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Abstract Background While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa. Methods MBTNF-α was synthesized via a biotin–streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. Results On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P

Cellular energy metabolism plays a crucial role in the regulation of macrophage polarization and in the execution of immune functions. A recent study showed that Slc6a8-mediated creatine uptake from exogenous supplementation modulates macrophage polarization, yet little is known about the role of the de novo creatine de novobiosynthesis pathway in macrophage polarization. Here, we observed that glycine amidinotransferase (GATM), the rate-limiting enzyme for creatine synthesis, was upregulated in alternative (M2) polarized macrophages, and was dependent on the transcriptional factor STAT6, whereas GATM expression was suppressed in the classical polarized (M1) macrophage. Next, we revealed that exogenous creatine supplementation enhanced IL-4-induced M2 polarization, confirming recent work. Furthermore, we revealed that genetic ablation of GATM did not affect expression of M1 marker genes (Nos2, IL1b, IL12b) or the production of nitric oxide in both peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). By contrast, expression levels of M2 markers (Arg1, Mrc1, Ccl17 and Retnla) were lower following GATM deletion. Moreover, we found that deletion of GATM in resident alveolar macrophages (AMs) significantly blocked M2 polarization but with no obvious effect on the number of cells in knockout mice. Lastly, an upregulation of GATM was found in lung tissue and bronchoalveolar lavage fluid macrophages from HDM-induced asthmatic mice. Our study uncovers a previously uncharacterized role for the de novo creatine biosynthesis enzyme GATM in M2 macrophage polarization, which may be involved in the pathogenesis of related inflammatory diseases such as an T helper 2 (Th2)-associated allergic asthma.

Glioma is the most common primary malignant tumor in the central nervous system, and directly affects the quality of life and cognitive function of patients. Ferroptosis, is a new form of regulated cell death characterized by iron-dependent lipid peroxidation. Ferroptosis is mainly due to redox imbalance and involves multiple intracellular biology processes, such as iron metabolism, lipid metabolism, and antioxidants synthesis. Induction of ferroptosis could be a new target for glioma treatment, and ferroptosis-related processes are associated with chemoresistance and radioresistance in glioma. In the present review, we provide the characteristics, key regulators and pathways of ferroptosis and the crosstalk between ferroptosis and other programmed cell death in glioma, we also proposed the application and prospect of ferroptosis in the treatment of glioma.

Carotenoid cleavage oxygenase (CCO) is an enzyme that can catalyze carotenoids to volatile aromatic substances and participate in the biosynthesis of two important phytohormones, i.e., abscisic acid (ABA) and strigolactone (SL). However, the genome-wide identification and analysis of the CCO gene family in the rare and endangered woody plant Liriodendron chinense has not been reported. Here, we performed a genome-wide analysis of the CCO gene family in the L. chinense genome and examined its expression pattern during different developmental processes and in response to various abiotic stresses. A total of 10 LcCCO genes were identified and divided into 6 subfamilies according to the phylogenetic analysis. Subcellular localization prediction showed that most of the LcCCO proteins were located in the cytoplasm. Gene replication analysis showed that segmental and tandem duplication contributed to the expansion of this gene family in the L. chinense genome. Cis-element prediction showed that cis-elements related to plant hormones, stress and light response were widely distributed in the promoter regions of LcCCO genes. Gene expression profile analysis showed that LcNCED3b was extensively involved in somatic embryogenesis, especially the somatic embryo maturation, as well as in response to heat and cold stress in leaves. Furthermore, qRT-PCR analysis showed that LcNCED3b obviously responded to drought stress in roots and leaves. This study provides a comprehensive overview of the LcCCO gene family and a potential gene target for the optimization of the somatic embryogenesis system and resistance breeding in the valuable forest tree L. chinense.

The largest Precambrian gas field in China has been found in the central Sichuan Basin. It is assumed as a mound-shoal microfacies-controlled dolomite reservoir. Recently, a large strike-slip fault system has been identified in the gas field that needs further study of its effect on the Ediacaran reservoirs for highly efficient exploitation of the gas field. For this contribution, we study the matrix reservoir and fractured reservoir along the strike-slip fault damage zones by the cores, FMI (Formation MicroScanner Image) and logging interpretation data, seismic description and production data. It has shown that the matrix reservoir is tight (porosity less than 3%, permeability less than 0.5 mD) that cannot support economical production by conventional exploitation technology in the deep subsurface. On the other hand, the porosity and permeability of the Ediacaran fractured reservoirs could be increased more than one time and 1–3 orders of magnitude. Except for a few localized fracture zones, the fracture elements and fractured reservoirs show a paw-law distribution with the distance to the fault core. Furthermore, the fault effect is more favorable for the increase in the porosity and permeability of the matrix reservoir in the intraplatform than in the platform margin. The overlapping of mound-shoal microfacies, fracturing and karstification could result in large-scale “sweet spots” of the fractured reservoirs in the fault damage zone. The “sweet spot” of fractured reservoir in the fault damage zone is a new favorable exploitation target in the deep central Sichuan Basin.

Background and aim: Diagnosing nonalcoholic steatohepatitis (NASH) is challenging. This study intended to explore the diagnostic value of multiple technical acoustic measurements in the diagnosis of NASH, and to establish a diagnostic model combining technical acoustic measurements with clinical parameters to improve the diagnostic efficacy of NASH. Methods: We consecutively enrolled 75 patients with clinically suspected nonalcoholic fatty liver disease (NAFLD) who underwent percutaneous liver biopsy in our hospital from June 2020 to December 2021. All cases underwent multiple advanced acoustic measurements for liver such as shear wave dispersion (SWD), shear wave speed (SWS), attenuation imaging (ATI), normalized local variance (NLV), and liver–kidney intensity ratio (Ratio) examination before liver biopsies. A nomogram prediction model combining the technical acoustic measurements and clinical parameters was established and the model is proposed to improve the diagnostic performance of NASH. Results: A total of 75 cases were included in this study. The classification of pathological grade for NASH was as follows: normal liver, (n = 15, 20%), nonalcoholic fatty liver (NAFL), (n = 44, 58.7%), and NASH, (n = 16, 21.3%). There were statistically significant differences in SWS (p = 0.002), acoustic coefficient (AC) (p = 0.018), NLV (p = 0.033), age (p = 0.013) and fasting blood glucose (Glu) (p = 0.049) between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH, and the calibration curves showed good calibrations in both training and validation sets. The AUCs of the combined nomogram model for the training set and validation set were 0.8597 and 0.7794, respectively. Conclusion: There were statistically significant differences in SWS, AC, NLV, age and Glu between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH. The predictive model has a higher diagnostic performance than a single factor model in the diagnosis of NASH and has good clinical application prospects.

