Tailoring Advanced N-Defective and S-Doped g-C3 N4 for Photocatalytic H2 Evolution.

Although challenges remain, synergistic adjusting various microstructures and photo/electrochemical parameters of graphitic carbon nitride (g-C3 N4 ) in photocatalytic hydrogen evolution reaction (HER) are the keys to alleviating the energy crisis and environmental pollution. In this work, a novel nitrogen-defective and sulfur-doped g-C3 N4 (S-g-C3 N4 -D) is designed elaborately. Subsequent physical and chemical characterization proved that the developed S-g-C3 N4 -D not only displays well-defined 2D lamellar morphology with a large porosity and a high specific surface area but also has an efficient light utilization and carriers-separation and transfer. Moreover, the calculated optimal Gibbs free energy of adsorbed hydrogen (ΔGH* ) for S-g-C3 N4 -D at the S active sites is close to zero (≈0.24 eV) on the basis of first-principle density functional theory (DFT). Accordingly, the developed S-g-C3 N4 -D catalyst shows a high H2 evolution rate of 5651.5 µmol g-1  h-1 . Both DFT calculations and experimental results reveal that a memorable defective g-C3 N4 /S-doped g-C3 N4 step-scheme heterojunction is constructed between S-doped domains and N-defective domains in the structural configuration of S-g-C3 N4 -D. This work exhibits a significant guidance for the design and fabrication of high-efficiency photocatalysts.

Nickel-Catalyzed Asymmetric Hydroaryloxy- and Hydroalkoxycarbonylation of Cyclopropenes.

The asymmetric Reppe carbonylation reactions provide a straightforward access to α-chiral carbonyl compounds. The reported paradigms predominantly adopted precious palladium as the catalyst. Here we report a nickel-catalyzed asymmetric carbonylation of cyclopropenes with phenyl formate and CO/ROH, respectively. This asymmetrical synthetic protocol features high atom economy, good functional group tolerance, which rapidly constructs polysubstituted cyclopropanecarboxylic derivatives with excellent diastereo- and enantioselectivity. The synthetic utility is demonstrated by facile conversion of the chiral products into bioactive molecules such as (-)-Tranylcypromine and (-)-Lemborexant.

Disturbed Resting-State Whole-Brain Functional Connectivity of Striatal Subregions in Bulimia Nervosa.

BACKGROUND: Disturbed self-regulation, taste reward, as well as somatosensory and visuospatial processes were thought to drive binge eating and purging behaviors that characterize bulimia nervosa. Although studies have implicated a central role of the striatum in these dysfunctions, there have been no direct investigations on striatal functional connectivity in bulimia nervosa from a network perspective. METHODS: We calculated the functional connectivity of striatal subregions based on the resting-state functional Magnetic Resonance Imaging data of 51 bulimia nervosa patients and 53 healthy women. RESULTS: Compared with the healthy women, bulimia nervosa patients showed increased positive functional connectivity in bilateral striatal nuclei and thalamus for nearly all of the striatal subregions, and increased negative functional connectivity in bilateral primary sensorimotor cortex and occipital areas for both ventral striatum and putamen subregions. Only for the putamen subregions, we observed reduced negative functional connectivity in the prefrontal (bilateral superior and middle frontal gyri) and parietal (right inferior parietal lobe and precuneus) areas. Several striatal connectivities with occipital and primary sensorimotor cortex significantly correlated with the severity of bulimia. CONCLUSIONS: The findings indicate bulimia nervosa-related alterations in striatal functional connectivity with the dorsolateral prefrontal cortex supporting self-regulation, the subcortical striatum and thalamus involved in taste reward, as well as the visual occipital and sensorimotor regions mediating body image, which contribute to our understanding of neural circuitry of bulimia nervosa and encourage future therapeutic developments for bulimia nervosa by modulating striatal pathway.

In Situ Assessment of Donghu Lake China Using Rare Minnow (Gobiocypris rarus).

