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This article established a rapid detection method for 34 pesticides in vegetables by combining QuEChERS purification method with high-performance liquid chromatography triple quadrupole linear ion trap tandem mass spectrometry. The samples were extracted with acetonitrile (containing 1% acetic acid), 1.5 g sodium acetate, 4 g anhydrous magnesium sulfate, and 1 g sodium chloride. The extract was further purified using 20 mg graphitized carbon black (GCB), 300 mg primary secondary amine (PSA), 200 mg octadecylsilane chemically bonded silica (C18), and 1000 mg MgSO4. Acetonitrile-water was chosen as mobile phase. The samples were analyzed using MRM-IDA-EPI mode, and an EPI database was established. Qualitative analysis was performed based on retention time, ion pair peak ratio, and EPI database, and quantification was carried out using matrix-matched external standard method. The study results indicated that using eggplant, garlic chives, cowpea, and spinach as representative matrices, the 34 pesticides showed good linear correlation with R2≥0.99011. The detection limits ranged from 0.16 to 1.81 μg/kg, and the quantification limits ranged from 0.52 to 6.02 μg/kg. The spiked recoveries of the samples were between 73.51% and 118.77%, and the precision was in the range of 0.01% to 14.27%. Vegetable samples were tested, with a detection rate of 58.23% for thiamethoxam. This method was characterized by its rapid and effective detection, simple operation, accurate data, and high sensitivity, making it suitable for the detection of 34 pesticides in vegetables.

Abstract It is important to ensure the nutritional quality and safe production of rice. Here, plot experiments were used to analyze the effects of three soil amendments—10 t ha−1 of biochar (BC), 1.5 t ha−1 of lime (LM), and 2.25 t ha−1 of silicon–calcium fertilizer (SC)—on the soil characteristics, rice yield and quality of double-cropping rice grown in mildly cadmium-polluted paddy fields. Compared with the control treatment (CK), the BC and SC treatments significantly improved rice processing, appearance and nutritional quality, but reduced cooking quality. All three soil amendments significantly reduced cadmium (Cd) content in brown rice. Soil amendments could significantly increase soil pH and reduce soil available Cd content. The application of the BC and SC treatments increased the content of each nutrient index in the soil (SOM, NN, AP, AK). Correlation analysis showed that the improvement in rice processing, appearance, and nutritional quality was mainly affected by the comprehensive effects of soil SOM, NN, AP and AK; the hygiene quality was mainly affected by soil pH and available Cd. In terms of benefit analysis combined with cost, the SC treatment had the highest benefit effect. Taken together, in mildly cadmium-polluted paddy fields, the application of silicon–calcium fertilizer improved the soil quality, thereby increased the yield and quality of rice, and had the best effect on increasing income.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography–tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements. HIGHLIGHT Etomidate (ET) use has spread rapidly, and it is now one of the most seriously abused substances in China. Our study first developed a simple, fast, and sensitive direct injection method for the quantitative determination of ET and etomidate acid in wastewater. After optimizing the UPLC–MS/MS and sample pretreatment conditions, the method was applied to authentic wastewater samples (n = 245) from several WWTPs in China.;

Objective In the central Yunnan region, the geological structure is complex and karst formations are prevalent. Sudden water gushing and attenuation of spring flow are among the most difficult problems in tunnel construction. The Mengkuanggou karst water system exhibits a high degree of karst conduitization, with significant differences between karst fissures and karst conduits. Methods This study employs the MODFLOW-CFPv2 dual medium numerical model to simulate the karst water system of Mengkuanggou, providing a detailed description of karst pipeline and diversion tunnel to understand the influence of tunnel construction on groundwater flow and spring flow. Results The results show that (1) The MODFLOW-CFPv2 model can describe the complex geological structure of karst areas, and simulate the dynamic characteristics of the groundwater level and the response characteristics of karst spring flow in the study area. (2) Under the condition of strong discharge, the water inflow per unit length of the tunnel is 164 m3/d·m, with a stable water inflow of 69 m3/d·m, while the Mengkuanggou karst spring flow shows a significant downwards trend. During the simulation period, the average spring flow decreased from 1 578 L/s under natural conditions to 1 098 L/s, an overall decrease of 30.4%, and the peak flow rate decreased from 2 133 L/s to 1 375 L/s, a decrease of 35.5%. The construction of strong discharge conditions will have a significant impact on tunnel construction and the groundwater environment. Under the condition of limited discharge, the maximum water inflow of the tunnel is 39 m3/d·m, and the stable water inflow is 24 m3/d·m. The water inflow of the tunnel is significantly reduced, and the downwards trend of the karst spring flow in Mengkuanggou is also improved to a certain extent. During the simulation period, the average spring flow is reduced to 1 284 L/s, a reduction of 18.6%, and the peak flow is reduced to 1 617 L/s, a decrease of 22.1%. Conclusion The MODFLOW-CFPv2 dual-medium model used in this study accurately describes highly heterogeneous karst water systems with pipelines, karst caves and fissures in karst areas. It can be used to quantitatively evaluate the karst water of Mengkuanggou during Xianglushan Tunnel construction.

The reasonable lap of high-level directional drilling holes in adjacent drilling sites is an important link to ensure the stable extraction effect and improve the effective utilization rate of drilling holes. According to the results of the research on the mechanism of gas extraction in the high-level directional drilling holes of the roof fracture zone, by analyzing the influencing factors of the extraction effect such as the spatial position of the high-level directional drilling holes, the distribution characteristics of the roof fracture zone of the coal seam, and the drilling trajectory, the reasonable overlapping part of the borehole for successful replacement was determined, and the engineering application was carried out in Dangjiahe Coal Mine. The application shows that the overlapping length of 80-121 m borehole can meet the gas extraction effect, and the outer end of the lapping position can reduce the drilling amount of each borehole by about 40 m.