The COBRA gene encodes a plant-specific glycosylphosphatidylinositol (GPI)-anchored protein (GAP), which plays an important role in cell wall cellulose deposition. In this study, a total of 7 COBRA-like (COBL) genes were identified in the genome of the rare and endangered woody plant Liriodendron chinense (L. chinense). Phylogenetic analysis showed that these LcCOBL genes can be divided into two subfamilies, i.e., SF I and II. In the conserved motif analysis of two subfamilies, SF I contained 10 predicted motifs, while SF II contained 4–6 motifs. The tissue-specific expression patterns showed that LcCOBL5 was highly expressed in the phloem and xylem, indicating its potential role in cellulose biosynthesis. In addition, the cis-element analysis and abiotic stress transcriptomes showed that three LcCOBLs, LcCOBL3, LcCOBL4 and LcCOBL5, transcriptionally responded to abiotic stresses, including cold, drought and heat stress. In particular, the quantitative reverse-transcription PCR (qRT-PCR) analysis further confirmed that the LcCOBL3 gene was significantly upregulated in response to cold stress and peaked at 24–48 h, hinting at its potential role in the mechanism of cold resistance in L. chinense. Moreover, GFP-fused LcCOBL2, LcCOBL4 and LcCOBL5 were found to be localized in the cytomembrane. In summary, we expect these results to be beneficial for research on both the functions of LcCOBL genes and resistance breeding in L. chinense.

Abstract In adaptive filtering applications, the Gaussian distribution cannot be used to model the signal/noise with frequent spikes accurately. In fact, the rational model to simulate the behaviour of such signal/noise is the α‐stable distribution process. In this letter, a fractional‐order complex correntropy algorithm is proposed to deal with the case that both signal and noise processes are modelled as complex‐valued α‐stable signals. Compared with the classical approaches, the proposed fractional‐order complex correntropy extends the Gaussian assumption of signal/noise in the complex domain to the assumption of α‐stable distributions without second‐order and higher order statistical moments. Benefitting from the fractional‐order calculus and correntropy criterion, fractional‐order complex correntropy shows great robustness to the jittery behaviour of complex‐valued α‐stable signal/noise. In addition, a convergence analysis for fractional‐order complex correntropy has been carried out. Simulations on system identification revealed that the filtering performance is significantly improved by using fractional‐order complex correntropy.

Abstract Background Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) have been shown to play roles in the pathophysiological processes of sepsis. Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to investigate the potential role and downstream molecular mechanism of exosomal miR-27b in sepsis. Methods Inflammation was induced in bone marrow-derived macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by cecal ligation and puncture (CLP). The expression pattern of miR-27b in MSC-derived exosomes was characterized using RT-qPCR, and its downstream gene was predicted by in silico analysis. The binding affinity between miR-27b, Jumonji D3 (JMJD3), or nuclear factor κB (NF-κB) was characterized to identify the underlying mechanism. We induced miR-27b overexpression or downregulation, along with silencing of JMJD3 or NF-κB to examine their effects on sepsis. The production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 was detected by ELISA. Results miR-27b was highly expressed in MSC-derived exosomes. Mechanistic investigations showed that miR-27b targeted JMJD3. miR-27b decreased expression of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-κB at gene promoter region. Through this, MSC-derived exosomal miR-27b diminished production of pro-inflammatory cytokines in LPS-treated BMDMs and septic mice, which could be rescued by upregulation of JMJD3 and NF-κB. Besides, in vitro findings were reproduced by in vivo findings. Conclusion These data demonstrated that exosomal miR-27b derived from MSCs inhibited the development of sepsis by downregulating JMJD3 and inactivating the NF-κB signaling pathway.

Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most malignant digestive tumors, and its insidious onset and rapid progression are the main reasons for the difficulty in effective treatment. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a key enzyme that regulates phospholipid metabolism of the cell membrane. However, the mechanism by which LPCAT1 regulates HCC metastasis remains unknown. This study aimed to explore its biological function and potential mechanisms concerning migration and invasion in HCC. Materials and methods: LPCAT1 expression in HCC tissues and its association with clinical outcomes were investigated by western blotting and bioinformatic methods, respectively. The role of LPCAT1 in migration and invasion was assessed via Transwell assays. The expression pattern of epithelial-mesenchymal transition (EMT) markers was quantified by western blotting. The biological behaviors of LPCAT1 in vivo were evaluated using xenograft tumor models and caudal vein metastatic models. Signaling pathways related to LPCAT1 were predicted using gene set enrichment analysis (GSEA) and further confirmed by western blotting. Results: LPCAT1 expression was significantly upregulated in HCC tissues and indicated a poor prognosis of HCC patients. Several EMT-related markers were found to be regulated by LPCAT1. HCC cells overexpressing LPCAT1 exhibited remarkably high migration and invasion capacities, upregulated expression of mesenchymal markers and reduced E-cadherin expression. In vivo, LPCAT1 promoted HCC pulmonary metastasis. Furthermore, the Wnt/β-catenin signaling pathway was confirmed to be activated by LPCAT1. Conclusions: LPCAT1 could serve as a promising biomarker of HCC and as a novel therapeutic target for the treatment of metastatic HCC.

Abstract Background Fulvic acid (FA) is a kind of plant growth regulator, which can promote plant growth, play an important role in fighting against drought, improve plant stress resistance, increase production and improve quality. However, the function of FA in tea plants during drought stress remain largely unknown. Results Here, we examined the effects of 0.1 g/L FA on genes and metabolites in tea plants at different periods of drought stress using transcriptomics and metabolomics profiles. Totally, 30,702 genes and 892 metabolites were identified. Compared with controlled groups, 604 and 3331 differentially expressed metabolite genes (DEGs) were found in FA-treated tea plants at 4 days and 8 days under drought stress, respectively; 54 and 125 differentially expressed metabolites (DEMs) were also found at two time points, respectively. Bioinformatics analysis showed that DEGs and DEMs participated in diverse biological processes such as ascorbate metabolism (GME, AO, ALDH and L-ascorbate), glutathione metabolism (GST, G6PDH, glutathione reduced form and CYS-GYL), and flavonoids biosynthesis (C4H, CHS, F3’5’H, F3H, kaempferol, quercetin and myricetin). Moreover, the results of co-expression analysis showed that the interactions of identified DEGs and DEMs diversely involved in ascorbate metabolism, glutathione metabolism, and flavonoids biosynthesis, indicating that FA may be involved in the regulation of these processes during drought stress. Conclusion The results indicated that FA enhanced the drought tolerance of tea plants by (i) enhancement of the ascorbate metabolism, (ii) improvement of the glutathione metabolism, as well as (iii) promotion of the flavonoids biosynthesis that significantly improved the antioxidant defense of tea plants during drought stress. This study not only confirmed the main strategies of FA to protect tea plants from drought stress, but also deepened the understanding of the complex molecular mechanism of FA to deal with tea plants to better avoid drought damage.

