase in risk per unit increase in NLR (HR: 1.17, 95% CI: 1.10-1.25). No significant interactions were observed in stratified analyses. Our study revealed the U-shaped relationship between NLR and all-cause mortality, and a positive linear relationship with cardiovascular mortality in CVD patients with diabetes or pre-diabetes., (© 2024. The Author(s).)

Northwest China has undergone notable alterations in climate and vegetation growth in recent decades. Nevertheless, uncertainties persist concerning the response of different vegetation types to climate change and the underlying mechanisms. This study utilized the Normalized Difference Vegetation Index (NDVI) and three sets of meteorological data to investigate the interannual variations in the association between vegetation and climate (specifically precipitation and temperature) from 1982 to 2015. Several conclusions were drawn. (1) R NDVI-GP (relationship between Growing Season NDVI and precipitation) decreased significantly across all vegetation, while R NDVI-GT (relationship between Growing Season NDVI and temperature) showed an insignificant increase. (2) Trends of R NDVI-GP and R NDVI-GT exhibited great variations across various types of vegetation, with forests displaying notable downward trends in both indices. The grassland exhibited a declining trend in R NDVI-GP but an insignificant increase in R NDVI-GT , while no significant temporal changes in R NDVI-GP or R NDVI-GT were observed in the barren land. (3) The fluctuations in R NDVI-GP and R NDVI-GT closely aligned with variations in drought conditions. Specifically, in regions characterized by VPD (vapor pressure deficit) trends less than 0.02 hpa/yr, which are predominantly grasslands, a rise in SWV (soil water volume) tended to cause a reduction in R NDVI-GP but an increase in R NDVI-GT. However, a more negative trend in SWV was associated with a more negative trend in both R NDVI-GP and R NDVI-GT when the VPD trend exceeded 0.02 hPa/yr, primarily in forests. Our results underscore the variability in the relationship between climate change and vegetation across different vegetation types, as well as the role of drought in modulating these associations., (© 2024. The Author(s).)

The current study aimed to evaluate the effect of lymph node ratio (LNR) on the short-term and long-term outcomes of colorectal cancer (CRC) patients who underwent radical CRC surgery. We retrospectively collected CRC patients who underwent radical surgery from Jan 2011 to Jan 2020 in a single-center hospital. The patients were divided into the high LNR group and the low group according to the median. The baseline information and the short-term outcomes were compared between the high group and the low group. Univariate and multivariate logistic regression was performed to analyze the independent predictors for overall survival (OS) and disease-free survival (DFS). A 1:1 proportional propensity score matching (PSM) was used to reduce the selection bias between the two groups. Kaplan-Meier method was used to estimate the OS and DFS between the two groups in different T stages. A total of 1434 CRC patients undergoing radical surgery were enrolled in this study, and there were 730 (50.9%) patients in the low LNR group and 704 (49.1%) patients in the high LNR group. After the PSM, there were 618 patients in both groups, the baseline characteristics between the two groups had no significant difference (p > 0.05). After comparing the Surgery-related information and The Short-term outcomes, the high LNR group had a longer hospital stay (after PSM, p < 0.01). In univariate and multivariate logistic regression analyses, age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.020; multivariate analysis, p = 0.024), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor size (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were independent risk factors for OS, and age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.032; multivariate analysis, p = 0.031), T stage (univariate analysis, p < 0.01; multivariate analysis, p = 0.014), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were identified as independent risk factors for DFS. The high LNR group had a worse OS in T3 (p < 0.01) and T4 (p < 0.01) as well as a worse DFS in T3 (p < 0.01) and T4 (p < 0.01). No association was found between LNR and postoperative complications, but the high LNR group had a longer hospital stay. LNR was identified as an independent predictor for OS and DFS. Furthermore, high LNR had a worse OS and DFS under T3 and T4 stages. Therefore, LNR was more prognostically significant for CRC patients under T3 and T4 stages., (© 2024. The Author(s).)

Late Holocene relative sea-level (RSL) data are important to understand the drivers of RSL change, but there is a lack of precise RSL records from the Sunda Shelf. Here, we produced a Late Holocene RSL reconstruction from coral microatolls in Singapore, demonstrating for the first time the utility of Diploastrea heliopora microatolls as sea-level indicators. We produced 12 sea-level index points and three marine limiting data with a precision of < ± 0.2 m (2σ) and < ± 26 years uncertainties (95% highest density region). The data show a RSL fall of 0.31 ± 0.18 m between 2.8 and 0.6 thousand years before present (kyr BP), at rates between - 0.1 ± 0.3 and - 0.2 ± 0.7 mm/year. Surface profiles of the fossil coral microatolls suggest fluctuations in the rate of RSL fall: (1) stable between 2.8 and 2.5 kyr BP; (2) rising at ~ 1.8 kyr BP; and (3) stable from 0.8 to 0.6 kyr BP. The microatoll record shows general agreement with published, high-quality RSL data within the Sunda Shelf. Comparison to a suite of glacial isostatic adjustment (GIA) models indicate preference for lower viscosities in the mantle. However, more high quality and precise Late Holocene RSL data are needed to further evaluate the drivers of RSL change in the region and better constrain GIA model parameters., (© 2024. The Author(s).)

Storage batteries with elevated energy density, superior safety and economic costs continues to escalate. Batteries can pose safety hazards due to internal short circuits, open circuits and other malfunctions during usage, hence real-time surveillance and error diagnosis of the battery's operational state is imperative. In this paper, a three-dimensional model of electrochemical-magnetic field-thermal coupling is formulated with lithium-ion pouch cells as the research focus, and the spatial distribution pattern of the physical field such as magnetic field and temperature when the battery is operational is acquired. Furthermore, this manuscript also investigates the diagnostic methodology for defective batteries with internal short circuits and fissures, that is, the operational state of the battery is evaluated and diagnosed by the distribution of the magnetic field surrounding the battery. To substantiate the method's practical viability, the present study extends its examination to the 18650-battery pack. We obtained the magnetic field images of the normal operation of the battery pack and the failure state of some batteries and analyzed the relationship between the magnetic field distribution characteristics and the performance of the battery pack, providing a new method for the health monitoring and fault diagnosis of the battery pack. This non-contact method incurs no damage to the battery, concurrently exhibiting elevated sensitivity and extremely rapid response time. Meanwhile, it provides an effective means for non-destructive research on the batteries and can be applied to areas such as battery safety screening and non-destructive testing. This research not only helps to facilitate our understanding of the battery's operating mechanism, but also provides robust support for safe operation and optimal battery design., (© 2024. The Author(s).)

