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The prediction of bus single-trip time is essential for passenger travel decision-making and bus scheduling. Since many factors could influence bus operations, the accurate prediction of the bus single-trip time faces a great challenge. Moreover, bus single-trip time has obvious nonlinear and seasonal characteristics. Hence, in order to improve the accuracy of bus single-trip time prediction, five prediction algorithms including LSTM (Long Short-term Memory), LR (Linear Regression), KNN (K-Nearest Neighbor), XGBoost (Extreme Gradient Boosting), and GRU (Gate Recurrent Unit) are used and examined as the base models, and three ensemble models are further constructed by using various ensemble methods including Random Forest (bagging), AdaBoost (boosting), and Linear Regression (stacking). A data-driven bus single-trip time prediction framework is then proposed, which consists of three phases including traffic data analysis, feature extraction, and ensemble model prediction. Finally, the data features and the proposed ensembled models are analyzed using real-world datasets that are collected from the Beijing Transportation Operations Coordination Center (TOCC). Through comparing the predicting results, the following conclusions are drawn: (1) the accuracy of predicting by using the three ensemble models constructed is better than the corresponding prediction results by using the five sub-models; (2) the Random Forest ensemble model constructed based on the bagging method has the best prediction accuracy among the three ensemble models; and (3) in terms of the five sub-models, the prediction accuracy of LR is better than that of the other four models.

To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P0.05 or P0.01).EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Objective Endogenous hormones regulate numerous physiological processes in humans. Some of them are routinely measured in blood, saliva and/or urine for the diagnosis of disorders. The analysis of fluids may, however, require multiple samples collected at different time points to avoid the high variability in the concentration of some hormones. In contrast, hair analysis has been proposed as an interesting alternative to reveal average hormone levels over a longer period. In this work, we developed and validated an analytical method for analyzing 36 endogenous steroid and thyroid hormones and one pineal hormone in human hair using ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS). Methods Sample preparation involved hair decontamination, pulverization, methanol extraction, and purification with C18-solid phase extraction. Extracts were then divided into two portions, respectively injected into an UPLC-MS/MS system, and analyzed using two different instrumental methods. The method was applied to a healthy female population aged 25–45 years. Results The method was validated on supplemented hair samples for the 37 targeted hormones, and its application to the population under study allowed to detect 32 compounds in 2–100% of the samples. Complete reference intervals (2.5–97.5th percentiles) were established for estrone, 17β-estradiol, androstenedione, dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, cortisone, cortisol and 3,3’,5-triiodo-L-thyronine. Hair cortisone, cortisol, tetrahydrocortisone and tetrahydrocortisol concentrations were highly correlated with each other, with Kendall’s τ correlation coefficients ranging from 0.52 to 0.68. Conclusion Allowing the detection of 32 hormones from different chemical classes, the present method will allow to broaden hormonal profiling for better identifying endocrine disorders.

Parkin is a crucial E3 ubiquitin ligase for initiating mitophagy through the PINK1/Parkin pathway. Regulating the expression and activity of parkin can remedy mitophagy and human disease. We developed an efficient method to isolate natural parkin ligands from herbal medicines by combining centrifugal ultrafiltration and liquid chromatography/mass spectrometry. The heterologous expression technology identified functionally active and pure parkin proteins. After evaluating the reliability of the method using DL-selenomethionine and DL-dithiothreitol as positive controls, this method was successfully applied to capture parkin ligands from Polygoni Cuspidati Rhizoma et Radix and Sophorae Flavescentis Radix. LC/MS identified seven novel parkin-targeting compounds, namely, 7,4 ′ -dihydroxy-5-methoxy-8-(γ, γ-dimethylallyl)-flavanone, kushenol I, kurarinone, sophoraflavanone G, torachrysone-8-O-glucoside, apigenin, and emodin, supported by the molecular docking analysis. Five of the seven novel compounds (kushenol I, kurarinone, sophoraflavanone G, apigenin, and emodin) can activate parkin in in vitro autoubiquitination assays. Meanwhile, kushenol I and kurarinone had antisteatosis activity in fat emulsion-damaged human hepatocytes. These results confirmed the effectiveness of the method for identifying parkin ligands from complex preparations, useful to advance drug discovery from medicinal herbs.