Abstract Background To obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis. In this paper, we present a targeted PCa imaging strategy using a real-time molecular photoacoustic imaging system integrated with a handheld US probe (PAI/US) and synthesized an integrin α v β 3 targeted probe based on ICG (cRGD–ICG). Methods To prepare cRGD–ICG, ICG-NHS was linked to cRGD through carboxyl-co-reaction. In vitro PA imaging ability of cRGD–ICG was tested. Orthotopic PCa-bearing rats were used as animal models. After injected with either cRGD–ICG or non-targeted probe, rats were implemented with PA imaging to confirm the specific accumulation of cRGD–ICG at tumor region. Moreover, pathological frozen slices were made to observe distribution of the probe in prostate tissue ex vivo. Results A small molecular PAI probe was synthesized and exhibited excellent targeted imaging ability in vitro. In vivo photoacoustic imaging was carried out after intravenous injection of cRGD-ICG in orthotopic PCa-bearing rats under the facilitation of the PAI/US system. Maximum molecular photoacoustic signals were observed in the tumor area in vivo after the probe injection, which showed 3.8-fold higher signal enhancement than that in the control group (P

Abstract Background Different mulches have variable effects on soil physicochemical characteristics, bacterial and fungal communities and ecosystem functions. However, the information about soil microbial diversity, community structure and ecosystem function in tea plantation under different mulching patterns was limited. In this study, we investigated bacterial and fungal communities of tea plantation soils under polyethylene film and peanut hull mulching using high-throughput 16S rRNA and ITS rDNA gene Illumina sequencing. Results The results showed that the dominant bacterial phyla were Proteobacteria, Actinobacteria, Acidobacteria and Chloroflexi, and the dominant fungal phyla were Ascomycota, Mortierellomycota and Basidiomycota in all samples, but different mulching patterns affected the distribution of microbial communities. At the phylum level, the relative abundance of Nitrospirae in peanut hull mulching soils (3.24%) was significantly higher than that in polyethylene film mulching soils (1.21%) in bacterial communities, and the relative abundances of Mortierellomycota and Basidiomycota in peanut hull mulching soils (33.72, 21.93%) was significantly higher than that in polyethylene film mulching soils (14.88, 6.53%) in fungal communities. Peanut hull mulching increased the diversity of fungal communities in 0–20 cm soils and the diversity of bacterial communities in 20–40 cm soils. At the microbial functional level, there was an enrichment of bacterial functional features, including amino acid transport and metabolism and energy production and conversion, and there was an enrichment of fungal functional features, including undefined saprotrophs, plant pathogens and soils aprotrophs. Conclusions Unique distributions of bacterial and fungal communities were observed in soils under organic mulching. Thus, we believe that the organic mulching has a positive regulatory effect on the soil bacterial and fungal communities and ecosystem functions, and so, is more suitable for tea plantation.

Due to high mobility and flexibility, unmanned aerial vehicles (UAVs) have attracted significant attention from both academia and industry in wireless communications. Different types of UAVs are used for different wireless applications. However, there is a dilemma that no suitable approach is available to provide continuous available long-time wireless coverage from UAV-mounted base stations (UBSs) since rotary-wing UAVs require frequent energy replenishment while fixed-wing UAVs cannot hover at fixed locations. In this paper, the fixed-wing UBS is considered for providing continuous available wireless services to ground users with a novel dynamic resource allocation framework. In particular, the optimal resource allocations for both out-band and in-band wireless backhaul schemes are derived using convex optimization theory. Moreover, the sequential convex optimization method is used to obtain the energy-efficient trajectories. Finally, extensive simulation results are provided to verify the effectiveness of our proposed method. A comparison of out-band and in-band backhaul schemes is also provided.

A Virtual Power Plant (VPP) is a network of distributed power generating units, flexible power consumers, and storage systems. A VPP balances the load on the grid by allocating the power generated by different linked units during periods of peak load. Demand-side energy equipment, such as Electric Vehicles (EVs) and mobile robots, can also balance the energy supply-demand when effectively deployed. However, fluctuation of the power generated by the various power units makes the supply power balance a challenging goal. Moreover, the communication security between a VPP aggregator and end facilities is critical and has not been carefully investigated. This paper proposes an AI-enabled, blockchain-based electric vehicle integration system, named AEBIS for power management in a smart grid platform. The system is based on an artificial neural-network and federated learning approaches for EV charge prediction, in which the EV fleet is employed as a consumer and as a supplier of electrical energy within a VPP platform. The evaluation results show that the proposed approach achieved high power consumption forecast with R2 score of 0.938 in the conventional training scenario. When applying a federated learning approach, the accuracy decreased by only 1.7%. Therefore, with the accurate prediction of power consumption, the proposed system produces reliable and timely service to supply extra electricity from the vehicular network, decreasing the power fluctuation level. Also, the employment of AI-chip ensures a cost-efficient performance. Moreover, introducing blockchain technology in the system further achieves a secure and transparent service at the expense of an acceptable memory and latency cost.

BackgroundThe crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored.MethodsTranscriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTLhigh and DTLlow expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations.ResultsThe DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted.ConclusionsPatients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTLlow group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion.

BackgroundThe AtyPical Asthma in China (APAC) cohort is a multi-center prospective, observational cohort set-up to investigate the clinical, pathophysiological features, prognosis, and mechanisms of cough variant asthma (CVA).ObjectivesTo present the characteristics of newly physician-diagnosed adults with CVA (n = 328) compared to mild-moderate classic asthma (CA, n = 206).Methods and Main ResultsCVA subjects showed a higher proportion of female (67.1 vs. 55.3%, P = 0.0084), abnormal laryngopharyngeal sensations (71 vs. 51%, p < 0.0001) than CA, but presented with near normal spirometry and higher methacholine PD20-FEV1 values [4.2 (1, 8.6) vs. 0.8 (0.4, 4.7), P < 0.0001]. Lower fractional exhaled nitric oxide (FENO) levels [38.5 (19.8, 72.5) vs. 53. (28.5, 92.2), P = 0.0019], blood eosinophil counts [0.2 (0.1, 0.4) vs. 0.3 (0.2, 0.5), P = 0.0014], and sputum eosinophils [2.3 (0.3, 8.0) vs. 12.2 (2, 34.5), p < 0.0001] were found in CVA. Despite lower total serum IgE levels in CVA, there was similar proportion of atopy in both groups. The prevalence of cough in CA was 86.4%, while CVA reported more severe cough on Visual Analog Scale, Cough Evaluation Test, and Leicester Cough Questionnaire, similar anxiety and depression scores but better asthma control scores as reflected by Asthma Control Test compared to CA. No correlation was found between cough assessment outcomes and sputum eosinophil count, blood eosinophil count, FENO, spirometry variables, or PD20-FEV1.ConclusionCough variant asthma is distinctive from classic asthma in regard to clinical features, lung function, and airway inflammation. Quality of life is badly impaired as well in spite of better asthma control scores.