Ditylenchus destructor is a migratory plant-parasitic nematode that severely harms many agriculturally important crops. The control of this pest is difficult, thus efficient strategies for its management in agricultural production are urgently required. Cathepsin L-like cysteine protease (CPL) is one important protease that has been shown to participate in various physiological and pathological processes. Here we decided to characterize the CPL gene (Dd-cpl-1) from D. destructor. Analysis of Dd-cpl-1 gene showed that Dd-cpl-1 gene contains a signal peptide, an I29 inhibitor domain with ERFNIN and GNFD motifs, and a peptidase C1 domain with four conserved active residues, showing evolutionary conservation with other nematode CPLs. RT-qPCR revealed that Dd-cpl-1 gene displayed high expression in third-stage juveniles (J3s) and female adults. In situ hybridization analysis demonstrated that Dd-cpl-1 was expressed in the digestive system and reproductive organs. Silencing Dd-cpl-1 in 1-cell stage eggs of D. destructor by RNAi resulted in a severely delay in development or even in abortive morphogenesis during embryogenesis. The RNAi-mediated silencing of Dd-cpl-1 in J2s and J3s resulted in a developmental arrest phenotype in J3 stage. In addition, silencing Dd-cpl-1 gene expression in female adults led to a 57.43% decrease in egg production. Finally, Dd-cpl-1 RNAi-treated nematodes showed a significant reduction in host colonization and infection. Overall, our results indicate that Dd-CPL-1 plays multiple roles in D. destructor ontogenesis and could serve as a new potential target for controlling D. destructor., (© 2024. The Author(s).)

Low-light object detection is an important research area in computer vision, but it is also a difficult issue. This research offers a low-light target detection network, NLE-YOLO, based on YOLOV5, to address the issues of insufficient illumination and noise interference experienced by target detection tasks in low-light environments. The network initially preprocesses the input image with an improvement technique before suppressing high-frequency noise and enhancing essential information with C2fLEFEM, a unique feature extraction module. We also created a multi-scale feature extraction module, AMC2fLEFEM, and an attention mechanism receptive field module, AMRFB, which are utilized to extract features of multiple scales and enhance the receptive field. The C2fLEFEM module, in particular, merges the LEF and FEM modules on top of the C2f module. The LEF module employs a low-frequency filter to remove high-frequency noise; the FEM module employs dual inputs to fuse low-frequency enhanced and original features; and the C2f module employs a gradient retention method to minimize information loss. The AMC2fLEFEM module combines the SimAM attention mechanism and uses the pixel relationship to obtain features of different receptive fields, adapt to brightness changes, capture the difference between the target and the background, improve the network's feature extraction capability, and effectively reduce the impact of noise. The AMRFB module employs atrous convolution to enlarge the receptive field, maintain global information, and adjust to targets of various scales. Finally, for low-light settings, we replaced the original YOLOv5 detection head with a decoupled head. The Exdark dataset experiments show that our method outperforms previous methods in terms of detection accuracy and performance., (© 2024. The Author(s).)

Accurately obtaining accurate information about the future traffic flow of all roads in the transportation network is essential for traffic management and control applications. In order to address the challenges of acquiring dynamic global spatial correlations between transportation links and modeling time dependencies in multi-step prediction, we propose a spatial linear transformer and temporal convolution network (SLTTCN). The model is using spatial linear transformers to aggregate the spatial information of the traffic flow, and bidirectional temporal convolution network to capture the temporal dependency of the traffic flow. The spatial linear transformer effectively reduces the complexity of data calculation and storage while capturing spatial dependence, and the time convolutional network with bidirectional and gate fusion mechanisms avoids the problems of gradient vanishing and high computational cost caused by long time intervals during model training. We conducted extensive experiments using two publicly available large-scale traffic data sets and compared SLTTCN with other baselines. Numerical results show that SLTTCN achieves the best predictive performance in various error measurements. We also performed attention visualization analysis on the spatial linear transformer, verifying its effectiveness in capturing dynamic global spatial dependency., (© 2024. The Author(s).)

The existence of causal relationship between dietary factors and respiratory diseases is uncertain. We comprehensively investigated the association between dietary factors and respiratory diseases by using Mendelian randomization (MR). Genetic variants linked to dietary factors were selected as instrumental variables with genome-wide significance. These instrumental variables were obtained from large GWAS databases. These databases include Biobank, the FinnGen study, and other large consortia. We used multivariate MR analyses to control the effects of smoking and education. Median analysis was conducted to evaluate whether body mass index (BMI) played a role in dietary factors in respiratory diseases. Dried fruit intake was found to be associated with a decreased risk of chronic obstructive pulmonary disease (COPD) (OR: 0.211; 95% CI 0.117-0.378; P < 0.001) and asthma (OR: 0.539; 95% CI 0.357-0.815; P = 0.003). Conversely, pork intake was associated with an increased risk of international pharmaceutical federation (IPF) (OR: 1.051*10 2 , 95% CI 4.354-2.56*10 3 , P = 0.004). However, no significant associations were observed between the 20 dietary factors and obstructive sleep apnea (OSA). In addition, multivariate MR analyses showed that the above results were unchanged in smoking and nonsmoking populations, while the effect of dried fruit intake on asthma was significantly attenuated after corrective education. The results of the mediator variable analysis indicated that BMI could serve as a mediator of the above results. This study found that dried fruits slowed the progression of COPD and asthma, while pork promoted IPF. However, no effect of dietary factors on OSA was found. Meanwhile, we showed that the above results were unchanged in smoking and non-smoking populations. In contrast, education could influence the role of diet on asthma, and BMI could be used as a mediating variable to influence the above results., (© 2023. The Author(s).)