The Forchheimer equation is one of the basic equations widely used in non-Darcy seepage. The determination of coefficients A and B in the equation has always been a hotspot and difficulty in the field of porous media seepage. Different studies have proposed various empirical formulas for the coefficients A and B from seepage experiments. However, there are few studies evaluating the applicability of each empirical formula under homogeneous condition and heterogeneous with mixed particle size. In this study, to provide basic information for selecting the empirical formula of the Forchheimer equation under different porous media conditions, the normalized objective function (NOF) and linear regression method are used to evaluate the applicability of the empirical formula of the Forchheimer equation, on the basis of the seepage resistance experiment. The results show that: for homogeneous porous media, Sidiropoulou’s formula has a good prediction effect on hydraulic gradient. For the porous media mixed two kinds of particle size, the mass ratio and size factors of the mixed particle size should be considered based on the average particle size. The prediction effect of the Macdonald formula is slightly affected by the mass ratio and the mixed particle size; while the predicted hydraulic gradient from the Kadlecan and Knight formula is relatively stable. As to the porous media mixed five kinds of particle size, the predictive effect of using d60 as the characteristic particle size is fine.The Kadlecan and Knight formula is suitable to predict coefficient A, and the Ergun formula is effective to predict coefficient B. This study can provide a basis for selecting the Forchheimer equation for seepage of homogeneous and heterogeneous loose sand and gravel porous media in engineering.

Abstract This paper presents a state‐space average model of a three‐level photovoltaic (PV) inverter to understand short‐circuit currents transient characteristics. Analytical solution of the model is also derived. The proposed model is validated with PV system controller hardware in‐loop (HIL) test method. The errors between simulation and HIL tests results under various conditions are evaluated, testifying the validity of the proposed model. With the model and analytical solution, the decaying time constants of sub‐transient and transient processes are derived, which shows that the time constants of a three‐level PV inverter are not fixed and they vary with voltage dips. The analytical expression of short‐circuit currents is also formulated. The findings from this study are essential to short‐circuit current calculations of a power grid with large‐scale PV plants, coordination of power system protections, and grid planning.

Abstract Background Right-side heart mass can be found incidentally on routine transthoracic echocardiography (TTE). Accurate diagnosis of cardiac mass often requires more than one imaging method. We present a mid-age woman with non-Hodgkin lymphoma who was found to have multiple right atrial masses mimicking metastases on routine TTE, which were finally diagnosed as thrombi by multimodal cardiac imaging. Case presentation A 52-year-old woman was diagnosed with primary mediastinal diffuse large B cell lymphoma (DLBCL) almost six months prior. The TTE revealed multiple masses in the right atrium with normal cardiac function when she was being evaluated for the next chemotherapy. On arrival, she was hemodynamically stable and asymptomatic. Physical examination was no remarkable. Laboratory findings showed leukocytosis of 17,900 cells/mm3, hemoglobin of 7.5 mg/dL, and a normal D-dimer level. The suspicious diagnosis of right atrial metastasis was made by TEE. However, the diagnosis of right atrial thrombi was made by contrast CMR. Finally, the 18 F-FDG PET-CT demonstrated no metabolic activity in the right atrium, which further supported the diagnosis of thrombi. Eventually, the masses were removed by cardiopulmonary bypass thoracotomy because of a high risk of pulmonary embolism. Histopathology confirmed the diagnosis of thrombi. Conclusions This case highlights the importance of multimodality cardiac imaging in the appropriate diagnosis of a RA masses in patient of lymphoma. Diagnosis of RA masses can be made using multimodal cardiac imaging like TTE, TEE and CMR, even PET. Echocardiography is the most commonly used on multimodal imaging in cardiac thrombus. CMR has high specificity in differentiating a tumor from thrombus, while 18 F-FDG PET has good sensitivity to determine the nature of the masses.

Abstract Laser state active controlling is challenging under the influence of inherent loss and other nonlinear effects in ultrafast systems. Seeking an extension of degree of freedom in optical devices based on low-dimensional materials may be a way forward. Herein, the anisotropic quasi-one-dimensional layered material Ta2PdS6 was utilized as a saturable absorber to modulate the nonlinear parameters effectively in an ultrafast system by polarization-dependent absorption. The polarization-sensitive nonlinear optical response facilitates the Ta2PdS6-based mode-lock laser to sustain two types of laser states, i.e., conventional soliton and noise-like pulse. The laser state was switchable in the single fiber laser with a mechanism revealed by numerical simulation. Digital coding was further demonstrated in this platform by employing the laser as a codable light source. This work proposed an approach for ultrafast laser state active controlling with low-dimensional material, which offers a new avenue for constructing tunable on-fiber devices.

The importance of determining the radon exhalation rate from water surface is emphasized by the increased use of radon and its daughter products as tracers in large-scale circulation studies of the atmosphere. There were many methods to measure radon exhalation from water surface. With the development of radon exhalation rate measurement methods and instruments on the surface of the soil, the rock and building materials, so the radon exhalation rate from water surface can be more accurately measured by applying these improved methods and instruments. In this paper, a cuboid accumulation chamber surrounded by foam boards and a RAD7 were used to measure the radon exhalation rate on the water surface at three different positions by Yixin lake. Each measurement was performed 2 h. The radon exhalation rate from the water surface was about 6 × 10−3 Bq m−2s−1. The thoron exhalation rate from the water surface also can be estimated, it is about 0.16 Bq m−2s−1. These results hint that the radon transmission from the lake bottom soil to water and then into the atmosphere.

IntroductionThe microalga Chlorella sp. NeZha, recently isolated from a balcony environment, shows significant adaptability across various salinity conditions, including seawater (SeaW), freshwater (FreshW), and high salinity levels (45‰). This study investigates its potential for sustainable aquaculture and biotechnological applications.MethodsMorphological and genetic identification were conducted using optical microscopy and DNA sequencing. The microalga was cultivated in a 400 L outdoor photobioreactor, and its biochemical composition, including chlorophyll a, carbohydrate, protein, and lipid content, was analyzed. Its compatibility with zooplankton and growth in aquaculture wastewater were also evaluated.ResultsChlorella sp. NeZha produced chlorophyll a at concentrations exceeding seaweed and Spirulina by 10- and 5-fold, respectively, with a dry weight chlorophyll a content of 34.25 mg/g and 25 pg./cell. The microalga also contained carbohydrate (~33%), protein (~20%), and lipids (~14%). It was compatible with zooplankton species, such as rotifers and brine shrimp, and showed promising growth in aquaculture wastewater.DiscussionThe findings suggest that Chlorella sp. NeZha is a viable candidate for sustainable aquaculture and biotechnological applications, offering high nutritional value and environmental resilience. Its adaptability to diverse salinity conditions and ability to thrive in wastewater highlight its potential for bioremediation and use as feedstock for zooplankton. Further research is recommended to optimize its cultivation and explore broader applications.

