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Food-derived bioactive peptides are considered as the important sources of natural bioactive ingredients. Approximately 3094 peptides were identified by nESI-LC–MS/MS in the hydrolyzed yak milk residue. Peptide KALNEINQF (T10) is the strongest antioxidant peptide. The damage model of H2O2-induced human umbilical vein endothelial cells (HUVECs) was used to evaluate the antioxidant effect. After treatment with 25, 50, or 100 μg/mL T10 peptide, T10 obviously decreased H2O2-induced damage and increased the cell survival. Comparing with the H2O2-induced damage group, superoxide dismutase (SOD) activities were significantly increased 1.03, 1.1, and 1.33 times, and glutathione reductase (GR) activities were significantly increased 1.11, 1.30, and 1.43 times, respectively. Malondialdehyde (MDA) also reduced 1.41, 1.54, and 1.72 times, respectively. T10 inhibited H2O2-induced apoptosis in HUVECs, and protein expressions of the apoptosis-related genes bcl-2 and bax were increased and decreased by 1.95 and 1.44 times, respectively, suggesting T10 decreases apoptosis of the mitochondria-dependent pathway. Comparing with the H2O2-induced damage group, the RNA expressions of Nrf2, HO-1, and NQO1 were significantly increased by 2.00, 2.11, and 1.94 times; the protein expressions of p-Nrf2, HO-1, and NQO1 were significantly increased by 2.67, 1.73, and 1.04 times; and Keap1 was downregulated by 3.9 and 1.32 times, respectively. T10 also regulated the Nrf2 pathway and expressions of related genes (Keap1, HO-1, and NQO1), and blocking the Nrf2 pathway in the model decreased the protective effect of T10. Taken together, T10 peptide isolated from yak milk residue has a protective effect against H2O2-induced damage in HUVECs and the molecular mechanisms are involved in the regulation of Nrf2 signaling pathway and cell apoptosis.

Background: Systemic lupus erythematosus (SLE), known as lupus, is a chronic autoimmune disease and there is no cure for SLE. The western medication can improve syndromes to some extent; however, severe adverse drug reactions appear at the same time. Recently, it is confirmed that Chinese medicine also can have an excellent clinical efficacy on SLE. Methods and analysis: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. Major results: levels of total remission rate, SLEDAI. Secondary results: The laboratory index about C3 levels, Hb levels, white blood cell levels, and adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta analysis will be evaluated according to “Cochrane Handbook for Systematic Reviews of Interventions.” All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. Results: The curative effect and safety of Chinese herbal compound prescription treatment for SLE patients will be evaluated systematically. Conclusion: The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for SLE to further guide its promotion and application. Ethics and dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. Open Science Framework (OSF)registration number: https://osf.io/wvfrx/.

Background: Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc., mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but can not be cured, glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma. Methods: The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures. Results: This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions. Conclusion: this study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma.

This study provides comprehensive metabolic insights into the Hydrothermarchaeota from comparative genomics, evolution, and community-level perspectives. Members of the Hydrothermarchaeota synergistically participate in a wide range of carbon-utilizing and element cycling processes with other microorganisms in the community. We expand the current understanding of community interactions within the hydrothermal sediment and chimney, suggesting that microbial interactions based on sequential substrate metabolism are essential to nutrient and element cycling., Hydrothermal vents release reduced compounds and small organic carbon compounds into the surrounding seawater, providing essential substrates for microbial growth and bioenergy transformations. Despite the wide distribution of the marine benthic group E archaea (referred to as Hydrothermarchaeota) in the hydrothermal environment, little is known about their genomic repertoires and biogeochemical significance. Here, we studied four highly complete (>80%) metagenome-assembled genomes (MAGs) from a black smoker chimney and the surrounding sulfur-rich sediments on the South Atlantic Mid-Ocean Ridge and publicly available data sets (the Integrated Microbial Genomes system of the U.S. Department of Energy-Joint Genome Institute and NCBI SRA data sets). Genomic analysis suggested a wide carbon metabolic diversity of Hydrothermarchaeota members, including the utilization of proteins, lactate, and acetate; the anaerobic degradation of aromatics; the oxidation of C1 compounds (CO, formate, and formaldehyde); the utilization of methyl compounds; CO2 incorporation by the tetrahydromethanopterin-based Wood-Ljungdahl pathway; and participation in the type III ribulose-1,5-bisphosphate carboxylase/oxygenase-based Calvin-Benson-Bassham cycle. These microbes also potentially oxidize sulfur, arsenic, and hydrogen and engage in anaerobic respiration based on sulfate reduction and denitrification. Among the 140 MAGs reconstructed from the black smoker chimney microbial community (including Hydrothermarchaeota MAGs), community-level metabolic predictions suggested a redundancy of carbon utilization and element cycling functions and interactive syntrophic and sequential utilization of substrates. These processes might make various carbon and energy sources widely accessible to the microorganisms. Further, the analysis suggested that Hydrothermarchaeota members contained important functional components obtained from the community via lateral gene transfer, becoming a distinctive clade. This might serve as a niche-adaptive strategy for metabolizing heavy metals, C1 compounds, and reduced sulfur compounds. Collectively, the analysis provides comprehensive metabolic insights into the Hydrothermarchaeota. IMPORTANCE This study provides comprehensive metabolic insights into the Hydrothermarchaeota from comparative genomics, evolution, and community-level perspectives. Members of the Hydrothermarchaeota synergistically participate in a wide range of carbon-utilizing and element cycling processes with other microorganisms in the community. We expand the current understanding of community interactions within the hydrothermal sediment and chimney, suggesting that microbial interactions based on sequential substrate metabolism are essential to nutrient and element cycling.

OBJECTIVE: : To investigate the effect of high-altitude hypoxia on the pharmacokinetics parameters of gliquidone. METHODS: : Twelve healthy male Wistar rats were randomly divided into plain group and high-altitude group with 6 rats in each group. Blood samples were collected after intragastric administration of gliquidone (6.3 mg/kg). Ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was used to determine the concentration of gliquidone in rat plasma samples. And the expression of CYP2C9 in rat liver tissues was determined by Western blotting. RESULTS: : Compared with the plain group, the peak concentration of gliquidone in the high-altitude rats was significantly increased, the absorption rate constant was decreased, the elimination rate constant and the absorption half-life were increased, the elimination half-life was shortened, the mean residence time and apparent volume of distribution were decreased (all P

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the “read-on-ski” law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated “read-on-ski” imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.

In this study, we selected eight cis-elements: AAAG, ACGTG, CCGA, ACTCAT, GGTCA, TATCC, TGAC and GATAA, which are closely related to plant growth and development, signal transduction and stress response. The CEAP primers were 18 nucleotides long and consisted of a central cis-element nucleotide core flanked by a filler sequence at the 5’ end and di- or tri-nucleotides at the 3’ end. A total of two hundred and twenty-four primers were developed, and the PCR procedure consisted of 5 cycles of low-temperature annealing and 35 subsequent cycles of annealing at 50°C. The PCR products are electrophoretically separated by 1.8–2.3% agarose. The polymorphism of the CEAP marker was amplified in eight mango (Mangifera indica L.) species. The results showed that the CEAP primers could amplify clear, repeatable bands in mango and combine at least four cis-elements from which a large number of bands were amplified and six highly polymorphic primers for each cis-element can reach an accurate clustering result. The results of CEAP marker assays compared with ISSR, CBDP and iPBS marker assays showed that CEAP marker was better than the other three markers in the number of fragment bands, H and I indexes. In addition, we also tested the CEAP markers in rice, tomato, potato, wax gourd, citrus and longan and the results showed that the CEAP marker assay could amplify clear polymorphic bands in different species. Our results indicate that the CEAP markers could be universally used in different species for genetic diversity analysis, relationship analysis, and marker-assisted selection for breeding. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01212-5.

