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Abstract Improving wind power generation efficiency and lowering maintenance and operational costs are possible through the early and efficient diagnosis and repair of surface defects in wind turbines. To solve the lightweight deployment difficulty and insufficient accuracy issues of the traditional detection methods, this paper proposes a high-precision PC-EMA block based on YOLOv8 using partial convolution (PConv) combined with an efficient multiscale attention (EMA) channel attention mechanism, which replaces the bottleneck layer of the YOLOv8 backbone network to improve the extraction of target feature information from each layer of the network. In the feature fusion phase, GSConv, which can retain more channel information, is introduced to balance the model’s complexity and accuracy. Finally, by merging two branches and designing the PConv head with a low-latency PConv rather than a regular convolution, we are able to effectively reduce the complexity of the model while maintaining accuracy in the detection head. We use the WIoUv3 as the regression loss for the improved model, which improves the average accuracy by 5.07% and compresses the model size by 32.5% compared to the original YOLOv8 model. Deployed on Jetson Nano, the FPS increased by 11 frames/s after a TensorRT acceleration.

Study region: Taihu Basin, China Study focus: Floods threaten humans, the environment, economic activity, and infrastructure. In this study, a new trend test and flood-frequency methods were adopted to detect extreme floods and their distributions based on flood-event identification. To fully understand the phased process of the influence of human activities on extreme hydrological processes, 12 copula functions were employed creatively in combined static and dynamic time-varying correlation aspects between extreme precipitation and floods. New hydrological insights for the region: Although both significant and insignificant increasing trends of the annual maximum water level in all three hydrological districts were examined, the periodic oscillations of all the stations were similar. Thus, it was significant to fully detect the periodical variation of floods. Extreme floods occurred mainly in the 1990s, as measured by frequency estimates. Generally, the nonstationary response relationship between heavy rain and an extreme water level was gradually strengthened; that is, a certain magnitude precipitation seemed to induce a greater-intensity flood event as time passed. Through the identification of historical flood events and the analysis of the rise and fall processes of floods, we found that the main reason for variation in the response relationship was the increase in the water level before the rising stage, rather than the water level rising in the Taihu Basin. Our study findings further existing knowledge on the regional flood-control design standard and can ensure the coexistence of humans and water systems in the future.

Dysregulation of lncRNAs is a critical factor in the migration and invasion of tumors. Here our study reveals that lncRNA HIF1A-AS2 is highly expressed in breast cancer tissues and various TNBC cell lines. Moreover, we present compelling evidence supporting the role of HIF1A-AS2 in promoting TNBC cell proliferation, metastasis, invasion, and resistance to paclitaxel treatment. Additionally, our transcriptome sequencing analysis identifies MRPS23 as a potential downstream target protein regulated by HIF1A-AS2 and knockdown of HIF1A-AS2 leads to decreased expression of MRPS23 in TNBC cells. Moreover, MRPS23 exhibits similar effects on enhancing cell proliferation, metastasis, invasion, and paclitaxel resistance in TNBC cells. Furthermore, downregulating HIF1A-AS2 suppresses the enhanced functionality observed in TNBC cells due to upregulated MRPS23 expression. These findings suggest that modulation of MRPS23 protein expression by HIF1A-AS2 may influence cellular processes and paclitaxel sensitivity in TNBC cells.

This paper proposed a Doppler-only point-solution algorithm and analyzed the Doppler positioning performance based on the Starlink constellation.The Doppler positioning accuracy was about 3～6 m.To achieve the meter-level positioning accuracy, the satellite position and velocity errors should be within several meters and several centimeters per second, respectively.The ionospheric delay rates of C-band signal would cause about 2 m error in Doppler positioning.The positioning error would increase by dozens of meters if there were no corrections for the tropospheric errors.To ensure convergence in the LEO-based Doppler positioning, the initial receiver position error should be less than 300 km when the satellites orbit at an altitude of 550 km.

At present, the use of hybrids is becoming more and more widespread, and the study of its traditional cultivation methods also needs to pay attention to the combination of good seed and good methods to achieve maximum economic benefits. “Good seed” is selected from varieties with high production potential and strong resistance to stress. To investigate the effects of sowing dates on biomass accumulation and photosynthetic characteristics of hybrid winter wheat, this study was conducted over two growing seasons (2021–2023) using a hybrid variety, Jingmai 17, and a conventional variety, Jimai 22. Three sowing dates were tested: October 13 (D1), October 23 (D2), and November 2 (D3). Results indicated that Jingmai 17 had a larger leaf area per culm (LAC) post-anthesis, and a lesser variation in SPAD values throughout the middle and late irrigation phases, leading to enhanced photosynthetic performance and higher biomass accumulation at maturity. It outperformed Jimai 22 by approximately 10% in yield. The optimal sowing date (D2) allowed both varieties to maintain a favorable LAC, which supported higher SPAD values, net photosynthetic rates (Pn), and stomatal conductance (Gs) during late grain filling. Correlation analysis revealed a positive relationship between post-anthesis biomass accumulation and yield, suggesting that increased accumulation at this stage underpins yield formation. Under D2 conditions, Jingmai 17 and Jimai 22 achieved yields of 9603.70 kg·ha−1, 9058.68 kg·ha−1 and 8785.44 kg·ha−1, 8294.89 kg·ha−1, respectively, which are 3.4%, 4.6% and 3.4%, 12.4% higher than under D1 conditions, respectively, and 10.7%, 12.4% and 12.8%, 14.5% higher than under D3 conditions, respectively. D1 had higher thousand-grain weight (TGW) but lower number of grains per unit area (GN); D3 had lower TGW, while the GN was not significantly higher, and D2 was effective in improving seed yield. Overall, Jingmai 17 demonstrated significant photosynthetic and yield advantages, maximizing yield potential through optimal interactions among spike number (SN), grain number per spike, and TGW at the October 23 sowing date.

