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Aim Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in humans and is caused by mutations in the PKD1 or PKD2 gene. ADPKD is heterogeneous with regard to locus and allele heterogeneity and phenotypic variability. Methods Using targeted capture associated with next generation sequencing (NGS), we performed a mutational analysis of Han Chinese patients with ADPKD from 62 unrelated families. Multivariate Cox proportional hazard modelling of their different clinical characteristics and mutation classes was performed. Results The detection rate for a PKD1 and PKD2 mutation in the Chinese ADPKD patients was 95.2% (59/62). We identified pathogenic mutations in 64.4% (38/59) of patients, including 32PKD1 mutations (15 nonsense mutations, 15 frameshift mutation, one splice mutation, and one large deletion) and six PKD2 mutations (three nonsense mutations and three frameshift mutations). Of the pathogenic variants we identified, 50% (19/38) were novel variants and 50% (19/38) were known variants. Patients with PKD2 mutations had milder and indistinguishable phenotypes. Significant phenotypic differences were observed among the various types of PKD1 mutations. Conclusion Our results show that targeted capture associated with next-generation sequencing is an effective strategy for genetically testing ADPKD patients. This mutation analysis of ADPKD in Han Chinese extends our understanding of the genetic diversity of different ethnic groups, enriches the mutation database, and contributes to the genetic counselling of ADPKD patients.

The SiCp/Al composites was modified by electroless nickel plating, the corrosion behavior of Ni-coated SiCp/Al composites in 0.05 M NaCl solution was investigated by situ electrochemical techniques. The surface properties of the Ni-coated SiCp/Al composites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive spectrometer (EDS). The results showed that: The Ni-P layer is the most uniform with a thickness of 15 μm after electroless nickel plating for 60 min; Soak in 0.05 M NaCl solution, Ni-coated SiCp/Al composites exhibits higher corrosion potential and impedance values than non-coated SiCp/Al composite, showed that a greater corrosion resistance of Ni-coated SiCp/Al composite, and the corrosion resistance of SiCp/Al composite is the best after 60 min nickel plating. The Scanning Electrochemical Microscopy (SECM) measurements showed that the formation of the corrosion-resistant passive film in the Ni-coated SiCp/Al composites are easier, and the main corrosion mechanism of composites is local corrosion. The nickel phosphorus compound is easily produced on the surface of Ni-coated SiCp/Al composites after polarizing 1 h, which inhibits the corrosion of the composite. Thus, the Ni-coated SiCp/Al composite has greater corrosion resistance in a chloride-containing environment than the SiCp/Al composite.

Estimation and hypothesis test for partial linear single-index multiplicative models are considered in this paper. To estimate unknown single-index parameter, we propose a profile least product relative error estimator coupled with a leave-one-component-out method. To test a hypothesis on the parametric components, a Wald-type test statistic is proposed. We employ the smoothly clipped absolute deviation penalty to select relevant variables. To study model checking problem, we propose a variant of the integrated conditional moment test statistic by using linear projection weighting function, and we also suggest a bootstrap procedure for calculating critical values. Simulation studies are conducted to demonstrate the performance of the proposed procedure and a real example is analyzed for illustration.

We consider quantile additive models with dynamic (time-varying) component functions. We allow some of the component functions to be non-dynamic, and show, as expected but technically nontrivially, that estimators of the non-dynamic functions have a faster convergence rate. A penalization-based method, called dynamic structure pursuit, is proposed to automatically identify these non-dynamic functions. Finally, in the sparse setting, a four-stage estimation procedure is proposed which first identifies the nonzero component functions and then applies the identification strategy of the non-dynamic functions. Theoretical and numerical results are provided to illustrate the performance of the estimators.

The accurate and effective retrieval of forage phosphorus (P) content can provide significant information for the management of pastoral agriculture and grazing livestock. In this study, we constructed 39 models to estimate the forage P of alpine grassland in the east of Tibetan Plateau based on hyperspectral remote sensing and multiple factors (topography, soil, vegetation and meteorology) using a machine learning algorithm. The results show that (1) first derivative (FD) and continuum removal (CR) spectra can retrieve more feature bands that are mainly located in the near infrared (NIR) and shortwave infrared (SWIR) regions than log transformed (Log (1/R)) and original (OR) spectra for the forage P estimation; (2) in terms of the model precision, the combination of important bands (IBs) and important factors (longitude and monthly mean temperature) increase the accuracy of forage P estimation as compared with the models that used IBs alone; and (3) considering the precision, stability and simplicity of the model comprehensively, the FD-IBs + support vector machine (SVM) model is the optimum forage P inversion model, which presents coefficient of determination (R2) and root mean squared error (RMSE) values of 0.67 and 0.0472%, respectively, and standard deviations (SDs) of 0.2386 and 0.0050%, respectively. This model can account for 88% of the variation of forage P in alpine grassland. This study demonstrates the importance of using a multi-factor modeling approach and spectral transformation techniques for estimating the forage P of grasslands and provides a scientific basis for the reasonable use and management of alpine grassland resources.