Dioscorea alata L. (Dioscoreaceae), commonly known as greater yam, water yam, or winged yam, is a popular tuber vegetable/food crop worldwide, with nutritional, health, and economical importance. China is an important domestication center of D. alata, and hundreds of cultivars (accessions) have been established. However, genetic variations among Chinese accessions remain ambiguous, and genomic resources currently available for the molecular breeding of this species in China are very scarce. In this study, we generated the first pan-plastome of D. alata, based on 44 Chinese accessions and 8 African accessions, and investigated the genetic variations, plastome evolution, and phylogenetic relationships within D. alata and among members of the section Enantiophyllum. The D. alata pan-plastome encoded 113 unique genes and ranged in size from 153,114 to 153,161 bp. A total of four whole-plastome haplotypes (Haps I–IV) were identified in the Chinese accessions, showing no geographical differentiation, while all eight African accessions shared the same whole-plastome haplotype (Hap I). Comparative genomic analyses revealed that all four whole plastome haplotypes harbored identical GC content, gene content, gene order, and IR/SC boundary structures, which were also highly congruent with other species of Enantiophyllum. In addition, four highly divergent regions, i.e., trnC–petN, trnL–rpl32, ndhD–ccsA, and exon 3 of clpP, were identified as potential DNA barcodes. Phylogenetic analyses clearly separated all the D. alata accessions into four distinct clades corresponding to the four haplotypes, and strongly supported that D. alata was more closely related to D. brevipetiolata and D. glabra than D. cirrhosa, D. japonica, and D. polystachya. Overall, these results not only revealed the genetic variations among Chinese D. alata accessions, but also provided the necessary groundwork for molecular-assisted breeding and industrial utilization of this species.

Nesfatin-1, an anorexic neuropeptide discovered in 2006, is widely distributed in the central nervous system and peripheral tissues. It has been shown to be involved in the regulation of food intake and lipid metabolism, inhibiting fat accumulation, accelerating lipid decomposition, and in general, inhibiting the development of lipid-related diseases, such as obesity and metabolic syndrome. Potential mechanisms of Nesfatin-1 action in lipid metabolism and lipid-related diseases will be discussed as well as its role as a biomarker in cardiovascular disease. This review expected to provide a new strategy for the diagnosis and prevention of clinically related diseases.

Strategies on the construction of enantiomerically pure silicon-stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh-catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon-centered" racemic hydrosilanes that enables the facile preparation of silicon-stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non-diastereopure-type mixed phosphine-phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the S

A new aerotolerant strain of Clostridium beijerinckii LY-5 was isolated from the pit mud of the Chinese Baijiu-making process for butanol production. Plackett-Burman design and artificial neural network were used to optimize the fermentation medium and a total of 13.54 ± 0.22 g/L butanol and 19.91 ± 0.52 g/L ABE were attained under aerotolerant condition. Moreover, distillers' grain waste (DGW), the main by-product in the Baijiu production process, was utilized as potential substrate for butanol production. DGW was hydrolyzed by α-amylase and glucoamylase and then fermented after a detoxifying process of overliming. Butanol and ABE concentrations were 9.02 ± 0.18 and 9.57 ± 0.19 g/L with the yield of 0.21 and 0.23 g/g sugar, respectively. The higher ratio of butanol to ABE might be caused by the inhibitors in DGW medium affecting the metabolic pathways of C. beijerinckii LY-5 and approximately 1.48 ± 0.04 g/L isopropanol was found at the end of fermentation. This work highlights the feasibility of using DGW as a promising feedstock for butanol production by a new aerotolerant strain of C. beijerinckii LY-5, with benefit to the environment.

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.

Polystyrene (PS) is selected as a representative nanoplastic and persistent pollutant for its difficult degradation and wide application. The environmental risk assessment of PS is obstructed by the toxic dye-based fluorescent PS, which false positives could be induced by the leakage of dye. For high biocompatibility, low toxicity, hydrophilicity, good water dispersibility, strong fluorescent stability, graphene oxide quantum dots (o-CQDs) are selected and embedded into PS microspheres, i.e., o-CQDs@PS, by microemulsion polymerization and denoted as CPS. Meanwhile, the sizes of CPS, e.g., 100, 150, and 200 nm, could be controlled by optimizing the type and number of water-soluble initiators. The anti-interference, low toxicity, and in vivo fluorescent tracing of CPS are proven by the coexistence of metals (including Fe

BACKGROUND In clinical work, 85%-90% of malignant thyroid diseases are papillary thyroid cancer (PTC); thus, clinicians neglect other types of thyroid cancer, such as medullary thyroid carcinoma (MTC). CASE SUMMARY We report a 53-year-old female patient with a preoperative calcitonin level of 345 pg/mL. There was no definitive diagnosis of MTC by preoperative fine-needle aspiration cytology or intraoperative frozen pathology, but the presence of PTC and MTC was confirmed by postoperative paraffin pathology. The patient underwent total thyroidectomy and bilateral central lymph node dissection. Close follow-up at 1.5 years after surgery revealed no signs of recurrence or metastasis. CONCLUSION The issue in clinical work-up regarding types of thyroid cancer provides a novel and challenging idea for the surgical treatment of MTC. In the absence of central lymph node metastasis, it is worth addressing whether patients with high calcitonin can undergo total thyroidectomy and bilateral central lymph node dissection without bilateral lateral neck lymph node dissection.