This study explores the impact of internal pre-damage from early drying shrinkage on the delayed ettringite formation (DEF) expansion behavior of cement-based materials subjected to high-temperature processes. Specimens of cement paste and mortar with water-cement (W/C) ratios of 0.4, 0.5, and 0.6 were characterized after curing under relative humidity (RH) conditions of 50, 70, and 100 for 56 days. The parameters assessed were drying shrinkage, dynamic elastic modulus, and free water content. Subsequent DEF expansion over time was quantified, and the underlying mechanism was analyzed using XRD and SEM techniques after 270 days of underwater curing. Results indicate that: (1) a lack of adequate early curing humidity significantly reduces the dynamic elastic modulus with more than a 10% drop in cement paste following 56 days at RH50; (2) a higher W/C ratio and lower early curing humidity lead to more internal damage due to shrinkage, thereby promoting DEF expansion; (3) drying intensifies internal pre-damage in the interfacial transition zone (ITZ), causing an earlier deterioration of DEF expansion in mortar compared to cement paste. However, the presence of aggregates constrains this, leading to lesser DEF expansion in mortar; (4) dynamic elastic modulus changes as measured by ultrasonic methods can quantitatively characterize the extent of deterioration caused by DEF expansion, thus offering a tool for non-destructive testing and DEF expansion deterioration analysis.

After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable, so many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication.

Background: Depressive symptoms (DS) can erode physical and mental health; social support (SS) is considered a buffer for DS and a promoter for improving coping and recovery abilities. However, there is almost no research on the mediating role of negative coping (NC) in SS and DS, especially among firefighters. Methods: A cross-sectional survey was conducted among firefighters in Chongqing, China, and the valid data of 407 firefighters were collected through questionnaires distributed on the WeChat platform in 2020. Statistical Product and Service Solutions (SPSS) 26.0 is used for descriptive statistics and correlation analysis. Structural equation modeling was adopted to analyze the association among SS, NC, and DS. The mediation effect is also evaluated. Results: Firefighters' detection rate of DS is 23.3%, and when they receive more SS were less likely to develop DS. NC was positively correlated with DS (β = 0.54, p

Understanding the complex variations in water use efficiency (WUE) is critical for optimizing agricultural productivity and resource management. Traditional analytical methods often fail to capture the nonlinear and multiscale variations inherent in WUE, where multifractal theory offers distinct advantages. Given its limited application in WUE studies, this paper analyzes the spatiotemporal characteristics and influencing factors of the WUE in Anhui Province from 2001 to 2022 using a multifractal, multiscale approach. The results indicated that the WUE exhibited significant interannual variation, peaking in summer, especially in August (2.4552 gC·mm−1·m−2), with the monthly average showing an inverted “V” shape. Across different spatial and temporal scales, the WUE displayed clear multifractal characteristics. Temporally, the variation in fractal features between years was not prominent, while inter-seasonal variation was most complex in August during summer. Spatially, the most distinct multifractal patterns were observed in hilly and mountainous areas, particularly in regions with brown soil distribution. Rainfall was identified as the primary natural driver influencing regional WUE changes. This study aims to promote the sustainable use of water resources while ensuring the stability of agricultural production within protected farmlands.

Passive internet of things (IoT) is the fundamentally enabling technology of promoting digital transformation and upgrading of industries.In recent years, passive IoT communication technology such as radio frequency identification has been widely used in asset management fields due to its advantages of low cost, zero power consumption, and easy deployment.In this context, passive IoT communication technology and the latest research progress were introduced, the potential evolution prospects of passive IoT were analyzed.Based on that, development bottlenecks and challenges of passive IoT communication were given, a novel passive IoT communication system with deep fusion of the cellular system was presented, and the key technology research directions of this field were proposed.It is aimed to inspire new thoughts for the development of passive IoT communication technology.

In this study, comprehensive investigation of the shrinkage compensation mechanisms of calcium-based expansive agents (CEAs), their effects on the properties of (ultra) high-strength concrete (HSC/UHSC), and the existing problems in applying this methodology was conducted. Analyses showed that the rational use of CEAs under certain conditions could greatly or completely inhibit the development of autogenous shrinkage of HSC/UHSC and significantly reduce the risk of associated cracking. However, it was found that the hydration of the CEAs affected the hydration process of other binders, thereby altering the microstructure of concrete. This, in turn, led to a reduction in mechanical properties such as compressive strength, flexural strength, and elastic modulus, with the rate of reduction increasing as the amount of CEA used increased. Moreover, when attempting to improve the shrinkage compensation effects, increasing the amount of CEA presented a risk of delayed expansion cracking of the HSC/UHSC. Neither the expansion mechanism, expansion conditions, nor the inhibition methods have yet been fully clarified in the current stage. Lastly, newly proposed Ca–Mg composite EAs were outlined, and the research prospects of Ca–Mg composite EAs in HSC/UHSC were explored.

