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AbstractContext Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain.Objective To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP).Materials and methods Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR).Results Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively.Conclusions The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Background: Closed-loop electronic medication management systems are effective measures for preventing medication errors (MEs). However, there is limited evidence supporting this, and few studies have evaluated the long-term effects of these systems on safe medication. Objective: To evaluate the long-term effects of implementing a closed-loop medication order executive system on the safe clinical use of medications. Design: A quasi-experimental design. Method: Data from 2017 to 2023 were extracted and retrospectively analyzed. The primary outcome indicator was the ME rate. Secondary outcome indicators were the accuracy of order verification and patient identification and the implementation rate of fresh medicine dispensing. The autoregressive integrated moving average (ARIMA) model in time-series analysis was used to evaluate the level and trend changes in ME rates using SPSS 25.0 before and after system implementation. Root cause analysis and descriptive statistics were used to assess changes in types, stages, and causes of ME rates. The independent samples t -test was used to analyze secondary outcomes. Results: Overall, 295 MEs were reported with a mean of 0.26 ± 0.26 ME rates per month during 2017–2023. The ARIMA model showed a decrease in the average level of ME rates after system implementation, with no statistically significant decrease in the long term, and a significant drop in the ME rate in the short and medium term ( p

The precise segmentation of Zanthoxylum bungeanum clusters is crucial for developing picking robots. An improved Mask R-CNN model was proposed in this study for the segmentation of Zanthoxylum bungeanum clusters in natural environments. Firstly, the Swin-Transformer network was introduced into the model’s backbone as the feature extraction network to enhance the model’s feature extraction capabilities. Then, the SK attention mechanism was utilized to fuse the detailed information into the mask branch from the low-level feature map of the feature pyramid network (FPN), aiming to supplement the image detail features. Finally, the distance intersection over union (DIOU) loss function was adopted to replace the original bounding box loss function of Mask R-CNN. The model was trained and tested based on a self-constructed Zanthoxylum bungeanum cluster dataset. Experiments showed that the improved Mask R-CNN model achieved 84.0% and 77.2% in detection mAP50box and segmentation mAP50mask, respectively, representing a 5.8% and 4.6% improvement over the baseline Mask R-CNN model. In comparison to conventional instance segmentation models, such as YOLACT, Mask Scoring R-CNN, and SOLOv2, the improved Mask R-CNN model also exhibited higher segmentation precision. This study can provide valuable technology support for the development of Zanthoxylum bungeanum picking robots.

Buckwheat is a globally recognized, nutritionally rich crop with robust adaptability, serving as a multi-purpose plant for its health benefits. Achieving precise and mechanized plot seed harvesting is a critical step in obtaining accurate results in breeding experiments. However, plot breeding requires no seed retention, no mixing, and ensures no accumulation of seed in the threshing unit. A self-cleaning technology was developed to prevent seed retention, mixing, and accumulation in the multistage tangential cylinder threshing unit. The newly designed cleaning system has five air inlets and a centrifugal fan for pneumatic cleaning. CFD simulations were conducted for each inlet position, coupled with four varying inlet velocities and the rotation speed of the main threshing cylinder. During the post-processing stage of the CFD modeling, a line consisting of fifty points was drawn beneath the threshing drums, and the air velocity at these points was recorded. The optimal configuration of inlet position, inlet air velocity, and main threshing drum rotation speed for efficient cleaning was identified based on the ratio of points beneath the drums where the airflow speed surpassed the suspension speed of buckwheat to the points where the airflow speed was lower than the suspension speed of buckwheat. The optimal configuration for ''inlet_1'' was identified based on the suspension velocity of buckwheat grain, with an inlet velocity of 4 m/s and a main threshing drum speed of 450 rpm.

As one of the critical branches of medical image processing, the task of segmentation of breast cancer tumors is of great importance for planning surgical interventions, radiotherapy and chemotherapy. Breast cancer tumor segmentation faces several challenges, including the inherent complexity and heterogeneity of breast tissue, the presence of various imaging artifacts and noise in medical images, low contrast between the tumor region and healthy tissue, and inconsistent size of the tumor region. Furthermore, the existing segmentation methods may not fully capture the rich spatial and contextual information in small-sized regions in breast images, leading to suboptimal performance. In this paper, we propose a novel breast tumor segmentation method, called the transformer and graph convolutional neural (TS-GCN) network, for medical imaging analysis. Specifically, we designed a feature aggregation network to fuse the features extracted from the transformer, GCN and convolutional neural network (CNN) networks. The CNN extract network is designed for the image's local deep feature, and the transformer and GCN networks can better capture the spatial and context dependencies among pixels in images. By leveraging the strengths of three feature extraction networks, our method achieved superior segmentation performance on the BUSI dataset and dataset B. The TS-GCN showed the best performance on several indexes, with Acc of 0.9373, Dice of 0.9058, IoU of 0.7634, F1 score of 0.9338, and AUC of 0.9692, which outperforms other state-of-the-art methods. The research of this segmentation method provides a promising future for medical image analysis and diagnosis of other diseases.

Loquat leaves exhibiting obvious yellowing, blistering, mosaic, leaf upward cupping, crinkle, and leaf narrowing were identified in Panzhihua City, Sichuan Province, China. High-throughput sequencing (HTS) with the ribo-depleted cDNA library was employed to identify the virome in the loquat samples; only tomato mosaic virus (ToMV) and citrus exocortis viroid (CEVd) were identified in the transcriptome data. The complete genome sequence of ToMV and CEVd were obtained from the loquat leaves. The full-length genome of the ToMV-loquat is 6376 nt and comprises four open reading frames (ORFs) encoding 183 kDa protein, RNA-dependent RNA polymerase (RdRp), movement protein (MP), and coat protein (CP), respectively. A pairwise identity analysis showed that the complete sequence of the ToMV-loquat had a nucleotide identity between 98.5 and 99.3% with other ToMV isolates. A phylogenetic analysis indicated that ToMV-loquat was more closely related to ToMV-IFA9 (GenBank No. ON156781). A CEVd sequence with 361 nt in length was amplified based on the HTS contigs, sequence alignment indicated CEVd-loquat had the highest identity with the strain of CEVd-Balad (GenBank No. PP869624), phylogenetic analysis showed that CEVd-loquat was more closely related to CEVd-lettuce (GenBank No. ON993891). This significant discovery marks the first documentation and characterization of ToMV and CEVd infecting loquat plants, shedding light on potential threats to loquat cultivation and providing insights for disease management strategies.

Economic analysis of the tourism industry is a critical tool for local industries and governments to estimate, understand, and forecast the tourism potential and economic performance of a destination, especially amidst a crisis such as the COVID-19 pandemic. In this study, we take Macao as a case study, perform an analysis using an input-output framework. By constructing a tourism satellite account and a dynamic stochastic general equilibrium model, we estimate the contribution of the tourism industry to the economy of Macao and assess the ramifications of several government policies to mitigate the impact of COVID-19. Our findings provide the Macao government and local industrial stakeholders with critical information for pandemic mitigation and recovery strategies.