OBJECTIVE: To investigate the incidence, clinical characteristics, gene mutations and prognosis of fatty acid oxidation disorders (FAOD) in newborns in Chongqing. METHODS: Blood samples were collected from 35 374 newborns for screening of FAOD in the Neonatal Screening Center of Women and Children’s Hospital of Chongqing Medical University from July 2020 to February 2022. The acylcarnitine spectrum was detected by tandem mass spectrometry, the positive children in primary screening were recalled within 2 weeks, and the diagnosis of FAOD was confirmed by urine organic acid measurement, blood biochemistry testing and genetic analysis. The confirmed children were given early intervention, treatment and followed-up. RESULTS: Among 35 374 newborns, there were 267 positive children in primary screening, with a positive rate of 0.75%. Five children with FAOD were diagnosed by gene detection, with an incidence rate of 1/7075. Among them, there were 3 cases of primary carnitine deficiency (PCD, 1/11 791), 1 case of short-chain acyl-CoA dehydrogenase deficiency (SCADD, 1/35 374) and 1 case of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, 1/35 374). The c.1400C>G and c.338G>A were the common mutations of SLC22A5 gene in 3 children with PCD, while c.621G>T was a novel mutation. There were no clinical manifestations during the follow-up period in 2 children with supplementation of L-carnitine. Another child with PCD did not follow the doctor’s advice of L-carnitine treatment, and had acute attack at the age of 6 months. The child recovered after treatment, and developed normally during the follow-up. The detected ACADS gene mutations were c.417G>C and c.1054G>A in child with SCADD, who showed normal intelligence and physical development without any clinical symptoms. The mutations of ACADVL gene were c.1349G>A and c.1843C>T in child with VLCADD, who showed acute attack in the neonatal period and recovered after treatment; the child was fed with milk powder rich in medium-chain fatty acids and had normal development during the follow-up. CONCLUSIONS: : The incidence of FAOD in Chongqing area is relatively high. PCD is the most common type, and the clinical phenotype of VLCADD is serious. After early diagnosis through neonatal screening, standardized treatment and management is followed, most of FAOD children can have good prognosis.

Michelia amoena Q.F.Zheng et M.M.Lin is classified in Magnoliaceae and has a high economic value. Herein, we report the complete chloroplast genome of M. amoena using Illumina sequence data. The chloroplast genome is 160,088 bp in length and contains a large single copy (LSC) region of 88,118 bp and a small single-copy (SSC) region of 18,798 bp separated by two inverted repeat (IR) regions of 26,586 bp each. It contained a total of 131 genes, with an overall GC content of 39.26%. The phylogenetic analysis showed that M. amoena is closely related to Michelia figo. This study provides important sequence information for species identification and its phylogenetic relationship in the Magnoliaceae.

Circulating miRNA expression is most commonly measured by qRT-PCR, however, the lack of a suitable endogenous control hinders people from evaluating the accurate changes in miRNA expression levels and developing the non-invasive biomarkers. In this study, we aimed to screen the specific, highly stable endogenous control in esophageal squamous cell carcinoma (ESCC) to overcome the obstacle. We selected “housekeeping” miRNAs according to the published database and initially acquired 21 miRNAs. Subsequently, we screened these miRNAs using GSE106817 and TCGA datasets according to specific inclusion criteria and evaluated the suitability of “candidate” miRNAs. Among these miRNAs, the average abundance of miR-423-5p was relatively high in serum. Notably, miR-423-5p expression in serum showed no significant difference between ESCC patients and healthy controls (n = 188, P = 0.29). Moreover, among these miRNAs, miR-423-5p was the most stable miRNA using the NormFinder algorithms. Overall, these results indicate that miR-423-5p, as a novel and optimal endogenous control, could be used to quantify circulating miRNAs in ESCC.

In this paper, an ultra-high sensitive plasmonic sensor is theoretically proposed for refractive index based on D-shaped photonic crystal fiber (PCF) with graphene-coated Ag-grating in mid-infrared region. Surface plasmon polariton at the metal/dielectric interface can be effectively excited by the fundamental guiding mode, leading to the surrounding medium-dependent loss spectrum. This metallic-grating PCF sensor exhibits a maximum sensitivity of 18612 nm/RIU with a detection resolution of 4.16 × 10(−6) RIU in the index range from 1.33 to 1.395. Dependences of loss spectrum on the PCF parameters (air hole diameter and lattice constant) and the grating structure (grating thickness, period and width) are systematically analyzed. Moreover, the influence of the material parameters on the sensor performance is also investigated in term of graphene-layer number and the thickness of Ag layer. The compact design not only has great potentials in the applications of liquid detection, but also offers a guidance in the engineering of the metallic-grating fiber sensor.

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.

Chinese landscape painting is a complex form of visual art. More researchers pay more attention to the creation process and expressed intention of landscape painting. However, the appreciation of works of visual art is often related to cognitive processing, and it is influenced by the content of the works. This study hypothesized that the information of the figure in landscape paintings could guide the allocation of attention and affect cognitive processing. To test this hypothesis, the vertical landscape paintings of the Song and Ming Dynasties were used as experimental materials in the experiment, and the eye-movement technology was applied to record and compare the differences of the eye-movement indexes of landscape paintings with and without figures. The results showed that the dwell time of landscape painting with figure was significantly longer than that of landscape painting without figure, and the dwell time of the interest area of the figure was significantly longer than that of the interest area without figure. However, the first three fixation duration of the interest area with figures is significantly less than that of the interest area without figure, and there was no difference in the saccade counts and the distribution of fixation points between different landscape paintings. It suggested that the figure in the landscape painting can attract peoples’ attention, but it does not have attention priority. Meanwhile, peoples tend to holistic processing when they viewing the vertical landscape paintings, and it is not influenced by the information of figure.

OBJECTIVES: To describe hospital spending and length of stay for mental disorders in Hunan, China. METHODS: We extracted hospital care data for Hunan province from the Chinese National Health Statistics Network Reporting System. Patients with mental disorders (ICD-10 codes: F00 to F99) as the principal diagnosis and hospitalized between January 1, 2017 and December 31, 2019 were included. We retrieved information on age, sex, number of comorbidities, diagnosis, level of hospital, hospital costs, date of admission and discharge, length of stay (LOS), and method of payment of eligible participants. Spending at the provincial level, and spending and LOS at the individual level were described. Quantile regression and linear regression were conducted to investigate factors for hospital cost and LOS for major mental disorders. RESULTS: The 2019 annual spending on mental disorders in Hunan province was 160 million US dollars, and 71.7% was paid by insurance. The annual spending on schizophrenia was 84 million dollars, contributing to a primary burden of mental disorders. The median spending for mental disorders was $1,085 per patient, and the median hospital stay was 22 days. The study identified several significant factors associated with hospital cost and LOS, including age, sex, comorbidity, and level of the hospital. In particular, a higher level of the hospital was associated with a higher hospital spending but a shorter LOS. Women with schizophrenia had a comparable hospital spending but a significantly shorter LOS than men with schizophrenia. CONCLUSION: Hospitalization spending for patients with mental disorders is substantial. Schizophrenia is the major burden of hospitalization for mental disorders. While patients treated at a higher level of hospital had higher spending, they stayed shorter in these hospitals.