In this study, comprehensive investigation of the shrinkage compensation mechanisms of calcium-based expansive agents (CEAs), their effects on the properties of (ultra) high-strength concrete (HSC/UHSC), and the existing problems in applying this methodology was conducted. Analyses showed that the rational use of CEAs under certain conditions could greatly or completely inhibit the development of autogenous shrinkage of HSC/UHSC, and significantly reduce the risk of associated cracking. However, it was found that the hydration of the CEAs affected the hydration process of other binders, thereby altering the microstructure of concrete. This was in turn observed to lead to a degree of decrease in compressive strength, flexure strength and elastic modulus, and the decrease rate increasing as with the rise in proportion of CEAs. Moreover, when attempting to improve the shrinkage compensation effects, increasing the amount of CEA presented a risk of delayed expansion cracking of HSC/UHSC. Neither the expansion mechanism, expansion conditions, nor the inhibition methods have yet been fully clarified in the current stage. Lastly, newly proposed Ca-Mg composite EAs were outlined, and the research prospects of Ca-Mg composite EAs in HSC/UHSC were explored.

In this paper, a leaky-wave antenna (LWA) array based on substrate integrated waveguide (SIW) is proposed for generating bilateral secant-distributed radiation pattern, which can cover a wide angular range including broadside direction. The LWA array contains two antenna elements and a power recycling network. Each element contains a composite slot constructed by superposing three continuous cosine-shaped slots with different periods in a weighted way, which can achieve a unilateral beam-forming radiation pattern. The power recycling network makes the waves in adjacent antenna elements travel in opposite directions, so the two elements can radiate in reverse directions to generate a bilateral beamforming pattern. The proposed bilateral radiation LWA array is fabricated and measured to verify the efficiency of the design, and the measurement results are in good agreement with those of simulations.

In order to address the requirements of scientific multidisciplinary observation in diverse small-scale regions, we have introduced the Buoy-based Cable Seafloor Observatory System (BCSOS). This system offers a distinct advantage in contexts where the use of shorter cables is feasible, contrasting with the lengthy cables typically necessary for conventional observatories. The BCSOS consists of three primary components: the Real-Time Electric Communication (RTEC) Buoy, the Power Information Transmission System (PITS), and the Seafloor Observation Subsystem (SOS). The RTEC Buoy is equipped with instruments for measuring sea surface parameters and serves as a data and power hub. The PITS, comprising a robust EM cable, connects the buoy to the SOS, which houses instruments for seafloor observations. The system is designed for a maximum water depth of 100 m and has an expected lifespan of about 5 years. The BCSOS prototypes were deployed at the Huangqi Peninsula, Fujian Province, and successfully documented the process during Typhoon Doksuri (international code 2305) at the end of July 2023. The recorded data from the BCSOS revealed a significant increase in wave height and period as the storm approached the Huangqi Peninsula. Additionally, the RTEC buoy exhibited a notable response to the large waves. The data analysis revealed a distinct pattern between the buoy response and the direction of wave propagation across various sea conditions, that the buoy’s angular movement in pitch and roll directions follows a regular elliptical distribution corresponding to different wave propagation directions. Upon thorough evaluation, future enhancements to the system are slated to concentrate on refining its design, with a particular emphasis on bolstering stability and enhancing corrosion resistance. These improvements are aimed at cementing the system’s long-term viability and performance within the challenging marine environment.

Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular disease. It is located in the cytosol and perinuclear space. Missense mutations in this gene have been found to be more prevalent in patients with moyamoya disease compared with that in healthy individuals. Understanding the molecular function of RNF213 could provide insights into moyamoya disease. RNF213 contains a C3HC4-type RING finger domain with an E3 ubiquitin ligase domain and six AAA+ adenosine triphosphatase (ATPase) domains. It is the only known protein with both AAA+ ATPase and ubiquitin ligase activities. Recent studies have highlighted the role of RNF213 in fighting against microbial infections, including viruses, parasites, bacteria, and chlamydiae. This review aims to summarize the recent research progress on the mechanisms of RNF213 in pathogenic infections, which will aid researchers in understanding the antimicrobial role of RNF213.

Summary: The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of β-catenin. Ultimately, the nuclear localization of β-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

With the development of quantum computing, the application of quantum neural networks will be more and more extensive, and its security will also face more challenges. Although quantum communication has high security, quantum neural networks may have many internal and external insecure factors in the process of information transmission, such as noise impact during the preparation of input quantum states, privacy disclosure during transmission, and external attacks on the network structure, which may cause major security incidents. Because of the possible insecurity factors of quantum neural networks, this paper proposes a quantum sampling method to detect the state of quantum neural networks at each stage, so as to judge whether there are security risks in quantum neural networks and thus ensure their security. The method also provides a safe basis for further research on the stability and reliability of quantum neural networks.

