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Abstract Protein copy numbers constrain systems-level properties of regulatory networks, but proportional proteomic data remain scarce compared to RNA-seq. We related mRNA to protein statistically using best-available data from quantitative proteomics and transcriptomics for 4366 genes in 369 cell lines. The approach starts with a protein’s median copy number and hierarchically appends mRNA–protein and mRNA–mRNA dependencies to define an optimal gene-specific model linking mRNAs to protein. For dozens of cell lines and primary samples, these protein inferences from mRNA outmatch stringent null models, a count-based protein-abundance repository, empirical mRNA-to-protein ratios, and a proteogenomic DREAM challenge winner. The optimal mRNA-to-protein relationships capture biological processes along with hundreds of known protein-protein complexes, suggesting mechanistic relationships. We use the method to identify a viral-receptor abundance threshold for coxsackievirus B3 susceptibility from 1489 systems-biology infection models parameterized by protein inference. When applied to 796 RNA-seq profiles of breast cancer, inferred copy-number estimates collectively re-classify 26–29% of luminal tumors. By adopting a gene-centered perspective of mRNA–protein covariation across different biological contexts, we achieve accuracies comparable to the technical reproducibility of contemporary proteomics.

Plant nitrogen source in the soil is challenging to track. Compiling the most comprehensive global δ15N dataset, a new study shows the plant use of various available soil nitrogen forms (ammonium, nitrate, and organic nitrogen) is strongly controlled by temperature.

Abstract Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Abstract To enhance the energy efficiency and financial gains of the park integrated energy system (PIES). This paper constructs a bi-level optimization model of PIES-cloud energy storage (CES) based on source-load uncertainty. Firstly, the scheduling framework of PIES with refined power-to-gas (P2G), carbon capture and storage (CCS) and CES coupling is constructed. Moreover, a bi-level optimization model with the upper tier subject being the PIES operator and the lower tier subject being the CES operator is established under the ladder-type carbon price mechanism with reward and punishment (LCPMRP). Then a proposed entropy weight adaptive information gap decision theory method (EAIGDT) is proposed to eliminate the subjectivity factor and retain its non-probabilistic features while dealing with multiple source-load uncertainties, and according to the operator’s risk preference to build risk-averse (RA) and risk-seeking (RS) strategies, respectively. Finally, the measured data in a certain area of Xinjiang verifies the proposed optimal scheduling method. The results show that the method can effectively take into account the interests of various subjects and realise PIES low-carbon economic operation.

Abstract Background Premature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy. Methods The study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36). Discussion The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice. Trial registration Clinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Abstract The interfacial microstructures of Josephson junctions are vital for understanding the microscopic mechanism to improve the performance of superconducting qubits further. However, there remain significant concerns about well understanding the correlation between atomic structures and electrical behaviors. Here, we propose a new method to define the interface of the barrier in Josephson junctions, and investigate the factors that affect the electrical properties of junctions using material analysis techniques and first principles. We find that the aluminium–oxygen ratio of the interface contributes greatly to the electrical properties of junctions, which is consistent with the conclusions obtained by utilizing the generative adversarial network for data augmentation. When the aluminium–oxygen ratio of the interface is 0.67–1.1, the model exhibits a lower barrier height and better electrical properties of the junction. Moreover, when the thickness of the barrier is fixed, the impact of the aluminium–oxygen ratio becomes prominent. A detailed analysis of Josephson junctions using a microscopic model has led to identifying of process defects that can enhance the yield rate of chips. It has a great boost for determining the relationship between microstructures and macroscopic performances.

ABSTRACT Aims/Introduction To analyze the association between HbA1c level and the risk of all‐cause mortality in community patients with type 2 diabetes mellitus, and to provide a scientific basis for the management of type 2 diabetes mellitus in the community. Materials and Methods Based on a Zhejiang rural community type 2 diabetes mellitus cohort, a total of 10,310 patients with type 2 diabetes mellitus with complete baseline and follow‐up data were selected. The Cox proportional hazards regression model and the restricted cubic spline model were used to evaluate the relationship between the HbA1c level and the risk of all‐cause mortality. Results During a mean follow‐up of 5.5 years, 971 patients died. With HbA1c levels of 6.5–7.0% as the reference, after adjusting for relevant confounding factors, the HR(95%CI) of all‐cause mortality with HbA1c levels of 0.05). Conclusions The HbA1c levels were associated with the risk of all‐cause mortality in type 2 diabetes mellitus in a “J‐shaped” manner, a too high or a too low HbA1c level could increase the risk of death. Attention should be paid to the individual evaluation of patients and the setting of appropriate glycemic control goals.