BACKGROUND: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disease, whose pathogenesis remains unclear. Here, we conducted untargeted metabolomics and lipidomics to identify seminal plasma signatures of nCHH, and to study the effect of LH and FSH deficiency on semen. METHODS: Twenty-five diagnosed patients with nCHH (HH group) and twenty-three healthy participants (HC group) were enrolled. Laboratory parameters, seminal plasma samples and patients’ medical data were collected. Untargeted metabolomics and lipidomic profiling were performed using mass spectrometry (MS). RESULTS: The metabolomics profiling are altered among patients with nCHH and healthy controls. There are 160 kinds of differential metabolites and the main different lipid species are TAG, PC, SM and PE. CONCLUSIONS: The metabolomics profiles in patients with nCHH changed. We hope that this work provides important insights into the pathophysiology of nCHH.

Recent reports have revealed diverse and abundant fungal communities in the deep-sea biosphere, while their composition, distribution, and variations in seamount zones are poorly understood. Using a metabarcoding approach targeting the ITS2 regions, we present the structure of the fungal community in 18 sediment samples from the Magellan seamount area of the northwest Pacific. A total of 1,979 fungal OTUs was obtained, which were taxonomically assigned to seven phyla, 17 classes, 43 orders, 7 families, and 98 genera. The majority of these OTUs were affiliated to Basidiomycota (873 OTUs, 44.11% of total OTUs) and Ascomycota (486 OTUs, 24.56% of total OTUs), followed by other five minor phyla (Mortierellomycota, Chytridiomycota, Mucoromycota, Glomeromycota, and Monoblepharidomycota). Sordriomycetes is the most abundant class, followed by Eurotiomycetes, and Dothideomycetes. Five genera were common in most of the samples, including worldwide reported genera Aspergillus, Cladosporium, Fusarium, Chaetomium, and Penicillium. The environmental data we collected (sampling depth, sampling location latitude and longitude, organic carbon content, and organic nitrogen content in the sediment) had no significant influence on the composition and distribution of fungal communities. Our findings provide valuable information for understanding the distribution and potential ecological functions of fungi in the deep-sea sediments of the Magellan seamounts.

Background Digital image technology has made great progress in the field of foreign body detection and classification, which is of great help to drug purity extraction and impurity analysis and classification. Objective The detection and classification of foreign bodies in lyophilized powder are important. The method which can obtain a higher accuracy of recognition needs to be proposed. Methods We used digital image technology to detect and classify foreign bodies in lyophilized powder, and studied the process of image preprocessing, median filtering, Wiener filtering and average filtering balance to better detect and classify foreign bodies in lyophilized powder. Results Through industrial small sample data simulation, test results show that in the process of image preprocessing, 3 × 3 median filtering is best. In the aspect of foreign body recognition, the recognition based on principal component analysis (PCA) and support vector machine (SVM) algorithm and the recognition based on PCA and Third-Nearest Neighbor classification algorithm are compared and results show that the PCA+SVM algorithm is better. Conclusion We demonstrated that integrating PCA and SVM to classify foreign bodies in lyophilized powder. Our proposed method is effective for the prediction of essential proteins.

Protecting an anode from deterioration during charging/discharging has been seen as one of the key strategies in achieving high-performance lithium (Li)–O2 batteries and other Li–metal batteries with a high energy density. Here, we describe a facile approach to prevent the Li anode from dendritic growth and chemical corrosion by constructing a SiO2/GO hybrid thin layer on the surface. The uniform pore-preserving layer can conduct Li ions in the stripping/plating process, leading to an effective alleviation of the dendritic growth of Li by guiding the ion flux through the microstructure. Such a preservation technique significantly enhances the cell performance by enabling the Li–O2 cell to cycle up to 348 times at 1 A·g–1 with a capacity of 1000 mA·h·g–1, which is several times the cycles of cells with pristine Li (58 cycles), Li–GO (166 cycles), and Li–SiO2 (187 cycles). Moreover, the rate performance is improved, and the ultimate capacity of the cell is dramatically increased from 5400 to 25,200 mA·h·g–1. This facile technology is robust and conforms to the Li surface, which demonstrates its potential applications in developing future high-performance and long lifespan Li batteries in a cost-effective fashion.

Early weaning-induced stress causes diarrhoea, thereby reducing the growth performance of piglets. Gut bacterial dysbiosis has emerged as a leading cause of post-weaning diarrhoea. The present study aimed to investigate the effect of capsulized faecal microbiota transplantation (FMT) on the gut bacterial community, immune response and gut barrier function of piglets. Thirty-two weaned barrows were randomly divided into two groups. The recipient group was inoculated orally with capsulized faecal microbiota of healthy Tibetan pigs during the whole period of the trial, while the control group was given an empty capsule. The feed-to-gain ratio, diarrhoea ratio, and histological damage score of recipient piglets were significantly decreased. FMT treatment significantly increased the colon length of piglets. Furthermore, the relative abundances of Firmicutes, Euryarchaeota, Tenericutes, Lactobacillus, and Methanobrevibacter in the colon of recipient piglets were increased, and the relative abundances of Campylobacter and Proteobacteria were significantly decreased compared with those in the control group. CD4+ lymphocytes and CD4+/CD8+ ratio in the peripheral blood of recipient piglets were significantly increased. FMT treatment increased the IL-4 and IL-10 levels and decreased the TNF-α and INF-γ levels in the colonic tissue of piglets. The recipient piglets’ mRNA expression of TLR2, TLR8, NF-κB, and iNOS was significantly regulated. In addition, FMT significantly enhanced the gene expression of ZO-1. Overall, treatment with capsulized FMT ameliorated diarrhoea in piglets, with significant effects on limiting colon inflammatory responses, downregulating the TLR signalling pathway and the gene expression of iNOS, and strengthening intestinal barrier function by modulating the constituents of the gut microbiota.

To explore the effect of selenium-enriched yeast (SeY) on intestinal barrier functions in weaned pigs upon oxidative stress, a 2×2 factorial design was utilized and thirty-two pigs were randomly assigned into four groups. Pigs with or without exposure to oxidative stress (diquat challenge) were fed with a basal diet or a SeY-containing diet. The trial lasted for 21 days, and result showed that SeY supplementation attenuated body-weight reduction and significantly decreased the serum concentrations of diamine oxidase (DAO) and D-lactic acid in pigs upon diquat challenge (P<0.05). Diquat challenge decreased the villus height and the ratio of villus height to crypt depth (V/C) in the jejunum and ileum (P<0.05). However, SeY supplementation not only elevated the villus height and the ratio of V/C (P<0.05) but also improved the distribution and abundance of tight-junction protein ZO-1 in the jejunum epithelium. Interestingly, SeY supplementation acutely decreased the total apoptosis rate of intestinal epithelial cells in pigs upon diquat challenge (P<0.05). Moreover, SeY elevated the content of antioxidant molecules such as glutathione peroxidase (GSH-Px) and catalase (CAT) but significantly decreased the content of malondialdehyde (MDA) in the intestinal mucosa (P<0.05). Importantly, SeY elevated the expression levels of critical functional genes such as the nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), sodium/glucose cotransporter 1 (SGLT1), and B-cell lymphoma-2 (BCL-2) in the intestinal mucosa upon diquat challenge (P<0.05). Moreover, the expression of caspase-3 was downregulated by SeY in the duodenum and jejunum mucosa (P<0.05). These results indicated that SeY attenuated oxidative stress-induced intestinal mucosa disruption, which was associated with elevated mucosal antioxidative capacity and improved intestinal barrier functions.