In this work, rare minnow (Gobiocypris rarus) was applied as a sentinel organism and set in cages at control and test sampling sites in Donghu Lake for 4 weeks in March, June, September, and December 2016 to assess the biological toxicity of in situ water. Sampling for active biomonitoring and physicochemical variables was performed weekly. The control was obtained from the outdoor pool of the Institute of Hydrobiology, China. Superoxide dismutase, lipoperoxidation, metallothioneins, acetylcholinesterase activity, and Vtg mRNA expression were determined as biomarkers during the field exposure period. Survival and growth also were monitored to evaluate the overall physiological condition of the fish. The seasonal changes of organic pollutants and trace metals (As, Hg, Cr, Cu, Zn, Cd, Pb) in surface water were determined. The integrated biomarker response (IBR) index was applied to summarize biomarker responses and correlate stress levels with concentrations of organic pollutants and trace metals in the surface water. Results indicated that complex pollution by persistent organic pollutants and heavy metals was present in Donghu Lake and that the in situ exposed organisms were stressed. Moreover, the complex pollution of Donghu Lake in summer and autumn was more serious than that in spring and winter. Active biomonitoring combined with IBR analysis enabled good discrimination among different exposure seasons. The proposed protocol with caged rare minnow revealed marked biological effects caused by the investigated Lake and a useful approach that can easily be extended to monitor water pollution.

[Effect of pregnancy-induced hypertension syndrome on complications in very low birth weight preterm infants].

OBJECTIVE: To study the effect of pregnancy-induced hypertension syndrome (PIH) on complications in very low birth weight (VLBW) preterm infants. METHODS: The VLBW preterm infants were enrolled as research subjects, and according to the presence or absence of PIH in their mothers, they were divided into PIH group and non- PIH group. The incidence of major complications and length of hospital stay were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, sex, incidence rate of maternal diabetes, and use of antepartum hormone. The PIH group had a significantly higher rate of birth of small-for-gestational-age infants than the non-PIH group. The PIH group had a significantly lower incidence rate of bronchopulmonary dysplasia (BPD) than the non-PIH group, while there were no significant differences between the two groups in the incidence rates of apnea of prematurity, necrotizing enterocolitis, retinopathy of prematurity, and intraventricular hemorrhage-periventricular leukomalacia, and the length of hospital stay. There was no significant difference in the incidence rate of neonatal respiratory distress syndrome between the two groups, but the PIH group had a significantly lower proportion of infants who used pulmonary surfactant than the non-PIH group. CONCLUSIONS: PIH can alleviate respiratory complications and reduce the use of pulmonary surfactant and the incidence rate of BPD in preterm infants.

Enantioselective Synthesis of Axially and Centrally Chiral Styrenes via Nickel-Catalyzed Desymmetric Hydrocyanation of Biaryl Dienes.

Herein, a highly regio-, enantio-, and diastereoselective nickel-catalyzed desymmetric hydrocyanation of biaryl dienes for the simultaneous construction of axial and central chiralities is presented, which offers a convenient approach to a variety of tirenes containing the union of an axially chiral biaryl and a centrally α-chiral nitrile under mild conditions using a commercially available catalyst. The synthetic utility is highlighted by the development of a novel axially chiral phosphine ligand and biphenyl-based chiral diene ligand and their potential applications in the field of asymmetric catalytic reactions.

The melanocortin 1 receptor (MC1R) inhibits the inflammatory response in Raw 264.7 cells and atopic dermatitis (AD) mouse model.