Operando mass spectrometry is a powerful technique to probe reaction intermediates near the surface of catalyst in electrochemical systems. For electrochemical reactions involving gas reactants, conventional operando mass spectrometry struggles in detecting reaction intermediates because the batch-type electrochemical reactor can only handle a very limited current density due to the low solubility of gas reactant(s). Herein, we developed a new technique, namely flow electrolyzer mass spectrometry (FEMS), by incorporating a gas-diffusion electrode design, which enables the detection of reactive volatile or gaseous species at high operating current densities (>100 mA cm-2 ). We investigated the electrochemical carbon monoxide reduction reaction (eCORR) on polycrystalline copper and elucidated the oxygen incorporation mechanism in the acetaldehyde formation. Combining FEMS and isotopic labelling, we showed that the oxygen in the as-formed acetaldehyde intermediate originates from the reactant CO, while ethanol and n-propanol contained mainly solvent oxygen. The observation provides direct experimental evidence of an isotopic scrambling mechanism.

BACKGROUND: Icariin (ICA) has been widely used in the treatment of osteoporosis. However, the potential mechanism of its critical role in repairing knee cartilage damage still needs to be further clarified. METHODS: First, rabbit bone marrow mesenchymal stem cells (BMSCs) were isolated, cultured, and identified. Subsequently, BMSCs were treated with different concentrations of ICA. Cell Counting Kit 8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) were used to evaluate the cell proliferation in each group. Alcian Blue staining, immunofluorescence, and western blotting were used to evaluate the ability of BMSCs to differentiate cartilage. In addition, a rabbit knee cartilage injury model was established. Evaluation of cartilage defects in each group was performed according to the classification system outlined by the International Cartilage Repair Society (ICRS). Hematoxylin and eosin (HE), Alcian Blue, and immunohistochemistry were used to analyze the pathological status of knee cartilage. RESULTS: In vitro, the results showed that ICA promoted the cartilage differentiation of BMSCs as well as cell proliferation. In addition, ICA promoted the expression of type II collagen (COL2A1), aggrecan, and bone morphogenetic protein 2 (BMP2) in BMSCs, while BMP-Smad inhibitor (Noggin) reversed the repair effect of ICA on BMSCs. In vivo, our results showed that the ICRS score of the BMSC and ICA treatment group was higher. Moreover, BMSC and ICA treatment promoted the proliferation of chondrocytes and repaired the cartilage-like tissue on the surface of cartilage defect. CONCLUSIONS: The combined application of ICA and BMSCs can repair rabbit knee cartilage injury by regulating the BMP/Smads pathway, indicating that ICA and BMSCs may be a viable clinical treatment strategy for knee cartilage damage.

Rice developing prognostication is a key part of precise agricultural management, and its advancement is an intricate course of events involving the interplay of breed and environmental element. The traditional research method is based on data analysis of rice growth prediction modeling, mining the concealed rapport between rice productivity and circumstance element, for instance, weather, sunlight, and water, and then predicting its yield and analyzing the complex rapport between the circumstance element and growth in every developing phase. In this dissertation, the improved ElmanNN is accustomed to establish a prediction model, and the ElmanNN is accustomed to determine the rapport between the circumstance element and growth in every developing phase simultaneously so as to avoid the arithmetic falling into local optimum easily. In this dissertation, the improved genetic arithmetic is accustomed to optimize the initial weight and threshold of Elman neural network, and the range of weight value multitudinous layers in the mould are obtained by training the network with samples that have been tested in the last few years. Finally, the rapport between growth and yield in six different periods is independently modeled, and the training samples are build up separately one by one based on physiological parameters and environmental indicators of rice at every level. The experiments show that the accuracy for the prediction model in the light of the improved ElmanNN has been beneficial.

Pesticide exposure has been associated with hormonal disruption in both animals and humans. However, there is limited knowledge of the combined effects of complex mixtures of pesticides on endogenous hormone levels. Here, we used hair analysis to assess the impact of a pesticide mixture comprising 19 components from multiple chemical classes at eight doses of 0-400 μg/kg body weight (bw) three times per week per component on concentrations of 36 steroid and thyroid hormones in female rats over a 90-day exposure period. We detected 13 hormones in rat hair, namely estradiol (E2), androstenedione (AD), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (P5), progesterone (P4), 11-deoxycorticosterone (11-DOC), corticosterone (CORT), 3,3'-l-diiodothyronine (T2), 3,5,3'-l-triiodothyronine (T3), 3,3',5'-l-triiodothyronine (rT3), and 3,5,3',5'-l-tetraiodothyronine (T4). In comparison to the control group, hair E2 concentration was significantly lower in the two highest (200 and 400 μg/kg bw) exposure groups, whereas hair DHEAS and CORT concentrations were significantly higher in the 40 μg/kg bw and the highest exposure groups, respectively. Results from generalized additive models suggest that pesticide exposure resulted in monotonic dose responses in hair E2 concentration, CORT concentration and DHEA/CORT molar ratio but nonmonotonic dose responses in hair T concentration, DHEAS concentration, P4/P5 and DHEA/DHEAS molar ratios. The associations of E2, CORT and DHEA/CORT ratio with exposure intensity were confirmed by their significant linear relationships with hair concentrations of at least 23 of the 25 exposure biomarkers analyzed. Our results demonstrate that exposure to low levels of the pesticide mixture evaluated here can alter hair reproductive and adrenal hormones levels.