Due to poor electro-active and less structural differences of glucocorticoids, it is still a challenge to realize simultaneous electrochemical detection of different glucocorticoids in wastewater. In this study, an electrochemical biosensing platform was constructed through electrochemical in situ polymerization. A poly(sulphosalicylic acid) (PSSA) composite electrode was prepared based on polymerized L-arginine (Arg) doped with carbon quantum dots (QDs) and GCE-Arg-PSSA-QD sensor was obtained. Transmission electron microscopy, scanning electron microscopy and energy dispersive spectrometer were used to characterize the morphology and physical property of obtained electrodes. The PSSA layer mimics the sulfonated metabolism of glucocorticoids in vivo, allowing for direct reduction of glucocorticoids on the surface of electrode, thus enabling the capture of different glucocorticoids. Meanwhile, the fast electron transfer of QDs and the signal magnification effect of Arg allow a sensitive and direct detection of dexamethasone (DXM) and hydrocortisone (HC) simultaneously. Differential pulse voltammetry was used to investigate the analytical properties of prepared biosensing platform. The results show that GCE-Arg-PSSA-QD sensor delivered an analytical performance for both DXM and HC with a limit of detection of 9 nM and 37 nM. Then, the method was utilized for simultaneous detection of DXM and HC in real wastewater samples with favorable results.

Wenjing Yu,1,* Xiaowei Shi,2,* Xia Cui,1 Yan Niu,1 Wen Zhang,1 Xue Bai,3 Qian Wang,1 Lijun Hu,1 Sumei Wang4 1Department of Pediatrics, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China; 2School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China; 3Department of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China; 4Department of Pediatrics, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China *These authors contributed equally to this workPurpose: This study explored whether Jian-Pi-Zhi-Dong-Decoction (JPZDD) could regulate the metabolism of glutamate (GLU) and its transporters in the striatum to exert anti-tics effects in Tourette syndrome (TS) rats.Materials and methods: We randomly assigned 56 Sprague Dawley rats into four groups, each with 14 rats: control, model, tiapride (Tia), and JPZDD. TS groups (model, Tia, and JPZDD) received intraperitoneal injection of 3,3'-iminodipropionitrile for 7 days to establish TS model. Thereafter, rats in the four groups were treated differently once a day for 6 weeks. Behavioral evaluation was performed each week by using stereotypy recording and autonomic activity test. The level of GLU in the striatum was examined by high-performance liquid chromatography. Expression of EAAT1 and VGLUT1 were measured by quantitative real-time PCR (qRT-PCR) and laser scanning confocal microscope.Results: Compared with the model group, the stereotypy score and autonomic activity were decreased in Tia and JPZDD groups. Notably, the model group had increased concentration of GLU, which decreased after JPZDD and Tia treatments. In the model group, EAAT1 and glial cells were highly co-expressed and the relative fluorescence intensity (FI) of EAAT1 was significantly lower than that in the control group. Treatment with JPZDD and Tia increased the relative FI of EAAT1. The mRNA level of EAAT1 decreased in the model group compared to that in the control group, although it was significantly elevated following JPZDD or Tia treatment. In the model group, there was low co-expression of VGLUT1 and axon cells and the FI of VGLUT1 was remarkably increased relative to that in the control group and reduced following treatment with JPZDD and Tia. A similar trend was observed in the mRNA and protein expression of VGLUT1, although it was not statistically significant.Conclusion: The mechanism by which JPZDD alleviated behavioral dysfunction of TS rats may be associated with maintaining normal GLU transport by upregulating EAAT1 and downregulating VGLUT1 in the striatum. Keywords: Jian-Pi-Zhi-Dong-Decoction, Tourette syndrome, glutamate, EAAT1, VGLUT1&nbsp

Background Autism spectrum disorder is a neurodevelopmental disorder with increasing incidence. At present, the global incidence of the disease is on the rise, and the cause is unknown. There is no specific treatment for this disease at present, mainly education and training. Traditional Chinese medicine treatment has a certain effect on the improvement of the symptoms of the disease. The treatment methods are mainly oral Chinese medicine and acupuncture, but children are often not easy to cooperate. As a safe and effective green therapy, massage is easy to be accepted by children. Methods We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating autism spectrum disorders: Wanfang and PubMed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to March 2021. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. Results This proposed study will evaluate the effectiveness and safety of massage therapy for patients with autism spectrum disorders. The outcomes will include changes in autism spectrum disorder relief and adverse effect. Conclusion This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with autism spectrum disorders. Dissemination and ethics The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

Background Glioma stem-like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth. Methods GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC-87 and GSC-251, respectively. The interactions between miR-326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay. Results SNHG9 expression was significantly higher in GSC-87 and GSC-251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR-326 to elevate the expression of SOX9, a direct target of miR-326. Moreover, transfection with miR-326 inhibitor counteracted SNHG9 knockdown-mediated inhibition of GSC cell growth. Conclusions SNHG9 facilitates growth of GSCs via the miR-326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment.