Abstract Background Stress hyperglycemia ratio (SHR) is significantly related to adverse cardiovascular clinical outcomes and increased in-hospital mortality. However, the relationship between SHR and coronary artery disease (CAD) severity has hitherto not been reported. This study sought to clarify the relationship between the SHR and CAD severity of individuals with different glucose metabolic statuses. Methods A retrospective analysis was performed on 987 patients who underwent coronary angiography (CAG) from October 2020 to May 2022. Based on CAG results, patients were divided into single-vessel CAD and multi-vessel CAD groups. All subjects were stratified into three groups according to the tertiles of the SHR (T1 group: SHR

Mechanical weeding is an important technical means for organic and regenerative agricultural systems. Current weed control equipment has a variety of problems, such as difficulty adapting to high-stalk crops and poor operational quality. A high-clearance mid-tillage weeder (HMTW) has been developed to meet the mechanical weed control needs of high-stalk crops. The weeder mainly comprises a suspension device, a frame, parallel four-rod profiling mechanisms, weeding operation components, and depth-limiting soil-cutting devices. Based on the agronomic requirements of dryland flat planting, the overall structure of the HMTW was determined, and the weeding unit and flat shovel hoe were designed. Theoretical analysis was conducted on the depth stability of the HMTW, and an optimization mathematical model of the HMTW was established to further improve its tillage depth stability for agronomic requirements. The optimization objective was to minimize the deflection angle (∆β) of the profiling rod on a vertical plane, and the parameters of the parallel four-rod profiling mechanism were optimized. Based on the optimized structural parameters, a prototype of the HMTW was developed and evaluated. The test results show that the optimized HMTW exhibited a good weeding effect, and the tillage depth stability was within the design operating range. When the driving speed was 1.0 m/s and the tillage depth was 8 cm, the weed removal rate, seedling injury rate, seedling burial rate, and qualified rate of tillage depth were 90.8%, 3.2%, 4.1%, and 94%, respectively. The proposed HMTW successfully meets the weeding agronomic requirements of high-stalk crops for dryland farming, and the performance analysis and optimization models provide technical references for the design and development of such structures.

In this paper, we study the numerical solution of a parabolic complementarity problem which is a widely used model in many fields, such as option pricing, risk measures, etc. Using a power penalty method we represent the complementarity problem as a nonlinear parabolic partial differential equation (PDE). Then, we use the trapezoidal rule as the time discretization, for which we have to solve a nonlinear equation at each time step. We solve such a nonlinear equation by the fixed-point iteration and in this methodology solving a tridiagonal linear system is the major computation. We present an efficient backward substitution algorithm to handle this linear system. Numerical results are given to illustrate the advantage of the proposed algorithm (compared to the built-in command backslash in Matlab) in terms of CPU time.

Abstract Background Triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) are considered simple and reliable indicators of insulin resistance (IR). Although they have been associated with coronary artery disease (CAD), evidence supporting this is limited. Here, this is the first study to demonstrate the relationship between TyG-BMI index and CAD severity. The performance of the four non-insulin-based IR indexes in predicting CAD severity was explored. Methods We retrospectively analyzed 485 CAD patients between August 2020 and August 2021 in China, who were assigned into single- and multi-vessel CAD groups according to the coronary angiography (CAG) results. All patients were stratified into groups based on the tertiles of the TyG index, TyG-BMI index, TG/HDL-C ratio, and METS-IR. Results Patients in the multi-vessel CAD group had significantly higher TyG index, TyG-BMI index, TG/HDL-C ratio and METS-IR than those in the single-vessel CAD group. After adjusting for confounding factors, these four indicators were significantly associated with the risk of multi-vessel CAD. Notably, the highest tertile of TyG index, TyG-BMI index, TG/HDL-C ratio and METS-IR were significantly associated with the risk of multi-vessel CAD compared to participants in the lowest tertile. We also constructed receiver operating characteristic (ROC) curve, to assess CAD severity. The area under the curve (AUC) of the ROC plots was 0.673 (95% CI 0.620–0.726; P

Abstract Background Salvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway. Methods Male C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and β-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism. Results Dynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation. Conclusions Taken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.

Breeding technology is one of the necessary means for agricultural development, and the automatic identification of poor seeds has become a trend in modern breeding. China is one of the main producers of buckwheat, and the cultivation of Hongshan buckwheat plays an important role in agricultural production. The quality of seeds affects the final yield, and improving buckwheat breeding technology is particularly important. In order to quickly and accurately identify broken Hongshan buckwheat seeds, an identification algorithm based on an improved YOLOv5s model is proposed. Firstly, this study added the Ghost module to the YOLOv5s model, which improved the model’s inference speed. Secondly, we introduced the bidirectional feature pyramid network (BiFPN) to the neck of the YOLOv5s model, which facilitates multi-scale fusion of Hongshan buckwheat seeds. Finally, we fused the Ghost module and BiFPN to form the YOLOV5s+Ghost+BiFPN model for identifying broken Hongshan buckwheat seeds. The results show that the precision of the YOLOV5s+Ghost+BiFPN model is 99.7%, which is 11.7% higher than the YOLOv5s model, 1.3% higher than the YOLOv5+Ghost model, and 0.7% higher than the YOLOv5+BiFPN model. Then, we compared the FLOPs value, model size, and confidence. Compared to the YOLOv5s model, the FLOPs value decreased by 6.8 G, and the model size decreased by 5.2 MB. Compared to the YOLOv5+BiFPN model, the FLOPs value decreased by 8.1 G, and the model size decreased by 7.3MB. Compared to the YOLOv5+Ghost model, the FLOPs value increased by only 0.9 G, and the model size increased by 1.4 MB, with minimal numerical fluctuations. The YOLOv5s+Ghost+BiFPN model has more concentrated confidence. The YOLOv5s+Ghost+BiFPN model is capable of fast and accurate recognition of broken Hongshan buckwheat seeds, meeting the requirements of lightweight applications. Finally, based on the improved YOLOv5s model, a system for recognizing broken Hongshan buckwheat seeds was designed. The results demonstrate that the system can effectively recognize seed features and provide technical support for the intelligent selection of Hongshan buckwheat seeds.

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.

As an endocrine hormone, fibroblast growth factor 21 (FGF21) plays a crucial role in regulating lipid, glucose, and energy metabolism. Endogenous FGF21 is generated by multiple cell types but acts on restricted effector tissues, including the brain, adipose tissue, liver, heart, and skeletal muscle. Intervention with FGF21 in rodents or non-human primates has shown significant pharmacological effects on a range of metabolic dysfunctions, including weight loss and improvement of hyperglycemia, hyperlipidemia, insulin resistance, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). Due to the poor pharmacokinetic and biophysical characteristics of native FGF21, long-acting FGF21 analogs and FGF21 receptor agonists have been developed for the treatment of metabolic dysfunction. Clinical trials of several FGF21-based drugs have been performed and shown good safety, tolerance, and efficacy. Here we review the actions of FGF21 and summarize the associated clinical trials in obesity, type 2 diabetes mellitus (T2DM), and NAFLD, to help understand and promote the development of efficient treatment for metabolic diseases via targeting FGF21.