In order to study the “three zones” of spontaneous combustion in gob under different gas treatment conditions of high gas prone to spontaneous combustion and the change law of temperature field distribution, combined with the actual conditions of a high gas prone to spontaneous combustion working surface, a physical model of spontaneous ignition in goaf with “one face and four lanes” was constructed. The oxidation oxygen consumption and heat release parameters of coal samples obtained from temperature programmed experiment were applied to numerical simulation. The influence of different air supply, low and high pumping flow on the “three zones” of spontaneous combustion and temperature field distribution in goaf was studied. The variation of parameters such as maximum width of oxidation zone, area of oxidation zone and maximum temperature point of goaf with air supply, low and high pumping flow was quantitatively analyzed. The results show that in the range of simulation test, increasing air supply, low pumping flow and high pumping flow will cause the increase of air leakage in goaf, which is not conducive to the prevention and control of spontaneous combustion of coal left in goaf. The maximum temperature point does not change significantly (only within the range of 1K), and the influence of the change of high pumping flow rate on the width and area of the oxidation zone and the maximum temperature of the goaf is greater than that of the air supply volume and low pumping flow rate. The maximum width of oxidation zone increases with the increase of air supply, and the maximum temperature of goaf and the area of oxidation zone decrease with the increase of air supply. When the air supply increases from 1600 m3/min to 1900 m3/min, the maximum width of oxidation zone increases by 2 m (74−76 m), and the maximum temperature decreases by 0.1 K (315.38−315.28 K). The oxidation zone area decreased by 180.08 m2 (8 669.49−8 489.41 m2). The maximum width of oxidation zone increases with the increase of low extraction flow rate, the maximum temperature of goaf and the area of oxidation zone increase with the increase of extraction flow rate. When the low extraction flow rate increases from 200 m3/min to 300 m3/min, the maximum width of oxidation zone increases by 2 m (75−77 m). The maximum temperature increased by 0.152 K (315.34−315.492 K), and the oxidation zone area expanded by 51.56 m2 (8 553.79−8 605.35 m2). When the high pumping rate increased from 80 m3/min to 240 m3/min, the maximum width of the oxidation zone remained at about 75 m, and the maximum temperature increased by 0.76 K (315.13−315.89 K).

Fibroblast growth factor 1 (FGF1) regulates vertebrate cell growth, proliferation and differentiation, and energy metabolism. In this study, we cloned rainbow trout (Oncorhynchus mykiss) fgf1 and fgf1a, prepared their recombinant proteins (rFGF1 and rFGF1a), and described the molecular mechanisms by which they improve glycolipid metabolism in carnivorous fish. A 31-d feeding trial was conducted to investigate whether they could enhance glycolipid metabolism in rainbow trout on high-carbohydrate diets (HCD). A total of 720 rainbow trout (8.9 ± 0.5 g) were equally divided into 4 groups: the chow diet (CD) group injected with PBS, the HCD group injected with PBS, the HCD group injected with rFGF1 (400 ng/g body weight), and the HCD group injected with rFGF1a (400 ng/g body weight). The results showed that short-term HCD had a significant positive effect on the specific growth rate (SGR) of rainbow trout (P

Phthalates are endocrine disruptors of increasing concern for human health; however, previous studies have only assessed the association between internal exposure and human health. We aimed to assess the non-carcinogenic and carcinogenic risks of non-dietary exposure to phthalates in indoor environments among primary school children and their correlations with health indicators. A study involving 54 children was conducted in Jinan, Shandong Province, China. Questionnaires and health examinations were conducted, dust in hard-to-clean corners of students’ classrooms and homes was collected, and airborne phthalates in the middle of classrooms and family living rooms were sampled. The gas-phase phthalate concentrations, individual exposure, and non-carcinogenic and carcinogenic risks were calculated. Associations were estimated using linear mixed models. The findings revealed that phthalates posed a non-carcinogenic risk to 7.4 % of the children and a moderate carcinogenic risk to 27.8 % of the children, with higher non-carcinogenic and carcinogenic risks to girls than to boys. Five phthalates were negatively correlated with body mass index, dimethyl phthalate and diethyl phthalate (DEP) were significantly correlated with waist circumference, and di-iso-butyl phthalate (DiBP) was negatively correlated with hip circumference. DiBP, di-n-butyl phthalate, and DEP, were significantly correlated with cardiovascular disease, DEP and di (2-n-butoxyethyl) phthalate were correlated with decreased lung function, and di-n-octyl phthalate influenced airway inflammation. The findings indicated that phthalate exposure may negatively impact children's health, thereby warranting further comprehensive research on the health effects of these chemicals.

Abstract Fog is an important water source that alleviates vegetation water stress, especially for dryland ecosystems. Comprehensive knowledge of fog and rainfall effects can help us better understand dryland vegetation responses to current and future climates. However, the differences between fog and rainfall effects on vegetation are poorly understood. This study compared the effects of fog and rainfall on vegetation greenness changes based on the ground‐level meteorological observations in the Namib Desert and the satellite vegetation index. The vegetation index and its first derivative were utilized to indicate vegetation greenness and its change rate, respectively. Results showed that fog played a more significant role than rainfall in explaining vegetation greenness change rates, while accumulated rainfall was more important than fog in determining vegetation greenness. Soil temperature was an important factor in explaining vegetation greenness changes. These findings offer key insights into how fog and rainfall differentially contribute to vegetation greenness changes.

For DC grid based on the hybrid modular multilevel converter (MMC), the traditional DC fault current clearance scheme takes a long time and greatly affects the active power transmission. A novel DC fault current clearance coordinated control strategy is proposed, which can quickly interrupt the fault current and reduce the impact of DC fault on the DC grid and AC system. For fault-line connected MMC (FLMMC), a negative DC voltage control is employed, which can improve the current attenuation speed and ensure reliable fault isolation. For non-fault-line connected MMC (NFLMMC), the active current-limiting control (ACLC) based on the virtual reactor is adopted, which can reduce the current flow to the fault location and further shorten fault isolation time. To reduce the impact on the AC system during the DC fault, a short-time active power support control is designed. Finally, a four-terminal DC grid simulation model is built based on the RT-LAB OP5600 real-time digital simulation platform. The simulation results show that the proposed coordinated control strategy for the DC grid can quickly clear DC fault current, shorten DC fault isolation time, and strengthen active power support capability.