Abstract The development of high‐performance artificial synaptic neuromorphic devices poses a significant challenge in the creation of biomimetic sensing neural systems that seamlessly integrate both sensory and computational functionalities. In pursuit of this objective, promising bionic opto‐olfactory co‐sensory artificial synapse devices are constructed utilizing the BP‐C/CNT (2D/1D) hybrid filter membrane as the resistive layer. Experimental results demonstrated that the devices seamlessly integrated the light modulation, gas detection, and biological synaptic functions into a single device while addressing the challenge with separating artificial synaptic devices from sensors. These devices offered the following advantages: 1) Simulating visual synapses, they can effectively replicate fundamental synaptic functions under both electrical and optical stimulation. 2) By emulating olfactory synapse responses to specific gases, they can achieve ultra‐low detection limits and rapid identification of ethanol and acetone gases. 3) They enable photo‐olfactory co‐sensing simulations that mimic synaptic function under light‐modulated pulse conditions in distinct gas environments, facilitating the study of synaptic learning rules and Pavlovian responses. This work provides a pioneering approach for exploring highly stable 2D BP‐based optoelectronics and advancing the development of biomimetic neural systems.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Abstract Background A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. Methods A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. Results In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. Conclusions This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Under the forces of expansive soil and landslides, the construction of the tunnel entrance is more likely to cause engineering disasters, such as surface cracking and landslides. The application of micro piles in the tunnel has advantages over anti slide piles. Based on the homogenization theory and upper limit analysis, this study calculates the stability of expansive soil landslide at the entrance of an expressway tunnel, and evaluates the treatment effect of different combinations of micro pile groups and cutting-unloading. In the calculation, to improve the calculation efficiency, the micro pile groups and soil around the piles are equivalent to the plus solid conforming to the Mohr-Coulomb strength criterion based on the homogenization theory. the results then are verified by monitoring the landslide deformation after the cutting and micro pile group reinforcement treatment in the field. This study indicates that compared with the strength parameters of soil, the internal friction angle of equivalent reinforcement remains constant, and the cohesion increases from 26 kPa to 85.36 kPa. The evaluated landslide stability before and after treatment show that the sliding surface of the landslide extends from the rock-soil interface above the landslide to the front of the tunnel portal without treatment; when only using micro pile group reinforcement, the landslide safety factor is about 1.17, and the sliding surface extends from the rock-soil interface to the tunnel portal; when only using both micro pile group reinforcement and cutting-unloading, the safety factor increases from 1.26 to 1.28, and the upper edge of the sliding surface moves forward from the rock-soil interface. The field deformation monitoring shows that the deformation of surface and deep soil are less than 3 mm, which can keep the landslide stable, and also verifies the effectiveness of the calculation method. This study provides beneficial information for similar projects.

Abstract The rendering of urban 3D scenes involves a large number of models. In order to render scenes more efficiently, the main solution is to build a level of detail model (LOD). This may have the problem of building fragmentation, while relying on building a level of detail model (LOD) alone cannot meet the accuracy and fluency of large‐scale scene visualisation. Effective and reasonable data organisation has important research significance for the authors to achieve accurate and fast rendering of scenes. Therefore, the authors propose a large‐scale city model data organisation method considering building distribution to solve the above problems. This method first classifies the buildings in the scene at macro‐, meso‐ and microscales and records the classification using R‐trees. Then an adaptive quadtree is used to construct the data index of the city model. Finally, the data organisation of the large‐scale 3D city model is achieved by using the information of each node of the R‐tree as a constraint and combining with the adaptive quadtree. The results show that the method not only ensures the integrity of the user's area of interest but also can improve the efficiency of 3D scene construction.

Anaerobic digestion (AD) has been widely used as a promising technology for the treatment of kitchen waste (KW). The effects of several acidification-resisting methods were compared, which included the supplementation of trace elements (TEs) and zero-valent iron (ZVI) / powdered activated carbon (PAC), and the application of the sludge domesticated by acetic acid (HAc) and KW as inoculum. The results showed that the supplementation of TEs and ZVI/PAC at total solid (TS) content of 6% and optimal addition doses resulted in an increase in methane yield to 346 and 366 mL/g VS, respectively. In addition, the methane yields of 327 and 241 mL/g VS were obtained by applying the sludge domesticated with KW and HAc as inoculum, while the methane yield of the control was only 89.2 mL/g VS, representing a relative increase of 288%, 311%, 267%, and 170%. The acidification could be alleviated by applying these methods, and also the methanogenic profile was improved. Furthermore, microbial community analysis revealed that the enrichment of Methanosarcina, which enhanced the substrate utilization capacity and subsequently increased methane production, was achieved through the addition of TEs and ZVI/PAC, along with the application of sludge domesticated by KW.

Abstract Background Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism. Methods Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization. Results Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95—0.98, p = 2.47 × 10−4), osteoarthrosis (OR = 0.97, 95% CI: 0.96—0.98, P=1.10 × 10−8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10−6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects. Conclusions We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced.

Abstract Merging structural variations (SVs) at the population level presents a significant challenge, yet it is essential for conducting comprehensive genotypic analyses, especially in the era of pangenomics. Here, we introduce PanPop, a tool that utilizes an advanced sequence-aware SV merging algorithm to efficiently merge SVs of various types. We demonstrate that PanPop can merge and optimize the majority of multiallelic SVs into informative biallelic variants. We show its superior precision and lower rates of missing data compared to alternative software solutions. Our approach not only enables the filtering of SVs by leveraging multiple SV callers for enhanced accuracy but also facilitates the accurate merging of large-scale population SVs. These capabilities of PanPop will help to accelerate future SV-related studies.