BackgroundWhile chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy.Methods112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events.ResultsThe radiation dose to PBM (V5~V45, Dmean, P10~V35, Dmean, P5~V40, Dmean, PPP>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05).ConclusionsApplying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

Selection for favorable inflorescence architecture to improve yield is one of the crucial targets in crop breeding. Different tomato varieties require distinct inflorescence-branching structures to enhance productivity. While a few important genes for tomato inflorescence-branching development have been identified, the regulatory mechanism underlying inflorescence branching is still unclear. Here, we confirmed that SISTER OF TM3 (STM3), a homolog of Arabidopsis SOC1, is a major positive regulatory factor of tomato inflorescence architecture by map-based cloning. High expression levels of STM3 underlie the highly inflorescence-branching phenotype in ST024. STM3 is expressed in both vegetative and reproductive meristematic tissues and in leaf primordia and leaves, indicative of its function in flowering time and inflorescence-branching development. Transcriptome analysis shows that several floral development-related genes are affected by STM3 mutation. Among them, FRUITFULL1 (FUL1) is downregulated in stm3cr mutants, and its promoter is bound by STM3 by ChIP-qPCR analysis. EMSA and dual-luciferase reporter assays further confirmed that STM3 could directly bind the promoter region to activate FUL1 expression. Mutation of FUL1 could partially restore inflorescence-branching phenotypes caused by high STM3 expression in ST024. Our findings provide insights into the molecular and genetic mechanisms underlying inflorescence development in tomato.

Breast cancer is one of the most commonly diagnosed malignancies in women and is an important cause of cancer death. In this paper, the anti - breast cancer components of ginsenoside derivatives were studied by computer simulation. In this paper, effective components of ginseng were retrieved from TCSMP database, and target genes of active components were obtained from UniPort database. Through molecular docking technology, the key genes differentially expressed in the active components of ginseng and breast cancer were scored by molecular docking to obtain the active components of ginseng with the highest binding degree, and the next cell experiment was conducted for verification. The results of this study show that G_Rh2, a key active component of Chinese herbal medicine ginseng, can inhibit the proliferation, ha migration and invasion of human breast cancer cell lines MDA-MB-231 and MDA-MB-468. This result can provide a molecular basis for the further study of ginseng in the treatment of breast cancer, and also indicates the feasibility of using network pharmacology to connect large-scale target data to discover the mechanism of TCM components interfering with the disease.

Edible oils and oil-containing foods have been regarded as the main source of 3-monochloropropane-1, 2-diol (3-MCPD) esters. A total of 3,847 individual food samples were collected in China to carry out 3-MCPD fatty acid esters analysis. The samples comprising edible oils, fried foods and bakery foods from 31 Chinese provinces, municipalities and autonomous regions were obtained from the national food contaminant information system during 2015-2017. The dietary exposure and potential risks associated with the consumption of 3-MPCD esters from edible oils and oil-containing foods were estimated using a semi-probabilistic assessment model. Concentrations of 3-MCPD fatty acid esters in food samples were detected by gas chromatography-mass spectrometry (GC-MS). The mean levels of 3-MCPD fatty acid esters in edible oils, fried foods and bakery foods were 0.862, 0.249 and 0.145 mg/kg, respectively. The range of mean dietary intakes of 3-MCPD esters in different subpopulation groups (classified by gender and age) was from 0.586 to 1.539 μg/kg bw/day, which were all lower than 2 μg/kg bw/day - the tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA). The range of dietary intake of 3-MCPD esters in high consumers (95th percentile) in each group was from 1.511 to 4.027 μg/kg bw/day, which accounted for 75.6% to 201.4% of the TDI. The 3-MCPD esters exposure level of 3.5% of the total Chinese population exceeded the TDI. The findings indicate that the potential health risks caused by dietary 3-MCPD esters from edible oils and oil-containing foods were of low concern for most of the Chinese population. However, the exposure risk of the consumers with excessive edible oil consumption calls for attention.

As a typical steroid hormone drug, estradiol (E2) is also one of the most frequently detected endocrine disrupting chemicals (EDCs) in the aquatic environment. Herein, in response to the potential risk of E2 in steroid hormone pharmaceutical industry wastewater to human and wildlife, a novel carbon nanotubes / amine-functionalized Fe

Partially linear generalized single index models are widely used and have attracted much attention in the literature. However, when the covariates are subject to measurement error, the problem is much less studied. On the other hand, instrumental variables are important elements in studying many errors-in-variables problems. We use the relation between the unobservable variables and the instruments to devise consistent estimators for partially linear generalized single index models with binary response. We establish the consistency, asymptotic normality of the estimator and illustrate the numerical performance of the method through simulation studies and a data example. Despite the connection to (Scand. J. Statist. 42 (2015) 104–117) in its general layout, the mathematical derivations are much more challenging in the context studied here.

Aristolochic acid Ⅰ is a nephrotoxic compound and exist in some traditional Chinese medicines at trace level. Up to now, specific enrichment of aristolochic acid Ⅰ remains important procedure and key problem in its analysis. In this study, melamine was proposed as the recognition unit and grafted on the surface of metal-organic framework to fabricate a specific material for aristolochic acid Ⅰ. This material was prepared by using a two-step strategy and the preparation process was optimized. The physical and chemical properties were investigated using scanning electron microscopy, Fourier-transfer infrared spectroscopy, X-ray diffraction and nitrogen adsorption-desorption techniques. Adsorption properties were evaluated by binding experiments. The melamine modified material exhibited a uniform morphology, high specific surface area (460.20 m2 g-1), high adsorption capacity (25.57 mg g-1), fast mass transfer rate and excellent selectivity. Further, a specific and sensitive method was established by using this material as adsorbent of mini-solid phase extraction. The limit of detection was as low as 0.02 μg mL-1. Therefore, melamine modified metal-organic framework is an ideal adsorbent for the recognition and enrichment of aristolochic acid Ⅰ.