The alpha melanocyte stimulating hormone receptor (MC1R) is one of five G-protein coupled receptors belonging to the melanocortin subfamily, MC1R gene has been known to play a major role in regulating of fur color in mammals, and α-MSH and ACTH are endogenous nonselective agonists for MC1R. However, we found that MC1R was highly expressed in Raw 264.7 cells which were important inflammatory cells involved in the initiation of inflammatory responses. In addition, Cyclic AMP is not only a key molecule in the MC1R signal transduction pathway, but dampen innate immune-mediated responses. These intriguing biological results triggered the further conformation studies; it suggested that MC1R was very likely to be an important role in immunoregulation. In this study, we were to investigate the immunosuppressive effects of MC1R on inflammation in lipopolysaccharide (LPS) stimulated Raw 264.7 cells and LPS induced vivo 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced atopic dermatitis (AD) model. The effects of the MC1R antagonist psoralen on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay, western blot, real-time fluorescence quantitative PCR and Histological analysis. Our results show a consistent and marked effect of high concentrations of MC1R antagonist psoralen increased the level of MC1R mRNA in Raw 264.7 cells by cumulative feedback regulation through preferential binding of MC1R. Moreover, as evidenced by inhibiting the LPS-induced TNF-α, IL-6 and enhancing the expression level of cyclic AMP protein in vitro. In vivo study it was also observed that psoralen promoted on histopathologic changes in the skin tissue of TNCB-induced AD mice. Taken together, our results suggest that MC1R decrease the inflammation in vitro and vivo, and might be a therapeutic signaling pathway to against inflammatory diseases.

Not all side population cells contain cancer stem-like cells in human gastric cancer cell lines.

INTRODUCTION: Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissue have demonstrated presence of SP cells including different gastric cancer cell lines. However, is that true all SP cells contain cancer stem-like cells in gastric cancer cell lines? MATERIALS AND METHODS: MKN-45 and BGC-823 cells labeled with Hoechst 33342 were chosen to obtain SP cells, then characterized the cancer stem-like properties of SP cells both in vitro and in vivo. Five stemness-related genes expression profiles, including OCT-4, SOX-2, NANOG, CD44 and ATP-binding cassette transporters gene ABCG-2, were tested in SP and MP cells using quantitative real-time RT-PCR. Western blot was chosen to show the difference of protein expression between SP and MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells from MKN-45 showed higher tumorigenesis tendency than MP cells, but SP cells from BGC-823 showed same tumorgenesis tendency as MP cells. CONCLUSION: SP cells from MKN-45 possess cancer stem cell properties and proved that they were gastric cancer stem-like cells. SP cells from BGC-823 didn't possess cancer stem cell properties and proved that not all SP cells contain cancer stem-like cells in gastric cancer cell lines.

Xiang-Qi-Tang and its active components exhibit anti-inflammatory and anticoagulant properties by inhibiting MAPK and NF-κB signaling pathways in LPS-treated rat cardiac microvascular endothelial cells.

Xiang-Qi-Tang (XQT) is a Chinese herbal formula containing Cyperus rotundus, Astragalus membranaceus and Andrographis paniculata. Alpha-Cyperone (CYP), astragaloside IV (AS-IV) and andrographolide (AND) are the three major active components in this formula. XQT may modulate the inflammatory or coagulant responses. We therefore assessed the effects of XQT on lipopolysaccharide (LPS)-induced inflammatory model of rat cardiac microvascular endothelial cells (RCMECs). XQT, CYP, AS-IV and AND inhibited the production of tumor necrosis factor alpha (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1), and up-regulated the mRNA expression of Kruppel-like factor 2 (KLF2). XQT and CYP inhibited the secretion of tissue factor (TF). To further explore the mechanism, we found that XQT, or its active components CYP, AS-IV and AND significantly inhibited extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 phosphorylation protein expression as well as decreased the phosphorylation levels of nuclear factor κB (NF-κB) p65 proteins in LPS-stimulated RCMECs. These results suggested that XQT and its active components inhibited the expression of inflammatory and coagulant mediators via mitogen-activated protein kinase (MAPKs) and NF-κB signaling pathways. These findings may contribute to future research on the action mechanisms of this formula, as well as therapy for inflammation- or coagulation-related diseases.

Peimine impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-κB and MAPK in LPS-induced RAW264.7 macrophages.