Both antibiotic‐impregnated poly(methyl acrylate, methyl methacrylate) (PMMA) and antibiotic‐impregnated calcium sulfate have been successfully used as local antibiotic delivery vehicles for the management of chronic osteomyelitis. Here, we examined the antibiotic elution characteristics and antibacterial properties of a composite drug delivery system consisting of PMMA/calcium sulfate carrying vancomycin (dual carrier‐v) against Staphylococcus aureus, with PMMA loaded with vancomycin (PMMA‐v) as a control. Vancomycin gradually degraded from dual carrier‐v and PMMA‐v up to about 8 and 6 weeks, respectively. At different elution time points, the inhibition zones of the dual carrier‐v were larger than the inhibition zones of the PMMA‐v (P, A dual poly(methyl acrylate, methyl methacrylate) (PMMA)/calcium sulfate carrier of vancomycin is more effective than PMMA‐vancomycin at inhibiting Staphylococcus aureus growth in vitro. The PMMA/calcium sulfate carrying vancomycin thus may have potential as an alternative strategy for the management of osteomyelitis.

Summary Despite their important roles in host nutrition and metabolism, and potential to cause disease, our knowledge of the fungal community in the mammalian gut is quite limited. To date, diversity and composition of fungi in swine gut still remains unknown. Therefore, the first internal transcribed spacer of fungi in faecal samples from three breeds of pigs (10 pigs for each breed) was sequenced based on an Illumina HiSeq 2500 platform, and the relationship between the fungal community and the concentrations of main short‐chain fatty acids (SCFAs) was also analysed. Results indicated that Chenghua (local, higher body fat rate), Yorkshire (foreign, higher lean meat and growth rate) and Tibetan (plateau, stronger disease resistance) pigs harboured distinct fungal community. The Basidiomycota and Ascomycota presented as the two predominant phyla, with Loreleia, Russula and Candida as the top three genera in all samples. Network analysis revealed a total of 35 correlations among different fungal genera, with 27 (77.14%) positive and 8 (22.86%) negative pairwise interactions. Canonical correspondence analysis suggested that fungi in the faeces of pigs were more correlated to the concentration of acetate and butyrate rather than propionate. Spearman’s correlation further showed that Tomentella was positively correlated to both acetate and butyrate, and Loreleia was positively correlated to propionate (P, Results of the current study indicateed that Chenghua (local, higher body fat rate), Yorkshire (foreign, higher lean meat and growth rate) and Tibetan (plateau, stronger disease resistance) pigs harbored distinct fungal community. The Basidiomycota and Ascomycota presented as the two predominant phyla, with Loreleia, Russula and Candida as the top three genera in all samples. Fungi in the feces of pigs were more correlated to the concentration of acetate and butyrate rather than propionate. Of those fungal genera, Tomentella was positively correlated to both acetate and butyrate, and Loreleia was positively correlated to propionate, while Nephroma and Taiwano fungus were negatively correlated to acetate and propionate. These findings expanded our knowledge on the intestinal fungi in pigs with different genotypes and phenotypes, indicating that fungi may play an indispensable role during the metabolism of host and the maintenance of intestinal health. The cross‐feeding between fungi and other microorganisms may be crucial during the digestion of dietary carbohydrates and the associated physiological processes, which is worthy to be further studied.

Gene vectors play a critical role in gene therapy. To achieve efficient transfection, we developed a novel nonvirus cationic liposome (Lipo-Par), which was bound covalently with the cationic polypeptide pardaxin (Par). Interestingly, the Lipo-Pars exhibited highly enhanced gene transfection efficiency in various cell lines compared to that of the non-Par-bonded liposomes (Lipo-Nons). As a result, the internalization and intracellular transport mechanisms of the Lipo-Pars were investigated, and the findings indicated their ability to actively target the endoplasmic reticulum (ER) by moving along the cell cytoskeleton after undergoing caveolin-mediated endocytosis. This intracellular transport process is similar to that of some viruses. It was also found that ER stress and calcium level disturbances can affect the Lipo-Par-mediated expression of certain exogenous genes. A possible, yet non-negligible explanation for the high transfection efficiency of the Lipo-Par is its virus-like intracellular behavior and the intimate relationship between the ER membrane and the nuclear envelope., To take advantage of the high efficiency of virus vectors and make up for its shortcomings, a virus-like nonvirus cationic liposome was designed, which can target ER and achieve exciting efficiency.

Objective This study aims to explore the roles of long non-coding RNAs (lncRNAs) for predicting survival in hepatocellular carcinoma (HCC) patients with cirrhosis. Methods A set of lncRNAs differentially expressed between HCC patients with or without cirrhosis was identified using expression profiles of The Cancer Genome Atlas database, and these lncRNAs were screened for their risk scoring system to predict recurrence-free survival (RFS) or overall survival (OS). Predictive ability of risk scoring systems was confirmed using uni- and multivariate Cox analyses while adjusting for clinical features. Predictive lncRNAs were analyzed by functional enrichment analysis. Results Our screen identified 22 lncRNAs that were upregulated in the presence of cirrhosis and 59 that were downregulated. To predict OS of HCC patients with cirrhosis, a risk scoring system was developed with four lncRNAs (LINC02086, LINC00880, LINC01549 and AC136475.3); to predict RFS in these patients, the risk scoring system contained five lncRNAs (SH3RF3-AS1, AC104117.3, AC136475.3, LINC00239 and MRPL23-AS1). All risk scoring systems were associated with an area under the receiver operating characteristic curve > 0.7. Based on uni- and multivariate Cox analyses, the risk scoring system could serve as a significant independent predictor for OS in HCC patients with cirrhosis. Functional enrichment analysis suggested that the lncRNAs in the risk scoring systems are involved primarily in the pathway of Wnt signal and cytokine-cytokine receptor interaction. Conclusion Risk scoring systems based on lncRNAs can effectively predict OS of HCC patients with cirrhosis. The system should be further developed and validated in larger, preferably multi-site patient populations. .

Background PD-1/PD-L1 blockade has received approval for clinical application due to its encouraging benefit with improving prognosis in selected populations. Unfortunately, the response to immunotherapy for many patients remains unsatisfactory. It remains a great challenge to generate potential combinations that will outperform single agents alone with regard to anti-tumor activity. Methods Using NSCLC cell lines and mouse models, we explored the effects of combined niclosamide and PD-L1 blockade on tumor growth and T cell function. Furthermore, we investigated the relationship between PD-L1 and p-STAT3 expression in tumor samples from patients with NSCLC using IHC, as well as their relationship to patient survival. Results In vitro, niclosamide, an antihelmintic drug, enhanced the cancer cell lysis mediated by T cells in the presence of PD-L1 blockade. Accordingly, mice treated with niclosamide and PD-L1 antibody showed significant delay in tumor growth and increased survival which were associated with the increase of tumor infiltrating T cells and granzyme B release. Importantly, we found niclosamide could decrease the expression of PD-L1 in both a concentration- and time-dependent manner in NSCLC cells, which was linked to the blockage of p-STAT3 binding to the promoter of PD-L1. Conclusions An enhancement of PD-L1 antibody by niclosamide was observed in inhibition of NSCLC growth in vitro and in vivo, which was involved in blockage of p-STAT3 binding to promoter of PD-L1 and finally downregulation of PD-L1 expression. These encourage the combination therapy of niclosamide and PD-1/PD-L1 blockade to be further studied in clinic. Supplementary information Supplementary information accompanies this paper at 10.1186/s40425-019-0733-7.