Urea, nickel (Ni) and dissolved organic matter (DOM) from land varied with different sources have a great impact on the offshore ecosystem. The heterogeneity of Ni bioavailability and toxicity of Prorocentrum donghaiense influenced by DOM fractions incubated in urea was investigated in this study. On the occasion, chlorophyll (Chl a) concentration, growth rate, and photosynthesis parameters were monitored to track changes occurring in the test organism. Chl a concentration and photosynthesis parameters in the treatment of hydrophilic DOM (HPI) with Ni-free was significantly higher than that in the control treatment, and similar data were shown in the treatment of hydrophobic DOM（HPO）with the low Ni environment (0.17μmol L

As an important gas signaling molecule, hydrogen sulfide (H2S) plays a crucial role in regulating cold tolerance. H2S cooperates with phytohormones such as abscisic acid, ethylene, and salicylic acid to regulate the plant stress response. However, the synergistic regulation of H2S and auxin in the plant response to cold stress has not been reported. This study showed that sodium hydrosulfide (NaHS, an H2S donor) treatment enhanced the cold stress tolerance of cucumber seedlings and increased the level of auxin. CsARF5, a cucumber auxin response factor (ARF) gene, was isolated, and its role in regulating H2S-mediated cold stress tolerance was described. Transgenic cucumber leaves overexpressing CsARF5 were obtained. Physiological analysis indicated that overexpression of CsARF5 enhanced the cold stress tolerance of cucumber and the regulation of the cold stress response by CsARF5 depends on H2S. In addition, molecular assays showed that CsARF5 modulated cold stress response by directly activating the expression of the dehydration-responsive element-binding (DREB)/C-repeat binding factor (CBF) gene CsDREB3, which was identified as a positive regulator of cold stress. Taken together, the above results suggest that CsARF5 plays an important role in H2S-mediated cold stress in cucumber. These results shed light on the molecular mechanism by which H2S regulates cold stress response by mediating auxin signaling; this will provide insights for further studies on the molecular mechanism by which H2S regulates cold stress. The aim of this study was to explore the molecular mechanism of H2S regulating cold tolerance of cucumber seedlings and provide a theoretical basis for the further study of cucumber cultivation and environmental adaptability technology in winter.

Hierarchical SiC nanowire-supported Pd nanoparticles showed high photocatalytic activity for the C-X (X = Br, I) borylation of aryl halides at 30 °C. The SiC/Pd Mott-Schottky contact enhances the rapid transfer of the photogenerated electrons from SiC to the Pd nanoparticles. As a result, the concentrated energetic electrons in the Pd nanoparticles can facilitate the cleavage of C-I or C-Br bonds, which normally requires high-temperature thermal processes. We show that the present Pd/SiC photocatalyst is capable of catalyzing the transformation of a large variety of aryl halides to their corresponding boronate esters under visible light irradiation, with excellent yields.

Background Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of non-alcoholic fatty liver disease (NAFLD). Polygonatum kingianum (PK) has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet (HFD)-induced NAFLD by promoting mitochondrial functions. To date, the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear. Aim To identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats. Methods NAFLD model was induced in rats with HFD. The rats were intragastrically administered PK (4 g/kg per day) for 14 wk. Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways. Results PK significantly restored the metabolites' levels in the mitochondrial samples. Ten potential biomarkers were identified in the analyzed samples. These biomarkers are involved in riboflavin metabolism. Conclusion PK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions. Thus, PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases.

Polycyclic aromatic hydrocarbons (PAHs) have been shown to influence endogenous hormones levels in animal models, but little is known about the effects of their mixtures. For hormone measurements, hair analysis is a promising approach to provide information on long-term status of hormones. Herein we used hair analysis to assess the combined effects of 13 PAHs on steroid and thyroid hormones levels in a rat model. The PAH mixture was administered orally three times per week to female rats at doses of 0, 10, 20, 40, 80, 200, 400 and 800 μg/kg of body weight for each compound over a 90-day exposure period. Fourteen out of 36 analyzed hormones were detected in rat hair, including pregnenolone (P5), 17α-hydroxyprogesterone (17-OHP4), corticosterone (CORT), dehydroepiandrosterone (DHEA), androstenedione (AD), 3,3'-diiodo-L-thyronine (T2), 3,3',5-triiodo-L-thyronine (T3), and 3,5,3',5'-triiodo-L-thyronine (T4). The PAH mixture significantly elevated P5 and DHEA levels at the doses of 200 and 400 μg/kg but reduced T2 and T3 levels at the highest dose as compared to the control. While P5, DHEA, 17-OHP4 and AD concentrations exhibited inverted U-shaped dose responses, T2, T3 and T4 concentrations exhibited inverse linear dose responses, which are further confirmed by their relationships with hair hydroxylated PAHs (OH-PAHs) concentrations. Likewise, there were significant nonmonotonic relationships of hormone molar ratios (e.g., AD/17-OHP4 and DHEA/CORT ratios) with exposure intensity and OH-PAHs. Overall, our results demonstrate the capability of PAH mixtures to interfere with steroid and thyroid hormones in female rats.