The sugarcane harvester vibration has a bad effect on the sugarcane cutting quality. The effect of sugarcane field roughness on the sugarcane harvester vibration is much more significant than those of cutting forces and the engine. In order to simulate sugarcane field roughness, a simulated sugarcane field exciter (SSFE) was developed to actuate a self-developed sugarcane harvester experiment platform (SHEP). The dynamics and the mathematical models of the SHEP were established. Simulations of the mathematical model show these two models are reasonable. The dynamic characteristic experiment of the SSFE shows it matches characteristics of sugarcane field roughness, but great lateral oscillations existed when it worked. Then the SSFE II was developed. The dynamic characteristic experiment of the SSFE II shows it matches characteristics of sugarcane field roughness and improves the SSFE. The modal test of the SHEP was done to further study dynamic characteristics of the SSFE II. With the SSFE II, simulated experiments of sugarcane harvesters under complete vibration causing conditions can be done in labs instead of sugarcane fields to avoid the low efficiency, poor security, and bad reliability during experiments in sugarcane fields.

One-stage stochastic linear complementarity problem (SLCP) is a special case of a multi-stage stochastic linear complementarity problem, which has important applications in economic engineering and operations management. In this paper, we establish asymptotic analysis results of a sample-average approximation (SAA) estimator for the SLCP. The asymptotic normality analysis results for the stochastic-constrained optimization problem are extended to the SLCP model and then the conditions, which ensure the convergence in distribution of the sample-average approximation estimator for the SLCP to multivariate normal with zero mean vector and a covariance matrix, are obtained. The results obtained are finally applied for estimating the confidence region of a solution for the SLCP.

Background: Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor (HDACi) romidepsin was approved for relapsed and refractory (R/R-PTCL) in 2011. This meta-analysis was performed to assess the efficacy and safety of romidepsin in PTCL.Methods: We searched for articles on the HDAC inhibitor romidepsin in the treatment of PTCL in Embase, Web of Science, and PubMed. The methodology is further detailed in PROSPERO (CRD42020213651, CRD42020213553). The 2-year overall survival (OS), 2-year progression-free survival (PFS), and their corresponding to 95% confidence intervals (CIs) were measured. Besides, corresponding 95% CIs were pooled for the complete response (CR), partial response (PR), duration of response (DoR), and risk of adverse events (AEs).Results: Eleven studies containing 388 patients were incorporated into the quantitative synthesis, of which R/R-PTCL patients were the dominant portion, accounting for 94.3% (366/388). For all studies, the CR rate was 20% (95% CI, 13–27%, random effects model), and the PR rate was 18% (95% CI, 12–25%, random effects model). The 2-year OS was 48% (95% CI, 38–59%, fixed effects model), and the 2-year PFS was 17% (95% CI, 13–21%, fixed effects model). There were no significant differences between romidepsin monotherapy and romidepsin plus additional drugs. Hematological toxicities, such as lymphopenia and granulocytopenia, remained the most continually happening grade 3 or higher AEs, accounting for 46 and 28%, respectively. None of the studies reported any drug-related mortality.Conclusions: Considering that most of the included patients had R/R-PTCL, the addition of romidepsin significantly enhance the efficacy. And AEs were tolerable as the grade 3/4 AEs in romidepsin monotherapy was 7% (95% CI, 6–8%). It is imperative to further expand the first-line application of romidepsin and carry out personalized therapy based on epigenomics, which will improve the survival of PTCL patients.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213651 and https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213553.

Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HT2CR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients’ appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HT2CR in the hypothalamus. It is known that the mCPP, a kind of 5-HT2CR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HT2CR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HT2CR was expressed in both mouse pancreatic β cells and β-cell–derived MIN6 cells. Dose-dependent activation of 5-HT2CR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HT2CR abolished lorcaserin’s effect in vitro. Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca2+)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca2+)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca2+ influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HT2CR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin.

Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.

Phosphate-solubilizing bacteria (PSB) can alleviate available phosphorus deficiency without causing environmental pollution, unlike chemical phosphate fertilizers. However, the phosphate solubilization mechanisms of PSB are still unclear. Transcriptome sequencing was used to analyze the expression patterns of differential expressed genes (DEGs) of the phosphate-solubilizing bacterium W134 under the conditions of soluble phosphorus (group A), insoluble phosphorus (group B), and lacking phosphorus (group C). Nine DEGs in three different groups were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Then, high performance liquid chromatography (HPLC) was applied to detect the concentrations and composition of organic acids. Compared with group A, Gene Ontology (GO) annotation showed that the cluster of W134 DEGs in groups B and C were basically the same. Besides, the results of enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated that genes in the Citrate cycle (TCA cycle) pathway closely related to organic acid production were significantly upregulated. The qRT-PCR results were almost consistent with the expression trends of the transcriptome data. The HPLC results showed that the formic acid, ascorbic acid, acetic acid, citric acid, and succinic acid concentrations were significantly increased in group B and C (p < 0.05), while the contents of lactic acid and malic acid were significantly increased in group B (p < 0.05). The above results provided further validation that the upregulated genes should be related to W134 secretion of organic acids. Our study revealed several potential candidate genes and tried to explain phosphate solubilization mechanisms. This provides a new insight for calcareous reclaimed soil, and it will reduce the need of chemical phosphate fertilizers to promote environmentally friendly agriculture.

Age-related macular degeneration (AMD), featured with dysfunction and loss of retinal pigment epithelium (RPE), is lacking efficient therapeutic approaches. According to our previous studies, human amniotic epithelial stem cells (hAESCs) may serve as a potential seed cell source of RPE cells for therapy because they have no ethical concerns, no tumorigenicity, and little immunogenicity. Herein, trichostatin A and nicotinamide can direct hAESCs differentiation into RPE like cells. The differentiated cells display the morphology, marker expression and cellular function of the native RPE cells, and noticeably express little MHC class II antigens and high level of HLA-G. Moreover, visual function and retinal structure of Royal College of Surgeon (RCS) rats, a classical animal model of retinal degeneration, were rescued after subretinal transplantation with the hAESCs-derived RPE like cells. Our study possibly makes some contribution to the resource of functional RPE cells for cell therapy. Subretinal transplantation of hAESCs-RPE could be an optional therapeutic strategy for retinal degeneration diseases.