Flesh color is an important target trait in peach [Prunus persica (L.) Batsch] breeding. In this study, two white-fleshed peach cultivars were crossed [Changsong Whitepeach (WP-1) × ‘Xiacui’], and their hybrid F1 generation showed color segregation of white flesh (BF1) and yellow flesh (HF1). Metabolome analysis revealed that the flesh color segregation in the hybrid F1 generation was related to the carotenoid content. The decrease in β-carotene and β-cryptoxanthin in BF1 flesh and increase in β-cryptoxanthin oleate, rubixanthin caprate, rubixanthin laurate and zeaxanthin dipalmitate in HF1 flesh contributed to their difference in carotenoid accumulation. Transcriptome analysis demonstrated that compared with BF1, HF1 showed significant up-regulation and down-regulation of ZEP and CCD8 at the core-hardening stage, respectively, while significant down-regulation of NCED in the whole fruit development stage. The down-regulation of NCED might inhibit the breakdown of the violaxanthin and its upstream substances and further promote the accumulation of carotenoids, resulting in yellow flesh. Therefore, NCED may be a key gene controlling the fruit color traits of peach. In this study, targeted metabolomics and transcriptomics were used to jointly explore the mechanism controlling the fruit color of peach, which may help to identify the key genes for the differences in carotenoid accumulation and provide a reference for the breeding of yellow-fleshed peach.

Gibberellin (GA) is an important phytohormone that can participate in various developmental processes of plants. The study found that application of GA3 can induce parthenocarpy fruit and improve fruit set. However, the use of GA3 affects endogenous hormones in fruits, thereby affecting fruit quality. This study mainly investigates the effect of exogenous GA3 on endogenous hormones in sweet cherries. The anabolic pathways of each hormone were analyzed by metabolome and transcriptome to identify key metabolites and genes that affect endogenous hormones in response to exogenous GA3 application. Results showed that exogenous GA3 led to a significant increase in the content of abscisic acid (ABA) and GA and affected jasmonic acid (JA) and auxin (IAA). At the same time, the key structural genes affecting the synthesis of various hormones were preliminarily determined. Combined with transcription factor family analysis, WRKY genes were found to be more sensitive to the use of exogenous GA3, especially the genes belonging to Group III (PaWRKY16, PaWRKY21, PaWRKY38, PaWRKY52, and PaWRKY53). These transcription factors can combine with the promoters of NCED, YUCCA, and other genes to regulate the content of endogenous hormones. These findings lay the foundation for the preliminary determination of the mechanism of GA3’s effect on endogenous hormones in sweet cherry and the biological function of WRKY transcription factors.

In the production process of sweet cherry, there are unreasonable planting densities and tree shape selections. With increasing tree age, the crown of the tree continues to expand and the tree body is prone to canopy closure, which leads to the inability to efficiently use space and light energy. Low-light has become a major limiting factor in the quality of sweet cherry. Therefore, we analyzed the changes of various physiological indicators and the transcriptome of ‘Hongdeng’ sweet cherry under shading treatment in this study to investigate the effects of low-light stress on the photosynthetic characteristics of sweet cherry leaves and fruit physiology and biochemistry. The results showed that shading significantly reduces the light capture capacity of leaves, damages the photosystem, reduces carbon assimilation capacity, and consumes the majority of the captured light energy as photochemical energy, thereby restricting the growth and development of leaves and reducing the accumulation of nutrients in fruits. Shading significantly reduced fruit weight, sugar content, and vitamin C content at maturity and significantly increased acid content. Transcriptomic data demonstrated that low-light stress produces a large number of differential genes related to carbon metabolism, organic acid metabolism, and stress resistance, thereby suggesting that low-light stress may affect the expression of these related genes and inclusions in the fruit. The results of this study will provide theoretical and technical support for the physiological response mechanism of low-light tolerance in sweet cherry, the selection and breeding of low-light tolerant sweet cherry varieties, and the cultivation of sweet cherry in facilities.

The extract of Marsdeniatenacissima (Roxb.) Moon [Apocynaceae] (MTE) has shown a significant anti-cancer effect on hepatocellular carcinoma (HCC), but its mechanism remains unclear. In this study, we used transcriptomics methods to investigate the underlying mechanism of MTE against HCC. Both MHCC97H and HepG2 cell lines were treated with MTE. The cell viability and migration were measured using the cell counting kit-8 assay and transwell assay. RNA-sequencing was used to identify differentially expressed genes (DEGs) between HepG2 cells treated with and without MTE. The expression levels of selected DEGs—vascular endothelial growth factor-A (VEGFA), platelet-derived growth factor receptor-β (PDGFRB), and von Willebrand factor (VWF)—were verified by RT-PCR and Western blot. The effect of conditioned medium from HCC cells with MTE treatment (CM-MTE) on blood vessels was observed by tube formation assay of HUVECs and chick chorioallantoic membrane (CAM) assay. A mouse model of HCC patient-derived tumor xenograft (PDX) was established and treated with MTE. The effect of MTE on the growth and angiogenesis of HCC-PDX was analyzed. The results demonstrated that MTE inhibited the viability and migration of HCC cells. RNA-seq showed that MTE treatment downregulated multiple genes associated with metabolism and angiogenesis. The expression levels of VEGFA, VWF, PDGFB, and PDGFRB in HCC cells were significantly suppressed by MTE. Meanwhile, MTE effectively inhibited the tube-forming capability of HUVECs and the angiogenesis of chick CAM. In vivo experiments revealed that the extract reduced tumor volume, inhibited the proliferation of HCC cells, and expanded the necrotic area of the tumor. Immunohistochemical results showed that the expression levels of CD31, PDGFB, VEGF, VWF, and PDGFRB in the HCC-PDX tumor tissues were all downregulated by MTE in a dose-dependent manner. Taken together, MTE could inhibit angiogenesis by repressing the expression of VEGF, VWF, PDGF, and PDGFRB in HCC cells, a mechanism that may enable MTE to counter HCC development.

The activated c-Jun N-terminal kinase (JNK) specifically combined with SH3 domain-binding protein 5 (Sab) may mediate damage to the mitochondrial respiratory chain. Whether mitochondrial dysfunction induced by the JNK/Sab signaling pathway plays a pivotal role in the lipotoxic injury of nonalcoholic steatohepatitis (NASH) remains a lack of evidence. Scoparone, a natural compound from Traditional Chinese Medicine herbs, has the potential for liver protection and lipid metabolism regulation. However, the effect of scoparone on NASH induced by a high-fat diet (HFD) as well as its underlying mechanism remains to be elucidated. The HepG2 and Huh7 cells with/without Sab-knockdown induced by palmitic acid (PA) were used to determine the role of JNK/Sab signaling in mitochondrial dysfunction and cellular lipotoxic injury. To observe the effect of scoparone on the lipotoxic injured hepatocytes, different dose of scoparone together with PA was mixed into the culture medium of HepG2 and AML12 cells to incubate for 24 h. In addition, male C57BL/6J mice were fed with an HFD for 22 weeks to induce the NASH model and were treated with scoparone for another 8 weeks to investigate its effect on NASH. Molecules related to JNK/Sab signaling, mitochondrial function, and lipotoxic injury were detected in in vitro and/or in vivo experiments. The results showed that PA-induced activation of JNK/Sab signaling was blocked by Sab knockdown in hepatocytes, which improved mitochondrial damage, oxidative stress, hepatosteatosis, cell viability, and apoptosis. Scoparone demonstrated a similar effect on the PA-induced hepatocytes as Sab knockdown. For the NASH mice, treatment with scoparone also downregulated the activation of JNK/Sab signaling, improved histopathological changes of liver tissues including mitochondrial number and morphology, lipid peroxide content, hepatosteatosis and inflammation obviously, as well as decreased the serum level of lipid and transaminases. Taken together, this study confirms that activation of the JNK/Sab signaling pathway-induced mitochondrial dysfunction plays a crucial role in the development of NASH. Scoparone can improve the lipotoxic liver injury partially by suppressing this signaling pathway, making it a potential therapeutic compound for NASH.