The purpose of this study was to investigate whether patients with colorectal cancer (CRC) combined with hyperuricemia remitted 1 year after CRC surgery. CRC patients combined with hyperuricemia who underwent radical surgery were included from a single clinical center from Jan 2016 to Dec 2021. Baseline characteristics was compared between the remission group and the non-remission group. Multivariate logistic regression was used to find the possible predictive factors of hyperuricemia remission. A total of 91 patients were included for data analysis, retrospectively. There were 34 (37.4%) patients in the remission group and 57 (62.6%) patients in the non-remission group. The mean preoperative weight and body mass index (BMI) were 61.2 ± 10.7 (kg) and 24.1 ± 3.3 (kg/m 2 ). 21 (23.1%) patients had a history of drinking. We found that the weight and BMI were not significantly different before and 1 year after CRC surgery (P > 0.05). In contrast, uric acid values were significantly decreased (P < 0.01). Meanwhile, the outcomes showed there were no significant differences in the baseline characteristics between the remission and non-remission groups (P > 0.05). According to multivariate logistic regression, we found that the history of drinking was a predictive factor of hyperuricemia remission (OR = 0.046, 95% CI 0.005-0.475, P = 0.010). CRC patients with hyperuricemia had a 37.4% remission from hyperuricemia 1 year after CRC surgery. Tumor location, tumor stage, and tumor size did not predict the remission of hyperuricemia. Notably, the history of drinking was a predictive factor of hyperuricemia remission., (© 2023. The Author(s).)

The input of seismic wave with different frequency has a significant impact on loess slope instability. On the basis of field investigation and experiments, the particle flow software PFC 2D was used to explore the effect of seismic frequency spectrum on slope instability through the process of calibrating soil microscopic parameters, model establishment, seismic wave input and other processes. The results show that: 1. The low-frequency component of the input wave is the main frequency band that causes the slope instability, the slope has amplifying effect on the low-frequency input wave, and the slope has a "filtering" effect on the high-frequency input wave; 2. The instability of the slope will cause an increase in frequency components above 10 Hz; 3. The special structure of the slope is one of the main reasons for the instability of the slope. This result has theoretical and practical significance for earthquake landslide prevention and monitoring and early warning., (© 2023. The Author(s).)

The implementation of exercise intervention (EI) presents a promising and economical way for patients with hip fracture. However, the optimal type of EI remains unclear. The objective of this study is to evaluate the efficacy of various EI approaches and identify the optimal intervention for improving the prognosis of patients with hip fracture. A comprehensive search of Medline (via PubMed), Web of Science, Embase, Cochrane Central Register of Controlled Trials, CINAHL, CNKI, Wan Fang, VIP, and CBM was conducted from their earliest records to June 2022. The included randomized controlled trials (RCTs) included at least one type of exercise for patients with hip fracture. The methodological quality of these trials was assessed using the Cochrane Collaboration Risk of Bias Tool. All direct and indirect comparisons were analyzed by Stata 14.0 and OpenBUGS 3.2.3 software. The primary outcome was hip function, and the secondary outcomes were activity of daily living (ADL), walking capacity and balance ability of patients. Based on the ranking probabilities, resistance exercise (RE) was ranked as the most effective among all exercise interventions (surface under cumulative ranking curve values [SUCRA]: 94.8%, [MD]: - 11.07, [Crl]: - 15.07 to - 7.08) in improving the efficacy of patients' hip function, followed by balance exercise (BE) ([SUCRA]:81.1%, [MD]: - 8.79, [Crl]: - 13.41 to - 4.18) and muscle strength exercise ([SUCRA]:57.6%, [MD]: - 5.35, [Crl]: - 9.70 to - 0.95). For the improvement of ADL for patients with hip fracture, BE ([SUCRA]:98.4%, [MD]: - 17.38, [Crl]: - 23.77 to - 11.04) may be the best EI. The findings of this study indicate that RE and BE might be the best approach to improve prognosis for patients with hip fracture. However, further rigorous and meticulously planned RCTs are required to substantiate the conclusions drawn from this study., (© 2023. The Author(s).)

The physiological effect of Lp(a) on platelet activity is unclear. Previous studies explored the relationship between Lp(a) and platelet aggregation in patients taking statins and antiplatelet agents, but few was conducted in individuals without the bias of those drugs that either influence Lp(a) or platelet activity. The aim of this study was to assess the relationship between Lp(a) levels and platelet aggregation in subjects not taking statins or antiplatelet drugs. A hospital-based cross-sectional study was conducted to investigate the independent contribution of Lp(a) to platelet activity by controlling the effects of potential confounding factors including lipoprotein-associated phospholipase A2 [Lp-PLA2]. Blood samples were collected from 92 subjects without statins or antiplatelet agents from the Second Xiangya Hospital. The univariate correlation analysis showed a significant correlation between AA-induced average aggregation rate [AAR] and ApoB (r = 0.324, P = 0.002), ApoA1 (r = 0.252, P = 0.015), Lp(a) (r = 0.370, P < 0.001), Lp-PLA2 (r = 0.233, P = 0.025) and platelet counts [PLT] (r = 0.389, P < 0.001). Multivariate regression analysis suggested that Lp(a) contributed independently to AA-induced average aggregation rate (β = 0.023, P = 0.027) after controlling for the effects of ApoB, Lp-PLA2 and platelet counts. Lp(a) is positively associated with platelet aggregation independent of Lp-PLA2, which may partly account for the atherothrombotic effect of Lp(a)., (© 2022. The Author(s).)

As a key parameter of hydrological process modeling, the near-surface air temperature lapse rate reflects the vertical changes in air temperature characteristics in alpine basins but often lacks the support of sufficient ground observation data. This study estimated the lapse rate of the Lhasa River Basin (LRB) from the monthly air temperature dataset (2001-2015), which was derived based on good relationships between the observed air temperature at eight gauged stations and the corresponding gridded land surface temperature of MODIS. The estimated annual average air temperature lapse rate was approximately 0.62 °C/100 m. The monthly lapse rate in different years varied seasonally in the range of 0.45-0.8 °C/100 m; the maximum was in May, and the relatively low value occurred from September to January. The snow cover in the zones with relatively low altitudes showed seasonal variation, which was consistent with the air temperature variation. Permanent snow cover appeared in the area above 5000 m and expanded with increasing elevation., (© 2022. The Author(s).)