Background: Temozolomide (TMZ) resistance is a serious hindrance in clinical chemotherapy for glioma. Circular RNA homeodomain interacting protein kinase 3 (circHIPK3) can be involved in regulating...

Gap-filling eddy covariance flux data using quantitative approaches has increased over the past decade. Numerous methods have been proposed previously, including look-up table approaches, parametric methods, process-based models, and machine learning. Particularly, the REddyProc package from the Max Planck Institute for Biogeochemistry and ONEFlux package from AmeriFlux have been widely used in many studies. However, there is no consensus regarding the optimal model and feature selection method that could be used for predicting different flux targets (Net Ecosystem Exchange, NEE; or Evapotranspiration –ET), due to the limited systematic comparative research based on the identical site-data. Here, we compared NEE and ET gap-filling/prediction performance of the least-square-based linear model, artificial neural network, random forest (RF), and support vector machine (SVM) using data obtained from four major row-crop and forage agroecosystems located in the subtropical or the climate-transition zones in the US. Additionally, we tested the impacts of different training-testing data partitioning settings, including a 10-fold time-series sequential (10FTS), a 10-fold cross validation (CV) routine with single data point (10FCV), daily (10FCVD), weekly (10FCVW) and monthly (10FCVM) gap length, and a 7/14-day flanking window (FW) approach; and implemented a novel Sliced Inverse Regression-based Recursive Feature Elimination algorithm (SIRRFE). We benchmarked the model performance against REddyProc and ONEFlux-produced results. Our results indicated that accurate NEE and ET prediction models could be systematically constructed using SVM/RF and only a few top informative features. The gap-filling performance of ONEFlux is generally satisfactory (R2 = 0.39–0.71), but results from REddyProc could be very limited or even unreliable in many cases (R2 = 0.01–0.67). Overall, SIRRFE-refined SVM models yielded excellent results for predicting NEE (R2 = 0.46–0.92) and ET (R2 = 0.74–0.91). Finally, the performance of various models was greatly affected by the types of ecosystem, predicting targets, and training algorithms; but was insensitive towards training-testing partitioning. Our research provided more insights into constructing novel gap-filling models and understanding the underlying drivers affecting boundary layer carbon/water fluxes on an ecosystem level.

Background: Cervical cancer (CC) is a common gynecological malignancy with a high risk of recurrence and death. Circular RNAs play a crucial role in the occurrence and development of tumors. This study aimed to investigate the function and mechanism of circ_0000745 in CC. Methods: The levels of circ_0000745, miR-409-3p, and activating transcription factor 1 (ATF1) were determined by quantitative real-time polymerase chain reaction or western blot assay. Cell proliferation was assessed by colony formation assay. Cell migration and invasion were evaluated by transwell assay. Glycolysis was analyzed by measuring extracellular acidification rate, glucose uptake, and lactate production. Also, the protein levels of glucose transporter 1 and lactate dehydrogenase A were detected using western blot. The relationship among circ_0000745, miR-409-3p, and ATF1 were confirmed by dual-luciferase reporter assay. Moreover, xenograft assay was performed to analyze tumor growth in vivo. Results: Circ_0000745 and ATF1 were upregulated, whereas miR-409-3p was downregulated in CC tissues and cells. Knockdown of circ_0000745 repressed proliferation, migration, invasion, and glycolysis of CC cells. Circ_0000745 regulated CC progression by targeting miR-409-3p. Circ_0000745 modulated ATF1 expression through sponging miR-409-3p. MiR-409-3p hindered CC progression by targeting ATF1. Furthermore, depletion of circ_0000745 impeded tumor growth in vivo. Conclusion: Circ_0000745 promoted the progression of CC through modulating miR-409-3p/ATF1 axis, indicating a promising biomarker for CC therapy.

To perform a comprehensive meta-analysis of all available evidence on the efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction.We searched English and Chinese databases and calculated the weighted mean difference or standardized mean difference and 95% confidence intervals to estimate the efficacy and safety of renal denervation for heart failure. All relevant studies were screened and a meta-analysis was conducted using Review Manager 5.4.A total of 11 studies were identified for the meta-analysis. For the primary outcomes, the results showed that renal denervation significantly improved ejection fraction (weighted mean difference 6.42), left ventricular end-systolic diameter (weighted mean difference -3.95), left ventricular end-diastolic diameter (weighted mean difference -4.17) and left atrial diameter (weighted mean difference -4.09). For the secondary outcomes, renal denervation reduced the B-type natriuretic peptide level, heart rate, systolic blood pressure and diastolic blood pressure. However, further analysis revealed that renal denervation improved heart function but did not further reduce the heart rate and blood pressure compared with the control group.Treatment with renal denervation can significantly improve heart function and structure in patients with heart failure. In addition, the level of B-type natriuretic peptide can be reduced after renal denervation treatment. Renal denervation did not further reduce heart rate and blood pressure compared with the control group. Therefore, the treatment of heart failure with renal denervation is effective and safe.