ObjectiveTo identify the correlation between finger-to-floor distance(FFD) and the spinal function indices and disease activity scores of ankylosing spondylitis (AS) via a multicentre case–control study, and to calculate the optimal cutoff value of FFD using statistical methods.MethodsPatients with AS and healthy individuals were recruited, and the FFD and other spinal mobility values were measured. The correlation between the FFD and the Bath Ankylosing Spondylitis Metric Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) was analyzed using Spearman rank correlation analysis. Receiver operating characteristic (ROC) curves of FFD stratified by gender and age were drawn and their optimal cutoff values were determined.ResultsA total of 246 patients with AS and 246 healthy subjects were recruited. The FFD was strongly correlated with BASMI (r = 0.72, p

Wireless Sensor Networks (WSNs) have emerged as an efficient solution for numerous real-time applications, attributable to their compactness, cost-effectiveness, and ease of deployment. The rapid advancement of 5G technology and mobile edge computing (MEC) in recent years has catalyzed the transition towards large-scale deployment of WSN devices. However, the resulting data proliferation and the dynamics of communication environments introduce new challenges for WSN communication: (1) ensuring robust communication in adverse environments and (2) effectively alleviating bandwidth pressure from massive data transmission. In response to the aforementioned challenges, this paper proposes a semantic communication solution. Specifically, considering the limited computational and storage resources of WSN devices, we propose a flexible Attention-based Adaptive Coding (AAC) module. This module integrates window and channel attention mechanisms, dynamically adjusts semantic information in response to the current channel state, and facilitates adaptation of a single model across various Signal-to-Noise Ratio (SNR) environments. Furthermore, to validate the effectiveness of this approach, the paper introduces an end-to-end Joint Source Channel Coding (JSCC) scheme for image semantic communication, employing the AAC module. Experimental results demonstrate that the proposed scheme surpasses existing deep JSCC schemes across datasets of varying resolutions; furthermore, they validate the efficacy of the proposed AAC module, which is capable of dynamically adjusting critical information according to the current channel state. This enables the model to be trained over a range of SNRs and obtain better results.

The absorption and scattering of light in water usually result in the degradation of underwater image quality, such as color distortion and low contrast. Additionally, the performance of acquisition devices may limit the spatial resolution of underwater images, resulting in the loss of image details. Efficient modeling of long-range dependency is essential for understanding the global structure and local context of underwater images to enhance and restore details, which is a challenging task. In this paper, we propose an agent-guided non-local attention network using a multi-color space for underwater image enhancement and super-resolution. Specifically, local features with different receptive fields are first extracted simultaneously in the RGB, Lab, and HSI color spaces of underwater images. Then, the designed agent-guided non-local attention module with high expressiveness and lower computational complexity is utilized to model long-range dependency. Subsequently, the results from the multi-color space are adaptively fused with learned weights, and finally, the reconstruction block composed of deconvolution and the designed non-local attention module is used to output enhanced and super-resolution images. Experiments on multiple datasets demonstrated that our method significantly improves the visual perception of degraded underwater images and efficiently reconstructs missing details, and objective evaluations confirmed the superiority of our method over other state-of-the-art methods.

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-γ by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-γ. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated.MethodsIn this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown.ResultsGNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells.ConclusionGNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

Bullying is one of the most common forms of school violence. Although the negative impact of bullying victimization on students' mental health outcomes has been well documented, the underlying mechanism of the association lacks investigation, especially in the rural Chinese boarding school context. This study examined (1) the associations between bullying victimization and mental health (i.e., subjective well-being and depressive symptoms), and (2) the mediating roles of cognitive reappraisal and expressive suppression in Chinese boys and girls from a rural boarding school in Gansu province. This cross-sectional study involved 655 Chinese rural adolescents in a boarding school in Gansu province (M[subscript age] = 15.68 years, SD = 0.96; 408 girls). Structural equation modelling (SEM) was used to evaluate the mediation model, and the bootstrap approach was used to test the indirect effect. The total effects from bullying victimization to subjective well-being (for boys: [beta] = - 0.32, p < 0.001; for girls: [beta] = - 0.35, p < 0.001) and depressive symptoms (for boys: [beta] = 0.29, p < 0.001; for girls: [beta] = 0.32, p < 0.001) were significant in boys and girls. The indirect effect of bullying victimization through cognitive reappraisal on subjective well-being ([beta] = -0.11, 95% CI - 0.17 to - 0.06) and depressive symptoms ([beta] = 0.09, 95% CI 0.05 to 0.15) was significant in girls, whereas the indirect effect was not significant in boys. The indirect effect through expressive suppression was not significant in both boys and girls. This study extends the literature by demonstrating the underlying mechanism linking bullying victimization to poor mental health. Gender differences were identified regarding the indirect effects. These findings have cultural implications for bullying victimization intervention on Chinese rural adolescents' mental health.

Drip irrigation can reduce water and fertilizer use; however, the frequency of topdressing required for drip irrigation for wheat in the Huang-Huai-Hai region is still unclear. Through two continuous wheat season field experiments, yield related traits under traditional surface irrigation (border irrigation) and three drip fertilization frequencies (DF2, DF3, DF4, that was, topdressing water and fertilizer twice, three or four times in the same way during the growth period) of three wheat cultivars (Jimai 22, Jimai 20, Shiluan 02-1) were studied. Increasing the frequency of drip irrigation fertilization could prolong the time of high-level photosynthesis, increase the dry matter distribution amount (DMDA) of stems and leaves, and add the weight of 1000 grains; it could increase the DMDA and nitrogen distribution amount (NDA) of the stems, leaves, and grains of Jimai 22, forming higher harvest index (HI) and nitrogen harvest index (NHI), but could reduce the DMDA of the grains of Jimai 20 and Shiluan 02-1, increasing NDA, reducing the harvest index but forming a higher nitrogen harvest index. The increase in drip irrigation fertilization frequency can improve protein content, increase grain number per spike, decrease spike number, improve the yield of medium gluten wheat, and improve nitrogen partial productivity and water use efficiency, while strong gluten wheat has a decrease in yield, nitrogen partial productivity, and water use efficiency. In summary, medium gluten wheat is more suitable for higher fertilization frequency in the Huang-Huai-Hai wheat region, while strong gluten wheat is the opposite.