This paper presents a new optimal method for model estimation of the unknown parameters of circuit-based proton exchange membrane fuel cells (PEMFCs). The main idea is to minimize the sum of squared error (SSE) value between the actual data and the estimated results. The optimization process here is based on an Improved Fluid Search Optimization Algorithm (IFSO). For verification of the suggested method, it is applied to three practical case studies including Horizon H-12 stacks, NedStack PS6, and Ballard Mark V 5 kW under different operating conditions with temperature variations between 30 oC and 55oC and pressure variations between 1.0/1.0 Bar and 3.0/3.0 Bar. The results of these case studies are also compared with CGOA, MRFO, and basic FSO algorithm to show the proposed method’s effectiveness. The results show that the minimum value of SSE among different algorithms is 0.7845, 2.15, and 0.084, respectively that are reached by the suggested IFSO algorithm.

Since a combined harvester’s grain-cleaning method depends on the pneumatic separation of grain and chaff, the airflow’s aerodynamic forces significantly affect cleaning efficiency. Based on buckwheat’s theoretical and mechanical properties, a new threshing drum with cleaning key parts was developed to reduce the variability of cleaning efficiency of buckwheat community threshers caused by inefficient threshing and accumulation of residue within the threshing system. This cleaning arrangement includes two wind speed inlets, each composed of four thin pipes of the same length as the threshing drum. The computational fluid dynamics modelling approach simulated the threshing and cleaning performance at different wind velocities within the threshing unit. The results showed that when the two inlets work simultaneously and adopt different wind speeds, i.e., 12 m/s and 15 m/s, the wind speed is higher than the critical value of the floating rate buckwheat kernel. Under this condition, the wind speed inlet area was increased, and the flow field velocity between the threshing drum and the concave grid plate ranged from 3.8 m/s-8.3 m/s. The flow velocity below the plate ranged from 7 m/s-15 m/s, higher than the floating speed of buckwheat kernels, which was the best choice. Based on these simulation results, a centrifugal fan was designed, which meets the buckwheat thresher’s cleaning performance.

Abstract Background To promote the integration of medical resources, Beijing has built medical alliances since 2012, but this reform has not changed the state of disordered medical treatment. Patients are still willing to go to high-level hospitals for medical treatment. What causes patients to prefer high-level hospitals? To explore the reasons behind this preference for high-level medical treatment among patients and to guide patients to make visits in an orderly manner, we conducted this study and compared patients’ satisfaction with hospitals of different levels in the context of medical resource integration. Methods This study conducted a questionnaire survey among 1250 patients who were selected in 18 medical alliances in Beijing from October to December 2016. The study type is a comparative study based on cross-sectional data. Patient satisfaction was the main outcome, and descriptive analysis, chi-square tests, nonparametric tests and binary logistic regression analysis were used. The level of statistical significance was set at p

Abstract Background Saline-alkaline stress is a major abiotic stress that is harmful to plant growth worldwide. Two peach cultivars (GF677 and Maotao) display distinct phenotypes under saline-alkaline stress. The molecular mechanism explaining the differences between the two cultivars is still unclear. Results In the present study, we systematically analysed the changes in GF677 and Maotao leaves upon saline-alkaline stress by using cytological and biochemical technologies as well as comparative transcriptome analysis. Transmission electron microscopy (TEM) observations showed that the structure of granum was dispersive in Maotao chloroplasts. The biochemical analysis revealed that POD activity and the contents of chlorophyll a and chlorophyll b, as well as iron, were notably decreased in Maotao. Comparative transcriptome analysis detected 881 genes with differential expression (including 294 upregulated and 587 downregulated) under the criteria of |log2 Ratio| ≥ 1 and FDR ≤0.01. Gene ontology (GO) analysis showed that all differentially expressed genes (DEGs) were grouped into 30 groups. MapMan annotation of DEGs showed that photosynthesis, antioxidation, ion metabolism, and WRKY TF were activated in GF677, while cell wall degradation, secondary metabolism, starch degradation, MYB TF, and bHLH TF were activated in Maotao. Several iron and stress-related TFs (ppa024966m, ppa010295m, ppa0271826m, ppa002645m, ppa010846m, ppa009439m, ppa008846m, and ppa007708m) were further discussed from a functional perspective based on the phylogenetic tree integration of other species homologues. Conclusions According to the cytological and molecular differences between the two cultivars, we suggest that the integrity of chloroplast structure and the activation of photosynthesis as well as stress-related genes are crucial for saline-alkaline resistance in GF677. The results presented in this report provide a theoretical basis for cloning saline-alkaline tolerance genes and molecular breeding to improve saline-alkaline tolerance in peach.

With the negative impact of COVID-19, the continuous recession of economic globalization, and the increasing market competition, enterprise transformation gradually becomes the theme of enterprise management. Although more and more scholars and companies have paid attention to the importance of enterprise transformation, most of the research on it is still at the qualitative level of theoretical descriptions and lacks a comprehensive consideration and empirical research on its motivation and performance. In view of this, this study analyzes the overall driving effect of technological innovation and the internal and external environment on enterprise transformation from the perspective of its drivers and analyzes in depth its causes and consequences for different industries (construction and real estate industries). The study also analyzes the antecedents and consequences of enterprise transformation and its differences in different industries (construction and real estate). In this study, a sample of middle and senior management of 10 companies with a valid sample of 401 is collected. Structural equation modeling results indicate that competitive advantage, technological innovation, and market pressure significantly affect enterprise transformation, which is an antecedent of corporate performance. Further, the results of the multiple-group analysis also reveal some significant differences between the theoretical models of the construction and real estate communities. Finally, suggestions are made based on the findings.

In order to better analyze human health status and guide people to carry out reasonable physical training, this paper puts forward the construction method of human health status evaluation model after sports training based on big data. Firstly, the characteristic information of human health status after sports training is collected based on big data technology, and the evaluation index and evaluation algorithm of human health status after sports training are constructed. The evaluation system of human health status after sports training is constructed. Finally, the experiment proves that the proposed evaluation model of human health status after sports training based on big data has high practicability in the process of practical application and fully meets the research requirements.

In order to understand the effect of digital marketing on brand visibility of wineries in the age of internet 2.0, the researchers conducted a qualitative research to five Napa Valley wineries. Based on the primary and secondary data collected through the communication between the researchers and the wineries via email, home website, and different platforms of social media, a behavioral model proposed by Capitello (2013) was introduced to examine the effectiveness of digital marketing towards brand visibility. Some of the parameters and dimensions in the model were adjusted to fit the appropriateness of the study. As a result, communication style impacts significantly on consumer’s first impression to the company, and the wineries need to allocate the resources wisely. The researchers also proposed a further study about the relationship between the brand recognition and online marketing efforts under a sufficient period and similar brand positioning so as to have a fuller picture about the topic.