Amino acid neurotransmitters have been shown to correlate with Tourette syndrome (TS) and its comorbidities. In this study, we investigated the effects of Jian-Pi-Zhi-Dong Decoction (JPZDD), a formula containing 10 different Chinese medical herbs, on amino acid neurotransmitters in rats. We established a rat model of Tourette syndrome and comorbid anxiety with an iminodipropionitrile injection plus uncertain empty water bottle stimulation for 3 weeks. Then the rats were randomly divided into four groups: control group and model group were gavaged with saline, while the remaining two treatment groups were gavaged with fluoxetine hydrochloride or JPZDD for four consecutive weeks. We recorded the behaviors of the rats with TS and comorbid anxiety by stereotypy recording, open field test, and elevated plus maze. We observed mitochondrial changes with transmission electron microscopy. We measured the content of glutamate (GLU) and γ-aminobutyric acid (GABA) both in the serum and striatum and the expression of their receptors by Western blot and real-time polymerase chain reaction. The study revealed that JPZDD was effective in alleviating the behavioral symptoms of both tic and anxiety in the rat model groups. These results might be associated with the increase in GABA levels and decrease in GLU levels in the serum, as well as an increase in striatal GABA level by the activation of GABA receptors Type A (GABAAR). JPZDD treatment also reversed the mitochondrial dysfunction both in the striatum and cortex in affected animals.

Background Breast cancer is the most frequently diagnosed malignancy among women and the second leading cause of cancer death worldwide. Among which nuclear estrogen receptor (nER) negative breast cancer is always with much poor prognosis. Recently, membrane G protein coupled estrogen receptor (GPER), a newly recognized estrogen receptor has been documented to take essential part in the development and treatment of breast cancer. The present study was designed to investigate the anti nER negative breast cancer effect of cryptotanshinone (CPT), an important active compound of traditional Chinese medicine Danshen and its possible molecular pathway. Methods The following in vitro tests were performed in nER negative but GPER positive breast cancer SKBR-3 cells. The effect of CPT on cell proliferation rate and cell cycle distribution was evaluated by MTT cell viability test and flow cytometry assay respectively. The role of PI3K/AKT pathway and the mediated function of GPER were tested by western blot and immunofluorescence. Technique of gene silence and the specific GPER agonist G-1 and antagonist G-15 were employed in the experiments to further verify the function of GPER in mediating the anticancer role of CPT. Results The results showed that proliferation of SKBR-3 cells could be blocked by CPT in a time and dose dependent manner. CPT could also exert antiproliferative activities by arresting cell cycle progression in G1 phase and down regulating the expression level of cyclin A, cyclin B, cyclin D and cyclin-dependent kinase 2 (CDK2). The antiproliferative effect of CPT was further enhanced by G-1 and attenuated by G-15. Results of western blot and immunofluorescence showed that expression of PI3K and p-AKT could be downregulated by CPT and such effects were mediated by GPER which were further demonstrated by gene silence test. Conclusion The current study showed that the antiproliferative action of CPT on SKBR-3 cells was realized by inhibition of GPER mediated PI3K/AKT pathway. These findings provide further validation of GPER serving as useful therapeutic target.

This paper studies the measure of symmetry or asymmetry of a continuous variable under the multiplicative distortion measurement errors setting. The unobservable variable is distorted in a multiplicative fashion by an observed confounding variable. First, two direct plug-in estimation procedures are proposed, and the empirical likelihood based confidence intervals are constructed to measure the symmetry or asymmetry of the unobserved variable. Next, we propose four test statistics for testing whether the unobserved variable is symmetric or not. The asymptotic properties of the proposed estimators and test statistics are examined. We conduct Monte Carlo simulation experiments to examine the performance of the proposed estimators and test statistics. These methods are applied to analyze a real dataset for an illustration.

A method is described for the functionalization of magnetic carbon nanotubes to recognize aristolochic acid Ⅰ and Ⅱ. 3-Glycidyloxypropyltrimethoxysilane was used as a coupling agent to immobilize adenine on a solid support. The morphology and structure of adenine-coated magnetic carbon nanotubes was investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and a vibrating sample magnetometer (VSM). The adsorption performance of the adenine-coated magnetic carbon nanotubes was evaluated via adsorption isotherms, the kinetics and selectivity tests. The adsorption capacity of the adenine-functionalized sorbent for aristolochic acid Ⅰ was determined to be 24.5 μg mg−1. By combining magnetic solid phase extraction with HPLC detection, a method was developed to enrich and detect aristolochic acids used in traditional Chinese medicine. A satisfactory recovery (92.7 - 97.5% for aristolochic acid Ⅰ and 92.6 - 99.4% for aristolochic acid Ⅱ) and an acceptable relative standard deviation (