Abstract Background Snakebites can lead to lifelong consequences and is one of the main causes of death among military troops worldwide. However, few Chinese military medics know the proper first aid procedures for snakebites. Therefore, this study aimed to explore the impact of the Standard Operation Procedure (SOP) and checklist on Chinese military medics’ ability to manage snakebite first aid. Methods This study was a prospective single-blind randomized controlled trial conducted in a military medical university of China from May to June 2017. A questionnaire-based survey was performed to collect the participants’ socio-demographic profiles before the baseline measurement. During the baseline measurement, participants were requested to provide corresponding first aid that was responsive to the simulative situation portrayed by the SPs (standardized patients) and the evaluators then scored their performances according to a checklist for snakebite first aid scoring table. After the baseline measurement, they were randomly assigned to one of three intervention groups after stratification according to their baseline performance scores: group A received a self-learning course with textbooks (n = 27), group B received a self-learning training on the SOP and checklist (n = 27) and group C was engaged in an interactive discussion panel regarding the SOP and checklist (n = 26). After the interventions, participants received outcome measurements about snakebite first aid key points capability from the same evaluator and SP for each group to avoid observational error. The reviewers were blinded about the grouping in the trial. Results The baseline measurement yielded no significant difference (H = 1.647, P = 0.439) among the three groups. The post-intervention scores were higher than the pre-intervention scores for all three (A, B and C) groups (P = 0.008, P

Abstract Background Deep brain stimulation (DBS) has a good prospect for treating many brain diseases. Recent studies have shown that axonal activation induced by pulse stimulations may play an important role in DBS therapies through wide projections of axonal fibers. However, it is undetermined whether the downstream neurons are inhibited or excited by axonal stimulation. The present study addressed the question in rat hippocampus by in vivo experiments. Methods Pulse stimulations with different frequencies (10–400 Hz) were applied to the Schaffer collateral, the afferent fiber of hippocampal CA1 region in anaesthetized rats. Single-unit spikes of interneurons and pyramidal cells in the downstream region of stimulation were recorded and evaluated. Results Stimulations with a lower frequency (10 or 20 Hz) did not change the firing rates of interneurons but decreased the firing rates of pyramidal cells (the principal neurons) significantly. The phase-locked firing of interneurons during these stimulations might increase the efficacy of GABAergic inhibitions on the principal neurons. However, stimulations with a higher frequency (100–400 Hz) increased the firing rates of both types of the neurons significantly. In addition, the increases of interneurons’ firing were greater than the increases of pyramidal cells. Presumably, increase of direct excitation from afferent impulses together with failure of GABAergic inhibition might result in the increase of pyramidal cells’ firing by a higher stimulation frequency. Furthermore, silent periods appeared immediately following the cessation of stimulations, indicating a full control of the neuronal firing by the stimulation pulses during axonal stimulation. Furthermore longer silent periods were associated with higher stimulation frequencies. Conclusions Low-frequency (10–20 Hz) and high-frequency (100–400 Hz) stimulations of afferent axonal fibers exerted opposite effects on principal neurons in rat hippocampus CA1. These results provide new information for advancing deep brain stimulation to treat different brain disorders.

Abstract Background Lysine crotonylation, as a novel evolutionarily conserved type of post-translational modifications, is ubiquitous and essential in cell biology. However, its functions in tea plants are largely unknown, and the full functions of lysine crotonylated proteins of tea plants in nitrogen absorption and assimilation remains unclear. Our study attempts to describe the global profiling of nonhistone lysine crotonylation in tea leaves and to explore how ammonium (NH4 +) triggers the response mechanism of lysine crotonylome in tea plants. Results Here, we performed the global analysis of crotonylome in tea leaves under NH4 + deficiency/resupply using high-resolution LC-MS/MS coupled with highly sensitive immune-antibody. A total of 2288 lysine crotonylation sites on 971 proteins were identified, of which contained in 15 types of crotonylated motifs. Most of crotonylated proteins were located in chloroplast (37%) and cytoplasm (33%). Compared with NH4 + deficiency, 120 and 151 crotonylated proteins were significantly changed at 3 h and 3 days of NH4 + resupply, respectively. Bioinformatics analysis showed that differentially expressed crotonylated proteins participated in diverse biological processes such as photosynthesis (PsbO, PsbP, PsbQ, Pbs27, PsaN, PsaF, FNR and ATPase), carbon fixation (rbcs, rbcl, TK, ALDO, PGK and PRK) and amino acid metabolism (SGAT, GGAT2, SHMT4 and GDC), suggesting that lysine crotonylation played important roles in these processes. Moreover, the protein-protein interaction analysis revealed that the interactions of identified crotonylated proteins diversely involved in photosynthesis, carbon fixation and amino acid metabolism. Interestingly, a large number of enzymes were crotonylated, such as Rubisco, TK, SGAT and GGAT, and their activities and crotonylation levels changed significantly by sensing ammonium, indicating a potential function of crotonylation in the regulation of enzyme activities. Conclusions The results indicated that the crotonylated proteins had a profound influence on metabolic process of tea leaves in response to NH4 + deficiency/resupply, which mainly involved in diverse aspects of primary metabolic processes by sensing NH4 +, especially in photosynthesis, carbon fixation and amino acid metabolism. The data might serve as important resources for exploring the roles of lysine crotonylation in N metabolism of tea plants. Data were available via ProteomeXchange with identifier PXD011610.

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

In machine-type communication (MTC) consisting high-mobility machines, such as vehicles, aircrafts, robots, etc., there is a strong demand for fast wireless networking. With radars extensively applied in these machines for environment awareness, radar assisted fast neighbor discovery (ND) for wireless ad hoc networks is proposed to realize fast wireless networking for MTC. Four neighbor discovery algorithms are designed according to the accuracy level of prior information provided by radar. Then, the performance of neighbor discovery algorithms is analyzed theoretically. Simulation results are further provided to compare neighbor discovery algorithms with and without the prior information from radar. The results demonstrate that the time consumption of neighbor discovery is greatly reduced with prior information of radar. Moreover, the time consumption with prior information from radar increases with the number of nodes. However, the increasing speed is much slower than the neighbor discovery without prior information from radar. This paper proves the advantages of radar assisted neighbor discovery, which may motivate the study of radar assisted wireless networking schemes in the future.