Purpose. To determine the percentage of parents who report quitting spontaneously and examine the factors associated with these quits. Methods. As part of a cluster randomized control trial addressing parental smoking in a pediatric outpatient setting, 12-month follow-up survey data were collected from parents who had self-identified as smokers when exiting from 10 control practices. Parents were considered to have made a spontaneous quit if they reported not smoking a cigarette, even a puff, in the last 7 days and chose the statement “I did not plan the quit in advance; I just did it” when describing how their quit attempt started. Results. Of the 981 smoking parents enrolled at baseline, 710 (72%) completed the 12-month follow-up. Of these, 123 (17%) reported quitting, of whom 50 (41%) reported quitting spontaneously. In multivariable analysis, parents who reported smoking on some days vs. every day (OR 3.06 (95% CI 1.42, 6.62)) and that nobody had smoked in their home/car vs. someone had smoked in these settings in the past 3 months (OR 2.19 (95% CI 1.06, 4.54)) were more likely to quit spontaneously. Conclusions. This study shows that, of parents who quit smoking, a substantial percentage report quitting spontaneously and that intermittent smoking and smoke-free home/car policies are associated with reports of quitting spontaneously. Promoting smoke-free home/car policies, especially when parents are not willing to make a plan to quit smoking, might increase the likelihood that parents decide to quit without advance planning. Pediatric healthcare providers are uniquely positioned to use the child’s visit to motivate parents to quit smoking and eliminate their child’s exposure to tobacco smoke, regardless of the frequency of smoking or a readiness to plan a quit attempt. Clinical Trial Registration. This trial is registered with NCT01882348.

Chinese herbal Fu-Zheng-Qu-Xie (FZQX) prescription has been found to improve the immune function and survival of patients with early-stage lung cancer. However, the therapeutic efficacy needs to be evaluated objectively, and the precise mechanism remains unclear. In the present study, a double-center, prospective cohort study was carried out to assess the clinical efficacy of the FZQX prescription in preventing the recurrence and metastasis of postoperative early-stage lung adenocarcinoma. Our results indicated that the FZQX prescription could significantly reduce the 3-year postoperative recurrence rate and improve the life quality. Moreover, the peripheral blood indices showed that the positive immune index (CD4+T/CD8+T) increased and the negative immune indices (CD8+T, Myeloid-derived suppressor cells (MDSCs), Treg) decreased after treatment with the FZQX prescription. Since the positive regulatory effect of the FZQX prescription on immune function, a series of experiments were conducted to verify the tumor-suppressive effect and elucidate the underlying mechanisms. Through the MDSC clearance xenograft model, we confirmed that the FZQX prescription could effectively suppress tumor growth with lesser side effects in vivo, and MDSCs may be involved in the biological process of the FZQX prescription’s intervention in lung cancer progression. By establishing the coculture system of MDSCs/LLC to simulate the immune microenvironment of lung cancer, the tumor suppression effect of the FZQX prescription was further validated by in vitro experiments. Besides, it was confirmed that the FZQX prescription could regulate MDSCs to remodel the immunosuppressive tumor microenvironment, thus exerting its preventive effect on relapse of lung cancer. Finally, the pathway activator and inhibitor were further used to explore the potential molecular mechanism. Results demonstrated that the IL-1β/NF-κB signaling pathway was one of the critical signaling pathways of FZQX prescription regulating MDSCs to prevent the recurrence and metastasis of lung adenocarcinoma.

Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto’s thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto’s Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto’s thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.

Functional brain networks have been shown to undergo fundamental changes associated with aging or schizophrenia. However, the mechanism of how these factors exert influences jointly or interactively on brain networks remains elusive. A unified recognition of connectomic alteration patterns was also hampered by heterogeneities in network construction and thresholding methods. Recently, an unbiased network representation method regardless of network thresholding, so called minimal spanning tree algorithm, has been applied to study the critical skeleton of the brain network. In this study, we aimed to use minimum spanning tree (MST) as an unbiased network reconstruction and employed structural equation modeling (SEM) to unravel intertwined relationships among multiple phenotypic and connectomic variables in schizophrenia. First, we examined global and local brain network properties in 40 healthy subjects and 40 schizophrenic patients aged 21–55 using resting‐state functional magnetic resonance imaging (rs‐fMRI). Global network alterations are measured by graph theoretical metrics of MSTs and a connectivity‐transitivity two‐dimensional approach was proposed to characterize nodal roles. We found that networks of schizophrenic patients exhibited a more star‐like global structure compared to controls, indicating excessive integration, and a loss of regional transitivity in the dorsal frontal cortex (corrected p, Different minimum spanning tree global organizations. On the top is the hypothesized normal structure, which should be expected to be seen in healthy adults. The state is an intermediate configuration between two extremes. When nodes become increasingly segregated, the tree would transform into the line‐like structure in the lower‐left corner; on the other hand, the star‐like structure represent highly centralized network arrangement.

Summary Production of the high‐value carotenoid astaxanthin, which is widely used in food and feed due to its strong antioxidant activity and colour, is less efficient in cereals than in model plants. Here, we report a new strategy for expressing β‐carotene ketolase and hydroxylase genes from algae, yeasts and flowering plants in the whole seed using a seed‐specific bidirectional promoter. Engineered maize events were backcrossed to inbred maize lines with yellow endosperm to generate progenies that accumulate astaxanthin from 47.76 to 111.82 mg/kg DW in seeds, and the maximum level is approximately sixfold higher than those in previous reports (16.2–16.8 mg/kg DW) in cereals. A feeding trial with laying hens indicated that they could take up astaxanthin from the maize and accumulate it in egg yolks (12.10–14.15 mg/kg) without affecting egg production and quality, as observed using astaxanthin from Haematococcus pluvialis. Storage stability evaluation analysis showed that the optimal conditions for long‐term storage of astaxanthin‐rich maize are at 4 °C in the dark. This study shows that co‐expressing of functional genes driven by seed‐specific bidirectional promoter could dramatically boost astaxanthin biosynthesis in every parts of kernel including embryo, aleurone layer and starch endosperm other than previous reports in the starch endosperm only. And the staple crop maize could serve as a cost‐effective plant factory for reliably producing astaxanthin.

Introdution. Calycosin, a major active component in Astragali radix, has antitumour and anti-inflammation properties, but its effects on PM 2.5-induced injury in vitro and in vivo have not been clarified. Methods. Phospho-AMP-activated protein kinase (p-AMPK) and AMP-activated protein kinase (AMPK) were detected by western blot. Immunofluorescence staining was used to validate changes in the levels of nuclear factor kappa B (NF-кB) p65 nuclear translocation. Mice were administered intraperitoneally with calycosin one hour before anaesthesia and endotracheal instillation of PM 2.5. The extent of lung injury was evaluated in the H&E-stained lung sections. Apoptotic cells were detected by TUNEL staining. Results. Administration of calycosin was increased in PM 2.5-treated B2B cells in a dose-dependent manner in vitro. Fluorescence signals from anti-NF-кB p65 were increased in nuclei of cells pretreated with calycosin. The level of p-AMPK was increased by calycosin in vitro and in vivo. After pretreatment with compound C, the inhibitory effects of calycosin on cytotoxicity, levels of inflammatory cytokines and p-AMPK, and levels of NF-кB p65 nuclear translocation were not significantly decreased in vitro or in vivo. Conclusions. Calycosin effectively decreased the release of inflammatory cytokines and alleviated injury caused by PM 2.5. These effects were mediated through activation of AMPK to suppress NF-κB signalling.