Hydrological modeling in the Third Pole remains challenging due to the complex topography and scarcity of in-situ precipitation observations. In this study, we assessed five satellite precipitation products (SPPs) including TRMM3B42, PERSIANN-CDR, GPM-IMERG, CMORPH, and GSMaP, and simulated daily streamflow in the Yarlung Zangbo River Basin (YZRB) with VIC model. The performance of SPPs was evaluated by CC, RB, RMSE, POD and FAR, to compare with daily observations. Overall, all SPPs showed decreasing trends of precipitation from east to west compared to 10 km rainfall data. PERSIANN had the highest values of POD (0.65), RB (91.6%) and FAR (0.59) but worst performed in streamflow. CMORPH, GPM and TRMM fit well with the observations annually but overestimate the precipitation in the southeast during wet seasons. Simulation from GPM and CMORPH yield satisfactory results (NSE of 0.86 and 0.82, RE of - 20% and - 13%, respectively), while TRMM outperformed GPM in modeling runoff with smaller relative error. Results indicated the potential of GPM and CMORPH in providing alternative rainfall information in YZRB. Accurate evaluation of multi-source SPPs and their hydrological utility in YZRB would benefit further hydrometeorological studies and water resources management in this area., (© 2022. The Author(s).)

In this study, red mud modified by manganese dioxide(MRM) was utilized as an adsorbent to effectively remove Cd 2+ from aqueous solution. The characteristics were analysed by SEM-EDS, XRD, BET, FTIR and XPS. Different factors that affected the Cd 2+ removal on MRM, such as dosage, initial pH, initial Cd 2+ concentration, were investigated using batch adsorption experiments. Simultaneously, the adsorption kinetics, adsorption isotherms and adsorption thermodynamics of Cd 2+ were also investigated using adsorption experiments data. The characterization results showed that MRM had a rougher, larger specific surface area and pore volume (38.91 m 2 g -1 , 0.02 cm 3 g -1 ) than RM (10.22 m 2 g -1 , 0.73 cm 3 g -1 ). The adsorption experiments found that the equilibrium adsorption capacity of MRM for Cd 2+ was significantly increased to 46.36 mg g -1 , which was almost three times that of RM. According to the fitting results, the pseudo-second-order kinetic model described the adsorption process better than the pseudo-first-order kinetic model. The Langmuir model fitted the adsorption isotherms well, indicating that the adsorption process was unimolecular layer adsorption and the maximum capacity was 103.59 mg g -1 . The thermodynamic parameters indicated that the adsorption process was heat-trapping and spontaneous. Finally, combined XPS and FTIR studies, it was speculated that the adsorption mechanisms should be electrostatic attachment, specific adsorption (i.e., Cd-O or hydroxyl binding) and ion exchange. Therefore, manganese dioxide modified red mud can be an effective and economical alternative to the removal of Cd 2+ in the wastewater treatment process., (© 2022. The Author(s).)

In patients with coronary artery disease (CAD), further increasing the level of high-density lipoprotein (HDL) cholesterol (HDL-C) as an add-on to statins cannot reduce cardiovascular risk. And it has been reported that HDL functional metric-cholesterol efflux capacity (CEC) may be a better predictor of CAD risk than HDL-C. CEC measurement is time-consuming and not applicable in clinical settings. Thus, it is meaningful to explore an easily acquired index for evaluating CEC. Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this cross-sectional study. All CAD patients had acute coronary syndrome (ACS). CEC was measured using a [ 3 H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. CEC was significantly impaired in CAD patients (11.9 ± 2.3%) compared to controls (13.0 ± 2.2%, p = 0.022). In control group, CEC was positively correlated with enzymatically measured HDL-C levels (r = 0.358, p = 0.006) or with NMR-determined HDL-C levels (NMR-HDL-C, r = 0.416, p = 0.001). However, in CAD group, there was no significant correlation between CEC and HDL-C (r = 0.216, p = 0.206) or NMR-HDL-C (r = 0.065, p = 0.708). Instead, we found that the level of high-sensitivity C-reactive protein (hsCRP) was inversely associated with CEC (r = - 0.351, p = 0.036). Multiple regression analysis showed that the hsCRP level was associated with CEC after adjusting other cardiovascular risk factors and HDL-C, although the association would not reach significance if adjusting for multiple testing. NMR spectroscopy showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. In patients with CAD, the level of HDL-C cannot reflect HDL function. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. These hypothesis-generating data suggest that hsCRP levels, a marker of acute inflammation, may associate with HDL dysfunction in ACS subjects. Due to the design limited to be correlative in nature, not permitting causal inference and a larger, strictly designed study is still needed.

Platycodin D and platycoside E are two triterpenoid saponins in Platycodon grandiflorus, differing only by two glycosyl groups structurally. Studies have shown β-Glucosidase from bacteria can convert platycoside E to platycodin D, indicating the potential existence of similar enzymes in P. grandiflorus. An L 9 (3 4 ) orthogonal experiment was performed to establish a protocol for calli induction as follows: the optimal explant is stems with nodes and the optimum medium formula is MS + NAA 1.0 mg/L + 6-BA 0.5 mg/L to obtain callus for experimental use. The platycodin D, platycoside E and total polysaccharides content between callus and plant organs varied wildly. Platycodin D and total polysaccharide content of calli was found higher than that of leaves. While, platycoside E and total polysaccharide content of calli was found lower than that of leaves. Associating platycodin D and platycoside E content with the expression level of genes involved in triterpenoid saponin biosynthesis between calli and leaves, three contigs were screened as putative sequences of β-Glucosidase gene converting platycoside E to platycodin D. Besides, we inferred that some transcription factors can regulate the expression of key enzymes involved in triterpernoid saponins and polysaccharides biosynthesis pathway of P. grandiflorus. Totally, a candidate gene encoding enzyme involved in converting platycoside E to platycodin D, and putative genes involved in polysaccharide synthesis in P. grandiflorus had been identified. This study will help uncover the molecular mechanism of triterpenoid saponins biosynthesis in P. grandiflorus.