Abstract Background Continuity of care (COC) has become a primary point of concern for care providers in both developed and developing countries, which is regarded as the “cornerstone of care” and an “essential element” of good health care. A robust and proper instrument is of necessity to identify problems and evaluate intervention aimed at improving continuity of care. This study aimed to adapt Nijmegen continuity questionnaire (NCQ) into a Chinese version (NCQ-C) and to delineate the status of COC as well as explore its influencing factors for hypertensive patients in China. Methods A forward-back-translation procedure was adopted for the determination of the adaption of NCQ. Then a total of 448 patients completed questionnaires and 24-h ambulatory blood pressure monitoring (ABPM). Proper indexes were calculated to test the reliability and validity of NCQ-C. Logistic analysis were used to detect the influencing factors of COC. Results The NCQ-C had excellent intraclass correlation coefficient of 0.855 and internal consistency of seven dimensions varied from 0.907 to 0.944. The item-content validity index ranged from 0.71 to 1.00. For construct validity, seven-factor structure was confirmed as original questionnaire and all the fit indices indicated acceptable levels. Gender, education level, medical insurance and frequency of family visits, blood pressure level, depression status as well as general health perception were demonstrated to be statistically related to COC. Conclusions In addition, all the parameters of ABPM were negatively significant with COC. The NCQ-C has shown acceptable level of reliability and validity. The related factors of COC should arouse care providers’ attention.

The return of straw is a widely used agricultural practice for increasing the soil organic carbon (SOC) content and improving soil structure in Mollisols, owing to the decline caused by continuous high-intensity tillage. We conducted a field experiment where corn straw was continuously returned for 10 years to investigate effects of the straw on the size distribution and stability of soil aggregates and on SOC density fractions. The treatments were no straw return (CK) and four rates of straw return: 6000 kg hm−2 (S1), 9000 kg hm−2 (S2), 12,000 kg hm−2 (S3), and 15,000 kg hm−2 (S4). SOC contents after straw return for bulk soil, a free light fraction (F-LF), an occluded light fraction (O-LF), and a heavy fraction (HF) were significantly higher by 27.0, 644.3, 720.0, and 69.2%, respectively, in S4 than CK. The contents of F-LF, O-LF, and HF in aggregates >2.00 mm were significantly higher by 194.2, 162.1, and 35.8%, respectively, in S4 than CK. Structural equation modeling indicated that SOC contents and aggregates >0.25 mm were directly correlated with the amount of straw returned. We conclude that returning 15,000 kg m−2 of straw would be an effective agronomic practice to restore Mollisol fertility.

Background: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. Methods: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL. Results: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern. Conclusions: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease.

Introduction: Noninvasive ventilation (NIV) has been used to alleviate hypoxemia and dyspnea, but there is no consensus on the application of NIV in patients with coronavirus disease 2019 (COVID-19). Some staff use NIV as the rescue therapy which might lead to the adverse outcomes. This study was to identify early factors associated with intubation to help the medical staff select appropriate patients for receiving NIV treatment.Methods: Patients with laboratory-confirmed COVID-19 who were treated with NIV in emergency department or ICU of the Third People's Hospital (the only designated hospital for treating COVID-19 in Shenzhen) between January 1 and August 31, 2020, were retrospectively analyzed.Results: Thirty-nine patients with COVID-19 treated with NIV were included; of them, 16 (41%) received endotracheal intubation and 3 (8%) died. Significant differences were observed between intubated and non-intubated patients in PaO2/FiO2 before NIV initiation, hospitalization duration, NIV as the rescue therapy, and PaO2/FiO2 of ≤200 mmHg after 1–2 h of NIV initiation. Notably, 1–2 h after NIV initiation, a PaO2/FiO2 of ≤200 mmHg (odds ratio [OR], 9.35; 95% confidence interval [CI], 1.84–47.62; P = 0.007) and NIV as the rescue therapy (OR, 5.43; 95% CI, 1.09–27.12; P = 0.039) were the risk factors for intubation.Conclusions: In patients with COVID-19-related acute hypoxemic respiratory failure receiving NIV, close attention should be paid to PaO2/FiO2 after 1–2 h of NIV initiation. Also, using NIV as rescue therapy should draw our awareness that it might delay escalation of respiratory support and lead to adverse outcomes.

The clinical significance of mutation in multiple pulmonary nodules is largely limited by single gene mutation-directed analysis and lack of validation of gene expression profiles. New analytic strategy is urgently needed for comprehensive understanding of genomic data in multiple pulmonary nodules. In this study, we performed whole exome sequencing in 16 multiple lung nodules and 5 adjacent normal tissues from 4 patients with multiple pulmonary nodules and decoded the mutation information from a perspective of cellular functions and signaling pathways. Mutated genes as well as mutation patterns shared in more than two lesions were identified and characterized. We found that the number of mutations or mutated genes and the extent of protein structural changes caused by different mutations is positively correlated with the degree of malignancy. Moreover, the mutated genes in the nodules are associated with the molecular functions or signaling pathways related to cell proliferation and survival. We showed a developing pattern of quantity (the number of mutations/mutated genes) and quality (the extent of protein structural changes) in multiple pulmonary nodules. The mutation and mutated genes in multiple pulmonary nodules are associated with cell proliferation and survival related signaling pathways. This study provides a new perspective for comprehension of genomic mutational data and might shed new light on deciphering molecular evolution of early stage lung adenocarcinoma.

ABSTRACT Salmonella enterica serotype Kentucky is frequently associated with high-level fluoroquinolone resistance and has gained epidemiological importance globally. A retrospective screening was performed to understand the national prevalence of ciprofloxacin-resistant S. Kentucky in China. S. enterica strains (n = 15,405) were collected within the frame of two national surveillance networks between 2013 and 2017. Thirty-three S. Kentucky strains were detected in 5 of 10 provinces, and 27 were assigned to sequence type 198 (ST198). The 27 isolates were multidrug resistant, with high-level resistance to ciprofloxacin, and 21 isolates were further resistant to extended-spectrum cephalosporins (ESCs). Phylogenomic analysis classified ST198 isolates into two clades (198.1 and 198.2), and recent occurrences of inter-/intraregion and interhost transmission were identified. Phylogenetic reconstruction with a global collection showed that one subclade of clade 198.2 was clustered with historical strains from Egypt, and the other one was clustered with strains from Southeast Asia. Isolates of clade 198.1 were clustered with strains isolated from North America. The various patterns of mutations detected in quinolone resistance-determining regions of GyrA and ParC are accordant with the phylogenetic structure. These findings indicate that our isolates may have various origins. SGI1 was exclusively detected in isolates of clade 198.2 with a highly mosaic structure, which were mainly identified as SGI1-K derivatives. Plasmid-mediated quinolone resistance genes qnrS1 and aac(6′)-Ib-cr were identified in three isolates, and blaCTX-M-9 and blaCTX-M-27 were detected in 20 of 21 ESC-resistant isolates. This is the first report of the genetic and epidemiological characterization for the S. Kentucky epidemic clone ST198 in China, warranting the necessity of surveillance for the high-risk clone. IMPORTANCE Ciprofloxacin and extended-spectrum cephalosporins are the choice for treatment of severe nontyphoidal S. enterica infections in adults. S. enterica serotype Kentucky ST198 has gained epidemiological importance globally, because the clone is frequently resistant to both of these high-level-resistance drug groups. The genetic and epidemiological characterization of S. Kentucky has been well studied in Western countries; however, the information is unclear for China. To fill in the gap, we here did a retrospective screening on a large collection in China, and ST198 isolates were systematically analyzed by whole-genome sequencing. Our study revealed that multidrug-resistant ST198 has spread in five provinces, and the occurrences of interregion and cross-host clonal disseminations were detected. Of note, phylogenomic analysis suggests that the Chinese isolates may have emerged with diverse origins, including Egypt, Southeast Asia, and North America. This study warrants the necessity of surveillance for the high-risk clone to prevent its further dissemination in China.