Mulberry, an important woody tree, has strong tolerance to environmental stresses, including salinity, drought, and heavy metal stress. However, the current research on mulberry resistance focuses mainly on the selection of resistant resources and the determination of physiological indicators. In order to clarify the molecular mechanism of salt tolerance in mulberry, the physiological changes and proteomic profiles were comprehensively analyzed in salt-tolerant (Jisang3) and salt-sensitive (Guisangyou12) mulberry varieties. After salt treatment, the malondialdehyde (MDA) content and proline content were significantly increased compared to control, and the MDA and proline content in G12 was significantly lower than in Jisang3 under salt stress. The calcium content was significantly reduced in the salt-sensitive mulberry varieties Guisangyou12 (G12), while sodium content was significantly increased in both mulberry varieties. Although the Jisang3 is salt-tolerant, salt stress caused more reductions of photosynthetic rate in Jisang3 than Guisangyou12. Using tandem mass tags (TMT)-based proteomics, the changes of mulberry proteome levels were analyzed in salt-tolerant and salt-sensitive mulberry varieties under salt stress. Combined with GO and KEGG databases, the differentially expressed proteins were significantly enriched in the GO terms of amino acid transport and metabolism and posttranslational modification, protein turnover up-classified in Guisangyou12 while down-classified in Jisang3. Through the comparison of proteomic level, we identified the phenylpropanoid biosynthesis may play an important role in salt tolerance of mulberry. We clarified the molecular mechanism of mulberry salt tolerance, which is of great significance for the selection of excellent candidate genes for saline-alkali soil management and mulberry stress resistance genetic engineering.

Background. To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. Methods. VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer’s disease (AD) and healthy controls was also checked. Results. Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. Conclusions. VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC.

International audience; Humans are exposed to various anthropogenic chemicals in daily life, including endocrine-disrupting chemicals (EDCs). However, there are limited data on chronic, low-level exposure to such contaminants among the general population. Here hair analysis was used to investigate the occurrence of four polychlorinated biphenyls (PCBs), seven polybrominated diphenyl ethers (PBDEs) and two bisphenols (BPs) in 204 Chinese women living in the urban areas of Baoding and Dalian and 311 pregnant French women. All the PCBs and PBDEs tested here were more frequently detected in the hair samples of the French women than in those of the Chinese women. In both cohorts, PCB 180 and BDE 47 were the dominant PCB and PBDE congener, respectively. PCB 180 was found in 82% of the French women and 44% of the Chinese women, while the corresponding values of BDE 47 were 54% and 11%, respectively. A discriminant analysis further demonstrated the difference in PCBs and PBDEs exposure profile between the two cohorts. These results demonstrate that hair analysis is sufficiently sensitive to detect exposure to these pollutants and highlight differences in exposure between populations even at environmental levels. Although BPA and BPS were found in 100% of the hair samples in both cohorts, the French women had significantly higher levels of BPA and BPS than the Chinese women. The median concentrations of BPA were one order of magnitude higher than BPS in both the Chinese (34.9 versus 2.84 pg/mg) and the French women (118 versus 8.01 pg/mg) respectively. Our results suggest that both French and Chinese populations were extensively exposed to BPA and BPS.

Nine multifarious new meroterpenoids, cochlearols E-M (1-9), along with seven known meroterpenoids 10-16, were isolated from the fruiting bodies of Ganoderma cochlear. Racemic 1, 6-8, 10 and 13 were separated by chiral HPLC. The structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and calculated electronic circular dichroism (ECD). Their biological activities against renal fibrosis were evaluated by using rat normal and diseased renal interstitial fibroblast cells (NRK49F). The results show that compounds 7a, 7b, and 10a exhibit potent proliferation inhibition in TGF-β1-induced NRK-49F cells.