In the previous study, we found that peimine has good anti-inflammatory effects in vivo. However, the anti-inflammatory mechanism of peimine remains unclear. We, therefore, assessed the effects of peimine on inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that peimine (0-25 mg/L) significantly inhibited tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, and increased IL-10 production. Furthermore, peimine significantly inhibited the phosphorylation of p38, ERK and c-jun N-terminal kinase (JNK) as well as decreased p65 and IκB. The present results indicate that peimine inhibits the production of inflammatory cytokines induced by LPS through blocking MAPKs and NF-κB signaling pathways.

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head.

You-Gui-Yin (YGY) is a classic prescription for warming up kidney-Yang and filling in kidney essence in traditional Chinese medicine, and has been used to treat osteonecrosis of the femoral head (ONFH) effectively. However, the underlying mechanisms are still unknown. This study is aimed at exploring the possible mechanisms of action of the YGY in the treatment of ONFH based on network pharmacology and molecular docking. TCMSP was used to screen the active components and targets of YGY. The disease targets of ONFH were collected in several public databases. The protein-protein interaction (PPI) Network was constructed using the STRING platform. The Metascape database platform was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The key active components and core target proteins of YGY in the treatment of ONFH were verified by the molecular docking. 120 active components were obtained from YGY, among which 73 components were hit by the 117 drug-disease intersection targets. Key effective components included quercetin, kaempferol, beta-sitosterol, glycitein, beta-carotene, and so on. Core target proteins included ALB, AKT1, TNF, IL6, TP53, and so on. According to GO and KEGG analyses, there were 1762 biological processes, 94 cellular component, 138 molecular function and 187 signaling pathways involved. we selected the top 20 biological processes (BP), cellular components (CC), molecular functions (MF) and signaling pathways to draw the heat maps, showing that Lipid and atherosclerosis signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, relaxin signaling pathway and MAPK signaling pathway and other pathways may play a key role in the treatment of ONFH by YGY. The results of molecular docking showed that key effective components and corresponding core target proteins exhibited the good binding activity. YGY can treat ONFH through multicomponents, multitargets, and multipathways, which provides a reference for the subsequent research, development of targeted drugs and clinical application.

Highly Diastereoselective Synthesis of Polysubstituted Cyclopropanecarbonitriles via Palladium-Catalyzed Cyanoesterification of Cyclopropenes.

We herein develop a highly diastereoselective synthesis of cyano-substituted cyclopropanes via palladium-catalyzed direct cyanoesterification of cyclopropenes, which features mild reaction conditions, good functional group compatibility, and simple operation. This transformation represents a stepwise, highly atom economic, and scalable protocol for obtaining synthetically useful cyclopropanecarbonitriles.

Surgical treatment of specific Unified Classification System B fractures: potentially destabilising lesser trochanter periprosthetic fractures.

To investigate the clinical effects of specific Unified Classification System B (UCS B)-lesser trochanter periprosthetic fractures and determine whether they occur only with non-cemented stems. A retrospective analysis of 28 patients with specific UCS B2 fractures who underwent two surgical treatments, longer stem revision and internal fixation (LSRIF) and open reduction and internal fixation (ORIF), was performed. The patients were assessed at 1, 3, 6, 12, and 24 months and annually thereafter. Fracture healing, complications, Harris Hip Score (HHS), and the Short Form Health Survey questionnaire (SF-36) quality of life score were assessed at each follow-up. At the time of the last follow-up, seven patients had been lost: three were lost to contact, two died, and two were hospitalised elsewhere and unavailable for follow-up. The remaining 21 patients were followed for an average of 49.3 ± 15.4 (range: 24-74.4) months. Their average fracture healing time was 13.5 ± 1.1 (12-15.4) weeks. Complications included three cases (10.71%) of thrombus, one (3.57%) of heart failure, and one (3.57%) of pulmonary infection. There were no revisions due to prosthesis loosening, subsidence, or infection. At the last follow-up, the HHS, SF-36 mental score, and SF-36 physical score were recorded, LSRIF vs. ORIF (82.9 ± 6.6 vs. 74.7 ± 3.9, p = 0.059; 50.9 ± 7.6 vs. 38 ± 1.4, p = 0.012, and 51.7 ± 8.4 vs. 39.7 ± 3.4, p = 0.032, respectively). Specific UCS B2 fractures mostly occur with non-cemented stems. LSRIF with cables is the main treatment, while ORIF is an option for those elderly in poor condition.