This article proposes a method for diagnosing arc faults in the brush slip ring system of a Doubly-Fed Induction Generator (DFIG) using image recognition technology. The aim is to achieve automatic detection and diagnosis of arc faults. The experimental process of this diagnostic method includes collecting a large amount of arc faults image sample data through an industrial camera, preprocessing the collected data, completing data annotation, and creating a dataset. Build the YOLOv5 model using the PyTorch deep learning framework, train it using the arc faults image dataset, observe the convergence of the loss function during the model training process, and analyze the model testing results, taking into account evaluation indicators such as Precision, Recall, mean Average Precision (mAP), and Frames Per Second (FPS). This article proposes the K-YOLO++ model for diagnosing arc faults. The K-YOLO++ model is an improved model obtained by adding a small object detection layer on the basis of the YOLOv5 model, improving the multi-scale detection mechanism, and executing the K-means++ clustering algorithm to improve the anchors. The test results on the experimental dataset of arc faults in the brush slip ring system of Doubly-Fed Induction Generator indicate that the K-YOLO++ network model has improved Precision, Recall, and mAP. The mAP of the improved model is 88.36%, with a FPS of 50.62. The recognition effect of small targets is superior, effectively reducing missed and false detections, enabling efficient and accurate arc faults diagnosis.

Abstract Background Aberrant intracellular or intercellular signaling pathways are important mechanisms that contribute to the development and progression of cancer. However, the intercellular communication associated with the development of ccRCC is currently unknown. The purpose of this study was to examine the aberrant tumor cell-to-cell communication signals during the development of ccRCC. Methods We conducted an analysis on the scRNA-seq data of 6 ccRCC and 6 normal kidney tissues. This analysis included sub clustering, CNV analysis, single-cell trajectory analysis, cell–cell communication analysis, and transcription factor analysis. Moreover, we performed validation tests on clinical samples using multiplex immunofluorescence. Results This study identified eleven aberrantly activated intercellular signaling pathways in tumor clusters from ccRCC samples. Among these, two of the majors signaling molecules, MIF and SPP1, were mainly secreted by a subpopulation of cancer stem cells. This subpopulation demonstrated high expression levels of the cancer stem cell markers POU5F1 and CD44 (POU5F1hiCD44hiE.T), with the transcription factor POU5F1 regulating the expression of SPP1. Further research demonstrated that SPP1 binds to integrin receptors on the surface of target cells and promotes ccRCC development and progression by activating potential signaling mechanisms such as ILK and JAK/STAT. Conclusion Aberrantly activated tumor intercellular signaling pathways promote the development and progression of ccRCC. The cancer stem cell subpopulation (POU5F1hiCD44hiE.T) promotes malignant transformation and the development of a malignant phenotype by releasing aberrant signaling molecules and interacting with other tumor cells.

Summary: Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

The purpose of the current development is to investigate solar thermal radiations using advanced tetra-hybrid nano-structures in advanced industrial applications. The inclusion of tetra-hybrid nanoparticles into thermal energy storage devices is a vital mechanism while suspension nanoparticles can be treated as solar absorbers, absorbing solar light and converting it to heat. The current study reveals thermal efficiency by adding four kinds of nanoparticles in a time-dependent Casson fluid on a spinning sphere. Solar radiation, chemical reaction, heat sink and Soret effect, Dufour impact and electrohydrodynamic flow. Free-stream velocity changes with changes in time while the energy equation is tackled with convective boundary constraints. Similarity variables perform the role regarding conversion of (PDEs) partial-differential equations into desired (ODEs) ordinary-differential equations. Simulations have been tackled by a modified numerical approach called the finite element technique. Consequences are derived as by enhancing values E1 and A, it was found that velocity curves increase while velocity fields diminish when β and M. The Temperature curve is enhanced with large values of Hs,A and Ec and the temperature curve diminishes with large values of the Dufour parameter.

Intestinal disease is a group of complex digestive system diseases imposing a significant burden globally. Identifying the risk factors and potential complications of intestinal disease is important for its prevention and treatment. However, traditional observational clinical studies are limited by confounding factors and reverse causation, making causal inference challenging. Mendelian randomisation (MR) method has been developed to effectively mitigate these constraints and assess the causal relationships. This review briefly introduces the MR method, summarises MR research on intestinal disease and delineates the prospective avenues for future research. Conventional risk factors, such as lifestyle behaviours (eg, physical activity, smoking and alcohol consumption), nutrients (eg, selenium), obesity markers (eg, body mass index and waist-to-hip ratio) and inflammatory biomarkers, have been validated in MR studies. Multiomics MR studies are becoming novel hotspots, which provide a theoretical foundation for the exploration of pathogenesis and the investigation of new drug targets. However, most of the recent studies are based on European individuals, and thus it is necessary to replicate the results in other ancestries. Moreover, triangulation integrating MR and other epidemiology methods is suggested as a validated paradigm for causal inference in future MR studies.

IntroductionThe ratoon rice planting area is gradually expanding, but there has been relatively little research on ratoon rice grains contaminated with Cd.MethodsIn this study, five ratoon rice varieties were selected and divided into three groups according to early-maturity (growth duration: 100–110 days), mid-maturity (growth duration: 110–120 days) and late-maturity (growth duration: 120–130 days) varieties. Field experiments were done to study the differences in Cd accumulation among ratoon rice varieties with different growth duration.ResultsThe results showed that the Cd accumulation and concentration of grains spikelet at each growth stage in the main crop were in the order of late-maturity > mid-maturity > early-maturity varieties. However, the trends in Cd concentration and accumulation in grains spikelet during the ratoon crop were the opposite. Analysis found that as the growth duration of the variety extended, the accumulated temperature and daily average temperature in the main crop increased, which significantly increased the translocation factors of Cd from root, stem, and leaf to grains spikelet, and increased the daily average Cd accumulation rate in grains spikelet. The daily average temperature in the ratoon crop increased as the growth duration shortened. The early-maturity variety had higher Cd accumulation in stubble, which promoted the translocation of Cd from the root, stem, and leaf of the plant to the grains spikelet.DiscussionTherefore, appropriately shortening the growth duration of the main crop and extending the growth duration of the ratoon crop are important ways to reduce Cd accumulation in ratoon rice in areas with mild Cd pollution.

Summary: Background: This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. Methods: Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene–environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification. Findings: During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI = 1.01–1.06; P = 0.016) and poorer survival (HR, 1.13, 95% CI = 1.03–1.23; P = 0.010), particularly among participants with insufficient physical activity and ever smokers (Pinteraction > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM2.5 exposure (per 10 μg/m3 increment) and elevated CRC risk (RR,1.42, 95% CI = 1.12–1.79; P = 0.004; I2 = 90.8%). Genetically predicted methylation at PM2.5-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO2-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival. Interpretation: Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110. Funding: Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).