Salvia miltiorrhiza has numerous compounds with extensive clinical application. "Sweating", a processing method of Traditional Chinese Medicine (TCM), results in great changes in pharmacology and pharmacodynamics. Previously, chromatogram of 10 characteristic metabolites in S. miltiorrhiza showed a significant difference after "Sweating". Due to the complexity of TCM, changes in metabolites should be investigated metabolome-wide after "Sweating". An untargeted UPLC/MS-based metabolomics was performed to discover metabolites profile variation of S. miltiorrhiza after "Sweating". Multivariate analysis was conducted to screen differential metabolites. Analysis indicated distinct differences between sweated and non-sweated samples. 10,108 substance peaks had been detected altogether, and 4759 metabolites had been identified from negative and positive ion model. 287 differential metabolites were screened including 112 up-regulated and 175 down-regulated and they belong to lipids and lipid-like molecules, and phenylpropanoid and polyketides. KEGG analysis showed the pathway of linoleic acid metabolism, and glyoxylate and dicarboxylate metabolism were mainly enriched. 31 and 49 identified metabolites were exclusively detected in SSM and NSSM, respectively, which mainly belong to carboxylic acids and derivatives, polyketides and fatty acyls. By mapping tanshinones and salvianolic acids to 4759 identified metabolites library, 23 characteristic metabolites had been identified, among which 11 metabolites changed most. We conclude that "Sweating'' has significant effect on metabolites content and composition of S. miltiorrhiza.

Massively parallel sequencing (MPS) has rapidly become a promising method for forensic DNA typing, due to its ability to detect a large number of markers and samples simultaneously in a single reaction, and sequence information can be obtained directly. In the present study, two kinds of forensic genetic markers, short tandem repeat (STR) and identity-informative single nucleotide polymorphism (iiSNP) were analyzed simultaneously using ForenSeq DNA Signature Prep Kit, a commercially available kit on MPS platform. A total of 152 DNA markers, including 27 autosomal STR (A-STR) loci, 24 Y chromosomal STR (Y-STR) loci, 7 X chromosomal STR (X-STR) loci and 94 iiSNP loci were genotyped for 107 Tibetan individuals (53 males and 54 females). Compared with length-based STR typing methods, 112 more A-STR alleles, 41 more Y-STR alleles, and 24 more X-STR alleles were observed at 17 A-STRs, 9 Y-STRs, and 5 X-STRs using sequence-based approaches. Thirty-nine novel sequence variations were observed at 20 STR loci. When the flanking regions were also analyzed in addition to target SNPs at the 94 iiSNPs, 38 more alleles were identified. Our study provided an adequate genotype and frequencies data of the two types of genetic markers for forensic practice. Moreover, we also proved that this panel is highly polymorphic and informative in Tibetan population, and should be efficient in forensic kinship testing and personal identification cases.

Hand, foot, and mouth disease (HFMD) remains a threat to the Asia-Pacific region. The epidemiological characteristics and pathogen spectrum of HFMD vary with space and time. These variations are crucial for HFMD interventions but poorly understood in Sichuan Province, China, particularly after the introduction of the EV-A71 vaccine. Using descriptive methods, regression analyses, spatial autocorrelation analysis, and space-time scan statistics, we analysed the epidemiological and aetiological characteristics of HFMD surveillance data in Sichuan Province between 2011 and 2017 to identify spatio-temporal variations. The dominant serotypes of HFMD have changed from enterovirus 71 and coxsackievirus A16 to other enteroviruses since 2013. The seasonal pattern of HFMD showed two peaks generally occurring from April to July and November to December; however, the seasonal pattern varied by prefecture and enterovirus serotype. From 2011 to 2017, spatio-temporal clusters were increasingly concentrated in Chengdu, with several small clusters in northeast Sichuan. The clusters observed in southern Sichuan from 2011 to 2015 disappeared in 2016-2017. These findings highlight the importance of pathogen surveillance and vaccination strategies for HFMD interventions; future prevention and control of HFMD should focus on Chengdu and its vicinity.

Aurora kinase A (AURKA) is frequently overexpressed in several cancers. miRNA sequencing and bioinformatics analysis indicated significant downregulation of miR-4715-3p. We found that miR-4715-3p has putative binding sites on the 3UTR region of AURKA. Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Luciferase reporter assays confirmed binding of miR-4715-3p on the 3UTR region of AURKA. miR-4715-3p mediated a reduction in AURKA levels leading to G2/M delay, chromosomal polyploidy, and cell death. We also detected a remarkable decrease in GPX4, an inhibitor of ferroptosis, with an increase in cleaved PARP and caspase-3. Inhibition of AURKA using siRNA produced similar results, suggesting a possible link between AURKA and GPX4. Analysis of UGC samples and cell models demonstrated increased methylation levels of several CpG nucleotides upstream of miR-4715-3p. 5-Aza-2'-deoxycytidine induced demethylation of several CpG nucleotides, restoring miR-4715-3p expression, leading to downregulation of AURKA. In conclusion, our data identified a novel epigenetic mechanism mediating silencing of miR-4715-3p and induction of AURKA in UGCs. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis.

Meloidogyne incognita causes significant damage to many different crops. Previous studies showed that Streptomyces rubrogriseus HDZ-9-47 is a promising biocontrol agent. Combining it with biofumigation improved its efficacy against M. incognita. In the present study, the reason for the improved efficacy of the combination was investigated by analyzing its impact on both the soil microbial and the nematode communities in the field. The results showed that the combined application reduced root galls by 41% and its control efficacy was greater than each treatment alone. Cultivation-based analyses showed that the combination treatment affected the soil microbial community. Actinomycetes and bacterial densities were negatively correlated with the root knot score. In contrast, the fungal densities were positively correlated with the root knot score. Denaturing gradient gel electrophoresis (DGGE) results showed that the combination of S. rubrogriseus HDZ-9-47 and biofumigation enriched beneficial microbes and reduced certain soil-borne fungal phytopathogens, thereby enhancing the efficacies of both S. rubrogriseus HDZ-9-47 and biofumigation against M. incognita. And HDZ-9-47 could colonize in soil. The total abundance of nematode and plant parasites, the ratio of soil fungivore nematode to fungivore plus bacterivore nematode, and the nematode diversity indices all decreased with the combination treatment. Overall, the results of this study demonstrate that combined application of HDZ-9-47 with biofumigation was a useful and effective approach to suppress M. incognita by manipulating soil microbial communities in field.