Abstract Background Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. Methods We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. Results The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. Conclusions The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

Background To investigate the safety, efficacy, and follow-up outcomes of microwave ablation (MWA) in patients with breast fibroadenoma. Methods An institutional review board-approved this study of patients treated with MWA for breast fibroadenoma from October 2017 to March 2019. Clinical features of patients and breast fibroadenoma were analyzed. At follow-up all patients received physical examination and ultrasound imaging. Results In total, 171 patients with 271 lesions were enrolled. The mean lesion diameter was 1.35 ± 0.47 cm. The results revealed differential lesion states, including stability, enlargement, reduction, and complete regression, at 1-6, 6-12, and >12 months of follow-up. The size was reduced in 22.14% (31/140), 26.36% (29/110), and 36.36% (16/44) of the lesions at 1-6, 6-12, and >12 months of follow-up, respectively. The proportion of lesions with complete regression was 24.29% (34/140) at 1-6 months, 45.45% (50/110) at 6-12 months, and 40.91% (18/44) at >12 months of follow up. There was no significant relationship between the curative effect and age, lesion location, and blood flow in patients with breast fibroadenoma after MWA (p > .05), but there was statistically significant relationship with lesion diameter (categorized as

A high-accuracy unsupervised classification model is developed in a multimode self-interference microring resonator (SIMRR). For the SIMRR, there are many whispering gallery modes (WGMs) present. Each of these resonance modes supported by the SIMRR has a different response to different target parameters, so that the SIMRR-based sensor has the super capability to distinguish between multiple components. In the classification model, principal component analysis (PCA) is firstly used to reduce the dimensionality of this multimode sensing information from the SIMRR-based sensor. When the original higher-dimensional data points are projected onto the lower-dimensional data with only the first few principal components, they can be easily categorized into several different types by using density-based spatial clustering of application with noise (DBSCAN) algorithm. As an example, the unsupervised classification method is numerically validated based on a designed three-gas SIMRR-based sensor. The numerical results prove that the classification model can achieve an ultra high classification accuracy for the designed three-gas sensor with more than 60 dB in signal-to-noise ratio.

Breast cancer (BCa) is the most common malignancy in women and claudin-low breast cancer (CL-BCa) is a newly identified BCa subtype characterized by low expression of claudin 3&4&7. However, the hub genes associated with the recruitment of immune cells into CL-BCa were rarely described. This study aimed at exploring the differentially expressed hub genes associated with tumor-infiltrating immune cells in CL-BCa by a multi-approach bioinformatics analysis. The top 200 genes associated with CL-BCa were screened in the METABRIC dataset; the PPI network was constructed using STRING and Cytoscape; tumor-infiltrating immune cells were analyzed by TIMER 2.0; and the correlation of feature cytokines and claudins on survival was examined in METABRIC and TCGA datasets. Consequently, we found that the fraction of tumor-infiltrating immune cells, especially CD8+T cells and macrophages, increased in the CL-BCa. Differentially expressed cytokines (CCL5, CCL19, CXCL9 and CXCL10) were related to the overall survival, and their expression levels were also examined both in tumor tissues of CL-BCa patients by IHC and in typical CL-BCa cell lines by qPCR. Moreover, the BCa patients with low expression of these differentially expressed claudins (CLDN8, CLDN11 and CLDN19) showed a worse overall survival. This study sheds light on molecular features of CL-BCa on immune microenvironments and contributes to identification of prognosis biomarkers for the CL-BCa patients.

Wind farms have gained wide attention due to unlimited resources and clean energy. Considering that wind turbine systems are always in harsh conditions, subsystem failures could reduce the reliability of wind turbine systems. At present, the maintenance behaviors for wind turbine systems are various (e.g., corrective maintenance, preventive maintenance) when reliability is reduced below the threshold. Considering the maintenance cost and downtime, it is impossible to repair each component in a timely manner. One of the key problems is dividing components into maintenance groups to improve maintenance efficiency. In this paper, a grouping maintenance policy considering the variable cost (GMP-VC) is proposed to improve direct-drive permanent magnet (DPM) turbine systems. Grouping modes are proposed to fully consider the stated transition probability of turbine components and the variable cost of turbine systems. A maintenance model is formulated to select components as members of the group based on a RIM-VC index. An instance is given to verify the proposed GMP-VC method. The result indicates that the proposed maintenance policy may save maintenance costs over baseline plans.