Nickel-Catalyzed Enantioselective Hydrothiocarbonylation of Cyclopropenes.

Hydrothiocarbonylation of olefins using carbon monoxide and thiols is a powerful method to synthesize thioesters from simple building blocks. Owing to the intrinsic challenges of catalyst poisoning, transition-metal-catalyzed asymmetric thiocarbonylation, particularly when utilizing earth abundant metals, remains rare in the literature. Herein, we report a nickel-catalyzed enantioselective hydrothiocarbonylation of cyclopropenes for the synthesis of a diverse collection of functionalized thioesters in good to excellent yields with high stereoselectivity. This new method employs an inexpensive, air-stable nickel(II) precursor, which provides enhanced catalyst fidelity against CO poisoning compared to nickel(0) catalysts.

Circular RNA circ_0006089 regulates the IGF1R expression by targeting miR-143-3p to promote gastric cancer proliferation, migration and invasion.

Circular RNAs (circRNAs) figure prominently in regulating the progression of a variety of human malignancies. This study was performed to probe how circ_0006089 functioned in gastric cancer (GC). CircRNA expression profile GSE83521 was downloaded from Gene Expression Omnibus (GEO) database, and circRNAs and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure circ_0006089, microRNA-143-3p (miR-143-3p) and insulin-like growth factor 1 receptor (IGF1R) mRNA expressions in GC tissues and cell lines. Kaplan-Meier curves were used to detect the relationship between circ_0006089 expression and overall survival time of GC patients. Cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuridine (BrdU) assays were employed to detect the proliferative ability of GC cells after circ_0006089 was overexpressed or knocked down. Wound healing assay and Transwell assay were executed to examine the migration and invasion ability of GC cells. Western blot was adopted to detect IGF1R protein expressions. Circ_0006089 expression was up-regulated in GC samples and cell lines. And high circ_0006089 expression was associated with shorter survival time in GC patients. Circ_0006089 overexpression in GC cells significantly accelerated GC cell proliferation, migration and invasion, whereas circ_0006089 knockdown resulted in the opposite effects. Additionally, miR-143-3p was validated as a downstream target of circ_0006089, and circ_0006089 could positively regulate IGF1R expression via repressing miR-143-3p. Circ_0006089 is highly expressed in GC, and it promotes the malignancy of GC cells via modulating miR-143-3p/IGF1R axis, suggesting that circ_0006089 may serve as a promising therapeutic target for GC.

Development of the prediction model based on clinical-imaging omics: molecular typing and sentinel lymph node metastasis of breast cancer.