The overland flow erosion is common and became more serious because of the climate warming inducing more runoff in the Tibet Plateau. The purposes of this study were to evaluate the effects of flow rate, slope gradient, shear stress, stream power, unit stream power and unit energy of water-carrying section on the soil detachment capacity for the soil in the Tibet Plateau of China due to the information is limited. To achieve this aim, laboratory experiments were performed under six flow rates (5, 10, 15, 20, 25 and 30 L min -1 ) and six slope gradients (8.74%, 17.63%, 26.79%, 36.40%, 46.63 and 57.73%) by using a slope-adjustable steel hydraulic flume (4 m length, 0.4 m width, 0.2 m depth). The results indicated that soil detachment capacity ranged from 0.173 to 6.325 kg m -2 s -1 with 1.972 kg m -2 s -1 on average. The soil detachment capacity increased with power function as the flow rate and the slope gradient augmented (R 2  = 0.965, NRMSE = 0.177 and NSE = 0.954). The soil detachment capacity was more influenced by flow rate than by slope gradient in this study. The relation between soil detachment capacity and shear stress, stream power, unit stream power and unit energy of water-carrying section can be described by using the linear function and power function, the power function relationship performed better than the linear function in generally. The stream power exhibits the best performance in describing the soil detachment capacity among shear stress, stream power, unit stream power and unit energy of water-carrying section in this study. The erodibility value in this study was larger than and the critical shear stress was less than those for soil in the eastern China. There has a huge potential for the soil in the Tibet Plateau eroded by the water erosion when enough runoff exiting. More attention should be payed to the water erosion process and mechanism in the Tibet Plateau area in the future.

The microbiome has emerged as a new player on behavior, physiology and stress because of its significant effects on the brain-gut axis. The aim of this study was to increase our understanding of brain-gut function in dairy cows. We investigated the effects of a heat-stress (HS) environment and individual differences of heat sensitivity (IH) on bovine physiological characteristics and microbial composition. Results indicate that both HS and IH increased rectal temperature (RT) (P < 0.05). An HS environment increased plasma, as well as milk cortisol and cytokines in plasma; however, it decreased plasma, and milk oxytocin, triiodothyronine, and thyroxine (P < 0.05) levels. Exposure to an HS environment reduced the diversity of the fecal microbial population, and resulted in a higher expression of diseases, the environmental adaptation pathway, and the immune related pathway, whereas it lowered the expression of metabolic pathways (P < 0.05). High heat sensitive cows have upregulated metabolisms, environmental adaptation and cellular process pathways, and a downregulated neurodegenerative disease pathway (P < 0.05). Thus, we conclude that exposure to an HS environment modulates physiological characteristics, which may interplay with microbial activity, and in turn, alter the circulation levels of cytokines, implicating the role of the brain-gut axis in dairy cows. The HS environment affected physiological characteristics, cytokine levels, and microbial composition, but IH influenced RT and fecal microbial functions.

Phloem protein 2 (PP2) is one of the most abundant and enigmatic proteins in sieve elements and companion cells, which play important roles in the maintenance of morphology, photoassimilate transportation and wound protection in higher plants, but to date, no PP2 (BnPP2) genes had been identified in ramie. Here, a total of 15 full-length BnPP2 genes were identified. These BnPP2 genes exhibited different responses to abiotic stresses. Interestingly, the BnPP2 genes are more sensitive to insect pests than to other stresses. A study of the BnPP2-15 promoter revealed that pBnPP2-15 could drive specific GUS expression in the petiole, root and stamen and could also be induced by mechanical wounding and aphid infection in transgenic Arabidopsis lines. The subcellular localization of six BnPP2 proteins showed that GFP-BnPP2-1, GFP-BnPP2-6, GFP-BnPP2-7, GFP-BnPP2-9, GFP-BnPP2-11 and GFP-BnPP2-12 were predominantly located in the cytoplasm. These results provide useful information elucidating the functions of BnPP2 genes in ramie.

The outcome of bladder cancer after radical cystectomy is heterogeneous. We aim to evaluate the prognostic value of HALP (hemoglobin, albumin, lymphocyte and platelet) and explore novel prognostic indexes for patients with bladder cancer after radical cystectomy. In this retrospective study, 516 patients with bladder cancer after radical cystectomy were included. The median follow-up was 37 months (2 to 99 mo). Risk factors of decreased overall survival were older age, high TNM stage, high American Society of Anesthesiologists (ASA) grade and low HALP score. The predictive accuracy was better with HALP-based nomogram than TNM stage (C- index 0.76 ± 0.039 vs. 0.708 ± 0.041). By combining ASA grade and HALP, we created a novel index-HALPA score and found it an independent risk factor for decreased survival (HALPA score = 1, HR 1.624, 95% CI 1.139-2.314, P = 0.007; HALPA score = 2, HR 3.471, 95% CI: 1.861-6.472, P < 0.001).The present study identified the prognostic value of HALP and provided a novel index HALPA score for bladder cancer after radical cystectomy.

Nine influenza virus neuraminidase (NA) subtypes have been identified in poultry and wild birds. Few methods are available for rapid and simple NA subtyping. Here we developed a multiplex probe combination-based one-step real-time reverse transcriptase PCR (rRT-PCR) to detect nine avian influenza virus NA subtypes. Nine primer-probe pairs were assigned to three groups based on the different fluorescent dyes of the probes (FAM, HEX, or Texas Red). Each probe detected only one NA subtype, without cross reactivity. The detection limit was less than 100 EID 50 or 100 copies of cDNA per reaction. Data obtained using this method with allantoic fluid samples isolated from live bird markets and H9N2-infected chickens correlated well with data obtained using virus isolation and sequencing, but was more sensitive. This new method provides a specific and sensitive alternative to conventional NA-subtyping methods.