Aims To investigate coping strategies and identify their associated factors among Chinese clinical nurses during the early stage of coronavirus disease 2019 pandemic. Design A cross‐sectional study. Methods This study was conducted in seven designated hospitals involved in the diagnosis and treatment of the coronavirus disease 2019 in the southwest of China between 1 February and 31 March, 2020. Multiple linear regression was conducted to explore the association of different factors with the coping strategies of nurses. Results Nurses’ positive coping was associated with higher psychological capital (B = 0.185, 95% CI 0.158–0.213), social support (B = 0.292, 95% CI 0.244–0.340) and lower frustration (B = −0.065, 95% CI −0.123 to −0.007). In contrast, higher frustration (B = 0.091, 95% CI 0.044–0.139), lower performance (B = −0.054, 95% CI −0.101 to −0.007) and psychological capital (B = −0.035, 95% CI −0.055 to −0.014) were associated with negative coping.

Apolipoprotein M (ApoM) exhibits various anti‐atherosclerotic functions as a component of high‐density lipoprotein (HDL) particles. Scavenger receptor class B type I (SR‐BI) is a classic HDL receptor that mediates selective cholesterol uptake and enhances the efflux of cellular cholesterol to HDL. However, the effect of ApoM on cholesterol transport in macrophages remains unclear. In this study, we identified for the first time that ApoM is expressed in mouse macrophages and is involved in cholesterol uptake, similar to SR‐BI. NBD‐cholesterol uptake and efflux in cells were characterized using fluorescence spectrophotometry. The uptake ratios of cholesterol by macrophages from ApoM −/− SR‐BI−/− mice were significantly lower than those from ApoM+/+SR‐BI −/− and ApoM −/− SR‐BI+/+ mice. Real‐time fluorescence quantitative PCR was used to analyze the expression of cholesterol transport‐related genes involved in cholesterol uptake. ApoM‐enriched HDL (ApoM+HDL) facilitated more cholesterol efflux from murine macrophage Ana‐1 cells than ApoM‐free HDL (ApoM−HDL). However, recombinant human ApoM protein inhibited the ability of ApoM−HDL to induce cholesterol efflux. In conclusion, ApoM promotes cholesterol uptake and efflux in mouse macrophages. A better understanding of ApoM function may lead to the development of novel therapeutic strategies for treating atherosclerotic diseases., In this study, we mainly explore the role of ApoM in two aspects: the uptake and efflux of cholesterol in mouse macrophages. ApoM deficiency leads to decreased cholesterol uptake by mouse peritoneal macrophages. ApoM+HDL promotes cellular cholesterol efflux more efficiently than ApoM−HDL does. It is quite possible that ApoM promotes cholesterol efflux by SR‐BI‐dependent mechanisms.

Summary Salt stress is a major devastating abiotic factor that affects the yield and quality of maize. However, knowledge of the molecular mechanisms of the responses to salt stress in maize is limited. To elucidate the genetic basis of salt tolerance traits, a genome‐wide association study was performed on 348 maize inbred lines under normal and salt stress conditions using 557 894 single nucleotide polymorphisms (SNPs). The phenotypic data for 27 traits revealed coefficients of variation of >25%. In total, 149 significant SNPs explaining 6.6%–11.2% of the phenotypic variation for each SNP were identified. Of the 104 identified quantitative trait loci (QTLs), 83 were related to salt tolerance and 21 to normal traits. Additionally, 13 QTLs were associated with two to five traits. Eleven and six QTLs controlling salt tolerance traits and normal root growth, respectively, co‐localized with QTL intervals reported previously. Based on functional annotations, 13 candidate genes were predicted. Expression levels analysis of 12 candidate genes revealed that they were all responsive to salt stress. The CRISPR/Cas9 technology targeting three sites was applied in maize, and its editing efficiency reached 70%. By comparing the biomass of three CRISPR/Cas9 mutants of ZmCLCg and one zmpmp3 EMS mutant with their wild‐type plants under salt stress, the salt tolerance function of candidate genes ZmCLCg and ZmPMP3 were confirmed. Chloride content analysis revealed that ZmCLCg regulated chloride transport under sodium chloride stress. These results help to explain genetic variations in salt tolerance and provide novel loci for generating salt‐tolerant maize lines.

Numerous studies have examined the neural substrates of intertemporal decision‐making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task‐based functional brain networks whose topological properties are related to impulsivity., DMPFC represented both amount and delay‐time with distinct activation patterns. RCA‐based amount‐related and time‐related networks topological properties can predict k.

A large proportion of patients with obsessive–compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1‐Hz rTMS (14 days, 30 min/day) over the right pre‐supplementary motor area (preSMA). Resting‐state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale–Brown Obsessive Compulsive Scale than the sham group (F 1,35 = 6.0, p = .019). To show the neural mechanism involved, we identified an “ideal target connectivity” before treatment. Leave‐one‐out cross‐validation indicated that this connectivity pattern can significantly predict patients' symptom improvements (r = .60, p = .009). After real treatment, the average connectivity strength of the target network significantly decreased in the real but not in the sham group. This network‐level change was cross‐validated in three independent datasets. Altogether, these findings suggest that personalized magnetic stimulation on preSMA may alleviate obsessive–compulsive symptoms by decreasing the connectivity strength of the target network., A personalized repetitive transcranial magnetic stimulation protocol significantly alleviates clinical symptoms in obsessive‐compulsive disorder. Nearly half of the patients showed more than 35% symptom reduction after 2 weeks of treatment. The baseline profile of target connectivity significantly predicted symptom outcome.

More than 40 000 patients worldwide die from esophageal cancer annually. The 5‐year survival rate of patients is only ~ 15–20%, and thus, there is an ongoing need to improve diagnosis and treatment of esophageal cancer. Breast cancer type 1 susceptibility protein (BRCA1)‐associated protein (BAP1) is a marker of poor prognosis in several cancers, including uveal melanoma, renal cell carcinoma, cholangiocarcinoma, non‐small cell lung cancer, and colorectal cancer. BAP1 mutations are early and rare events in esophageal carcinoma, but the involvement of BAP1 in progression of esophageal carcinoma is unclear. Here, we report that cell proliferation and migration were significantly enhanced in esophageal carcinoma ECA109 cells overexpressing BAP1, while they were diminished upon BAP1 knockdown. In addition, the expression of Krüppel‐like factor 5 (KLF5), CyclinD1, and FGF‐BP1 was increased by BAP1 overexpression and decreased by BAP1 knockdown. Our data suggest that BAP1 promotes cell proliferation and migration, and enhances the expression of KLF5 and its downstream genes, including CyclinD1 and FGF‐BP1, in the esophageal carcinoma cell line ECA109., Overexpression of BAP1 in ECA109 results in enhanced cell proliferation and migration and increased expression of Krüppel‐like factor 5 (KLF5) and its downstream genes. Knockdown of BAP1 in ECA109 results in a decrease in cell proliferation and migration, as well as a reduction in the expression of KLF5 and its downstream genes.