Background: Imageology uses high-throughput and automatic computing methods to transform medical image data into quantitative data with feature space, and then makes accurate quantitative analysis, extracts features and builds models, which can intuitively observe the overall features of lesions and the surrounding tissues, and provide rich invisible information. At present, the research on the imaging features of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) to predict the molecular typing value has achieved results, but the imaging model based on DWI and DCE-magnetic resonance imaging (MRI) is not enough to predict the molecular subtypes, and the prediction value of the prediction model based on the three-dimensional volume of interest of the lesion to the four molecular subtypes of breast cancer has not been fully studied. Methods: The clinical data of 202 breast cancer patients at our hospital from October 2020 to November 2021 were collected. All patients were examined with multimodal MRI before surgery. Base on immunohistochemical recombinant Ki-67 protein (Ki-67), estrogen receptor (ER), human epidermal growth factor receptor-2 (HER-2) and progesterone receptor (PR) results, the tumors were divided into four types According to the results of the sentinel lymph node (SLN) biopsies, the patients were divided into SLN (+) and SLN (-) groups. 3-dimensional (3D) Slicer software was used to outline the region of interest (ROI), and AMni-Kinetics software was used for feature extraction. The imaging characteristics were screened using least absolute shrinkage and selection operator (LASSO)-Logistic regression model using R statistical software, and the receiver operating characteristic (ROC) curve was drawn using "pROC" software package to evaluate the prediction efficiency of the model. Results: The most efficacious model at predicting SLN (+) in breast cancer patients with different molecular subtypes and SLN metastasis was the model based on the imageological characteristics of fat inhibition, and T2-weighted imaging (T2WI), T1-weighted imaging + C (T1WI-C), and DWI combined sequences at the tumor + 2 mm periphery. AUC (sensitivity, specificity) of the validation group were 0.831 (0.856, 0.891), 0.832 (0.660, 0.877), 0.801 (0.772, 0.765), 0.904 (0.769, 0.873), and 0.819 (0.810, 0.500) respectively when the tumor was 2 mm around the tumor. Conclusions: The imaging features extracted from multi-parameter DWI, T1WI+C, and T2WI in breast cancer have certain value at predicting different molecular types and SLNs of breast cancer.

Whole genome sequence of Proteus mirabilis ChSC1905 strain harbouring a new SXT/R391-family ICE.

OBJECTIVES: The aim of this study was to characterise the whole genome sequence of a multidrug-resistant (MDR) Proteus mirabilis strain ChSC1905 isolated from a swine farm in China. METHODS: The genome was sequenced by Illumina NovaSeq and Oxford Nanopore platforms, and it was assembled via Canu v.1.5. The acquired antimicrobial resistance genes (ARGs) were identified by ResFinder. A conjugation experiment was carried out to determine the mobilisation of integrative and conjugative element. RESULTS: Strain ChSC1905 exhibited a MDR phenotype. The genome of strain ChSC1905 was 4 038 038 bp in length with a GC content of 39.1%, which contained 3645 coding sequences and 110 RNA genes. A total of 23 acquired ARGs were identified, among which 21 ARGs including the clinically important resistance genes blaCTX-M-65, cfr, fosA3, and aac(6')-Ib-cr were located on a SXT/R391 integrative and conjugative element (ICE). BLAST analysis showed that this new SXT/R391-family ICE (ICEPmiChnChSC1905 of 143 689 bp) was involved in sequence inversion mediated by ISVsa3 and genetic rearrangement mediated by IS26, and it could be transferred to E. coli EC600. CONCLUSION: In this study, we report the genome sequence of MDR P. mirabilis strain ChSC1905 that harboured a novel SXT/R391-family ICE (ICEPmiChnChSC1905) involved in genetic rearrangement in China, which promotes the diversity of ICE and should receive more attention.

Bioinformatics analysis of immune infiltration in glioblastoma multiforme based on data using a methylation chip in the GEO database.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive and malignant tumor of the central nervous system. The study was to obtain the data of immune cell infiltration based on the data of a methylation chip in the GEO, and to clarify its prognostic significance for GBM. METHODS: The methylation data of glioblastoma was obtained by using the Illumina human methylation 450k BeadChip. The corrected expression was obtained by using edge R. Limma was used to correct the expression amount of the samples, and EpiDISH was used to translate the methylation expression data, so that the expression amount was transformed into the expression matrix of immune cells. The immune cells were then co-expressed, and the proportion and correlation of related immune cells was determined. The results of the cells in each of two groups were analyzed by enrichment and PCA mapping to establish the relevant differences. RESULTS: The data of GBM patients were obtained from the methylation chip of the GEO database. Patients were divided into a long-term (SNU-LTS) (21 cases), and short-term survival group (SNU-STS) (12 cases). There were 73 genes with significant individual differences between the two groups (P<0.05). EpiDISH was used to translate the methylation expression data into the expression matrix of immune cells, which showed that the highest proportion of cells in groups were mono cells, while Gran cells and CD8T appeared in a very small number of samples. The positive correlation between mono and B cells was the strongest, while the negative correlation between mono and Gran cells was the strongest. A violin chart shows that there was no significant difference in the infiltration degree of six kinds of immune cells between the two groups. Principal component analysis (PCA) showed that there was individual difference between the two groups, but the overall consistency was high. CONCLUSIONS: Data on tumor immune cell infiltration can be obtained by using a methylation chip in the GEO database. This not only extends the application abilities of methylation chips but provides obvious individual differences. The study of tumor immune infiltrating cells may pave the way for targeted therapy in the treatment of GBM.