Summary: A microbial electrochemical system could potentially be applied as a biosynthesis platform by extracting wastewater energy while converting it to value-added chemicals. However, the unfavorable thermodynamics and sluggish kinetics of in vivo whole-cell cathodic catalysis largely limit product diversity and value. Herein, we convert the in vivo cathodic reaction to in vitro enzymatic catalysis and develop a microbe-enzyme hybrid bioelectrochemical system (BES), where microbes release the electricity from wastewater (anode) to power enzymatic catalysis (cathode). Three representative examples for the synthesis of pharmaceutically relevant compounds, including halofunctionalized oleic acid based on a cascade reaction, (4-chlorophenyl)-(pyridin-2-yl)-methanol based on electrochemical cofactor regeneration, and l-3,4-dihydroxyphenylalanine based on electrochemical reduction, were demonstrated. According to the techno-economic analysis, this system could deliver high system profit, opening an avenue to a potentially viable wastewater-to-profit process while shedding scientific light on hybrid BES mechanisms toward a sustainable reuse of wastewater.

Buckwheat is an important minor grain crop with medicinal and edible functions. The accurate judgment of buckwheat maturity is beneficial to reduce harvest losses and improve yield. With the rapid development of unmanned aerial vehicle (UAV) technology, it has been widely used to predict the maturity of agricultural products. This paper proposed a method using recursive feature elimination cross-validation (RFECV) combined with multiple regression models to predict the maturity of buckwheat in UAV-RGB images. The images were captured in the buckwheat experimental field of Shanxi Agricultural University in Jinzhong, Northern China, from September to October in 2021. The variety was sweet buckwheat of “Jinqiao No. 1”. In order to deeply mine the feature vectors that highly correlated with the prediction of buckwheat maturity, 22 dimensional features with 5 vegetation indexes, 9 color features, and 8 texture features of buckwheat were selected initially. The RFECV method was adopted to obtain the optimal feature vector dimensions and combinations with six regression models of decision tree regression, linear regression, random forest regression, AdaBoost regression, gradient lifting regression, and extreme random tree regression. The coefficient of determination (R2) and root mean square error (RMSE) were used to analyze the different combinations of the six regression models with different feature spaces. The experimental results show that the single vegetation index performed poorly in the prediction of buckwheat maturity; the prediction result of feature space “5” combined with the gradient lifting regression model performed the best; and the R2 and RMSE were 0.981 and 1.70 respectively. The research results can provide an important theoretical basis for the prediction of the regional maturity of crops.

Previous studies indicated that extensive genetic variations could be generated due to polyploidy, which is considered to be closely associated with the manifestation of polyploid heterosis. Our previous studies confirmed that triploid loquats demonstrated significant heterosis, other than the ploidy effect, but the underlying mechanisms are largely unknown. This study aimed to overcome the narrow genetic distance of loquats, increase the genetic variation level of triploid loquats, and systematically illuminate the heterosis mechanisms of triploid loquats derived from two cross combinations. Here, inter-simple sequence repeats (ISSRs) and simple sequence repeats (SSRs) were adopted for evaluating the genetic diversity, and transcriptome sequencing (RNA-Seq) was performed to investigate gene expression as well as pathway changes in the triploids. We found that extensive genetic variations were produced during the formation of triploid loquats. The polymorphism ratios of ISSRs and SSRs were 43.75% and 19.32%, respectively, and almost all their markers had a PIC value higher than 0.5, suggesting that both ISSRs and SSRs could work well in loquat assisted breeding. Furthermore, our results revealed that by broadening the genetic distance between the parents, genetic variations in triploids could be promoted. Additionally, RNA-Seq results suggested that numerous genes differentially expressed between the triploids and parents were screened out. Moreover, KEGG analyses revealed that “photosynthetic efficiency” and “glyco-metabolism” were significantly changed in triploid loquats compared with the parents, which was consistent with the results of physiological indicator analyses, leaf micro-structure observations, and qRT-PCR validation. Collectively, our results suggested that extensive genetic variations occurred in the triploids and that the changes in the “photosynthetic efficiency” as well as “glyco-metabolism” of triploids might have further resulted in heterosis manifestation in the triploid loquats.

Objective This study aims to explore a three-dimensional planting mode in orchards and provide theoretical basis for the efficient peach-Morchella planting and soil management after Morchella cultivation. Methods Next-generation sequencing was performed to investigate the variations in soil physicochemical properties, enzyme activities and fungal composition under peach-Morchella intercropping for one year and two years, by using the soil without peach-Morchella intercropping as the control group. Results Peach-Morchella intercropping decreased the soil bulk density, and significantly increased the maximum field capacity, non-capillary porosity and total porosity, organic matter, available potassium and available zinc, which together improved soil structure and soil fertility. Besides, the intercropping mode obviously enhanced soil enzyme activities and mineral absorption and transformation in peach orchard soils. The intercropping also resulted in a decline of soil fungal diversity, and the 2-year soil samples were of higher abundance of Zygomycota. More importantly, peach-Morchella intercropping elevated the yields of both peach and Morchella, bringing about obviously higher economic benefits. Conclusion Continuous peach-Morchella intercropping improves the soil structure and fertility while decreases soil fungal diversity, which can contribute to greater economic benefits of the peach orchard. Our findings shed new light on the intercropping-fungus-soil relationship, and may facilitate the further development of peach-Morchella intercropping.

Abstract Seedling emergence and establishment are fragile processes that determine the direction and structure of forest succession and regeneration. However, seedling emergence and establishment are easily affected by biotic and abiotic (environmental) factors. A dense and expanding understory of dwarf bamboo is one such important factor that can seriously hinder the seedling regeneration. We conducted a field experiment to investigate the emergence and establishment of canopy tree seedlings under artificially controlled densities of dwarf bamboo. We found that understory dwarf bamboo obstructed seedling emergence but reduced the death of seedlings. Although understory dwarf bamboo reduced the median retention time of seedlings, dense bamboo increased the mean survival time of seedlings. Our results suggest that understory dwarf bamboo has multiple selectivities for tree seedling emergence and establishment: high‐density dwarf bamboo was beneficial to evergreen species but lower‐density of bamboo was conducive to the survival of deciduous species, it means the dwarf bamboo potentially alters successional trajectories of forest communities. Path analysis revealed that the most important factors affecting tree seedling emergence and death were the abundance of seeds in the seed bank and the density of emerged seedlings, and that the soil temperature promoted seedling emergence but increased seedling death, the thickness of litter limited seedling emergence, and the leaf area index of the bamboo canopy limited seedling death. The present study suggests that dwarf bamboo can directly alter the microenvironment, significantly reducing light levels and soil temperature but increasing the thickness of litter and soil humus, thereby indirectly impacting the regeneration of tree seedlings. Our results indicate that various factors affected seedling emergence, and there were complex indirect relationships among these factors. In general, biological factors had a stronger influence on tree seedling regeneration than environmental factors.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) may increase the sensitivity to liver injury caused by stimulants such as drugs and poisons. The traditional Chinese medicine (TCM) Jiang-Zhi Granule (JZG) has been proven effective for improving liver function, reducing hepatic fat accumulation and inflammation in NAFLD. The purpose of this study is to evaluate the effect of JZG on the susceptibility of NAFLD rats to liver injury and to identify the relevant mechanism. Methods Forty wistar rats were randomly divided into five groups, normal group, normal+CCl4 group, high-fat diet (HFD) group, HFD + CCl4 group, and HFD + CCl4 + JZG group. NAFLD were established with HFD for 8 weeks. Then Low-dose CCl4 was given intraperitoneally to induce liver injury in NAFLD rats for 48 h. From the 5th week of HFD, intragastric administration of JZG was simultaneously given to the rats in the HFD + CCl4 + JZG group. At the end of the experiment, liver histological pathology, serum transaminase, lipid in liver and blood, as well as hepatic expression levels of endoplasmic reticulum stress (ERS) related molecules were evaluated. Results NAFLD rat model was established by eight-week HFD feeding, exhibiting elevated levels of hepatic lipid, blood lipid, serum transaminase and significantly increased expression of ERS related molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (EIF2α), and nuclear factor-kappa B (NFκB) in liver tissues. After injection of CCl4 in NAFLD rats, elevated serum transaminases, severe inflammation and focal necrosis were observed in liver tissue, but no obvious change was found in the rats of normal group. JZG reduced hepatic inflammation, hepatic necrosis, hepatic lipid, blood transaminases and blood lipids in HFD + CCl4 rats. ERS related molecules were significantly elevated by low-dose CCl4 in NAFLD rats, and were down-regulated by JZG. Conclusion The sensitivity to CCl4-induced liver injury is increased in NAFLD rats, which could be improved by JZG. The pharmacological mechanism may involve the regulation of ERS signaling pathway by JZG.