Summary: Background: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. Methods: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P

Transforming growth factor β-activated kinase 1 (TAK1) plays a significant role in controlling several signaling pathways involved with regulating inflammation and apoptosis. As such, it represents an important potential target for developing treatments for traumatic brain injury (TBI). Takinib, a small molecule and selective TAK1 inhibitor, has potent anti-inflammatory activity and has shown promising activity in preclinical studies using rat models to evaluate the potential neuroprotective impact on TBI. The current study used a modified Feeney's weight-drop model to cause TBI in mature Sprague-Dawley male rats. At 30 min post-induction of TBI in the rats, they received an intracerebroventricular (ICV) injection of Takinib followed by assessment of their histopathology and behavior. The results of this study demonstrated how Takinib suppressed TBI progression in the rats by decreasing TAK1, p-TAK1, and nuclear p65 levels while upregulating IκB-α expression. Takinib was also shown to significantly inhibit the production of two pro-inflammatory factors, namely tumor necrosis factor-α and interleukin-1β. Furthermore, Takinib greatly upregulated the expression of tight junction proteins zonula occludens-1 and claudin-5, reducing cerebral edema. Additionally, Takinib effectively suppressed apoptosis via downregulation of cleaved caspase 3 and Bax and reduction of TUNEL-positive stained cell count. As a result, an enhancement of neuronal function and survival was observed post-TBI. These findings highlight the medicinal value of Takinib in the management of TBI and offer an experimental justification for further investigation of TAK1 as a potential pharmacological target.

Abstract Understanding the forest evolution is vital to answering the reforestation potential in karst areas. Here, we present the first‐ever pollen record in karst depression sediment, combined with comprehensive dating methods (137Cs, 210Pbex, and 14C) and historical documents, to reveal plant change history in southwest Guangxi, a severe rocky‐desertification region. We inferred three stages of “virgin forest–deforestation–sparse tree planting” over the past three centuries. Before the 1780s, the barren mountains used to be a lush mixed broadleaf forest probably. However, maize cultivation, along with explosive population growth and migration, accelerated mountain reclamation and deforestation, leading to severe rocky desertification since the 1780s, featured by the co‐occurrence of Zea pollen appearance and Dicranopteris spore surge from 0.92% to 12.18%. Since the 1930s, sparse tree planting began, as Cupressaceae/Taxodiaceae pollen abruptly increased by 32%. Our study is significant in understanding the rocky desertification causes and guiding ecological restoration in the region.

Abstract Background Despite multiple therapeutic modalities, the overall survival of patients with gastric adenocarcinoma remains poor, especially for advanced tumor stages. Although the tyrosine kinase MerTK has shown therapeutic relevance in several tumor entities, its potential effects in gastric adenocarcinoma have not yet been sufficiently characterized. Methods MerTK expression and its influence on patient survival were evaluated by immunohistochemistry in a cohort of 140 patients with gastric adenocarcinoma. CRISPR/Cas9 knockout and siRNA knockdown of MerTK in the gastric cancer cell lines SNU1, SNU5, and MKN45 was used to analyze protein expression, growth, migration, and invasion properties in vitro and in a murine xenograft model. MerTK was pharmacologically targeted with the small molecule inhibitor UNC2025 in vitro and in vivo. Results In patients, high MerTK expression was associated with decreased overall survival (OS) and lymph node metastasis especially in patients without neoadjuvant therapy (p

Generative Artificial Intelligence (GAI) is an emerging and disruptive technology that has attracted considerable interest from researchers and educators across various disciplines. We discuss the relevance and concerns of ChatGPT and other GAI tools in environmental psychology research. We propose three use categories for GAI tools: integrated and contextualized understanding, practical and flexible implementation, and two-way external communication. These categories are exemplified by topics such as the health benefits of green space, theory building, visual simulation, and identifying practical relevance. However, we also highlight the balance of productivity with ethical issues, as well as the need for ethical guidelines, professional training, and changes in the academic performance evaluation systems. We hope this perspective can foster constructive dialogue and responsible practice of GAI tools.

In this study, a systematic investigation on the effect of solution treatment time (2–8 h) at 540 °C on the microstructure and mechanical properties in as-cast Mg-1Al-12Y (AY112, wt.%) alloy was performed. The results showed that the solution treatment did not cause the growth of grains and the change of texture; however, the mechanical properties had been significantly improved, which was mainly attributed to the precipitation of 18R long period ordered stacking (LPSO) phase in the solution-treated alloys. In addition, the dissolution of β-Mg24Y5 phase and the diffusion of solute atoms during the solution treatment were both beneficial to the mechanical properties. When the as-cast alloy was solution-treated at 540°C for 4 h (T4-4h alloy), the mechanical properties of the alloy are optimal. Compared with the as-cast alloy, the ultimate tensile strength (UTS) and elongation of the T4-4h alloy are increased by ∼23% and ∼179%, respectively. The deformation of the T4-4h alloys was dominated by a combination of basal slip and non-basal slip, and the presence of the LPSO phase effectively inhibited the nucleation of extension twin. Besides, the LPSO phase can also hinder the activation of basal dislocations and the movement of non-basal dislocations. Therefore, the LPSO phase simultaneously improves the strength and plasticity of the alloy.

Over the years, the Shaying River Basin has experienced frequent instances of river pollution. The presence of numerous critical pollutant discharge enterprises and sewage-treatment plants in the vicinity of the Shaying River has transformed it a major tributary with relatively serious pollution challenge within the upper reaches of Huaihe River Basin. To study the sources of manganese (Mn), chromium (Cr), nickel (Ni), arsenic (As), cadmium (Cd) and lead (Pb) in Shaying River water, 123 sets of surface water samples were collected from 41 sampling points across the entire basin during three distinct phases from 2019 to 2020, encompassing normal water period, dry season and wet season. The primary origins of heavy metals in river water were determined by analyzing the heavy metal contents in urban sewage wastewater, industrial sewage wastewater, groundwater, mine water, and the heavy metal contributions from agricultural non-point source pollution. The analytical findings reveal that Mn primarily originates from shallow groundwater used for agricultural irrigation, While Cr mainly is primarily sourced from urban sewage treatment plant effluents, coal washing wastewater, tannery wastewater, and industrial discharge related to metal processing and manufacturing. Ni is mainly contributed by urban sewage treatment plant effluents and industrial wastewater streams associated with machinery manufacturing and metal processing. Cd primarily linked to industrial wastewater, particularly from machinery manufacturing and metal processing facilities, while Pb is predominantly associated with urban sewage treatment plant effluents and wastewater generated in Pb processing and recycling wastewater. These research provides a crucial foundation for addressing the prevention and control of dissolved heavy metals at their sources in the Shaying River.