Abstract Dryland ecosystems cover 40% of our planet's land surface, support billions of people, and are responding rapidly to climate and land use change. These expansive systems also dominate core aspects of Earth's climate, storing and exchanging vast amounts of water, carbon, and energy with the atmosphere. Despite their indispensable ecosystem services and high vulnerability to change, drylands are one of the least understood ecosystem types, partly due to challenges studying their heterogeneous landscapes and misconceptions that drylands are unproductive “wastelands.” Consequently, inadequate understanding of dryland processes has resulted in poor model representation and forecasting capacity, hindering decision making for these at‐risk ecosystems. NASA satellite resources are increasingly available at the higher resolutions needed to enhance understanding of drylands' heterogeneous spatiotemporal dynamics. NASA's Terrestrial Ecology Program solicited proposals for scoping a multi‐year field campaign, of which Adaptation and Response in Drylands (ARID) was one of two scoping studies selected. A primary goal of the scoping study is to gather input from the scientific and data end‐user communities on dryland research gaps and data user needs. Here, we provide an overview of the ARID team's community engagement and how it has guided development of our framework. This includes an ARID kickoff meeting with over 300 participants held in October 2023 at the University of Arizona to gather input from data end‐users and scientists. We also summarize insights gained from hundreds of follow‐up activities, including from a tribal‐engagement focused workshop in New Mexico, conference town halls, intensive roundtables, and international engagements.

Constructing an ecological network is crucial to maintaining ecosystem stability, optimizing ecological space, and ensuring regional ecological security. Using circuit theory, the study integrated habitat condition, ecosystem function, and landscape structure to construct ecological network in Ulanqab. The ecological networks consist of four basic components, including sources, resistance surfaces, corridors and nodes. Ecological sources refer to patches with high habitat quality, while the resistance to species movement between patches is named as ecological resistance surfaces, the important corridors for movement between patches are referred to as ecological corridors, and the vital spots in ecological network are referred to ecological nodes. In addition, the drivers affecting these changes were also analyzed using geographical detector. The results indicated that the area of ecological sources dropped by 19.1 % and the area of high value of ecological resistance surfaces increased from 2000 and 2020. The length of ecological corridors increased by 793.80 km. Mean annual precipitation is the main natural factor influencing the ecological network, and land use intensity and human footprint are the main anthropogenic factors. Our findings suggest that in this region, urban developing should minimize the encroachment on grasslands, forests and waters. Additionally, the availability of water resources should be considered in the planning and implementation of ecological restoration and protection. The findings of the study offer reasonable suggestions for the protection and restoration of priority regions, as well as a scientific foundation optimization and sustainable development of the regional ecological network.

Realizing fast and continuous generation of reactive oxygen species (ROSs) via iron-based advanced oxidation processes (AOPs) is significant in the environmental and biological fields. However, current AOPs assisted by co-catalysts still suffer from the poor mass/electron transfer and non-durable promotion effect, giving rise to the sluggish Fe2+/Fe3+ cycle and low dynamic concentration of Fe2+ for ROS production. Herein, we present a three-dimensional (3D) macroscale co-catalyst functionalized with molybdenum disulfide (MoS2) to achieve ultra-efficient Fe2+ regeneration (equilibrium Fe2+ ratio of 82.4%) and remarkable stability (more than 20 cycles) via a circulating flow-through process. Unlike the conventional batch-type reactor, experiments and computational fluid dynamics simulations demonstrate that the optimal utilization of the 3D active area under the flow-through mode, initiated by the convection-enhanced mass/charge transfer for Fe2+ reduction and then strengthened by MoS2-induced flow rotation for sufficient reactant mixing, is crucial for oxidant activation and subsequent ROS generation. Strikingly, the flow-through co-catalytic system with superwetting capabilities can even tackle the intricate oily wastewater stabilized by different surfactants without the loss of pollutant degradation efficiency. Our findings highlight an innovative co-catalyst system design to expand the applicability of AOPs based technology, especially in large-scale complex wastewater treatment.

Abstract. Background:. Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease. Methods:. Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA. Results:. A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain (COL1A1) and synaptotagmin like 2 (SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8+ T cells. In addition, single-cell analysis indicated that fibroblasts and CD8+ T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions:. COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Abstract Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Abstract Mechanoluminescence (ML) sensing technologies open up new opportunities for intelligent sensors, self-powered displays and wearable devices. However, the emission efficiency of ML materials reported so far still fails to meet the growing application requirements due to the insufficiently understood mechano-to-photon conversion mechanism. Herein, we propose to quantify the ability of different phases to gain or lose electrons under friction (defined as triboelectric series), and reveal that the inorganic-organic interfacial triboelectricity is a key factor in determining the ML in inorganic-organic composites. A positive correlation between the difference in triboelectric series and the ML intensity is established in a series of composites, and a 20-fold increase in ML intensity is finally obtained by selecting an appropriate inorganic-organic combination. The interfacial triboelectricity-regulated ML is further demonstrated in multi-interface systems that include an inorganic phosphor-organic matrix and organic matrix-force applicator interfaces, and again confirmed by self-oxidization and reduction of emission centers under continuous mechanical stimulus. This work not only gives direct experimental evidences for the underlying mechanism of ML, but also provides guidelines for rationally designing high-efficiency ML materials.