Abstract Background To improve the efficiency of the use of medical resources, China has implemented medical alliances (MAs) to implement a hierarchical diagnosis and treatment system. The willingness to undertake a first visit to primary care institutions (PCIs) is an important indicator of the effect of this system. Beijing has also built MAs since 2013, but to date, there have been few studies on the first visit to PCIs in Beijing. The purpose of this study is to analyze patients’ willingness to make their first visit to PCIs and its influencing factors to provide references for the realization of a hierarchical diagnosis and treatment system. Methods Two relatively different districts with large differences in resources in Beijing, D and F, were selected, and a self-reported questionnaire and convenience sampling method were applied. A cross-sectional survey was administered to 1221 patients of MAs. The chi-square test and binary logistic regression were used to analyze the influencing factors of patients’ willingness to undertake a first visit to a PCI. Results Fewer patients in District D received medical alliance services (44.42%) than those in District F (59.25%), but patients in District D had a higher degree of satisfaction with the services they received (72.04%) than those in District F (28.96%). Patients in District D had a higher willingness to undertake a first visit (64.00%) than those in District F (58.18%). Patients of an older age, low medical expenses, participation in urban employees’ basic medical insurance, a high understanding of MAs and high satisfaction with medical services were indicators of being more willing to choose primary care institutions for their first visit. Conclusions The different medical resources and MA constructions in the two districts have resulted in a difference between the two districts in terms of the willingness of individuals to make their first visit to PCIs. Strengthening the service capabilities of PCIs remains a priority. The government should propose solutions to solve the problems encountered in practice and actively promote the realization of MAs and hierarchical diagnosis and treatment.

Abstract In this study, the secondary sequencing was used to profile circRNA expression in the tissue samples from three CRC patients with liver metastasis and three matched CRC patients. After verified some candidates in another 40 CRC and CRC-m samples by qRT-PCR, we further demonstrated that circRNA_0001178 and circRNA_0000826 were significantly upregulated in CRC-m tissues, and both of them had the potential for diagnosing liver metastases from colorectal cancer. Finally, the networks of circRNA-miRNA-mRNA base on these two circRNAs were constructed respectively. This study showed that differentially expressed circRNAs were existed between the tissue samples from colorectal cancer patients with and without liver metastasis. And also suggested that circRNA_0001178 and circRNA_0000826 may serve as a potential diagnostic biomarker for liver metastases from colorectal cancer.

D-2-hydroxyglutaric acid (D2HG) is overproduced as a result of the D-2-hydroxyglutaric aciduria and relevant cancers, caused by gene mutation. Accurate analysis of D2HG could help rapid diagnosis of these diseases and allow for timely treatment. In this work, a D-2-hydroxyglutarate dehydrogenase from Ralstonia solanacearum (RsD2HGDH) is cloned and recombinantly expressed. This enzyme features the direct electron transfer to chemical electron mediators (such as methylene blue (MB)) in the absence of additional coenzymes. Therefore, NAD+, a natural electron acceptor for the commercial D2HGDH and usually known for being unstable and difficult for immobilization can be avoided in the preparation of biosensors. The RsD2HGDH and MB are co-immobilized on a two-dimensional material, Ti3C2 MXene, followed by drop-coating on the gold screen-printed electrode (AuSPE) to construct a compact and portable biosensor. The D2HG in samples can be catalyzed by RsD2HGDH, where the current change is measured by chronoamperometry at −0.23 V. The biosensor shows a D2HG detection range of 0.5 to 120 µM (R2 = 0.9974) with a sensitivity of 22.26 μA mM−1 cm−2 and a detection limit of 0.1 µM (S/N = 3). The biosensor retains 72.52% performance of its incipient state after 30 days of storage. The samples of D2HG-containing fetal bovine serum and artificial urine were analyzed with the recovery of 99.56% to 106.83% and 97.30% to 102.47% further indicating the great application potential of our portable D2HG biosensor.

Abstract Background Noise induced hearing loss (NIHL) is a polygenic disease involving both genetic and environmental factors, and is one of the most important occupational health hazards worldwide. To date, the influence of Notch1 variants on the risk to develop NIHL has not been illuminated. This study was conducted to explore the effects of Notch1 polymorphisms on individual susceptibility to NIHL. Methods A total of 2689 industrial workers from one textile factory in east China were recruited to participate in the current study. Venous blood was collected, basic clinical data was obtained by questionnaires and pure-tone audiometry (PTA) tests were conducted by specialist physicians. Next we performed genotyping of three selected SNPs (rs3124594, rs3124599 and rs3124603) in the Notch1 gene in 535 NIHL patients and 535 controls. Subsequently, the main effects of the genotypes and their interactions were evaluated. Results Our results revealed that individuals with a GG of rs3124594, TT of rs3124603 (OR = 4.70 and 1.59 respectively) and the haplotype AAC (rs3124594-rs3124599-rs3124603) (OR = 14.95) were associated with an increased risk of NIHL in our study cohort. Stratified analysis showed that an increased NIHL risk was found in individuals exposed to work related noise for ≤16 years that also had the rs3124594 GG or rs3124603 CT/TT genotype with an OR of 4.20 and 1.73 respectively. Multifactor dimensionality reduction analysis indicated that rs3124594, rs3124599 and rs3124603 interacted with each other and were related to an increased risk to develop NIHL (OR = 3.60). Conclusions The genetic polymorphisms rs3124594 and rs3124603 within the Notch1 gene are associated with an increased risk of NIHL in a Chinese population and could potentially be used as biomarkers for NIHL in noise exposed workers.

This paper studies a hyperbolic tangent oscillator arising in a nonlinear packaging system. The high-order nonlinearity makes it difficult to study the system analytically. A modified homotopy perturbation method is proposed, where the initial guess is an approximate solution of the well-known Duffing oscillator; the solution accuracy can be improved by either improvement of the initial guess or continuous iteration. This paper gives a general approach to high-order nonlinear oscillators.