The plants of Prunus mostly bloom in early spring, and the flowers of various species possess their individual floral scent characteristics; Prunus mume, especially, can volatilize a large amount of benzenoid compounds into the air during the flowering phase. In order to elucidate the molecular basis of the differences in the volatile capacity of aromatic substances among Prunus flowers, the endogenous and the headspace volatile components and the expression of ABCG genes were studied among P. mume, P. armeniaca, and P. persica. We detected the floral components in the three species by gas chromatography-mass spectrometry (GC-MS), and we found that benzaldehyde was the key component. Meanwhile, the volatilization efficiency of benzaldehyde in P. mume and P. armeniaca were much higher than that in P. persica. Furthermore, 130, 135, and 133 ABC family members from P. mume, P. armeniaca, and P. persica were identified, respectively. WGCNA analysis demonstrated that candidate ABCG genes were positively correlated with benzaldehyde volatilization efficiency. Moreover, quantitative Real-time PCR indicated that ABCG17 was more likely to be involved in the transmembrane transport of benzaldehyde. This study aimed to provide a theoretical basis for elucidating the transmembrane transport of benzaldehyde and to further the valuable information for fragrant flower breeding in Prunus.

Abstract Background Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear. Objective The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long‐acting beta‐agonists was explored in a 52‐week multicenter, prospective, real‐world study. Results After 52 weeks of treatment with therapy regimens used for CA, the mean 5‐point Asthma Control Questionnaire (ACQ‐5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447‐0.900, P

China once suffered greatly from schistosomiasis japonica, a major zoonotic disease. Nearly 70 years of multidisciplinary efforts have achieved great progress in disease control, with infections in both humans and bovines significantly reduced to very low levels. However, reaching for the target of complete interruption of transmission at the country level by 2030 still faces great challenges, with areas of ongoing endemicity and/or re-emergence within previously 'eliminated' regions. The objectives of this study were, by using meta-analytical methods, to estimate the overall prevalence of Schistosoma japonicum infections in abundant commensal rodent species in mainland China after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. In doing so we thereby aimed to further assess the role of wild rodents as potential reservoirs in ongoing schistosome transmission. Published studies on infection prevalence of S. japonicum in wild rodents in mainland China since 1980 were searched across five electronic bibliographic databases and lists of article references. Eligible studies were selected based on inclusion and exclusion criteria. Risks of within and across study biases, and the variations in prevalence estimates attributable to heterogeneities were assessed. The pooled infection prevalence and its 95% confidence intervals (CIs) were calculated with the Freeman-Tukey double arcsine transformation. We identified a total of 37 relevant articles involving 61 field studies which contained eligible data on 8,795 wild rodents across mainland China. The overall pooled infection prevalence was 3.86% (95% CI: 2.16-5.93%). No significant change in the overall pooled prevalence was observed between 1980-2003 (n = 23 studies) and 2004-current (n = 38 studies). However, whilst the estimated prevalence decreased over time in the marshland and lake regions, there was an apparent increase in prevalence within hilly and mountainous regions. Among seven provinces, a significant prevalence reduction was only seen in Jiangsu where most endemic settings are classified as the marshland and lakes. These estimates changed over season, ranging from 0.58% in spring to 22.39% in winter, in association with increases in rodent density. This study systematically analyzed S. japonicum infections in wild rodents from the published literature over the last forty years after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. Although numbers of schistosomiasis cases in humans and bovines have been greatly reduced, no such comparable overall change of infection prevalence in rodents was detected. Furthermore, there appeared to be an increase in S. japonicum prevalence in rodents over time within hilly and mountainous regions. Rodents have been projected to become the dominant wildlife in human-driven environments and the main reservoir of zoonotic diseases in general within tropical zones. Our findings thus suggest that it is now necessary to include monitoring and evaluation of potential schistosome infection within rodents, particularly in hilly and mountainous regions, if we are ever to reach the new 2030 elimination goals and to maximize the impact of future public, and indeed One Health, interventions across, regional, national and international scales.

Loss of valued diadromous fishes and their habitats is one of the most critical problems in aquatic habitat connection and resource management worldwide. In China, the Poyang, Dongting, Gaobao, Gucheng, Dongping, and Taihu lakes were known to be historical migratory spawning sites of the anadromous estuarine tapertail anchovy Coilia nasus. However, except for Poyang Lake, it is believed that these lakes are no longer used by anadromous fish owing to overfishing, water pollution, and loss of connectivity. To confirm this assumption, we used an electron probe microanalyzer to analyze elemental strontium (Sr) and calcium (Ca) microchemical patterns in the otoliths of C. nasus individuals sampled from these lakes, in accordance with our previous analysis of the otolithic patterns of the same species sampled from habitat areas characterized by different salinity gradients. The results of line transect analysis of Sr/Ca ratios and Sr X-ray intensity maps of the otoliths indicated that all individuals from Dongting, Gaobao, Gucheng, Taihu, and Dongping lakes were characterized by a freshwater-resident life history. In contrast, individuals from Poyang Lake exhibited both freshwater-resident and anadromous life histories. The findings of this pilot study suggest that anadromous C. nasus can be found in Poyang Lake but are unlikely to be found in Dongting, Gaobao, Gucheng, Dongping, or Taihu lakes, despite these lakes being historical distribution areas or even spawning sites. This anchovy can possibly be used as a good model species for understanding the aforementioned global problem. Given that C. nasus is a commercially important species, restoration of its natural habitats and maintenance of their connections are recommended for its management and conservation.