Abstract Ecosystem‐scale photosynthetic efficiency (EPE) is proposed as an effective indicator to quantify gross primary productivity (GPP), but how the coupling between EPE and GPP varies as vegetation resilience decreases has not been evaluated. Here, we quantified forest resilience with optimized Bayesian models. With the use of multisource satellite and modeling data, our study revealed that forests on the Loess Plateau and in the Qinba Mountains in China are experiencing rapid resilience loss and are already facing mortality warnings after 2010. Reductions in resilience also drove the marked decoupling of GPP from EPE. Notably, the decline in resilience was accompanied by a decrease in EPE in about 74% of the forests while GPP increased. The mechanism underlying this decoupling could be attributed to enhanced atmospheric water demand and soil water constraints. The dynamic relationships found here could help to improve forest mortality models and enhance photosynthesis‐based GPP evaluation.

IntroductionThe distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing.MethodsThe parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice.ResultsRetrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon.DiscussionThese data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.

Indoor semivolatile organic compounds (SVOCs) pose a substantial threat to human health. However, identifying the sources of these emissions has been challenging owing to the scarcity of convenient and practical on-site methodologies. Herein, a novel method for source screening was proposed using aluminum silicate sampling strips to adsorb SVOCs from the surface air of indoor materials. The adsorbed SVOC levels indicate the emission intensity of these materials into indoor environments. Additionally, compact sampling strips can be readily fixed to any vertical surface using a static sticker, facilitating the characterization of various materials in practical settings. Laboratory-simulated experiments demonstrated the capability of the proposed method to differentiate between source and non-source materials within a 10-cm distance in the same space. In practical scenarios, the primary emission sources identified via this method exhibited a consistent correlation with the contents of the corresponding materials obtained from the traditional solvent-extraction method. As the adsorbed SVOCs were directly transferred to a GC–MS through thermal desorption instead of the solvent-extraction procedure, the proposed method demonstrated several-fold improvements in analytical sensitivity and efficiency. Using this versatile screening technique, some emerging and important SVOC species were identified within specific indoor materials. Eliminating these sources has been demonstrated as an effective approach to mitigate SVOC pollution. Overall, the proposed method offers a powerful tool for managing indoor pollutants and safeguarding human health.

Abstract Tropical cyclones are often accompanied by large amount of precipitation potentially impacting stream hydrochemistry. Global warming is altering typhoon disturbance regime. Little is known about how cyclone changes, especially cyclone‐frequency reduction may affect stream hydrochemistry. In this study, we compared water and nutrient input via precipitation and output via streamflow between a frequent‐typhoon period (2013–2017), with 1.2 typhoon yr−1, and a no‐typhoon period (2018–2022) at a long‐term monitoring site, the Fushan Experimental Forest of Taiwan. Precipitation and streamflow quantities were not different between the two periods because typhoons increased the fluctuation but not the mean of monthly precipitation in the major typhoon months (July–September). Inputs of Mg2+, NO3−, and SO42− via precipitation were greater in the frequent‐typhoon period than the no‐typhoon period while inputs of other ions were not different between the two periods. Only the output of Mg2+ was different between the two periods, greater in the frequent‐typhoon period. Output/input ratio of NO3− was greater in the no‐typhoon period than the frequent‐typhoon period despite the greater input in the frequent‐typhoon period, while no differences were found for others. Increases in mineralization rates due to warming is suggested to be the cause of the greater NO3− output/input ratio during the no‐typhoon period. Relationships between stream discharge and ion export were similar between the two periods both with and without removing typhoon events. The limited variation in hydrochemistry between periods of contrasting cyclone activities suggests high resilience of the undisturbed subtropical forests to changes in cyclone frequency at the decadal scale.

Abstract Multiple lines of evidence confirm a widespread increase in vegetation growth across China over the past few decades. The relationship between vegetation growth and water availability is thought to be becoming stronger under climate change, that is, water constraints on vegetation growth have been increasing. However, our understanding of how water constraints have influenced these vegetation greening trends, especially those climate change‐driven ones, remains limited. Here, we conduct a comprehensive evaluation of recent water constraints and their implications for vegetation growth in China between 1982 and 2015. By analyzing the spatiotemporal patterns of the relationship between vegetation growth and water availability, we reveal recent water constraints and their changes hidden within an overall greening trend in China. Further analysis demonstrates that two climate change‐related categories, defined broadly as “climate” (e.g., air temperature, precipitation, and so on) and “CO2” (i.e., atmospheric carbon dioxide), have exerted varying levels of importance in regulating vegetation growth across different water constraints. With increasing water constraints, the proportion of the climate‐dominated area has significantly risen, while that of the CO2‐dominated area has sharply declined. Our findings highlight that water constraints can mediate the dominance of climate and atmospheric CO2 on vegetation growth. This has the great potential to exacerbate the uncertainty surrounding current and future sustainable vegetation greening trends.

Abstract. Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations, while reliable biomarkers to detect or monitor are still under investigation. Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers, including proteins, ribonucleic acids (RNAs), and deoxyribonucleic acids (DNAs), for early detection of pathological changes in susceptible patients, rapid diagnosis at the bedside after onset, and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.