Understanding the effects of different combinations of nitrogen (N), phosphorus (P) and potassium (K) fertilizers and the effects of GA 3 (gibberellic acid) foliar spray on the fiber quality and yield of ramie are important for maximizing the economic value of these plants. Three pot experiments were conducted using low NPK (140:70:140 kg/ha), normal NPK (280:140:280 kg/ha), and low NPK + GA 3 (10 mg/L) treatments. In each experiment, following fertilizers were applied: no fertilizer (control), N, P, K, NP, NK, PK, and NPK. Ramie was harvested three times from each plant; ramie grown without fertilizers had significantly lower biomass and yield than plants grown with fertilizers. At both normal and low fertilization rates, application of NPK resulted in greater growth and yield than application of N, P, K, NP, NK, or PK. Unfertilized plants produced the thinnest fibres (22-24 µm), with lowest elongation rate (3.0-3.1%) and breaking strength (22.7-23.3 cN). Fibre yield and fibre quality were improved by application of GA 3  + fertilizers . Maximum fibre yield was obtained at low NPK + GA 3 treatment, resulting in 65-81% more yield than low NPK alone. GA 3 with low NPK treatment significantly improved fibre diameter, fibre elongation, and breaking strength compared to both NPK alone and control treatment.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes. Susceptibility genes for type 2 diabetes may also impact the susceptibility of DR. This case-control study investigated the effects of 88 type 2 diabetes susceptibility loci on DR in a Chinese population with type 2 diabetes performed in two stages. In stage 1, 88 SNPs were genotyped in 1,251 patients with type 2 diabetes, and we found that ADAMTS9-AS2 rs4607103, WFS1 rs10010131, CDKAL1 rs7756992, VPS26A rs1802295 and IDE-KIF11-HHEX rs1111875 were significantly associated with DR. The association between CDKAL1 rs7756992 and DR remained significant after Bonferroni correction for multiple comparisons (corrected P = 0.0492). Then, the effect of rs7756992 on DR were analysed in two independent cohorts for replication in stage 2. Cohort (1) consisted of 380 patients with DR and 613 patients with diabetes for ≥5 years but without DR. Cohort (2) consisted of 545 patients with DR and 929 patients with diabetes for ≥5 years but without DR. A meta-analysis combining the results of stage 1 and 2 revealed a significant association between rs7756992 and DR, with the minor allele A conferring a lower risk of DR (OR 0.824, 95% CI 0.743-0.914, P = 2.46 × 10 -4 ).

Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIII HDL ) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIII HDL and cholesterol efflux capacity was measured. The apoCIII HDL ratio (apoCIII HDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIII HDL and apoCIII HDL ratio were inversely correlated with cholesterol efflux capacity (r = -0.241, P = 0.0002; r = -0.318, P < 0.0001, respectively). Stepwise multiple regression analysis revealed that the apoCIII HDL ratio was an independent contributor to HDL-mediated cholesterol efflux capacity (standardized β = -0.325, P < 0.001). This study indicates that the presence of apoCIII in HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.

The northern root-knot nematode (Meloidogyne hapla) is a damaging nematode that has caused serious economic losses worldwide. In the present study, a sensitive, simple and rapid method was developed for detection of M. hapla in infested plant roots by combining a Flinders Technology Associates (FTA) card with loop-mediated isothermal amplification (LAMP). The specific primers of LAMP were designed based on the distinction of internal transcribed spacer (ITS) sequences between M. hapla and other Meloidogyne spp. The LAMP assay can detect nematode genomic DNA at concentrations low to 1/200 000, which is 100 times more sensitive than conventional PCR. The LAMP was able to highly specifically distinguish M. hapla from other closely related nematode species. Furthermore, the advantages of the FTA-LAMP assay to detect M. hapla were demonstrated by assaying infected root galls that were artificially inoculated. In addition, M. hapla was successfully detected from six of forty-two field samples using FTA-LAMP technology. This study was the first to provide a simple diagnostic assay for M. hapla using the LAMP assay combined with FTA technology. In conclusion, the new FTA-LAMP assay has the potential for diagnosing infestation in the field and managing the pathogen M. hapla.

Huge efforts have been devoted to develop therapeutic monoclonal antibodies targeting human Programmed death-ligand 1 (hPD-L1) for treating various types of human cancers. However, thus far there is no suitable animal model for evaluating the anti-tumor efficacy of such antibodies against hPD-L1. Here we report the generation of a robust and effective system utilizing hPD-L1-expressing mouse tumor cells to study the therapeutic activity and mode of action of anti-human PD-L1 in mice. The model has been validated by using a clinically proven hPD-L1 blocking antibody. The anti-hPD-L1 antibody treatment resulted in potent dose-dependent rejection of the human PD-L1-expressing tumors in mice. Consistent with what have observed in autochthonous mouse tumor models and cancer patients, the hPD-L1 tumor bearing mice treated by anti-hPD-L1 antibody showed rapid activation, proliferation and reinvigoration of the cytolytic effector function of CD8 + T cells inside tumor tissues. Moreover, anti-hPD-L1 treatment also led to profound inhibition of Treg expansion and shifting of myeloid cell profiles, showing bona fide induction of multilateral anti-tumor responses by anti-hPD-L1 blockade. Thus, this hPD-L1 mouse model system would facilitate the pre-clinical investigation of therapeutic efficacy and immune modulatory function of various forms of anti-hPD-L1 antibodies.

The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.

Cereal cyst nematodes are sedentary biotrophic endoparasites that maintain a complex interaction with their host plants. Nematode effector proteins are synthesized in the oesophageal glands and are secreted into plant tissues through the stylet. To understand the function of nematode effectors in parasitic plants, we cloned predicted effectors genes from Heterodera avenae and transiently expressed them in Nicotiana benthamiana. Infiltration assays showed that HaEXPB2, a predicted expansin-like protein, caused cell death in N. benthamiana. In situ hybridization showed that HaEXPB2 transcripts were localised within the subventral gland cells of the pre-parasitic second-stage nematode. HaEXPB2 had the highest expression levels in parasitic second-stage juveniles. Subcellular localization assays revealed that HaEXPB2 could be localized in the plant cell wall after H. avenae infection.This The cell wall localization was likely affected by its N-terminal and C-terminal regions. In addition, we found that HaEXPB2 bound to cellulose and its carbohydrate-binding domain was required for this binding. The infectivity of H. avenae was significantly reduced when HaEXPB2 was knocked down by RNA interference in vitro. This study indicates that HaEXPB2 may play an important role in the parasitism of H. avenae through targeting the host cell wall.