Fluconazole and voriconazole are the two broad-spectrum triazole antifungals. The present work described the fabrication method for the synthesis of the amino-modified magnetic metal–organic framework. This material was applied as a pre-sample treatment sorbent for the selective extraction of fluconazole and voriconazole in rat plasma samples. The material was fabricated by the chemical bonding approach method and was characterized by different parameters. The factors which affect the extraction efficiency of the sorbent material were also optimized in this study. Due to the optimization of solid-phase extraction conditions, the nonspecific interaction was reduced and the extraction recoveries of target drugs were increased in plasma samples. The extraction method was combined with the HPLC-UV method for the analysis. Excellent linearity (0.1–25 µg/mL), detections (0.02, 0.03 µg/mL) and quantification limits (0.04, 0.05 µg/mL) were resulted for fluconazole and voriconazole respectively. The maximum recoveries from spiked plasma samples of fluconazole and voriconazole were 86.8% and 78.6% and relative standard deviation were 0.9–2.8% and 2.2–3.6% respectively. Moreover, this sorbent material was used multiple times which was an improvement over single-use commercial sorbent materials. This validated method has practical potential for the simultaneous determination of these drugs in therapeutic drug monitoring studies as well as for routine pharmacokinetic evaluations.

For a two-layer finite difference scheme with second-order time accuracy of nonlinear diffusion equations, we present three iterative solving algorithms, including Picard, Picard-Newton and derivative-free Picard-Newton iterations. The main purpose of this paper is to solve the two-layer scheme efficiently and accurately, and give strict theoretical proofs of the convergence and efficiency of the three iterative methods. For the three iterative methods, two strategies are adopted to offer iterative initial evaluations, one is to use the value at the previous time step with first-order accuracy, the other is an extrapolation with second-order accuracy. With an induction reasoning technique, we prove that the solutions of the three iterative methods all converge to the exact solution of the diffusion problem with second-order accuracy both in space and time after two nonlinear iteration steps, even if the first-order initial value is used. It is also proved that the solutions of Picard iteration converge linearly to the solution of the discrete scheme, while Picard-Newton and derivative-free Picard-Newton iterative solutions converge with a quadratic speed. Moreover, no difference occurs in convergent speed with the two different initial values. Finally, some numerical tests are presented to verify our theoretical results, which show that compared with Picard iteration, Picard-Newton and derivative-free Picard-Newton iterations are more efficient for solving nonlinear problems.

TNF signaling mostly supports cell growth by activating NFκB and only induces cell death when NFκB activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NFκB signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.

Tomato (Solanum lycopersicum) is a major vegetable fruit grown and consumed worldwide. Modern cultivated tomatoes are derived from their wild relative, Solanum pimpinellifolium, a short-day plant that originated from the Andean region of South America. The molecular underpinnings of the regional adaptation and expansion of domesticated tomato remain largely unclear. In this study, we examined flowering time in wild and cultivated tomatoes under both long-day and short-day conditions. Using quantitative trait locus mapping in a recombinant inbred line population, we identified SELF PRUNING 5G (SP5G) as a major locus influencing daylength adaptation in tomato. Genetic diversity analysis revealed that the genomic region harboring SP5G shows signatures of a domestication sweep. We found that a 52-bp sequence within the 3ʹ untranslated region of SP5G is essential for the enhanced expression of this gene, leading to delayed flowering time in tomatoes through a promoter-enhancer interaction that occurs only under long-day conditions. We further demonstrate that the absence of the 52-bp sequence attenuates the promoter-enhancer interaction and reduces SP5G expression in cultivated tomatoes, making their flowering time insensitive to daylength. Our findings demonstrate that cis-regulatory variation at the enhancer region of the SP5G 3ʹ untranslated region confers reduced photoperiodic response in cultivated tomatoes, uncovering a regulatory mechanism that could potentially be used to manipulate flowering time in tomato through novel biotechnological approaches.

The study aimed to illuminate the role of G protein coupled estrogen receptor( GPER) and its mediated PI3 K/AKT signaling pathway in cryptotanshinone( CPT) induced apoptosis of breast cancer SKBR-3 cells,which is GPER positive and ER negative.The apoptosis rate of SKBR-3 cells was tested by Annexin V-FITC/PI staining and apoptosis effector caspase-3 was determined by Western blot. The key proteins in PI3 K/AKT signaling pathway mediated by GPER were detected by Western blot and immunofluorescence technique. Meanwhile,the agonist G1 and antagonist G15 of GPER and antagonist LY294002 of PI3 K were employed in the test to further clarify the effect of GPER and PI3 K/AKT pathway. The results indicated that the apoptosis rate was increased from 4. 7% to46. 1% and 69. 0% after treatment with 0,5,10 μmol·L~(-1) CPT for 48 h( P0. 01). The expression of PI3 K,AKT and p-AKT were inhibited( P0. 05 or P0. 01),while caspase-3 level increased obviously after treatment with CPT( P0. 01). Importantly,inhibitory effect of PI3 K/AKT signaling pathway by CPT was further enhanced by G1 and attenuated by G15. LY294002 also induced a further inhibition of expression of AKT and p-AKT. The mean fluorescence intensity of AKT and p-AKT could be decreased by CPT. Furthermore,CPT could downregulate GPER expression in SKBR-3 cells( P0. 01),which could be inhibited by G1 and enhanced by G15.In conclusion,CPT could induce the apoptosis of ER negative and GPER positive breast cancer SKBR-3 cells and the molecular mechanism is related to its regulatory effect of GPER and its mediated PI3 K/AKT signaling pathway.