Abstract Background Hepatitis B mother-to-child transmission interruption (PMTCT) poses a formidable challenge in underdeveloped regions of China. This study aims to evaluate the effectiveness of PMTCT and the health management team (HMT) model in Ningxia, China, as well as the risk factors for adverse outcomes. Methods The PMTCT + HMT model was established, and 360 pregnant women diagnosed with HBV infection in 2020–2022 were selected and divided into the control and the study groups based on different intervention modes. HBV serum markers and HBV DNA levels were assessed, the indicators of compliance behaviors and adverse outcomes were compared, and the factors influencing adverse outcomes were analyzed. Results The majority of subjects were residents of the local city, married, with secondary school or higher education, and employees of public sectors. The proportion of ethnic minorities was 40.8% and 34.2% in the control group and study group. HBeAg positivity was 23.3% and 26.3%, and the proportion with HBV DNA levels ≥ 2 × 105 IU/mL was 9.2% and 7.1%. Compared with the control group (PMTCT alone), the PMTCT + HMT model led to improved maternal knowledge (17.5% vs. 57.1%), voluntary counseling (34.2% vs. 63.3%), and testing (37.5% vs. 70.4%). The incidence of adverse pregnancy outcomes ((including miscarriage, preterm birth) decreased significantly (17.5% vs. 6.2%), as did adverse neonatal outcomes (low birth weight and congenital HBV) (26.9% vs. 10.5%). Adverse outcomes were associated with low educational attainment, non-locals, unmarried status, and ethnic minority identity. Additionally, HBeAg positivity and HBV DNA levels ≥ 2 × 105 IU/mL were risk factors for adverse outcomes. Conclusions The PMTCT + HMT model demonstrates significant effectiveness in preventing mother-to-child transmission of hepatitis B in Ningxia. The unique demographic structure of Ningxia region is closely linked to poor outcomes, emphasizing the importance of monitoring HBeAg status and HBV DNA viral load level.

Abstract This study was designed to explore the expression changes of P2Y1 receptors in the distal colonic myenteric layer of rats. An opioid induced constipation(OIC) rat model was generated by intraperitoneal (i.p) injection of loperamide. At 7 days post-treatment, the model rats were assessed by calculating the fecal water content and the gastrointestinal transit ratio. The immunofluorescence (IF)-based histochemical study was used to observe the distribution of P2Y1 receptors in the distal colonic myenteric plexus. Western blotting (WB) was performed to evaluate the expression changes of P2Y1 proteins in the myenteric layer, and the electrophysiological approaches were carried out to determine the regulatory roles of P2Y1 receptors on distal colonic motor function. IF showed that P2Y1 receptors are co-expressed MOR in the enteric nerve cells of the distal colonic myenteric plexus. Moreover, the WB revealed that the protein levels of P2Y1 were significantly decreased in the distal colonic myenteric layer of OIC rats. In vitro tension experiments exhibited that the P2Y1 receptor antagonist MRS2500 enhanced the spontaneous contraction amplitude, adding EM2 and β-FNA did not have any effect on MRS2500. Therefore, P2Y1 receptor expression could be associated with the occurrence of OIC in this rat model and the regulation of colonic motility by MOR may be related to the release of purine neurotransmitters such as ATP in the colonic nervous system.

Salinity is an essential parameter for evaluating water quality and plays a crucial role in maintaining the stability of lake ecosystems, particularly in arid and semi-arid climates. Salinity responds to changes in climate and human activity, with significant impacts on water quality and ecosystem services. In this study, Sentinel-2A/B Multi-Spectral Instrument (MSI) images and quasi-synchronous field data were utilized to estimate lake salinity using machine learning approaches (i.e., XGB, CNN, DNN, and RFR). Atmospheric correction for MSI images was tested using six processors (ACOLITE, C2RCC, POLYMER, MUMM, iCOR, and Sen2Cor). The most accurate model and atmospheric correction method were found to be the extreme gradient boosting tree combined with the ACOLITE correction algorithm. These were used to develop a salinity model (N = 70, mean absolute percentage error = 9.95%) and applied to eight lakes in Inner Mongolia from 2016 to 2024. Seasonal and interannual variations were explored, along with an examination of potential drivers of salinity changes over time. Average salinities in the autumn and spring were higher than in the summer. The highest salinities were observed in the lake centers and tended to be consistent and homogeneous. Interannual trends in salinity were evident in several lakes, influenced by evaporation and precipitation. Climate factors were the primary drivers of interannual salinity trends in most lakes.

In technology and industrial production, many applications require wide-bandwidth current measurements. In this paper, a signal fusion scheme for a current sensor comprising tunneling magnetoresistance and a current transformer is proposed, achieving a flat frequency response in the DC to MHz range. The measurement principles in different cases of the scheme are introduced, and the total transfer function of the entire scheme is derived by analyzing each section separately. Furthermore, the feasibility and selected parameters of the scheme are verified through a systematic simulation utilizing the MATLAB software. Based on the proposed scheme, a group of principal prototypes are built to experimentally evaluate the bandwidth, amplitude and phase flatness, accuracy, sensitivity, and impulse response. The relative amplitude variation in the passband of the fusion sensor is less than 4%, and the estimated bandwidth of the fusion sensor is close to 17 MHz. The accuracy is better than 0.6%, even when measuring the current at 1 MHz, and the relative standard deviation is 5% when measuring the impulse signal. The sensors developed using this scheme, with a low financial cost, have advantages in many wide-bandwidth current measuring scenarios.