Background Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. Methods This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18–70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the β regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. Results The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. Conclusions Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Background The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s–1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved. Methods In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis. Results Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p. Conclusion These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.

BackgroundThe aims of this pilot study were (1) to assess the efficacy of 3D-printed custom-made hemipelvic endoprosthesis in restoring the natural location of acetabulum for normal bodyweight transmission; (2) to evaluate the short-term function of the revision with this endoprosthesis and (3) to identify short-term complications associated with the use of this endoprosthesis.MethodsBetween February 2017 and December 2017, seven patients received revision with 3D-printed custom-made hemipelvic endoprosthesis. The body weight moment arm (BWMA) and cup height discrepancy (CHD) after primary and revisional surgery were analyzed to assess acetabulum location with plain radiography. After a median follow-up duration of 29 months (range 24–34), the function was evaluated with the Musculoskeletal Tumor Society (MSTS-93) score and Harris hip score (HHS). Complications were recorded by chart review.ResultsThe acetabulum locations were deemed reasonable, as evaluated by median BWMA (primary vs. revision, 10 cm vs. 10 cm) and median CHD (primary vs. revision, 10 mm vs. 8 mm). The median MSTS-93 score and HHS score were 21 (range 18–23) and 78 (range 75–82) after the revision. No short or mid-term complication was observed in the follow-up of this series.ConclusionsRevision with 3D-printed custom-made hemipelvic endoprostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening and fracture of modular hemipelvic endoprosthesis. The revision surgery and appropriate rehabilitation program improved patients’ function to a median MSTS score of 22 and pain-free ambulation. The incidence of the complications was low via this individualized workflow.

Background Studies suggest Porphyromonas gingivalis (Pg) increased the incidence of oral squamous cell carcinoma (OSCC). However, fimA genotypes distribution of Pg, the origination of Pg in tissue, and its prognostic value are inconclusive. We aimed to investigate the frequency of fimA genotypes in OSCC patients, study the association between Pg and OSCC, and explore the prognostic value of Pg. Methods The abundance of Pg in saliva from the OSCC group and the OSCC-free group was analysed by qPCR. The presence of Pg was explored in OSCC tissue and para-cancerous tissue by in situ hybridization. The frequency of fimA genotypes in saliva and OSCC tissue was determined by PCR, then PCR products were sequenced and compared. Clinical data were extracted, and patients followed up for a median period of 23 months. Clinicopathological variables were compared with the abundance of Pg using Pearson Chi-square test or Fisher’s exact test. The disease-free survival (DFS) rate was calculated by Kaplan–Meier method with log-rank tests. Results Comparing the OSCC-free group, 95 patients with OSCC showed a high abundance of Pg in saliva (P = 0.033), and OSCC tissue showed strong in situ expression of Pg compared with paired normal tissue. Patients with OSCC showed a dominant distribution of Pg with genotype I + Ib (21.1%), II (31.6%), and IV (21.1%). FimA genotypes detected in saliva were in accordance with those in OSCC tissue, there was, moreover, a significant similarity in amplified Pg fragments. Of the 94 responsive OSCC patients, the recurrence rate was 26.6% (25/94). Overabundance of Pg in saliva showed advanced pathologic staging (P = 0.008), longer disease-free time (P = 0.029) and lower recurrence rate (P = 0.033). The overabundance of Pg in saliva was associated with improved disease-free survival (P = 0.049). Conclusions This study indicated that Pg might involve in the pathogenesis of OSCC, Pg carrying fimA I, Ib, II, and IV were prevalent genotypes in patients with OSCC, the provenance of Pg in OSCC tissue might be from the salivary microbial reservoir, and the abundance of Pg in saliva might consider as a favorable potential prognostic indicator in OSCC.

Interleukin (IL)‐36α, a newly recognized IL‐1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL‐36α has potential anticancer effects against certain types of cancer. However, the expression pattern and functional role of IL‐36α in non‐small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL‐36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL‐36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion and shorter overall survival (OS). Intratumoral IL‐36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in patients with NSCLC. Overexpression of IL‐36α in lung cancer cells did not disturb cell proliferation, apoptosis or cell‐cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL‐36α reduced the expression and secretion of vascular endothelial growth factor A through inhibiting hypoxia‐inducible factor 1α expression. Finally, decreased IL‐36α expression was associated with high microvessel density and vascular endothelial growth factor A in patients with NSCLC. Together, our findings suggest that IL‐36α expression is a valuable marker indicating poor prognosis in patients with NSCLC., Interleukin (IL)‐36α is an IL‐1 family member with pivotal roles in autoimmunity diseases. Here, we report that IL‐36α is a potent antitumor cytokine in non‐small cell lung cancer (NSCLC). IL‐36α suppresses tumor growth by inhibiting tumor angiogenesis via suppression of hypoxia‐inducible factor‐1α/vascular endothelial growth factor A signaling. IL‐36α expression is an independent prognostic factor for overall survival in patients with NSCLC. IL‐36α expression might be a valuable marker indicating poor prognosis in patients with NSCLC.

Heteropolygonatum ginfushanicum is an endemic epiphytic herb in China. The complete chloroplast (cp) genome of H. ginfushanicum is reported in this study. The total length of the cp genome is 155,508 bp with a typical quadripartite structure consisting of a large single copy region (LSC) of 84,552 bp and a small single copy region (SSC) of 18,528 bp, separated by a pair of 26,214 bp inverted repeats (IRs). It encodes a total of 113 unique genes, including 79 protein-coding, 30 tRNA, and four rRNA genes. Phylogenetic analysis indicated that H. ginfushanicum is sister to Heteropolygonatum marmoratum within subfamily Nolinoideae.

Background ATP-binding cassette (ABC) transporters have been found to play important roles in metabolic transport in plant cells, influencing subcellular compartmentalisation and tissue distribution of these metabolic compounds. Salvia miltiorrhiza Bunge, known as Danshen in traditional Chinese medicine, is a highly valued medicinal plant used to treat cardiovascular and cerebrovascular diseases. The dry roots and rhizomes of S. miltiorrhiza contain biologically active secondary metabolites of tanshinone and salvianolic acid. Given an assembled and annotated genome and a set of transcriptome data of S. miltiorrhiza, we analysed and identified the candidate genes that likely involved in the bioactive metabolite transportation of this medicinal plant, starting with the members of the ABC transporter family. Results A total of 114 genes encoding ABC transporters were identified in the genome of S. miltiorrhiza. All of these ABC genes were divided into eight subfamilies: 3ABCA, 31ABCB, 14ABCC, 2ABCD, 1ABCE, 7ABCF, 46ABCG, and 10 ABCI. Gene expression analysis revealed tissue-specific expression profiles of these ABC transporters. In particular, we found 18 highly expressed transporters in the roots of S. miltiorrhiza, which might be involved in transporting the bioactive compounds of this medicinal plant. We further investigated the co-expression profiling of these 18 genes with key enzyme genes involved in tanshinone and salvianolic acid biosynthetic pathways using quantitative reverse transcription polymerase chain reaction (RT-qPCR). From this RT-qPCR validation, we found that three ABC genes (SmABCG46, SmABCG40, and SmABCG4) and another gene (SmABCC1) co-expressed with the key biosynthetic enzymes of these two compounds, respectively, and thus might be involved in tanshinone and salvianolic acid transport in root cells. In addition, we predicted the biological functions of S. miltiorrhiza ABC transporters using phylogenetic relationships and analysis of the transcriptome to find biological functions. Conclusions Here, we present the first systematic analysis of ABC transporters in S. miltiorrhiza and predict candidate transporters involved in bioactive compound transportation in this important medicinal plant. Using genome-wide identification, transcriptome profile analysis, and phylogenetic relationships, this research provides a new perspective on the critical functions of ABC transporters in S. miltiorrhiza.