A series of all-conjugated polythiophene diblock copolymers containing hydrophobic (hexyl) and hydrophilic (triethylene glycol) side chains were synthesized via a nickel-catalyzed quasi-living polymerization. The correlations between block ratios and the self-assembled nanostructures of the block copolymers in thin films and in various solutions were examined. The copolymers dispersed in water via a slow dialysis method produced molecular-level self-assembled core–shell nanospheres with a crystallized hydrophobic core and a hydrophilic amorphous shell, which was proved by TEM images. The size and quantum yield of polymer micelles could be easily tuned via the block ratio of copolymers. The resulting core–shell nanospheres of BP40 composed of 40 mol% P3HT blocks with an average size of 120 nm exhibit high quantum yield (19% in aqueous medium), good photostability and low cytotoxicity. Utilized as a far-red/near-infrared (FR/NIR) cellular probe, BP40 is internalized efficiently by the cells and accumulated in the cytoplasm to give bright fluorescence.

The selection of a suitable reference gene is an important prerequisite for the precise analysis of target gene expression by real-time quantitative PCR (qPCR). The present study aims to explore the expression pattern of the Macrobrachium nipponense (M. nipponense) β-actin gene under Aeromonas hydrophila bacterial infection conditions. The complete sequence of the β-actin gene from M. nipponense was cloned by PCR. Identified and named β-actin genes were searched in the NCBI database, and the characteristics of the β-actin gene were analyzed using bioinformatics methods. The expression profiles of β-actin under stresses challenged by bacteria after 3, 6, 12, 24 and 48 h were investigated by measuring Ct values by qPCR. The prokaryotic expression vector pET-30a-actin was constructed by PCR and recombinant DNA techniques. Fused protein was induced by IPTG in the transformed Escherichia coli BL21 (DE3). Recombinant rActin was purified by nickel column. The bioinformatics analysis result revealed that the deduced protein encoded by the β-actin gene from M. nipponense had the highest homology with other prawns in the homologous assay (99%). The phylogenetic tree indicates that the β-actin from M. nipponense and other crustaceans have a single cluster. The qPCR results revealed that a stable expression of β-actin was observed in response to the A. hydrophila challenge for 3-48 h, and the Ct value was 22 ± 1.5. β-actin was ranked as a stable gene after the bacterial challenge, which was selected as the appropriate reference gene in M. nipponense.

In northern China, low temperature is the most common abiotic stresses for tomato plants cultivated in solar-greenhouse in winter. We recently found that the expression and enzyme activity of fructose-1,6-bisphosphate aldolases (FBAs) in tomato, which are important enzymes in the Calvin-Benson cycle (CBC), were significantly altered in tomato seedlings subjected to heat/cold stresses. In order to study the role of FBA in photosynthesis and in regulating cold stress responses of tomato seedlings (Solanum lycopersicum), we transformed a tomato inbred line (FF) with RNA interference (RNAi) vector containing SlFBA7 reverse tandem repeat sequence. We found that the decreased SlFBA7 expression led to the decreased activities of FBA, as well as the activities of other main enzymes in the CBC. We also noticed a decrease in net photosynthetic rate, ribulose-1,5-bisphosphate and soluble sugar content, stem diameter, dry weight and seed size in RNAi SlFBA7 plants compared to wild-type. However, there are no changes in starch contents in the RNAi transgenic plants. RNAi SlFBA7 plants showed a decreased germination rate, and an increased levels of superoxide anions (O2·- ) and hydrogen peroxide (H2 O2 ) under low temperature (8/5°C) and low-light intensity (100 μmol m-2 s-1 photon flux density) growth conditions. These findings demonstrated the important role of SlFBA7 in regulating growth and chilling tolerance of tomato seedlings, and suggested that the catalytic activity of FBA in the CBC is sensitive to temperature.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with an extremely poor prognosis. Effective targets for anticancer therapy confirmed in PDAC are limited. However, the characteristics of genomics have not been fully elucidated in large-scale patients with PDAC from China.We collected both blood and tissue samples from 1080 Chinese patients with pancreatic cancer and retrospectively investigated the genomic landscape using next-generation sequencing (NGS).We found recurrent somatic mutations in KRAS (83.2%), TP53 (70.6%), CDKN2A (28.8%), SMAD4 (23.0%), ARID1A (12.8%) and CDKN2B (8.9%) in Chinese PDAC patients. Compared with primary pancreatic cancers, more genomic alterations accumulated especially cell cycle regulatory gene variants (45.4% vs 31.6%, P0.001) were observed in metastatic tumors. The most common mutation site of KRAS is p.G12D (43.6%) in pancreatic cancer. Patients with KRAS mutations were significantly associated with older age and mutations in the other three driver genes, while KRAS wild-type patients contained more fusion mutations and alternative mechanisms of RTK/Ras/MAPK pathway including a number of clinically targetable mutations. KRAS mutations in Chinese cohort were significantly lower than those in Western cohorts (all P0.05). A total of 252 (23.3%) patients with the core DNA damage response (DDR) gene mutations were detected. ATM (n =59, 5.5%) was the most frequent mutant DDR gene in patients with pancreatic cancer from China. Patients with germline DDR gene mutations were younger (P = 0.018), while patients with somatic DDR gene mutations were more likely to accumulate in metastatic lesions (P0.001) and had higher TMB levels (P0.001). In addition, patients with mutant DDR genes and patients carrying TP53 mutation were observed mutually exclusive (P0.001).We demonstrated the real-world genomic characteristics of large-scale patients with pancreatic cancer from China which may have promising implications for further clinical significance and drug development.The funders are listed in the Acknowledgement.