Urban road networks have promoted high-quality travel for residents by increasing connectivity and intelligence. But road congestion has not been effectively alleviated, causing a loss of time and energy. At present, the recovery of urban road networks mainly considers removing the failed edges. Considering the recovery cost and time, it is important to take active maintenance behavior to restore these networks. One of the key problems is dispatching traffic workers reasonably to achieve timely maintenance. In this paper, a flow-distribution-based process and execution (FD-PE) model is established for solving congestion. The maintenance centers (MC) study the reasons for and spread of congestion by edge flow. Based on the genetic algorithm (GA), two models of maintenance for urban road networks are developed, which include a single MC-centered dispatching plan and the co-scheduling of MCs. Both models aim at minimizing recovery time and allocating maintenance resources. The road network in Zhengzhou is borrowed as a case to explain the feasibility of the proposed models. The results show that on the premise of dividing network regions, it is reasonable to take a single MC to recover congestion. Compared with a single MC, the co-scheduling of MCs may save more time.

Cardio-cerebrovascular diseases (CVDs) are a serious threat to human health and account for 31% of global mortality. Ligusticum chuanxiong Hort. (CX) is derived from umbellifer plants. Its rhizome, leaves, and fibrous roots are similar in composition but have different contents. It has been used in Japanese, Korean, and other traditional medicine for over 2000 years. Currently, it is mostly cultivated and has high safety and low side effects. Due to the lack of a systematic summary of the efficacy of CX in the treatment of CVDs, this article describes the material basis, molecular mechanism, and clinical efficacy of CX, as well as its combined application in the treatment of CVDs, and has been summarized from the perspective of safety. In particular, the pharmacological effect of CX in the treatment of CVDs is highlighted from the point of view of its mechanism, and the complex mechanism network has been determined to improve the understanding of CX’s multi-link and multi-target therapeutic effects, including anti-inflammatory, antioxidant, and endothelial cells. This article offers a new and modern perspective on the impact of CX on CVDs.

Immune-mediated skin diseases have a high prevalence and seriously affect patients’ quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Gold nanoclusters fabricated by using peptides (pep-AuNCs) have appeared as potential biomedical nanomaterials because of their excellent biocompatibility, ease of fabrication and unique physicochemical properties. Glutathione (GSH) is an endogenous tripeptide and has been used for lightening the skin color. Therefore, we fabricated a well-defined gold nanocluster with GSH as an example to explore the immunomodulatory effect of AuNCs on a TNF-α-treated human keratinocyte cell line (HaCaT) in vitro, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis (ICD) model and the oxazolone (OXA)-induced psoriatic model in vivo. The results indicated that topically applied AuNCs successfully attenuated the severity of ICD and psoriasis-like lesions. In vitro and in vivo, AuNCs effectively inhibited the abnormal activation of the NF-κB pathway and the consequent overexpression of proinflammatory cytokines in keratinocytes. In particular, the transactivation of IL-17A, the most important cytokine in psoriasis pathology, was effectively inhibited by AuNCs treatment. In addition, AuNCs did not show any obvious cytotoxicity in HaCaT cells at doses even up to 100 µM and did not induce any irritation in the healthy skin and major organs, which indicated their favorable biosafety. These results indicate that biocompatible pep-AuNCs might be a promising gold-based nanomedicine for the treatment of inflammatory skin diseases.

Background Sophora alopecuroides L. (S. alopecuroides L.) is a perennial herb widely distributed throughout Xinjiang, China. It is characterized by its rapid diffusion ability. Methods To reveal the ecological mechanism of the rapid spread of S. alopecuroides, and to elucidate the ecological stoichiometric characteristics of C, N, and P (and the influencing factors) in the leaves of S. alopecuroides, leaves were sampled from four habitats—forest, roadside, farmland, and desert—across the Yili River Valley. The variation rules of the ecological stoichiometric characteristics of C, N, and P in the leaves of S. alopecuroides were analyzed. Correlations between the ecological stoichiometric characteristics of leaves and environmental factors were examined using redundancy analysis (RDA). Results (1) The C, N, and P contents of S. alopecuroides leaves were 391.30–533.10 g/kg, 8.90–43.14 g/kg, and 0.71–2.04 g/kg, respectively, and the C/N, C/P, and N/P ratios were 10.34–4.94, 209.05–698.73, and 10.78–31.43 respectively. (2) The C content and C/P ratio of S. alopecuroides leaves were the highest in the desert habitat, leaf N content and N/P ratio were the highest in the forest habitat, leaf P content was the highest in the farmland habitat, and the leaf C/N ratio was the highest in the roadside habitat. (3) RDA showed that available potassium (AK) and pH were the main factors affecting the ecological stoichiometric characteristics of S. alopecuroides leaves in Yili Valley (p ≤ 0.05), and these factors were positively correlated with C, N, P, and N/P, and negatively correlated with C/P and C/N. AK was the dominant factor that affected the P content of S. alopecuroides leaves, and appropriate reduction of K fertilizer would be conducive to restraining the spread of S. alopecuroides. Soil C, N, P, and K content, soil organic matter (OM), nitrate nitrogen (NO3−-N), ammonium nitrogen (NH4+-N), and AK had no significant effect on the ecological stoichiometric characteristics of leaves (p > 0.05).