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.

Insufficient studies in characterizing vertical structure of Chlorophyll-a (Chl-a) in the ocean critically limit better understanding about marine ecosystem based on global climate change. In this study, we developed a Gaussian-activation deep neural network (Gaussian-DNN) model to assess vertical Chl-a structure in the upper ocean at high spatial resolution. Our Gaussian-DNN model used the input variables including satellite data of sea surface Chl-a and in-situ vertical physics profiles (temperature and salinity) in the northwestern Pacific Ocean (NWPO). After validation test based on two independent datasets of BGC-Argo and ship measurement, we applied the Gaussian-DNN model to reconstruct temporal evolution of 3-D Chl-a structure in the NWPO. Our modelling results successfully explain over 80% of the Chl-a vertical profiles in the NWPO at a horizontal resolution of 1° × 1° and 1 m vertical resolution within upper 300 meters during 2004 to 2022. Moreover, according to our modelling results, the Subsurface Chlorophyll Maxima (SCMs) and total Chl-a within 0-300 m depths were extracted and presented seasonal variability overlapping longer-time trends of spatial discrepancies all over the NWPO. In addition, our sensitivity testing suggested that sea-water temperatures predominantly control 3-D structures of the Chl-a in the tropical NWPO, while salinity played a key role in the temperate gyre of the NWPO. Here, our development of the Gaussian-DNN model may also be applied to craft long term, 3-D Chl-a products in the global ocean.

The fault cavern type reservoir in Block 1 of Shunbei area is located in the ultra-deep layer and is classified as a volatile oil reservoir. The reservoir is characterized by very deep burial with an oil/gas ratio between 250 and 500 m3/tone and a saturation pressure range of 28–36 MPa. As of March 2021, the formation pressure has dropped to 30.5 MPa and the pressure retention rate is 35.8%. In order to effectively develop this reservoir, it was decided to use a water injection development method with a planned transition to natural gas injection in March 2022 to further enhance recovery and maintain formation pressure. Through evaluation and research, the pressure distribution, production capacity change and reservoir dynamic response during the water injection development stage were analyzed with respect to the characteristics of fracture-controlled fracture-cave type reservoir in Shunbei-1 block. On this basis, the necessity, feasibility, and expected effects of conversion to natural gas injection are explored, including improvement of displacement efficiency, reduction of fluid output, and enhancement of formation energy replenishment. In addition, this study also carries out in-depth research and prediction on the optimization of natural gas injection parameters, the selection of injection methods and possible problems, aiming to provide scientific basis and technical support for the efficient and sustainable development of this block. In order to smoothly promote the implementation of natural gas injection development, a special reservoir description technique applicable to fault cavern type reservoirs was adopted. Based on this foundation, an in-depth study was conducted on the mechanism of natural gas displacement, so as to optimize the layout of the well network and the setting of injection and extraction parameters. In addition, a set of evaluation system for natural gas injection effect in fault cavern type reservoirs was constructed. By adopting the natural gas injection development method and combining the corresponding supporting technology development and optimization measures, the reservoir development efficiency and oil (gas) production rate have been effectively improved, and the risk of gas flaring has been reduced at the same time. These research results are of great significance for ensuring the comprehensive development and effective utilization of oil and gas resources, and provide strong technical support for future development work.

Summary: Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

Abstract The development of heterogenous catalysts based on the synthesis of 2D carbon-supported metal nanocatalysts with high metal loading and dispersion is important. However, such practices remain challenging to develop. Here, we report a self-polymerization confinement strategy to fabricate a series of ultrafine metal embedded N-doped carbon nanosheets (M@N-C) with loadings of up to 30 wt%. Systematic investigation confirms that abundant catechol groups for anchoring metal ions and entangled polymer networks with the stable coordinate environment are essential for realizing high-loading M@N-C catalysts. As a demonstration, Fe@N-C exhibits the dual high-efficiency performance in Fenton reaction with both impressive catalytic activity (0.818 min−1) and H2O2 utilization efficiency (84.1%) using sulfamethoxazole as the probe, which has not yet been achieved simultaneously. Theoretical calculations reveal that the abundant Fe nanocrystals increase the electron density of the N-doped carbon frameworks, thereby facilitating the continuous generation of long-lasting surface-bound •OH through lowering the energy barrier for H2O2 activation. This facile and universal strategy paves the way for the fabrication of diverse high-loading heterogeneous catalysts for broad applications.

Aiming at the problems of large amount of residual coal and serious air leakage in the goaf of extra-thick and high top coal caving mining face, the gas products, oxygen consumption and heat release characteristics of coal oxidation spontaneous combustion process under the conditions of without nitrogen injection and nitrogen injection were analyzed by temperature programmed oxidation experiment and heat release test experiment. By using numerical simulation software, the inhibition of nitrogen injection on the risk zone of coal spontaneous combustion in goaf under different nitrogen injection positions was analyzed and the nitrogen injection plan are optimized. The results show that the process of oxidation and spontaneous combustion of coal can be inhibited by nitrogen injection. The temperature point of each gas product is delayed by 25-30 ℃, and the oxygen consumption rate and heat release are greatly reduced. The heat release without nitrogen injection is 5.67 times that of nitrogen injection. When nitrogen is injected at different positions, the risk area of coal spontaneous combustion in goaf is different and contracted. When nitrogen is injected at ports 2, 3, 4 and 5, that is, the intake side is 60 m, 80 m, 100 m, 120 m away from the working face when nitrogen is injected, the inhibition area of risk area accounts for 12.28%, 32.71%, 39.71% and 44.09% respectively. The change of temperature inhibition in goaf is mainly concentrated in the zone near the nitrogen injection port. Nitrogen injection ports 2 and 3 joint optimized plan can effectively inhibit 47.25 % of the risk area of coal spontaneous combustion in goaf.