Nitrite is one of the most common carcinogens in daily food. Its simple, rapid, inexpensive, and in-field measurement is important for food safety, based on the requirements of the standard from Codex Alimentarius Commission and China. Using polyacrylonitrile (PAN) and thin layer silica gel (SG), p-aminophenylcyclic acid (SA) and naphthalene ethylenediamine hydrochloride (NEH), as carriers and chromogenic agents, respectively, PAN-NSS as nitrite color sensor is proposed. After fixing and protecting of SA and NEH with layer-upon-layer PAN, the validity period of the test paper can be prolonged from 7 days to more than 30 days. The reproducibility of PAN-NSS preparation is ensured by electrospinning. Combined with PAN-NSS, deep convolutional neural network (DCNN) and APP as a visual monitoring platform, which has the functions of rapid sampling, data processing and transmission, intuitive feedback, etc., and provides a fully integrated detection system for field detection.

Gene transcription is a stochastic process manifested by the mRNA distribution data at the single-cell level, which can be fitted using the mass function P

A novel molecularly imprinted silica layer appended to FeSe quantum dots (MIP-FeSe-QDs) was fabricated and utilized as a recognition element to develop a selective and sensitive fluorescent nanosensor for cyfluthrin (CYF) determination. The MIP-FeSe-QDs were characterized by fluorescence spectrometry, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Excellent selectivity and high sensitivity of MIP-FeSe-QDs to CYF molecules were observed based on the fluorescence quenching of FeSe-QDs. Under optimal conditions, a good linear relationship was found between fluorescence quenching effect and increased CYF concentration within 0.010-0.20mg/L, with a correlation coefficient of 0.9911. The practicality of the developed sensor method for CYF detection in fish and sediment samples was further validated. Good recoveries ranging from 88.0% to 113.9% with

Aim of the Study: Several studies have evaluated the correlation between xeroderma pigmentosum Group A (XPA) A23G polymorphism (rs 1800975) and esophageal cancer in Chinese people. However, the results are inconsistent. To assess the effects of XPA A23G variants on the risk for development of esophageal cancer in the Chinese population, a meta-analysis was performed. Materials and Methods: Studies were identified using PubMed and Chinese databases through December 2015. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: This meta-analysis identified seven studies including 1514 esophageal cancer cases and 2120 controls. In the overall analysis, no significant association between XPA A23G polymorphism and esophageal cancer was found in the Chinese population. In the subgroup analyses by geographic area(s) and source of controls, significant results were only found in studies with hospital-based controls (GG vs. AA: OR = 0.42, 95% CI = 0.28–0.62; GG vs. AA + AG: OR = 0.55, 95% CI = 0.39–0.78; GG + AG vs. AA: OR = 0.54, 95% CI = 0.40–0.72; G vs. A: OR = 0.61, 95% CI = 0.50–0.75). Conclusions: This meta-analysis suggested that XPA A23G gene polymorphism may be one low-penetrant risk factor for esophageal cancer in Chinese individuals.

Objective To collect visualized proof of Tianmagouteng particles (TMGTP) in alleviating cognitive dysfunction and to explore its effects on brain activity in spontaneously hypertensive rats (SHRs) with hyperactivity of liver-yang (Gan Yang Shang Kang, GYSK). Methods Sixteen SHRs were randomized into treatment group and non-treatment. The SHR with GYSK was induced by gavaging aconite decoction (10 mL/kg at 0.2 g/mL). After the SHR models were prepared, the rats in the treatment group were administered TMGTP (10 mL/kg) once a day for 14 days.The rats in the non-treatment group or normal rats (control group) received an equivalent volume of saline. Morris water maze test was conducted before and after the treatment to observe cognitive function. Fluorine 18-deoxy glucose [F-18]FDG micro-PET brain imaging scans was performed after treatment. Data were analyzed with two-sample t -test ( P Results Compared with the non-treatment group, the escape latency significantly decreased but the frequency of entrance into the target zone significantly increased in the treatment group. Consistent with the alteration of cognitive functions, TMGTP induced strong brain activity in the following sites: right dorsolateral nucleus and ventrolateral nucleus of thalamus, amygdala, left met thalamus, cerebellum leaflets, original crack, front cone crack, loop-shaped leaflets; but deactivation of right medial frontal gyrus, bilateral corpus callosum, hippocampus, and left dentate gyrus. Conclusion TMGTP could alleviate cognitive dysfunction in SHRs with GYSK, which was possibly by inducing alteration of glucose metabolism in different brain regions with corresponding functions.