Abstract Background We aimed to investigate the protein pathways linking obesity and lifestyle factors to coronary artery disease (CAD). Methods Summary-level genome-wide association statistics of CAD were obtained from the CARDIoGRAMplusC4D consortium (60,801 cases and 123,504 controls) and the FinnGen study (R8, 39,036 cases and 303,463 controls). Proteome-wide Mendelian randomization (MR) analysis was conducted to identify CAD-associated blood proteins, supplemented by colocalization analysis to minimize potential bias caused by linkage disequilibrium. Two-sample MR analyses were performed to assess the associations of genetically predicted four obesity measures and 13 lifestyle factors with CAD risk and CAD-associated proteins’ levels. A two-step network MR analysis was conducted to explore the mediating effects of proteins in the associations between these modifiable factors and CAD. Results Genetically predicted levels of 41 circulating proteins were associated with CAD, and 17 of them were supported by medium to high colocalization evidence. PTK7 (protein tyrosine kinase-7), RGMB (repulsive guidance molecule BMP co-receptor B), TAGLN2 (transgelin-2), TIMP3 (tissue inhibitor of metalloproteinases 3), and VIM (vimentin) were identified as promising therapeutic targets. Several proteins were found to mediate the associations between some modifiable factors and CAD, with PCSK9, C1S, AGER (advanced glycosylation end product-specific receptor), and MST1 (mammalian Ste20-like kinase 1) exhibiting highest frequency among the mediating networks. Conclusions This study suggests pathways explaining the associations of obesity and lifestyle factors with CAD from alterations in blood protein levels. These insights may be used to prioritize therapeutic intervention for further study.

Abstract Background Sirtuin 7 (SIRT7) is an oncogene that promotes tumor progression in various malignancies, however, its role and regulatory mechanism in cervical squamous cell carcinoma (CSCC) is unknown. Herein, we attempted to investigate the functional role and molecular mechanism of SIRT7 underlying CSCC progression. Methods SIRT7 expression was evaluated in CSCC cells using various assays. We then used a series of function gain-and-loss experiments to determine the role of SIRT7 in CSCC progression. Furthermore, mechanism experiments were conducted to assess the interaction between SIRT7/USP39/FOXM1 in CSCC cells. Additionally, rescue assays were conducted to explore the regulatory function of USP39/FOXM1 in CSCC cellular processes. Results SIRT7 was highly expressed in CSCC patient tissues and cell lines. SIRT7 deficiency showed significant repression on the proliferation, and autophagy of CSCC cells in vitro and tumorigenesis in vivo. Similarly, apoptosis and ROS production in CSCC cells were accelerated after the SIRT7 knockdown. Moreover, SIRT7 and USP39 were found colocalized in the cell nucleus. Interestingly, SIRT7 was revealed to deacetylate USP39 to promote its protein stability in CSCC cells. USP39 protein was also verified to be upregulated in CSCC tissues and cells. USP39 silencing showed suppressive effects on CSCC cell growth. Mechanistically, USP39 was revealed to upregulate SIRT7 by promoting the transcriptional activity of FOXM1. Rescue assays also indicated that SIRT7 promoted autophagy and inhibited ROS production in CSCC cells by regulating USP39/FOXM1. Conclusion The SIRT7/USP39/FOXM1 positive feedback network regulates autophagy and oxidative stress in CSCC, thus providing a new direction for CSCC-targeted therapy. Graphical Abstract

Abstract Worldwide, Lung cancer is the leading cause of cancer-related death and poses a direct health threat, non-small cell lung cancer (NSCLC) is the most common type. In this study, we demonstrated that centrosomal protein 20 (CEP20) is upregulated in NSCLC tissues and associated with cancer invasion metastasis. Notably, CEP20 depletion inhibited NSCLC cell proliferation, migration, and microtubule polymerization. Mechanistically, we discovered that CEP20 is critical in the development of NSCLC by regulating microtubule dynamics and cell adhesion-related signaling pathways. Furthermore, the knockdown or overexpression of CEP20 affects microtubule polymerization in A549 cell lines. Our research provides a promising therapeutic target for the diagnosis and treatment of lung cancer, as well as a theoretical and experimental basis for clinical application.

As the most abundant group of mammals, rodents possess a very rich ecotype, which makes them ideal for studying the relationship between diet and host gut microecology. Zokors are specialized herbivorous rodents adapted to living underground. Unlike more generalized herbivorous rodents, they feed on the underground parts of grassland plants. There are two species of the genus Myospalax in the Eurasian steppes in China: one is Myospalax psilurus, which inhabits meadow grasslands and forest edge areas, and the other is M. aspalax, which inhabits typical grassland areas. How are the dietary choices of the two species adapted to long-term subterranean life, and what is the relationship of this diet with gut microbes? Are there unique indicator genera for their gut microbial communities? Relevant factors, such as the ability of both species to degrade cellulose, are not yet clear. In this study, we analyzed the gut bacterial communities and diet compositions of two species of zokors using 16S amplicon technology combined with macro-barcoding technology. We found that the diversity of gut microbial bacterial communities in M. psilurus was significantly higher than that in M. aspalax, and that the two species of zokors possessed different gut bacterial indicator genera. Differences in the feeding habits of the two species of zokors stem from food composition rather than diversity. Based on the results of Mantel analyses, the gut bacterial community of M. aspalax showed a significant positive correlation with the creeping-rooted type food, and there was a complementary relationship between the axis root-type-food- and the rhizome-type-food-dominated (containing bulb types and tuberous root types) food groups. Functional prediction based on KEGG found that M. psilurus possessed a stronger degradation ability in the same cellulose degradation pathway. Neutral modeling results show that the gut flora of the M. psilurus has a wider ecological niche compared to that of the M. aspalax. This provides a new perspective for understanding how rodents living underground in grassland areas respond to changes in food conditions.