Abstract This study was conducted to explore the effects of DNMT1 and DNMT3A polymorphisms on susceptibility to noise-induced hearing loss (NIHL) in Chinese workers. A total of 2689 industrial workers from a single textile factory were recruited. Venous blood was collected, as were questionnaire and pure-tone audiometry (PTA) data by specialist physicians. Four selected SNPs (rs7578575, rs749131, rs1550117, and rs2228611) in DNMT1 and DNMT3A were genotyped in 527 NIHL patients and 527 controls. Then, main effects of the genotypes and their interactions were evaluated. Results revealed that the GG genotype at rs749131 and the AG/GG genotypes at rs1550117 and rs2228611 [odds ratio (OR) = 1.87, 2.57, and 1.98 respectively], as well as the haplotypes AGGG and TGGA (rs7578578-rs749131-rs1550117-rs2228611) (OR = 1.35 and 1.56, respectively) were associated with an increased risk of NIHL in the Chinese population. Multifactor dimensionality reduction analysis indicated that rs7578575, rs749131, and rs2228611 interact and are related to increased NIHL risk (OR = 1.63). The genetic polymorphisms rs749131 G, rs1550117 G, and rs2228611 G within the DNMT1 and DNMT3A genes are associated with an increased risk of NIHL in the Chinese population and have the potential to act as biomarkers for noise-exposed workers.

Triple‐negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer‐related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesenchymal‐like and epithelial‐like states have been revealed in breast CSCs. Thus, strategies capable of simultaneously inhibiting bulk and CSC populations in both mesenchymal and epithelial states have yet to be developed. Wnt/β‐catenin and Hippo/YAP pathways are crucial in tumorigenesis, but importantly also possess tumor suppressor functions in certain contexts. One possibility is that TNBC cells in epithelial or mesenchymal state may differently affect Wnt/β‐catenin and Hippo/YAP signaling and CSC phenotypes. In this report, we found that YAP signaling and CD44high/CD24−/low CSCs were upregulated while Wnt/β‐catenin signaling and ALDH+ CSCs were downregulated in mesenchymal‐like TNBC cells, and vice versa in their epithelial‐like counterparts. Dual knockdown of YAP and Wnt/β‐catenin, but neither alone, was required for effective suppression of both CD44high/CD24−/low and ALDH+ CSC populations in mesenchymal and epithelial TNBC cells. These observations were confirmed with cultured tumor fragments prepared from patients with TNBC after treatment with Wnt inhibitor ICG‐001 and YAP inhibitor simvastatin. In addition, a clinical database showed that decreased gene expression of Wnt and YAP was positively correlated with decreased ALDH and CD44 expression in patients’ samples while increased patient survival. Furthermore, tumor growth of TNBC cells in either epithelial or mesenchymal state was retarded, and both CD44high/CD24−/low and ALDH+ CSC subpopulations were diminished in a human xenograft model after dual administration of ICG‐001 and simvastatin. Tumorigenicity was also hampered after secondary transplantation. These data suggest a new therapeutic strategy for TNBC via dual Wnt and YAP inhibition.

Abstract Background Activated pancreatic stellate cells (PaSCs) are the key cellular source of cancer-associated fibroblasts in the pancreatic stroma of patients with pancreatic ductal adenocarcinoma (PDAC), however, the activation mechanism of PaSCs is not yet known. The Notch signaling pathway, components of which are expressed in stromal cells, is involved in the fibrosis of several organs, including the lung and liver. In the current study, we investigated whether Notch signal transduction is involved in PaSC activation in PDAC. Methods The expression of Notch signaling pathway components in human PDAC was examined via immunohistochemical staining and assessed in mouse PaSCs using RT-qPCR and western blotting. Notch3 expression in both PDAC stromal cells and activated mouse PaSCs was evaluated using immunofluorescence, RT-qPCR and western blotting. The impact of siRNA-mediated Notch3 knockdown on PaSC activation was detected with RT-qPCR and western blotting, and the impact on PaSC proliferation and migration was detected using CCK-8 assays and scratch experiments. The effect of conditioned medium from PaSCs activated with Notch3 siRNA on pancreatic cancer (LTPA) cells was also detected with CCK-8 assays and scratch experiments. The data were analyzed for statistical significance using Student’s t-test. Results Notch3 was overexpressed in both human PDAC stromal cells and activated mouse PaSCs, and Notch3 knockdown with Notch3 siRNA decreased the proliferation and migration of mouse PaSCs. The levels of markers related to PaSC activation, such as α-smooth muscle actin (α-SMA), collagen I and fibronectin, decreased in response to Notch3 knockdown, indicating that Notch3 plays an important role in PaSC activation. Furthermore, we confirmed that inhibition of PaSC activation via Notch3 siRNA reduced the proliferation and migration of PaSC-induced mouse pancreatic cancer (LTPA) cells. Conclusions Notch3 inhibition in PaSCs can inhibit the activation, proliferation and migration of PaSCs and reduce the PaSC-induced pro-tumorigenic effect. Therefore, Notch3 silencing in PaSCs is a potential novel therapeutic option for patients with PDAC.

Abstract Background In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW remains unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues. The present study aimed at investigating effect of ZJW extracts on the biological function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/β-catenin signaling pathway. Methods In this study, the effect of ZJW extracts on 5-HTR1D expression and Wnt/β-catenin signaling pathway were investigated and contrasted with GR127935 (GR), a known 5-HTR1D antagonist, using the CRC cell line SW403. The cells were respectively treated with GR127935 and different doses of ZJW extracts. Proliferation, apoptosis, migration, and invasion of SW403 cells were compared between ZJW and GR127935 treatments. The expression of 5-HTR1D and signaling molecules involved in the canonic Wnt/β-catenin pathway were determined by Western blot analysis. Results After ZJW extracts treatment and GR127935 treatment, G1 arrest in cell cycle of SW403 was increased. Cell apoptosis was pronounced, and cell migration and invasion were suppressed. SW403 cells showed a dose-dependently decreased expression of 5-HTR1D, meanwhile, β-catenin level was significantly decreased in nucleus of cells cultured with GR127935. Treatment of ZJW extracts dose-dependently resulted in decreased 5-HTR1D and a concomitant reduction in the Wnt/β-catenin signal transduction, an effect indistinguishable from GR127935 treatment. Conclusion The anticancer activity of ZJW extracts may be partially achieved through attenuation of the 5-HTR1D-Wnt/β-catenin signaling pathway.