ChKRED20 is an efficient and robust anti-Prelog ketoreductase that can catalyze the reduction of ketones to chiral alcohols as pharmaceutical intermediates with great industrial potential. To overcome its limitation on the bioreduction of ortho-substituted acetophenone derivatives, the X-ray crystal structure of the apo-enzyme of ChKRED20 was determined at a resolution of 1.85 A and applied to the molecular modeling and reshaping of the catalytic cavity via three rounds of iterative saturation mutagenesis together with alanine scanning and recombination. The mutant Mut3B was achieved with expanded catalytic scope that covered all the nine substrates tested as compared with two substrates for the wild type. It exhibited 13-20-fold elevated k cat/K m values relative to the wild type or to the first gain-of-activity mutant, while retaining excellent stereoselectivity toward seven of the substrates (98-> 99% ee). Another mutant 29G10 displayed complementary selectivity for eight of the ortho-substituted acetophenone derivatives, with six of them delivering excellent stereoselectivity (90-99% ee). Its k cat/K m value toward 1-(2-fluorophenyl)ethanone was 5.6-fold of the wild type. The application of Mut3B in elevated substrate concentrations of 50-100 g/l was demonstrated in 50-ml reactions, achieving 75-> 99% conversion and > 99% ee.

Gastric cancer (GC) is one of the main causes of cancer death. The tumor microenvironment has a profound effect on inducing tumor growth, metastasis, and immunosuppression. Fibroblast activation protein-α (FAP) is a protein that is usually expressed in fibroblasts, such as cancer-associated fibroblasts, which are major components of the tumor microenvironment. However, the role of FAP in GC progression and treatment is still unknown. In this study, we explored these problems based on GC patient samples and experimental models. We found that high FAP expression was an independent prognosticator of poor survival in GC patients. FAP+ cancer-associated fibroblasts (CAFs) promoted the survival, proliferation, and migration of GC cell lines in vitro. Moreover, they also induced drug resistance of the GC cell lines and inhibited the antitumor functions of T cells in the GC tumor microenvironment. More importantly, we found that targeting FAP+ CAFs substantially enhanced the antitumor effects of immune checkpoint blockades in GC xenograft models. This evidence highly suggested that FAP is a potential prognosticator of GC patients and a target for synergizing with other treatments, especially immune checkpoint blockades in GC.

Mulberry sclerotiniose caused by Ciboria shiraiana is a devastating disease of mulberry (Morus alba L.) fruit in Northwest China. At present, no disease-resistant varieties are used in production, as the molecular mechanisms of this disease are not well understood. In this study, to explore new prevention methods and provide direction for molecular breeding, transcriptomic sequencing and un-targeted metabolomics were performed on healthy (CK), early-stage diseased (HB1), and middle-stage diseased (HB2) mulberry fruits. Functional annotation, gene ontology, a Kyoto encyclopedia of genes and genomes (KEGG) analysis, and a Mapman analysis of the differentially expressed genes revealed differential regulation of genes related to plant hormone signal transduction, transcription factors, and phenylpropanoid biosynthesis. A correspondence between the transcript pattern and metabolite profile was observed in the phenylpropanoid biosynthesis pathway. It should be noted that the log2 ratio of eugenol (isoeugenol) in HB1 and HB2 are 85 times and 23 times higher than CK, respectively. Our study shows that phenylpropanoid biosynthesis may play an essential role in response to sclerotiniose pathogen infection and eugenol(isoeugenol) enrichment in mulberry fruit, which may provide a novel method for mulberry sclerotiniose control.

Musashi 2 (MSI2), a member of the Musashi RNA-binding family, is reported to be an oncoprotein in pancreatic ductal adenocarcinoma (PDAC), but the mechanisms of MSI2 in the development and progression of PDAC have not been fully demonstrated. In this research, we studied the clinical significance, biologic effects and the underlying mechanism of MSI2 in the progression of PDAC. The expression of MSI2, Mps-binding protein 1 (MOB1) and Salvador family WW domain-containing protein 1 (SAV1) in PDAC tissues were analyzed immunohistochemically. The biologic effects of MSI2 regarding PDAC cell proliferation, migration and invasion were studied using gain- and loss-of-function assays. MSI2 regulated Hippo signaling pathway via SAV1 and MOB1 was tested in several PDAC cell lines, and the mechanisms were studied using molecular biologic methods. The expression of MSI2 was significantly increased in PDAC cell lines and tissues, and positively associated with tumor poorer differentiation, lymph nodes metastasis and TNM stages. Overexpression of MSI2 promoted PDAC cells proliferation, migration and invasion. Further studies demonstrated that MSI2 regulated the Hippo signaling pathway via directly binding to the mRNAs of SAV1 and MOB1, and controlled the translation and stability of SAV1 and the translation of MOB1. This study demonstrated that MSI2 regulated the Hippo signaling pathway via suppressing SAV1 and MOB1 at post-transcriptional level and promoted PDAC progression.