Soil moisture (SM) plays an important role in regulating terrestrial–atmospheric water circulation and energy balance. Most of the existing studies have explored the dynamic patterns of SM based on experimental methods. However, the analysis of large-scale regions and long-term SM sequences was limited. Alternatively, satellite remote sensing data is a potential source for SM analysis for large-scale basins. Therefore, the SM data from the European Space Agency (ESA) Climate Change Initiative (CCI) from 2000 to 2015 is used in this paper to analyze the SM spatial-temporal changes in the Yellow River Basin (YRB). Further, the Normalized Difference Vegetation Index (NDVI) and meteorological data are used to explore the relationships between SM and NDVI, precipitation, air temperature, and wind speed, respectively. The results showed that the overall trend of SM in the YRB was decreasing from southeast to northwest during the past 16 years. The upper reaches of the YRB had shown a humid trend, with a value of 0.00047 m3·m−3·year−1, mainly due to the increase in precipitation; there was an obvious drought trend in the middle reaches of the YRB, especially in Shanxi Province and Henan Province, with a value of −0.00030 m3·m−3·year−1, which may be owed to vegetation greening increasing the soil evaporation. Overall, it is determined that the main factors influencing SM changes were NDVI and precipitation, followed by air temperature and wind speed. This study can provide a scientific basis for the spatial-temporal distribution characteristics and attributions of SM in the YRB over a long time series.

Trichinella spiralis (T. spiralis) is a widely distributed pathogenic microorganism that causes trichinellosis, a disease that has the potential of causing severe harm to their host. Numerous studies have demonstrated that autophagy can be triggered by microbial infection, such as bacteria, viruses, protozoa, and parasitic helminths. However, it's still unknown whether autophagy can facilitate host resistance to T. spiralis infection. The present study examined the role of autophagy in striated muscle cell transformation following infection with T. spiralis in BALB/c mice. Transmission electron microscopy (TEM) was used to detect the production of the host diaphragm autophagosome after T. spiralis infection, and changes in the protein and transcriptional levels of autophagic marker proteins were also detected. The significance of autophagy in T. spiralis infection, namely inhibition of T. spiralis growth, was preliminarily evaluated by conducting in vivo experiments using autophagy inhibitors. Besides, we studied the effect of excretory-secretory products (ES) of T. spiralis on autophagy of C2C12 myoblasts. The changes in protein and gene expression levels in autophagy-related pathways in vitro and in vivo were measured as further evidence. The results showed that T. spiralis infection induced autophagy in the host muscle cells. Meanwhile, ES inhibited autophagy of myoblasts in vitro, but this did not affect the cell viability. The upregulation and downregulation of autophagy-related factors in skeletal muscle cells may indicate an adaptive mechanism providing a comfortable niche for the parasite.

Chemoresistance is considered to be a major cause of the recurrence and metastasis of breast cancer (BC). LncRNA SNHG7 has been reported to be upregulated in breast cancer and to promote tumor progression and metastasis. Nevertheless, the function and potential regulatory mechanism of SNHG7 in BC drug resistance are still largely unclear. This study indicated that SNHG7 was highly expressed in chemoresistant BC tissues and cells. Upregulated SNHG7 might predict a low pCR rate and poor clinical outcome in BC patients. Knockdown of SNHG7 enhanced drug sensitivity and drug-induced apoptosis in chemoresistant BC cells. In terms of the mechanism, miR-34a was found to be a target of SNHG7 and its expression in breast cancer tissues and chemoresistant cell lines was negatively correlated with SNHG7 expression. Importantly, sh-SNHG7 upregulated miR-34a expression, reduced the percentages of CD44+/CD24−cells, and inhibited sphere-formation and stem cell factor (Oct4, Nanog, SOX2) expression. Functional loss experiments showed that the repressive effect of SNHG7 knockdown on BC cell stemness was partially reversed by transfection with miR-34a inhibitors. In summary, this study indicated that SNHG7 contributed to the chemoresistance of BC and mediated chemoresistance and cancer stemness by sponging miR-34a.

Electrochemical (EC) and photoelectrochemical (PEC) water splitting represent promising strategies for renewable energy conversion and fuel production and require design of efficient catalysts for the oxygen evolution reaction (OER). Herein, we report the synthesis of two-dimensional (2D) Co-based metal organic framework (Co-MOF) nanosheets and their bifunctional catalytic properties for both EC and PEC OER. Benefiting from the large surface area and abundant isolated metal active sites, the Co-MOF nanosheets exhibited excellent OER activity and stability. The efficient electron–hole generation and separation of the nanosheets, owing to dimensional confinement, contributed to an improved visible light response in PEC OER. This study presents a new strategy to design EC/PEC bifunctional catalyst utilizing unique structural and electronic features of 2D MOF.

A facile sol-gel method was proposed to prepare fluorine-containing hydrophobic SiO2 coating using trifluoroethanol (TFE) as the dispersant and hydrophobic modifier simultaneously. FTIR and XPS analysis indicated that CF3 groups were incorporated onto the surface of SiO2 particles. The resultant SiO2 coating possessed excellent hydrophobicity with a water contact angle (WCA) of 145°. This provides a new method for the preparation of fluorine-containing sol-gel SiO2 coating without the expensive long-chain alkyl fluorosilane.