Karst regions are characterized by heterogeneous soil habitats, with shallow wide soil (SW) on hilly slopes and deep narrow soil (DN) in rocky trenches. To make full use of limited water and nutrients, plants have therefore developed a number of root extension strategies. This study investigated the effect of soil moisture on horizontal root extension in SW and vertical root extension in DN by assessing root growth responses, biomass allocation, and root distribution. A full two-way factorial blocked design of soil dimensions by water availability was followed. The perennial grass Lolium perenne L. was grown in SW and DN under high (W100%), moderate (W50%), and low (W30%) water availability, respectively. The main results were as follows: (1) The total biomass of L. perenne was not influenced either by soil habitat or by water application. Root length, root surface area, root biomass and root to shoot ratio all decreased with decreasing water application in SW, but not in DN soil. (2) With decreasing water application, the cumulative percentage of root length, root surface area and root biomass in 4 rings from the center out to 12 cm of SW soil showed a trend of W50% > W30% > W100% in SW, however, the cumulative percentage of root biomass in 4 layers from the surface to a depth of 36 cm was not significantly different between different water treatments in DN. (3) Under all three water treatments, specific root length showed an increase but root length density showed a decreasing trend from the center outward in SW soil or from the surface to bottom in DN soil. Overall, these results suggest that in SW habitat, soil moisture determines horizontal expansion of the roots in L. perenne, although the overall expansion ability was limited in severe drought. However, due to the relatively strong water retention ability, soil moisture changes were less obvious in DN, resulting in no significant vertical extension of the root system. The root response of L. perenne helps our understanding of how herbaceous plants can adjust their belowground morphology to support their growth in harsh karst soil environments.

For some companies, sales means arranging goods and selling them on the shelves. This kind of arrangement of goods regardless of priority brings a lot of internal consumption to the enterprise. With the rapid development of the Internet and industry, many large companies have gradually established and improved their production and sales processes. The traditional ABC classification method can no longer meet this demand. The new method that can compensate for the traditional ABC classification method is particularly important. This article uses association rules to use the ABC classification method to study the expected budget of commodities, uses the Apriori and FP-Growth algorithms in the association rules to collect frequent itemsets of the acquired data, calculates the corresponding association rules, and then classifies the commodities with ABC.

Objective(s):Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-14. Materials and Methods:The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA). The inhibitors SB203580, PD98059 and SP600125 were used for suppressing the expression of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The expression of filaggrin, p38 MAPK, p44/42 MAPK and SAPK/JNK, caspase-14, keratin1and keratin2 were detected by western blot. Results:In filaggrin-deficient NHEKs, the expression of p38, p44/42 MAPK and SAPK/JNK and caspase-14 were significantly decreased. The inhibition of p38 and SAPK/JNK reduced the expression of caspase-14, while the p44/42 MAPK showed no consistent effects. Moreover, the filaggrin knockdown decreased the expression of keratin2, but had no effects on the level of keratin1. Conclusion: The decreased expression of caspase-14 in filaggrin-deficient NHEKs may be induced by the inactivation of MAPK signaling pathway. These provide a novel perspective to understand the mechanism for the protective effects of filaggrin and caspase-14 on skin barrier function.

This paper illustrates a simple yet effective spectroscopic technique for the prediction of soil organic matter (SOM) from moist soil through the synchronous 2D correlation spectroscopy (2D-COS) analysis. In the moist soil system, the strong overlap between the water absorption peaks and the SOM characteristic features in the visible-near infrared (Vis-NIR) spectral region have long been recognised as one of the main factors that causes significant errors in the prediction of the SOM content. The aim of the paper is to illustrate how the tangling effects due to the moisture and the SOM can be unveiled under 2D-COS through a sequential correlogram analysis of the two perturbation variables (i.e., the moisture and the SOM) independently. The main outcome from the 2D-COS analysis is the discovery of SOM-related bands at the 597 nm, 1646 nm and 2138 nm, together with the predominant water absorbance feature at the 1934 nm and the relatively less important ones at 1447 nm and 2210 nm. This information is then utilised to build partial least square regression (PLSR) models for the prediction of the SOM content. The experiment has shown that by discarding noisy bands adjacent to the SOM features, and the removal of the water absorption bands, the determination coefficient of prediction (Rp2) and the ratio of prediction to deviation (RPD) for the prediction of SOM from moist soil have achieved Rp2 = 0.92 and the RPD = 3.19, both of which are about 5% better than that of using all bands for building the PLSR model. The very high RPD (=3.19) obtained in this study may suggest that the 2D-COS technique is effective for the analysis of complex system like the prediction of SOM from moist soil.

The cAMP-regulated phosphoprotein 19 (ARPP-19) plays a key role in cell mitotic G2/M transition. Expression of ARPP-19 was increased in human hepatocellular carcinoma (HCC) compared to adjacent non-tumorous liver tissues in 36 paired liver samples, and the level of ARPP-19 in HCC tissues was positively correlated with the tumor size. To determine the interrelationship between ARPP-19 expression and HCC, we silenced ARPP-19 expression in the human hepatocarcinoma HepG2 and SMMC-7721 cells using lentivirus encoding ARPP-19 siRNA. HepG2 and SMMC-7721 cells with ARPP-19 knockdown displayed lowered cell growth rate, retarded colony formation and increased arrest at the G2/M phase transition. Silencing ARPP-19 in HCC cells resulted in decreased protein levels of phospho-(Ser) CDKs substrates and increased levels of inactivated cyclin division cycle 2 (Cdc2). Therefore, ARPP-19 may play a role in HCC pathogenesis through regulating cell proliferation.

Background. Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of liver transplantation. Lingguizhugan decoction (LGZG), a classical Chinese herbal formula, has beneficial effects on NAFLD animal models. Our study examined the impact of LGZG on hepatic global transcriptome of high-fat-diet-induced NAFLD rats. Methods. Three groups of Wistar rats were included: normal, NAFLD model, and LGZG-treated NAFLD groups. Four weeks for the treatment, liver tissues were harvested for RNA sequencing. Differentially expressed genes (DEGs) and enriched pathways were detected on hepatic global transcriptome profile. Real-time PCR validated the regulatory patterns of LGZG on NAFLD rats. Results. DEGs between the NAFLD model and normal groups indicated the elevated peroxisome proliferator-activated receptor (PPAR) and hedgehog signaling pathways in NAFLD rats. In bile secretion pathway, genes involved in cholesterol secretion were activated by LGZG treatment. Increased expression of antioxidant OSIGN1 and decreased expression of genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG treatment on these oxidative stress-related genes were confirmed by real-time PCR. Conclusion. Our study revealed a “two-hits-targeting” mechanism of LGZG in the treatment for NAFLD: alleviating oxidative stress and activating cholesterol secretion.

The aim of this paper is to construct two new classes of multivariate risk statistics, and to study their properties. We, first, introduce the multivariate shortfall risk statistics and multivariate divergence risk statistics. Then, their basic properties are studied, and their representation results are provided. Furthermore, their coherency is also characterized by means of the corresponding loss function. Finally, entropic risk statistics are given to illustrate the proposed new classes of multivariate risk statistics. The relationship between multivariate shortfall and divergence risk statistics is also discussed.

Spacecraft dynamics belongs to rigid–elastic coupling dynamics in general. If thermal stress and thermal effect are further considered, it will cause the more complex rigid–elastic-thermal coupling dynamics. For the aforementioned kind of coupling dynamics, it is difficult to establish the basic equations directly. It has proved that a suitable way to study complex coupling problems is by work–energy theorem and the law of conversation of energy. Using the energy method, Hamilton principle of rigid–elastic-thermal coupling dynamics is established. The stationary value conditions of Hamilton principle of rigid–elastic-thermal coupling dynamics are derived. The physical meaning of the stationary value conditions is indicated. As an application of rigid–elastic-thermal coupling dynamics, the actual example of spacecraft is given to reveal that there existed thermal stiffening or softening problems in rigid–elastic-thermal coupling dynamics, just like dynamic hardening or softening problems in spacecraft dynamics.