Direct current (DC) bias induced by the DC transmission and geomagnetically induced current is a critical factor in the abnormal operation of electrical equipment and is widely used in the field of power transmission and distribution system state evaluation. As the main affected component, the vector magnetization state of a transformer core under DC bias has rarely been studied, resulting in inaccurate transformer operation state estimations. In this paper, a dynamic vector hysteresis model that considers the impact of rotating and DC-biased fields is introduced into the numerical analysis to simulate the distribution of magnetic properties, iron loss and temperature of the transformer core model and a physical 110 kV single-phase autotransformer core. The maximum values of B, H and iron loss exist at the corners and T-joint of the core under rotating and DC-biased fields. The corresponding maximum value of the temperature increase is found in the main core limb area. The temperature rise of the 110 kV transformer core under various DC-biased conditions is measured and compared with the FEM (Finite Element Method) results of the proposed model and the model solely based on the magnetization curve B||H. The calculation error of the temperature rise obtained by the improved model is approximately 3.76–15.73% and is much less than the model solely based on magnetization curve B||H (approximately 50.71–66.92%).

‘Duli’ (Pyrus betulifolia Bunge) is one of the main rootstocks of pear trees in China. Gibberellin (GA) is a key plant hormone and the roles of GA in nitrate (NO3−) uptake and metabolism in plants remain unclear. In this study, we investigated the effects of exogenous GA3 on the N metabolism of ‘Duli’ seedlings under NO3− deficiency. The results showed that exogenous GA3 significantly improves ‘Duli’ growth under NO3− deficiency. On the one hand, GA3 altered the root architecture, increased the content of endogenous hormones (GA3, IAA, and ZR), and enhanced photosynthesis; on the other hand, it enhanced the activities of N−metabolizing enzymes and the accumulation of N, and increased the expression levels of N absorption (PbNRT2) and the metabolism genes (PbNR, PbGILE, PbGS, and PbGOGAT). However, GA3 did not delay the degradation of chlorophyll. Paclobutrazol had the opposite effect on growth. Overall, GA3 can increase NO3− uptake and metabolism and relieve the growth inhibition of ‘Duli’ seedlings under NO3− deficiency.

Summary: Background: Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD. Methods: Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium (R2

Accurate and efficient mapping of road networks is crucial for evaluating urban development, transportation accessibility, and environmental impact. However, existing road extraction methods utilizing remote sensing images suffer from limited generalization ability and object occlusion, resulting in fragmented and discontinuous segmentation. Consequently, these limitations impede the practical applicability of these methods in multi-city and diverse-scenario road extraction applications. To address these challenges, we propose SWCARE, a road extraction method with SWitchable learning and Connectivity-Aware REfinement. We propose a flickering module with switchable learning which considers four types of auxiliary supervision information, namely road edge, road centerline, road corner, and road orientation, to improve the feature representativeness ability and enhance road extraction results. Furthermore, the proposed connectivity-aware refinement module aims to enhance the completeness and connectivity of road networks, thereby augmenting their practicality in real-world scenarios. We evaluate the performance of SWCARE on commonly used public road datasets and our constructed Large-And-Complex Road Dataset (LACRD). Our approach surpasses the state-of-the-art road extraction method in terms of both pixel-oriented and connectivity-oriented metrics, achieving a 4.41% higher Intersection over Union (IoU) and a 3.57% higher Average Path Length Similarity (APLS), respectively.

Abstract Environmental stressors and disturbances can cause changes in an ecosystem's community structure, which can be reflected in its functional diversity. As grazing intensity increases, this causes changes in the environment that inevitably lead to changes in the community structure, which can especially affect rodents due to their sensitivity to the environment. The effects of grazing prohibition and overgrazing on the functional diversity of desert rodent communities in Alxa were studied in April, July, and October of 2018–2020. The trap‐day method was used to study rodent communities in disturbed habitats. Five functional traits were selected and quantified: nutrition, life history, physiology, morphology, and activity rhythm. The results showed that: (1) The species composition of rodent communities in the Alxa Desert in spring and autumn was significantly correlated with the functional traits of the hibernation, reproductive cycle, and feeding habits. The species composition in the summer was only significantly correlated with the functional traits of reproductive cycle and diet. (2) The effects of overgrazing on the functional diversity of rodents in desert areas have significant temporal and spatial characteristics. (3) In spring and summer, overgrazing made the Functional Richness index of the rodent community lower than that of areas where grazing is prohibited, but the Functional Evenness index was higher than that of grazing‐prohibition areas. In autumn, overgrazing increased the Functional Richness index of the rodent community and decreased the Functional Evenness index. The Functional Divergence index was higher in overgrazing areas than in grazing‐prohibited ones. These results suggest that, in spring and summer, overgrazing reduced the ecological space utilization ability of rodent communities; however, the impact on the degree of utilization of community resources is more comprehensive. In autumn, overgrazing increases the ability of rodent communities to use ecological space but reduces resource efficiency. Overgrazing makes the niche differentiation of rodent communities higher, the degree of overlap lower, and the competition between species weaker. Therefore, overgrazing will affect the functional diversity of the community through the utilization of ecological space, resource utilization, interspecific competition, and niche.

Dipus sagitta is a major rodent found in arid environments and desert areas. They feed on plant seeds, young branches and some small insects, and have hibernating habits. Peak Dipus sagitta numbers impact the construction of the plant community in the environment, but also have a human impact as these rodents carry a variety of parasitic fleas capable of spreading serious diseases to humans. Based on 216 present distribution records of Dipus sagitta and seven environmental variables, this article simulates the potential distribution of Dipus sagitta during the Last Glacial Maximum, the mid-Holocene, the present and the future (2070s, RCP4.5, RCP8.5). This study also analyzes the geographic changes of the population distribution and evaluates the importance of climate factors by integrating contribution rate, replacement importance value and the jackknife test using the MaxEnt model. In this study, we opted to assess the predictive capabilities of our model using the receiver operating characteristic (ROC) and partial receiver operating characteristic (pROC) metrics. The findings indicate that the AUC value exceeds 0.9 and the AUC ratio is greater than 1, indicating superior predictive performance by the model. The results showed that the main climatic factors affecting the distribution of the three-toed jerboa were precipitation in the coldest quarter, temperature seasonality (standard deviation), and mean annual temperature. Under the two warming scenarios of the mid-Holocene and the future, there were differences in the changes in the distribution area of the three-toed jerboa. During the mid-Holocene, the suitable distribution area of the three-toed jerboa expanded, with a 93.91% increase in the rate of change compared to the Last Glacial Maximum. The size of the three-toed jerboa’s habitat decreases under both future climate scenarios. Compared to the current period, under the RCP4.5 emission scenario, the change rate is −2.96%, and under the RCP8.5 emission scenario, the change rate is −7.41%. This indicates a trend of contraction in the south and expansion in the north. It is important to assess changes in the geographic population of Dipus sagitta due to climate change to formulate population control strategies of these harmful rodents and to prevent and control the long-distance transmission of zoonotic diseases.