Design and Characterization of a DNA Vaccine Based on Spike with Consensus Nucleotide Sequence against Infectious Bronchitis Virus.

Avian coronavirus infectious bronchitis virus (IBV) causes severe economic losses in the poultry industry, but its control is hampered by the continuous emergence of new genotypes and the lack of cross-protection among different IBV genotypes. We designed a new immunogen based on a spike with the consensus nucleotide sequence (S_con) that may overcome the extraordinary genetic diversity of IBV. S_con was cloned into a pVAX1 vector to form a new IBV DNA vaccine, pV-S_con. pV-S_con could be correctly expressed in HD11 cells with corresponding post-translational modification, and induced a neutralizing antibody response to the Vero-cell-adapted IBV strain Beaudette (p65) in mice. To further evaluate its immunogenicity, specific-pathogen-free (SPF) chickens were immunized with the pV-S_con plasmid and compared with the control pVAX1 vector and the H120 vaccine. Detection of IBV-specific antibodies and cell cytokines (IL-4 and IFN-γ) indicated that vaccination with pV-S_con efficiently induced both humoral and cellular immune responses. After challenge with the heterologous strain M41, virus shedding and virus loading in tissues was significantly reduced both by pV-S_con and its homologous vaccine H120. Thus, pV-S_con is a promising vaccine candidate for IBV, and the consensus approach is an appealing method for vaccine design in viruses with high variability.

Molecular characterization of porcine epidemic diarrhea virus associated with outbreaks in southwest China during 2014-2018.

Porcine epidemic diarrhea virus (PEDV), which re-emerged in China since 2010, has swept across the whole country leading to tremendous economic losses. In this study, a total of 645 diarrhea samples collected from 156 pig farms in Sichuan and Guizhou province during 2014-2018 were tested for PEDV. We found that samples from 47.66% (84/156) of the farms were positive for PEDV with an overall detection rate of 35.81% (231/645). Fifty-two strains were selected for full-length S gene analyses, and these strains were classified into three subgroups, an S-INDEL subgroup (G1c), and two non-S-INDEL subgroups (G2b, AJ1102-like and G2c), accounting for 15.38% (8/52), 23.08% (12/52) and 59.62% (31/52) of the total analysed strains, respectively. We found these three subgroups of PEDV coexisted in Sichuan province, and the S-INDEL strain was detected in Guizhou. Further antigenic variation analysis of the neutralizing epitopes (S10, COE, SS2, SS6 and 2C10) on the spike protein revealed that the S-INDEL and non-S-INDEL strains shared similar variation features in COE and SS6, but exhibited distinct variation patterns in the S10 domain. Unique variation patterns on N-glycosylation sites in the S protein were also observed for the S-INDEL and non-S-INDEL strains. Moreover, nine strains (three from each subgroup) were subjected to full-genome characterization. Complete genome phylogeny showed an inconsistent tree topology for genotyping, with two G2c strains grouped into the GII-b (AH2012-like) genogroup and the remaining seven strains including three S-INDEL strains grouped into the GII-c genogroup. Further recombination analyses indicated that six of the GII-c strains probably originated from intra-genogroup recombinations. Notably, three newly emerged S-INDEL strains with novel recombination patterns were first identified. Together, our data revealed a new status of PEDV in southwest China, which can increase understanding of the prevalence, genetic characteristics and evolutionary profiles of circulating PEDV strains in China.