In the soil environment, Bacilli can affect nematode development, fecundity and survival. However, although many Bacillus species can kill nematodes, the virulence mechanisms Bacilli utilize remain unknown. In this study, we collected 120 strains comprising 30 species across the Bacillaceae and Paenibacillaceae families of the Bacillales order and measured their nematicidal activities in vitro. Comparison of these strains' nematicidal capacities revealed that nine species, including Bacillus thuringiensis, B. cereus, B. subtilis, B. pumilus, B. firmus, B. toyonensis, Lysinibacillus sphaericus, Brevibacillus laterosporus and B. brevis, were highly nematicidal, the first of which showed the highest activity. Genome sequencing and analysis identified many potential virulence factors, which grouped into five types. At least four possible mechanisms were deduced on the basis of the combination of these factors and the bacterial nematicidal activity, including a pore-forming mechanism of crystal proteins, an inhibition-like mechanism of thuringiensin and a degradation mechanism of proteases and/or chitinases. Our results demonstrate that 120 spore-forming Bacilli across different families share virulence factors that may contribute to their nematicidal capacity.

The persistent public health threat of animal to human transmission of influenza A virus (IAV) has stimulated interest in rapid and accurate detection of all IAV subtypes in clinical specimens of animal origin. In this study, a new set of primers and probes was designed for one-step pan-IAV reverse-transcription fluorescence resonance energy transfer (FRET)-PCR. The detection limit of one-step pan-IAV RT FRET-PCR was 10 copies of the matrix gene per reaction, and proved to be equivalent or superior to virus isolation in detecting nine IAV subtypes. Application of the pan-IAV RT FRET-PCR to oral-pharyngeal and cloacal swab specimens collected from healthy poultry in 34 live bird markets in 24 provinces of China revealed that 9.2% of the animals (169/1,839) or 6.3% of their oral-pharyngeal or cloacal swabs (233/3,678) were positive for IAV, and 56.8% of IAV-positive samples were of the H9N2 subtype. Paralleling detection of IAV in H9N2-infected SPF chickens and chickens from LBM showed that pan-IAV FRET-PCR had a higher detection limit than virus isolation in eggs while the results by FRET-PCR and virus isolation overall matched. It is expected that this strategy can be useful for facile surveillance for IAV in clinical samples from a variety of sources.

Bacteriophage has been recognized as a novel approach to treat bacterial infectious diseases. However, phage resistance may reduce the efficacy of phage therapy. Here, we described a mechanism of bacterial resistance to phage infections. In Gram-negative enteric pathogen Vibrio parahaemolyticus, we found that polar flagella can reduce the phage infectivity. Deletion of polar flagella, but not the lateral flagella, can dramatically promote the adsorption of phage to the bacteria and enhances the phage infectivity to V. parahaemolyticus, indicating that polar flagella play an inhibitory role in the phage infection. Notably, it is the rotation, not the physical presence, of polar flagella that inhibits the phage infection of V. parahaemolyticus. Strikingly, phage dramatically reduces the virulence of V. parahaemolyticus only when polar flagella were absent both in vitro and in vivo. These results indicated that polar flagella rotation is a previously unidentified mechanism that confers bacteriophage resistance.

Plant-parasitic nematodes (PPNs) cause serious harm to agricultural production. Bacillus firmus shows excellent control of PPNs and has been produced as a commercial nematicide. However, its nematicidal factors and mechanisms are still unknown. In this study, we showed that B. firmus strain DS-1 has high toxicity against Meloidogyne incognita and soybean cyst nematode. We sequenced the whole genome of DS-1 and identified multiple potential virulence factors. We then focused on a peptidase S8 superfamily protein called Sep1 and demonstrated that it had toxicity against the nematodes Caenorhabditis elegans and M. incognita. The Sep1 protein exhibited serine protease activity and degraded the intestinal tissues of nematodes. Thus, the Sep1 protease of B. firmus is a novel biocontrol factor with activity against a root-knot nematode. We then used C. elegans as a model to elucidate the nematicidal mechanism of Sep1, and the results showed that Sep1 could degrade multiple intestinal and cuticle-associated proteins and destroyed host physical barriers. The knowledge gained in our study will lead to a better understanding of the mechanisms of B. firmus against PPNs and will aid in the development of novel bio-agents with increased efficacy for controlling PPNs.

Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (ΔFPG), 2h glucose (Δ2hPG) and glycated hemoglobin (ΔHbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P = 0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P = 0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank = 0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy.

Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 × 10(-5) and 6.54 × 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 × 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 × 10(-8) and 4.43 × 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 × 10(-4) and 4.65 × 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.

Bacillus thuringiensis has been globally used as a microbial pesticide for over 70 years. However, information regarding its various adaptions and virulence factors and their roles in the entomopathogenic process remains limited. In this work, we present the complete genomes of two industrially patented Bacillus thuringiensis strains (HD-1 and YBT-1520). A comparative genomic analysis showed a larger and more complicated genome constitution that included novel insecticidal toxicity-related genes (ITRGs). All of the putative ITRGs were summarized according to the steps of infection. A comparative genomic analysis showed that highly toxic strains contained significantly more ITRGs, thereby providing additional strategies for infection, immune evasion, and cadaver utilization. Furthermore, a comparative transcriptomic analysis suggested that a high expression of these ITRGs was a key factor in efficient entomopathogenicity. We identified an active extra urease synthesis system in the highly toxic strains that may aid B. thuringiensis survival in insects (similar to previous results with well-known pathogens). Taken together, these results explain the efficient entomopathogenicity of B. thuringiensis. It provides novel insights into the strategies used by B. thuringiensis to resist and overcome host immune defenses and helps identify novel toxicity factors.

Moso bamboo is recognized as phytoremediation plant due to production of huge biomass and high tolerance in stressed environment. Hydroponics and pot experiments were conducted to investigate mechanism of copper tolerance and to evaluate copper accumulation capacity of Moso bamboo. In hydroponics experiment there was non significant variation in MDA contents of leaves compared with control. SOD and POD initially indicated enhancing trend with application of 5 μM Cu and then decreased consistently with application of 25 and 100 μM Cu. Application of each additional increment of copper have constantly enhanced proline contents while maximum increase of proline was observed with application of 100 μM copper. In pot experiment chlorophyll and biomass initially showed increasing tendency and decreased gradually with application of each additional increment of Cu. Normal growth of Moso bamboo was observed with application of 100 mg kg(-1) copper. However, additional application of 300 or 600 mg kg(-1) copper had significantly inhibited growth of Moso bamboo. The concentration of Cu in Moso bamboo has attained the levels of 340, 60, 23 mg kg(-1) in roots, stems and leaves respectively. The vacuoles were the main organs which accumulated copper and reduced toxicity of copper as studied by TEM-DEX technology.