Abstract Streamflow reductions have been attributed to the impacts of soil nutrient availability on plant transpiration, connecting soil biogeochemical and hydrological processes. Here we conducted a plot-scale acid addition experiment and monitored long-term hydrology in a subtropical watershed to provide direct evidence for the underlying mechanisms of these connections. These results showed that acid deposition enhanced plant growth and thus increased plant transpiration in the early treatment period. It indicates that plants can increase their transport of water and nutrients to satisfy physiological demands under continuous acid deposition. Acid deposition mainly contributed to increased evapotranspiration and decreased streamflow at the watershed scale. These results provide complementary evidence of plants adjusting to acid deposition-induced changes in soil nutrient availability and these acclimations result in streamflow reductions at the watershed scale. Our results call for integrating forest biogeochemical feedback into watershed hydrology.

Abstract Background The 2017 Oxford classification of immunoglobulin A nephropathy (IgAN) recently reported that crescents could predict a worse renal outcome. Early prediction of crescent formation can help physicians determine the appropriate intervention, and thus, improve the outcomes. Therefore, we aimed to establish a nomogram model for the prediction of crescent formation in IgA nephropathy patients. Methods We retrospectively analyzed 200 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic regression was applied to screen for influencing factors of crescent formation in IgAN patients. The performance of the proposed nomogram was evaluated based on Harrell’s concordance index (C-index), calibration plot, and decision curve analysis. Results Multivariate logistic analysis showed that urinary protein ≥ 1 g (OR = 3.129, 95%CI = 1.454–6.732), urinary red blood cell (URBC) counts ≥ 30/ul (OR = 3.190, 95%CI = 1.590–6.402), mALBU ≥ 1500 mg/L(OR = 2.330, 95%CI = 1.008–5.386), eGFR

This paper presents a charge pump circuit with a wide output range and low current mismatch applied to phase-locked loops. In this designed structure, T-shaped analog switches are adopted to suppress the non-ideal effects of clock feedthrough, switching time mismatch, and charge injection. A source follower and current splitting circuits are proposed to improve the matching accuracy of the charging and discharging currents and reduce the current mismatch rate. A rail-to-rail high-gain amplifier with a negative feedback connection is introduced to suppress the charge-sharing effect of the charge pump. A cascode current mirror with a high output impedance is used to provide the charge and discharge currents for the charge pump, which not only improves the current accuracy of the charge pump but also increases the output voltage range. The proposed charge pump is designed and simulated based on a 65 nm CMOS process. The results show that when the power supply voltage is 1.2 V, the output current of the charge pump is 100 μA, the output voltage is in the range of 0.2~1 V, and the maximum current mismatch rate and current variation rate are only 0.21% and 1.4%, respectively.

Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases. In this study, a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis, regulating inflammation, and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases. In particular, sodium alginate, calcium silicate and strontium carbonate were used to prepare injectable hydrogels, which was gelled within 10 min. More importantly, this composite hydrogel sustainedly releases bioactive Sr2+ and SiO32− ions within 28 days. The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs, SMCs, C2C12 and Raw 264.7 cells in vitro, and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo. The results showed that the composite hydrogel stimulated angiogenesis, developed new collateral capillaries, and re-established the blood supply. In addition, the bioactive hydrogel directly promoted the expression of muscle-regulating factors (MyoG and MyoD) to protect skeletal muscle from necrosis, inhibited M1 polarization, and promoted M2 polarization of macrophages to reduce inflammation, thereby protecting skeletal muscle cells and indirectly promoting vascularization. Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases.

Abstract Background Plant organs grow in a certain direction and organ twisted growth, a rare and distinctive trait, is associated with internal structure changes and special genes. The twisted branch mutant of Chinese jujube jujube, an important fruit tree native to China and introduced to nearly 50 countries, provides new typical materials for exploration of plant twisted growth. Results In this study, the cytological characteristics and related genes of twisted branches in Chinese jujube were revealed by microscopy observation and transcriptome analysis. The unique coexistence of primary and secondary structures appeared in the twisted parts of branches, and special structures such as collateral bundle, cortical bundles, and internal phloem were formed. Ninety differentially expressed genes of ‘Dongzao’ and its twisted mutant were observed, in which ZjTBL43, ZjFLA11, ZjFLA12 and ZjIQD1 were selected as candidate genes. ZjTBL43 was homologous to AtTBL43 in Arabidopsis, which was involved in the synthesis and deposition of cellular secondary wall cellulose. The attbl43 mutant showed significant inflorescence stem bending growth. The transgenic lines of attbl43 with overexpression of ZjTBL43 were phenotypically normal.The branch twisted growth may be caused by mutations in ZjTBL43 in Chinese jujube. AtIQD10, AtFLA11 and AtFLA12 were homologous to ZjIQD1, ZjFLA11 and ZjFLA12, respectively. However, the phenotype of their function defect mutants was normal. Conclusion In summary, these findings will provide new insights into the plant organ twisted growth and a reference for investigation of controlling mechanisms of plant growth direction.