Plasmid transfection in cells is widely employed to express exogenous proteins, offering valuable mechanistic insight into their function(s). However, plasmid transfection efficiency in primary vascular endothelial cells (ECs) and smooth muscle cells (SMCs) is restricted with lipid-based transfection reagents such as Lipofectamine. The STING pathway, activated by foreign DNA in the cytosol, prevents foreign gene expression and induces DNA degradation. To address this, we explored the potential of STING inhibitors on the impact of plasmid expression in primary ECs and SMCs. Primary human aortic endothelial cells (HAECs) were transfected with a bicistronic plasmid expressing cytochrome b5 reductase 4 (CYB5R4) and enhanced green fluorescent protein (EGFP) using Lipofectamine 3000. Two STING inhibitors, MRT67307 and BX795, were added during transfection and overnight post-transfection. As a result, MRT67307 significantly enhanced CYB5R4 and EGFP expression, even 24 hours after its removal. In comparison, MRT67307 pretreatment did not affect transfection, suggesting the inhibitor's effect was readily reversible. The phosphorylation of endothelial nitric oxide synthase (eNOS) at Serine 1177 (S1177) by vascular endothelial growth factor is essential for endothelial proliferation, migration, and survival. Using the same protocol, we transfected wild-type and phosphorylation-incapable mutant (S1177A) eNOS in HAECs. Both forms of eNOS localized on the plasma membrane, but only the wild-type eNOS was phosphorylated by vascular endothelial growth factor treatment, indicating normal functionality of overexpressed proteins. MRT67307 and BX795 also improved plasmid expression in human and rat aortic SMCs. In conclusion, this study presents a modification enabling efficient plasmid transfection in primary vascular ECs and SMCs, offering a favorable approach to studying protein function(s) in these cell types, with potential implications for other primary cell types that are challenging to transfect.

The ability to manipulate and focus particles within microscale fluidic environments is crucial to advancing biological, chemical, and medical research. Precise and high-throughput particle focusing is an essential prerequisite for various applications, including cell counting, biomolecular detection, sample sorting, and enhancement of biosensor functionalities. Active and sheath-assisted focusing techniques offer accuracy but necessitate the introduction of external energy fields or additional sheath flows. In contrast, passive focusing methods exploit the inherent fluid dynamics in achieving high-throughput focusing without external actuation. This review analyzes the latest developments in strategies of sheathless inertial focusing, emphasizing inertial and elasto-inertial microfluidic focusing techniques from the channel structure classifications. These methodologies will serve as pivotal benchmarks for the broader application of microfluidic focusing technologies in biological sample manipulation. Then, prospects for future development are also predicted. This paper will assist in the understanding of the design of microfluidic particle focusing devices.

Summary: Background: Mitochondrial dysfunction has been linked to the development of inflammatory bowel disease (IBD), but the genetic pathophysiology was not fully elucidated. We employed Mendelian randomization and colocalization analyses to investigate the associations between mitochondrial-related genes and IBD via integrating multi-omics. Methods: Summary-level data of mitochondrial gene methylation, expression and protein abundance levels were obtained from corresponding methylation, expression and protein quantitative trait loci studies, respectively. We obtained genetic associations with IBD and its two subtypes from the Inflammatory Bowel Disease Genetics Consortium (discovery), the UK Biobank (replication), and the FinnGen study (replication). We performed summary-data-based Mendelian randomization analysis to assess the associations of mitochondrial gene-related molecular features with IBD. Colocalization analysis was further conducted to assess whether the identified signal pairs shared a causal genetic variant. Findings: After integrating the multi-omics data between mQTL-eQTL and eQTL-pQTL, we identified two mitochondrial genes, i.e., PARK7 and ACADM, with tier 1 evidence for their associations with IBD and ulcerative colitis (UC). PDK1 and FISI genes were associated with UC risk with tier 2 and tier 3 evidence, respectively. The methylation of cg05467918 in ACADM was associated with lower expression of ACADM, which fits with the positive effect of cg05467918 methylation on UC risk. Consistently, the inverse associations between gene methylation and gene expression were also observed in PARK7 (cg10385390) and PDK1 (cg17679246), which were corroborated with the protective role in UC. At circulating protein level, genetically predicted higher levels of PARK7 (OR 0.36, 95% CI 0.25–0.52) and HINT1 (OR 0.47, 95% CI 0.30–0.74) were inversely associated with IBD risk; genetically predicted higher level of HINT1 was associated with a decreased risk of Crohn's disease (CD) (OR 0.26, 95% CI 0.14–0.49) and a higher level of ACADM (OR 0.67, 95% CI 0.55–0.83), PDK1 (OR 0.63, 95% CI 0.49–0.81), FIS1 (OR 0.63, 95% CI 0.47–0.83) was associated with a decreased risk of UC. Interpretation: We found that the mitochondrial PARK7 gene was putatively associated with IBD risk, and mitochondrial FIS1, PDK1, and ACADM genes were associated with UC risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to IBD, which may enhance the understanding of the pathogenic mechanisms of IBD development. Funding: XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and Healthy Zhejiang One Million People Cohort (K-20230085).

Abstract Background The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods Protein quantitative trait loci (pQTLs) were derived from seven published genome-wide association studies (GWASs) on plasma proteome, and summary-level data were extracted for 4853 circulating protein markers. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4957 cases and 304,197 controls), and the UK Biobank (9276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which four (GREM1, CLSTN3, CSF2RA, CD86) were prioritized with the most convincing evidence. These protein-coding genes are mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusions This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.