To determine the distribution characteristics of heavy metal pollution in farmland soils and related influencing factors in the Taige canal valley, and guarantee soil environmental quality and safety of agricultural products, 118 topsoil samples were collected from the Taige canal valley's farmland soils, and contents of chromium (Cr), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), nickel (Ni), lead (Pb), and cadmium (Cd) were measured. A single factor index and comprehensive index were used to assess soil heavy metal contamination with the soil background value of the Taihu Lake basin as the evaluation standard. The multivariate statistical analysis and the geostatistical analysis were combined to identify and apportion the pollution sources of soil heavy metals. The results showed that:The average concentrations of Cr, Hg, As, Cu, Zn, Ni, Pb, and Cd in soils were 63.25, 0.25, 7.83, 35.24, 77.25, 31.48, 38.37, and 0.16 mg·kg

Griseofulvin (GSF) is clinically employed to treat fungal infections in humans and animals. GSF was detected in surface waters as a pharmaceutical pollutant. GSF detection as an anthropogenic pollutant is considered as a possible source of drug resistance and risk factor in ecosystem. To address this concern, a new extraction and enrichment method was developed. GSF-surface molecularly imprinted polymers (GSF-SMIPs) were prepared and applied as solid phase extraction (SPE) sorbent. A dispersive solid phase extraction (DSPE) method was designed and combined with HPLC for the analysis of GSF in surface water samples. The performance of GSF-SMIPs was assessed for its potential to remove GSF from water samples. The factors affecting the removal efficiency such as sample pH and ionic strength were investigated and optimized. The DSPE conditions such as the amount of GSF-SMIPs, the extraction time, the type and volume of desorption solvents were also optimized. The established method is linear over the range of 0.1&ndash, 100 &micro, g/mL. The limits of detection and quantification were 0.01 and 0.03 &micro, g/mL respectively. Good recoveries (91.6&ndash, 98.8%) were achieved after DSPE. The intra-day and inter-day relative standard deviations were 0.8 and 4.3% respectively. The SMIPs demonstrated good removal efficiency (91.6%) as compared to powder activated carbon (67.7%). Moreover, the SMIPs can be reused 10 times for water samples. This is an additional advantage over single-use activated carbon and other commercial sorbents. This study provides a specific and sensitive method for the selective extraction and detection of GSF in surface water samples.

This paper considers estimation and variable selection for multiplicative linear regression models when neither the response variable nor the covariates can be directly observed, but are distorted by unknown functions of a commonly observable confounding variable. After taking logarithmic transformation on the response variable, we propose two estimation methods for the parameter. One is the least squares estimator, the second one is the moment-based estimator linked with varying coefficient models. The third one is the least product relative error estimator without logarithmic transformation. For the hypothesis testing of parametric components, restricted estimators under the null hypothesis and test statistics are proposed. The asymptotic properties for the estimators and test statistics are established. A bootstrap procedure is proposed to calculate critical values. A smoothly clipped absolute deviation penalty is employed to select the relevant variables. The resulting penalized estimators are shown to be asymptotically normal and have the oracle property. Simulation studies demonstrate the performance of the proposed procedure and a real example is analyzed to illustrate its practical usage.

Wild species can be used to improve various agronomic traits in cultivars; however, a limited understanding of the genetic basis underlying the morphological differences between wild and cultivated species hinders the integration of beneficial traits from wild species. In the present study, we generated and sequenced recombinant inbred lines (RILs, 201 F10 lines) derived from a cross between Solanum pimpinellifolium and Solanum lycopersicum tomatoes. Based on a high-resolution recombination bin map to uncover major loci determining the phenotypic variance between wild and cultivated tomatoes, 104 significantly associated loci were identified for 18 agronomic traits. On average, these loci explained ~39% of the phenotypic variance of the RILs. We further generated near-isogenic lines (NILs) for four identified loci, and the lines exhibited significant differences for the associated traits. We found that two loci could improve the flower number and inflorescence architecture in the cultivar following introgression of the wild-species alleles. These findings allowed us to construct a trait-locus network to help explain the correlations among different traits based on the pleiotropic or linked loci. Our results provide insights into the morphological changes between wild and cultivated tomatoes, and will help to identify key genes governing important agronomic traits for the molecular selection of elite tomato varieties.

Low well-being is common among Chinese pregnant women but few effective interventions currently exist to improve prenatal stress and negative emotions. Mindfulness-based stress reduction (MBSR) has been proved to be effective in reducing stress and rarely studies were focused on Chinese pregnant women. The aim of the current paper is to investigate the effects of 8-week MBSR on prenatal stress, anxiety and depression among Chinese pregnant women. A sample of 66 pregnant women randomly allocated into either the MBSR group (n=34) or the control group (n=32). Participants in the MBSR group received a group 8-week, 90-min each time intervention. The results found a significant interaction between time and condition for prenatal stress (F=45.51, p

Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change ( Δ Q c ) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that can regulate target gene expression during many plant growth and development processes. In recent years, several studies identified the miRNAs involved in fruit development, leaf development, and abiotic responses in tomato. However, little is known about the miRNAs that respond to insect attack. Here, miRNAs were identified by high-throughput sequencing at different stages after infections by the whitefly Bemisia tabaci in Solanum lycopersicum and Solanum habrochaites, which are susceptible and resistant to whitefly, respectively. A total of 44 known miRNA families were identified, and 33 were shared between the two species. Among these, 13 miRNA families were newly reported in tomato. After strict filtering, some novel miRNAs were also discovered. The global expression patterns of the miRNAs exhibited were different between the two species, reflecting their different responses and resistance levels to whitefly attack. Some of the predicted target genes of differentially expressed miRNAs may be involved in responding to, and defending against, diseases and insects. Thus, plant miRNAs are important in the responses to, and resistance against, insects and provide a useful resource for further investigations into the mechanism of miRNA-mediated plant–insect interactions. Keywords: Solanum lycopersicum, Solanum habrochaites, Bemisia tabaci, miRNAs, whitefly infection, high-throughput sequencing

Purpose This paper aims to provide a well-behaved nonlinear scheme and accelerating iteration for the nonlinear convection diffusion equation with fundamental properties illustrated. Design/methodology/approach A nonlinear finite difference scheme is studied with fully implicit (FI) discretization used to acquire accurate simulation. A Picard–Newton (PN) iteration with a quadratic convergent ratio is designed to realize fast solution. Theoretical analysis is performed using the discrete function analysis technique. By adopting a novel induction hypothesis reasoning technique, the L∞ (H1) convergence of the scheme is proved despite the difficulty because of the combination of conservative diffusion and convection operator. Other properties are established consequently. Furthermore, the algorithm is extended from first-order temporal accuracy to second-order temporal accuracy. Findings Theoretical analysis shows that each of the two FI schemes is stable, its solution exists uniquely and has second-order spatial and first/second-order temporal accuracy. The corresponding PN iteration has the same order of accuracy and quadratic convergent speed. Numerical tests verify the conclusions and demonstrate the high accuracy and efficiency of the algorithms. Remarkable acceleration is gained. Practical implications The numerical method provides theoretical and technical support to accelerate resolving convection diffusion, non-equilibrium radiation diffusion and radiation transport problems. Originality/value The FI schemes and iterations for the convection diffusion problem are proposed with their properties rigorously analyzed. The induction hypothesis reasoning method here differs with those for linearization schemes and is applicable to other nonlinear problems.

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

Cementitious composites with 0–1.5 wt.% Nano-SiO 2 (NS), nano-TiO 2 (NT), carbon nanotubes (CNTs), carbon nanofibers (CNFs) and carbon microfibers (CFs) are fabricated and tested. The enhancing effects of different fillers on the compressive strength and electrical resistivity of composites are compared, and the underlying modification mechanisms of fillers to composites are investigated by analyzing the difference in the morphology of fillers and rheology of composites. The compressive strength of composites containing 0.1% NS, 0.5% NT, 0.1% CNTs and 0.5% CFs by weight of cement presents approximately 12.5%, 20.8%, 16.8% and 21.4% higher than that of control sample, respectively. It is revealed that CFs also have improving effect on the compressive strength of composites besides flexural strength. When the composites with nano-fillers cannot be processed to ideal state, the reinforcing effect of nano-fillers is no better but even worse than that of micro-fillers. Composites with CNTs, CNFs and CFs possess good electrical conductivity. Composites with CNFs and CFs have a percolation threshold of electrical resistivity below 0.5%, while the percolation threshold of electrical resistivity of composites with CNTs is about 1%. Although CNFs do not have significant effect on compressive strength of composites, they have the best improvement to electrical resistivity.

Mutations in the COL4A5 gene result in X-linked Alport syndrome, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for autosomal recessive Alport syndrome, and heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant Alport syndrome or benign familial hematuria. Recently, the existence of a digenic inheritance in Alport syndrome has been demonstrated. We here report heterozygous COL4A3 and COL4A4 digenic mutations in cis responsible for benign familial hematuria. Using bioinformatics analyses and pedigree verification, we showed that COL4A4 c.1471C>T and COL4A3 c.3418 + 1G>T variants in cis are pathogenic and co-segregate with the benign familial hematuria. This result suggests that COL4A3 and COL4A4 digenic mutations in cis mimicking an autosomal dominant inheritance should be considered as a novel inheritance pattern of benign familial hematuria, although the disease-causing mechanism remains unknown.

In this study, reinforcement effect of 12 types of multiwalled carbon nanotubes (MWCNTs) on mechanical properties of cementitious composites was investigated Research results showed that among pristine MWCNTs with different diameters and lengths, the short MWCNTs with large diameter present the best reinforcing effect on strength of composites. Functionalization of MWCNTs is beneficial for enhancing strength of composites. Moreover, hydroxyl-functionalized MWCNTs feature a better reinforcement effect compared to carboxyl-functionalized MWCNTs. The best relative/absolute enhancements of 79%/74 MPa and 64.4%/5.6 MPa in compressive and flexural strength of composites are achieved by incorporating 0.5% of nickel-coated MWCNTs. XRD analyses revealed that the incorporation of MWCNTs decreases the orientation of CH in matrix, which is consistent with SEM observations. TG analyses showed that MWCNTs inhibit hydration of composites due to their absorption effect. However, extensive MWCNT networks improve microstructure of matrix and hinder the crack development under loading through fiber bridging and pull-out.