Abstract The vibration and noise of the permanent magnet synchronous motor (PMSM) is mainly caused by its electromagnetic force. Harmonic currents affect the vibration, and noise performance of PMSM by influencing its electromagnetic force. The regularity of electromagnetic force, vibration, and noise characteristics of PMSM for electric vehicles (EVs) under different working conditions influenced by the harmonic currents is studied. Firstly, the analytical model of electromagnetic force under the action of a harmonic current is derived, and the influence of harmonic currents on the electromagnetic force of PMSM is summarised. Secondly, a multi‐physical field coupled vibration, and noise calculation model considering harmonic currents is established using the finite element method, and the vibration, and noise characteristics of PMSM under different operating conditions are analysed. The results show that the harmonic currents have different patterns of influence on the vibration, and noise of the PMSM due to the different advance angles and the saturation degree of the magnetic material under different working conditions. Finally, the validity of the theoretical analysis is verified by experiments, which has academic significance for vibration, and noise reduction of PMSMs for EVs.

Abstract The desert ecosystem of the Qinghai–Tibet Plateau (QTP) is an important component of China's desert ecosystem. Studying the mechanisms shaping the taxonomic, phylogenetic, and functional beta diversity of plant communities in the QTP desert will help us to promote scientific conservation and management of the region's biodiversity. This study investigated the effects of environmental (including altitude, climate factors, and soil factors) and geographic distances on three facets of beta diversity as well as their turnover and nestedness components based on field survey data. The results showed that turnover components dominate the three facets of beta diversity. However, the turnover contributions to phylogenetic and functional beta diversity were lower than for taxonomic beta diversity. Environmental distance had a greater influence than geographic distance, with the former uniquely explaining 15.2%–22.8% of beta diversity and the latter explaining only 1.7%–2.4%. Additionally, the explanatory power of different factors for beta diversity differed between herbs and shrubs, with environmental distance being more important for the latter. Distance‐based redundancy analysis suggested that soil total potassium content had a substantial impact on the beta diversity of three dimensions, with mean temperature of the coldest month and soil total phosphorus content having a substantial impact on taxonomic and functional beta diversity as well. Our results support that environmental sorting plays a predominant role in shaping plant community composition across QTP desert ecosystems. To maintain the plant diversity of this region, it is crucial to prioritize the conservation of its diverse environmental conditions and actively mitigate its degradation by anthropogenic pressures.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

Background. Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. Purpose. The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. Materials and Methods. We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. Results. The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. Conclusion. JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.

Abstract A favorable environment can induce vegetation overgrowth to exceed the ecosystem carrying capacity, exacerbating water resource depletion and increasing the risk of lagged effects on vegetation degradation. This phenomenon is defined as structural overshoot, which can lead to large‐scale forest mortality and grassland deterioration. However, the current understanding of structural overshoot remains incomplete due to the complex time‐varying interactions between vegetation and climate. Here, we used a dynamic learning algorithm to decompose the contributions of vegetation and climate to drought occurrence, trace the connection between antecedent and concurrent vegetation dynamics, thus effectively capturing structural overshoot. This study focused on the climate‐sensitive hotspot in Northwest China drylands, where significant vegetation greening induced by a warming and wetting climate was detected during 1982–2015, leading to soil moisture deficit and aggravating vegetation degradation risks during droughts. We found that during this period, structural overshoot induced approximately 34.6% of the drought events, and lagged effects accounted for 16.7% of the vegetation degradation for these overshoot drought events. The occurrence of overshoot droughts exhibited an increasing trend over time, which was primarily driven by vegetation overgrowth followed by precipitation variation. Although the severity of overshoot and non‐overshoot droughts were generally comparable in spatial distribution, the impact of overshoot droughts is still becoming increasingly obvious. Our results indicate that the expected intensified overshoot droughts cannot be ignored and emphasize the necessity of sustainable agroecosystem management strategies.

Soil microorganisms play a crucial role in wetland ecosystems, but the specific mechanisms underlying their diversity and network stability across lakeshore wetlands, as well as their importance in microbial ecology, are still poorly understood. Here, we analyzed the biogeographical pattern and network stability of lakeshore wetland microbial communities across a regional scale, and identified the primary factors that influence their composition. The results revealed that α-diversity of wetland bacteria decreased linearly with increasing longitude and latitude, whereas the α-diversity of fungal showed an increasing trend in lakeshore wetlands. Species richness was the principal way that the biogeographical pattern of α-diversity was expressed. The β-diversity of soil microbial in lakeshore wetlands has a significant geographical attenuation pattern. Fungal communities were influenced by stochastic spatial diffusion, while bacterial communities were influenced by deterministic environmental filtration as they transition from semi-arid to arid regions. Community network stability was specifically determined by bacterial and fungal diversity. Structural equation modelling revealed that spatial distance and climate indirectly affect bacterial diversity by influencing soil and plant diversity, which in turn affects feedback network stability. These findings show that the geographical pattern of soil microbial diversity in lakeshore wetlands influences network stability at the spatial scale, offering insights into the adaptation of wetland ecosystem diversity and stability at the regional level.