Background Highly pathogenic avian influenza viruses (HPAIVs) of H5 subtype pose a great threat to the poultry industry and human health. In recent years, H5N6 subtype has rapidly replaced H5N1 as the most predominate HPAIV subtype circulating in domestic poultry in China. In this study, we describe the genetic and phylogenetic characteristics of a prevalent H5N6 strain in Guangdong, China. Results Nucleotide sequencing identified a H5N6 subtype HPAIV, designated as A/chicken/Dongguan/1101/2019 (DG/19), with a multibasic cleavage site in the hemagglutinin (HA). Phylogenetic analysis revealed DG/19 was a reassortant of H5N1, H5N2, H5N8, and H6N6 subtypes of avian influenza viruses. A number of mammalian adaptive markers such as D36N in the HA were identified. Conclusions Our results showed that HPAIV H5N6 strains still emerge in well-managed groups of chicken farms. Considering the increasing prevalence of H5N6 HPAIV, and the fact that H5N6 HPAIVs are well adapted to migratory birds, an enhanced surveillance for the East Asian-Australasian flyway should be undertaken to prevent potential threats to the poultry industry and human health.

Background There are few non-invasive monitoring methods that can reliably predict fluid responsiveness (FR) in children. Here, we interrogate the value of doppler ultrasound evaluation of passive leg raising (PLR)-induced changes in stroke volume (SV) and cardiac output (CO) as a predictor of FR in children with mechanical ventilation after congenital cardiac surgery. Methods A total of 40 children with mechanical ventilation following congenital cardiac surgery, who required volume expansion (VE) were included in this study. Hemodynamic parameters such as heart rate (HR), mean arterial pressure (MAP), SV, and central venous pressure (CVP) were monitored before and after PLR and VE. Besides, we assessed changes in SV and CO by bedside ultrasound. Patients showing > 10 % increase in SV in response to VE were considered to be responders (26 patients), while the rest (14 patients) were defined as non-responders. Results Our data demonstrated that ΔSV-PLR and ΔCO- PLR were positively correlated with ΔSV-VE (r = 0.683, p p = 0.017, respectively), and the area under the ROC curve (AUC) of ΔSV-PLR was 0.879 (95 % CI [0.745 1.000], p Conclusions Our study demonstrated that SV changes, as evaluated by noninvasive ultrasound combined with PLR, could effectively evaluate FR in children under mechanical ventilation after congenital cardiac surgery.

Electrocatalytic oxygen reduction reaction (ORR) provides an attractive alternative to anthraquinone process for H2O2 synthesis. Rational design of earth-abundant electrocatalysts for H2O2 synthesis via a two-electron ORR process in acids is attractive but still very challenging. In this work, we report that nitrogen-doped carbon nanotubes as a multi-functional support for CoSe2 nanoparticles not only keep CoSe2 nanoparticles well dispersed but alter the crystal structure, which in turn improves the overall catalytic behaviors and thereby renders high O2-to-H2O2 conversion efficiency. In 0.1 M HClO4, such CoSe2@NCNTs hybrid delivers a high H2O2 selectivity of 93.2% and a large H2O2 yield rate of 172 ppm·h−1 with excellent durability up to 24 h. Moreover, CoSe2@NCNTs performs effectively for organic dye degradation via electro-Fenton process. Electronic Supplementary Material Supplementary material (SEM images, EDX mapping images, XPS spectrum, XRD patterns, RRDE voltammogram, Tafel plots, cyclic voltammograms, UV-Vis spectra, and Tables S1) is available in the online version of this article at 10.1007/s12274-021-3474-0.

This paper provides empirical evidence on the incentive role of personnel control in China in the twenty-first century. Employing the city-level turnover data of political leaders in China between 2000 and 2018 and utilizing the fixed effects ordered logit model, we find that the likelihood of promotion of local leaders rises with their economic performance. This relationship holds more firmly in the municipal party secretary. The probability is also found to decrease with the economic performance of their immediate predecessors and neighboring cities. This finding is robust to various robustness tests. We interpret the finding as evidence that the relative economic performance (peer effects) also contributes to the local political turnover, in particular within a province. Moreover, after the Third Plenary Session of the 18th CPC Central Committee, a material change in the personnel arrangement within the party arises and this promotion mechanism shows a dynamic change. Our study sheds some light on the growing literature emphasizing the relationship between political turnover and economic performance.

Background. Totally extraperitoneal herniorrhaphy (TEP) is a therapeutic challenge because of its complex anatomical location in inguinal region. The aim of this study was to describe the related surgical anatomy through laparoscopic observation and share the lessons learned from a review of 250 primary inguinal hernia repair procedures performed at our hospital from January 2013 to November 2019. Patients and Methods. There were 245 men and 5 women (median age: 63.2 years). Right hernia (60.2%) was the most common site. Indirect hernia (60.5%) was the most common abnormality. The classification of type II (65.0%) was the most common form. Surgical techniques comprised retromuscular approach using cauterized dissection, management of variations of arcuate line, Retzius space and Bogros space dissection, hernia sac reduction, and mesh positioning. Results. The incidence of peritoneum injury was in 27 (10.1%). No epigastric vessels were injured. There were 8 (3%) hematoma and 18 (6.8%) seroma. No mesh infection, chronic pain, and recurrence were found after follow-up of an average of 35 months. Conclusion. A good understanding of the anatomically complex nature in the inguinal region can make it easier and safer to learn the TEP approach. Early and midterm outcomes after TEP are satisfactory.

Objective. The therapeutic effectiveness and safety of occipital nerve blockade (ONB) on occipital neuralgia- (ON-) like acute postcraniotomy headache (ON-APCH) was evaluated. Background. Persistent occipital neuralgia is a subclassification of chronic postcraniotomy headache and has been investigated sporadically in previous publications. The long-lasting neuralgic pain significantly impairs postoperative recovery and quality of life. However, little is known regarding ON-APCH and its management. Methods. All data were retrospectively acquired from consultation records and electronic institutional medical documents. Forty-one patients, who developed drug-resistant ON-APCH after elective craniotomy and received ONB with lidocaine for diagnoses, were included in this study, all of whom were treated using dexamethasone and lidocaine. Pain intensity and ONB correlated complications and side effects were collected and analyzed at three different time points: before ONB, at 1 day after ONB, and at discharge. Results. Nineteen males and twenty-two females aged 49.6 ± 15.2 years were diagnosed with drug-resistant ON-APCH. The mean NRS was 8.0 ± 0.9 before ONB, which later significantly decreased to 2.1 ± 1.4 and 1.6 ± 0.6 at 1 day after ONB and on discharge, respectively. At 1 month after ONB, thirty patients (73%) obtained complete pain relief without medication. At 3 months after ONB, only two (5%) patients had to continue oral medications to maintain pain relief. No adverse effects or complications were observed immediately after, or within 3 months, of the nerve blockade. Conclusions. For drug-resistant ON-APCH, early occipital nerve blockade with dexamethasone and lidocaine is an effective and safe technique, which provides adequate pain relief and may prevent further development of persistent presentation of refractory ON.