Intraocular pressure (IOP) generates stress and strains in the laminar cribrosa and sclera, which may affect the development and progression of glaucoma. Scleral stiffness and material components have changed under elevated IOP. However, the detailed changes of the components of the hypertensive sclera are not well understood. In this study, we aimed to investigate the changes of the main components in the scleral extracellular matrix (ECM), and matrix metalloproteinase 2 (MMP2) and their relationship with time under chronic elevated IOP in Sprague–Dawley rats. An ocular hypertension model was established in the right eyes by anterior chamber injection with 0.3% carbomer solution. The left eye was used as the contralateral control. Immunofluorescent imaging of the tissue frozen sections, Western blot analysis, and quantitative PCR (qPCR) were performed to detect the expressions of type I collagen (COL1), elastin, and MMP2 in the sclera. The ocular hypertension model was successfully established. As compared to the left eyes, the immunofluorescence imaging, Western blot analysis, and qPCR showed that COL1, elastin, and MMP2 were significantly increased in the right eyes at 1 week (all P < 0.05). At 2 weeks, COL1 in the right eyes tended to be lower than that in the left eyes, while elastin and MMP2 were still higher (all P < 0.05) in the right eyes. When the IOP was elevated for 4 weeks, both COL1 and MMP2 were lower than those in the left eyes (all P < 0.05), while elastin between the two eyes was similar (P > 0.05). Under this 4-week hypertensive state, COL1 and elastin were initially elevated at 1 week, and then obviously reduced from 2 to 4 weeks. Consistently, MMP2 was gradually increased, with a peak at 2 weeks, and then decreased at 4 weeks. In conclusion, the chronic elevated IOP induced dynamic scleral ECM alterations in rats in a pressure- and time-dependent manner. MMP2 may play an important role in the balance between ECM synthesis and degradation and could potentially be a novel target for glaucoma intervention.

Radiotherapy has been used in the clinic for more than one century and it is recognized as one of the main methods in the treatment of malignant tumors. Signal Transducers and Activators of Transcription 3 (STAT3) is reported to be upregulated in many tumor types, and it is believed to be involved in the tumorigenesis, development and malignant behaviors of tumors. Previous studies also found that STAT3 contributes to chemo-resistance of various tumor types. Recently, many studies reported that STAT3 is involved in the response of tumor cells to radiotherapy. But until now, the role of the STAT3 in radioresistance has not been systematically demonstrated. In this study, we will review the radioresistance induced by STAT3 and relative solutions will be discussed.

The present study aimed to investigate factors predicting inquiry-based teaching in science across One Belt One Road countries and regions (OBOR economies). Teacher-level ( N = 8,603) and school-level ( N = 1,385) data were drawn from the Program for International Student Assessment (PISA) 2015. Hierarchical linear modeling was adopted for data analysis. The results showed at the teacher level that teacher collaboration was positively correlated with inquiry-based teaching in OBOR economies, and that teacher beliefs were positively associated with inquiry-based teaching in each sample. At the school level, no consistent result was found among OBOR economies. School location was positively related to inquiry-based teaching in the Dominican Republic, Macao, and the United Arab Emirates. By contrast, science-specific resources showed a negative association with inquiry-based teaching in Taiwan, the Czech Republic, and Macao. Other specific findings were presented and the implications of all findings were discussed.

Lung cancer remains a leading cause of cancer-associated mortality worldwide, however, molecular mechanisms underlying lung cancer tumorigenesis and progression remain unknown. Here, we report evidence showing that one member of the mammalian methyltransferase-like family (METTL), METTL7B, is a potential molecular target for treatment of non-small cell lung cancer (NSCLC). METTL7B expression was elevated in the majority of NSCLC comparing to normal tissues. Increased expression of METTL7B contributed to advanced stages of tumor development and poor survival in NSCLC patients. Lentivirus-mediated shRNA silencing of METTL7B suppressed proliferation and tumorigenesis of cancer cells in vitro and in vivo. Investigation on gene expression profiles of NSCLC cells revealed that abundant cell cycle related genes were downregulated in the absence of METTL7B. Pathway enrichment analysis indicated that METTL7B participated in cell cycle regulation. Notably, CCND1, a key regulator for G1/S transition, was significantly decreased with the depletion of METTL7B, resulting in G0/G1 arrest, indicating that METTL7B is critical for cell cycle progression. Taken together, our findings implicate that METTL7B is essential for NSCLC development and progression. METTL7B might serve as a potential therapeutic target for NSCLC.

Drought and heat stresses can influence the expressions of genes, and thereby affect the growth and development of plants. Alternative splicing (AS) of genes plays crucial roles through increasing transcriptome diversity in plant stress responses. Tea plants, widely cultivated in the tropics and subtropics, are often simultaneously exposed to drought and heat stresses. In the present study, we performed a global transcriptome of tea leaves treated with drought, heat or their combination. In total, 19,019, 20,025 and 20,253 genes underwent AS in response to drought (DT), heat (HT) and their combined stress (HD), respectively, of which 12,178, 11,912 and 14,413 genes differentially spliced in response to DT, HT and HD, respectively. Also, 2,447 specific differentially spliced genes (DSGs) were found only in response to HD. All DSGs accounted for 48% of the annotated genes in tea tree genome. Comparison of DSGs and differentially expressive genes (DEGs) showed that the proportions of HT and HD-induced DSGs were 13.4% and 9.2%, while the proportion of DT increased to 28.1%. Moreover, the DEG-DSG overlapped genes tended to be enriched in a wide large of pathways in response to DT. The results indicated that the AS of genes in tea leaves was extensively triggered by drought, heat and their combined stresses. In addition, the AS enhanced the transcriptome adaption in response to drought and heat stresses, and the AS also provoked specific molecular functions in response to drought and heat synergy stress. The study might have practical significance for molecular genetic breeding of tea plants with stress resistance.

Improving the assessment of breast imaging reporting and data system (BI-RADS) 4 lesions and reducing unnecessary biopsies are urgent clinical issues. In this prospective study, a radiomic nomogram based on the automated breast volume scanner (ABVS) was constructed to identify benign and malignant BI-RADS 4 lesions and evaluate its value in reducing unnecessary biopsies. A total of 223 histologically confirmed BI-RADS 4 lesions were enrolled and assigned to the training and validation cohorts. A radiomic score was generated from the axial, sagittal, and coronal ABVS images. Combining the radiomic score and clinical-ultrasound factors, a radiomic nomogram was developed by multivariate logistic regression analysis. The nomogram integrating the radiomic score, lesion size, and BI-RADS 4 subcategories showed good discrimination between malignant and benign BI-RADS 4 lesions in the training (AUC, 0.959) and validation (AUC, 0.925) cohorts. Moreover, 42.5% of unnecessary biopsies would be reduced by using the nomogram, but nine (4%) malignant BI-RADS 4 lesions were unfortunately missed, of which 4A (77.8%) and small-sized (