Background A wetland is a special ecosystem formed by the interaction of land and water. The moisture content variation will greatly affect the function and structure of the wetland internal system. Method In this paper, three kinds of wetlands with different flooding levels (Phragmites australis wetland (long-term flooding), Calamagrostis epigeios wetland(seasonal flooding) and Ditch millet wetland (rarely flooded)) in Ili Valley of Xinjiang China were selected as research areas. The changes of microbial biomass carbon, soil physical and chemical properties in wetlands were compared, and redundancy analysis was used to analyze the correlation between soil physical and chemical properties, microbial biomass carbon and enzyme activities (soil sucrase, catalase, amylase and urease). The differences of soil enzyme activities and its influencing factors under different flooding conditions in Ili Valley were studied and discussed. Result The results of this study were the following: (1) The activities of sucrase and amylase in rarely flooded wetlands and seasonally flooded wetlands were significantly higher than those in long-term flooded wetlands; the difference of catalase activity in seasonal flooded wetland was significant and the highest. (2) Redundancy analysis showed that soil organic carbon, dissolved organic carbon, total phosphorus and soil microbial biomass carbon had significant effects on soil enzyme activity (p

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are challenging diseases with the high mortality in a clinical setting. Baicalin (BA) is the main effective constituent isolated from the Chinese medical herb Scutellaria baicalensis Georgi, and studies have proved that it has a protective effect on ALI induced by lipopolysaccharide (LPS) due to the anti-inflammatory efficacy. However, BA has low solubility which may limit its clinical application. Hence, we prepared a novel drug delivery system—Baicalin liposome (BA-LP) in previous research—which can improve some physical properties of BA. Therefore, we aimed to explore the effect of BA-LP on ALI mice induced by LPS. In pharmacokinetics study, the values of t1/2 and AUC0-t in the BA-LP group were significantly higher than that of the BA group in normal mice, indicating that BA-LP could prolong the duration time in vivo of BA. The BA-LP group also showed a higher concentration in lung tissues than the BA group. Pharmacodynamics studies showed that BA-LP had a better effect than the BA group at the same dosage on reducing the W/D ratio, alleviating the lung injury score, and decreasing the proinflammatory factors (TNF-α, IL-1β) and total proteins in bronchoalveolar lavage fluids (BALF). In addition, the therapeutic effects of BA-LP showed a dose-dependent manner. Western blot analysis indicated that the anti-inflammatory action of BA could be attributed to the inhibition of the TLR4-NFκBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.

This study aims at developing a green sustainable bio-inspired composite film by combining the flexible chitin/silk fibroin matrix (CT/SF) and the rigid cellulose nanocrystals (CNC) with the multi-layer chiral nematic structure. The effects of CNC concentration on the chemical bonding, optical- and micro-morphology, thermal stability and mechanical properies of chitin/silk fibroin/cellulose nanocrystal (CT/SF/CNC) were comprehensively investigated. The results indicate that a critical concentration for CNC at 2 wt% can display the obvious iridescent color domains of biocomposite films with potential optical functional property. There is a color shift from blue to yellow-red corresponding to the higher concentrations at 3.5 and 5.0 wt%, respectively. The concentration of CNC also affects the transition of conformation of SF from the random to the β -turn as well as the bonding ability between SF and CT. The CT/SF/CNC-3.5 wt% with the excellent optical and mechanical properties as well as the improved thermal stability breaks the conventional conflict between increased strength and compromised ductility. Its tensile strength and elongation at break effectively elevate by 282% and 42%, respectively.

Sea cucumber (Apostichopus japonicus) is mainly cultured in the coastal zone, where it is easily threatened by accidental oil spills. Chemical dispersant is one of the efficient oil spill responses for mitigating the overall environmental damage of oil spills. However, the impact of crude oil and chemical dispersants on sea cucumber is less well known. Hence, the present study focused on exploring the antioxidant response and oxidative stress in the respiratory tree of sea cucumber following exposure to GM-2 chemical dispersant (DISP), water-accommodated fractions (WAF), and chemically enhanced WAF (CEWAF) of Oman crude oil for 24 h. Results manifested that WAF exposure caused a significant increase in the reactive oxygen species (ROS) level (5.29 ± 0.30 AU·mgprot−1), and the effect was much more obvious in CEWAF treatment (5.73 ± 0.16 AU·mgprot−1). Total antioxidant capacity (T-AOC), as an important biomarker of the antioxidant defense capacity, showed an increasing trend following WAF exposure (0.95 ± 0.12 U·mgprot−1) while a significant reduction in T-AOC was observed following CEWAF exposure (0.23 ± 0.13 U·mgprot−1). Moreover, we also evaluated the oxidative damage of the macromolecules (DNA, protein, and lipid), and our results revealed that the presence of chemical dispersant enhanced oxidative damage caused by crude oil to sea cucumber.

2-Thiohydantoin derivatives are produced by heating a mixture of thiourea and an α-amino acid. The method described offers the advantages of simplicity, low cost, easy work-up and scalability.

Checkpoint/restart has been an effective mechanism to achieve fault tolerance for many long-running scientific applications. The common approach is to save computation states in memory and secondary storage for execution resumption. However, as the GPU plays a much bigger role in high performance computing, there is no effective checkpoint/restart scheme yet due to the difficulty of the GPU computation state handling. This paper proposes an application-level checkpoint/restart scheme to save and restore GPU computation states in annotated user programs. A pre-compiler and run-time support module are developed to construct and save states in CPU system memory dynamically, whereas secondary storage can be utilized for scalability and long-term fault tolerance. CUDA programs with complicated computation states are supported. State-related variables dissipated in various memory units are collected. Both stack and heap are duplicated at application level for state construction. Experimental results have demonstrated the effectiveness of the proposed scheme.