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Background: Acute pancreatitis in pregnancy is a rare but highly life-threatening gestational and perinatal disease.Objective: This study aimed to identify the risk factors for fetal death and acute pancreatitis severity.Methods: This retrospective cohort study enrolled patients with acute pancreatitis in pregnancy in our center from January 1, 2012, to August 1, 2020, and classified them according to two clinical endpoints, fetal outcome and disease severity. The groups were examined and compared according to gestational week, etiology, gravidity and parity, complications in pre- and post-delivery, and medical history. Logistic regression analysis was performed to identify the independent risk factors for fetal death and acute pancreatitis severity.Results: Of the 90 enrolled patients, 28 (31.1%) had fetal death and 43 (47.8%) had severe acute pancreatitis. Logistic regression analysis showed that pre-delivery acute respiratory distress syndrome (OR, 5.8; 95% CI, 1.5–22.4; p = 0.010) and gestational week (OR, 0.9; 95% CI, 0.8–1.0; p = 0.011) were risk factors for fetal death. Gestation week (OR, 1.2; 95% CI, 1.1–1.3; p = 0.003) and fetal intrauterine death (OR, 5.9; 95% CI, 1.8–19.4; p = 0.003) were risk factors for severe acute pancreatitis.Conclusions: Pre-delivery acute respiratory distress syndrome and gestational week were independent risk factors for fetal death. Fetal intrauterine death and gestational week were independent risk factors for severe acute pancreatitis.

Improving the understanding of the molecular mechanism of tuberculous pleurisy is required to develop diagnosis and new therapy strategies of targeted genes. The purpose of this study is to identify important genes related to tuberculous pleurisy. In this study, the expression profile obtained by sequencing the surgically resected pleural tissue was used to explore the differentially co-expressed genes between tuberculous pleurisy tissue and normal tissue. 29 differentially co-expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis methods. According to the functional annotation analysis of R clusterProfiler software package, these genes are mainly enriched in nucleotide−sugar biosynthetic process (biological process), ficolin−1−rich granule lumen (cell component), and electron transfer activity (molecular function). In addition, in the protein-protein interaction (PPI) network, 20 hub genes of DEGs and WCGNA genes were identified using the CytoHubba plug-in of Cytoscape. In the end, RPL17 was identified as a gene that can be the biomarker of tuberculous pleurisy. At the same time, there are seven genes that may have relationship with the disease (UBA7, NDUFB8, UQCRFS1, JUNB, PSMC4, PHPT1, and MAPK11).

Oregano essential oil (OEO), as a natural antimicrobial, has gained increased interest from food researchers and manufacturers. However, a few studies have investigated its possible antibacterial effects against Staphylococcus aureus using the proteomic tool. The present study aimed to explore the antibacterial effect and mechanism of a carvacrol-rich OEO extracted from Origanum vulgare “Hot & Spicy” on the inactivation of S. aureus. The gas chromatography–mass spectrometry analysis of the OEO allowed the detection of 27 compounds; the major constituent was carvacrol (84.38% of total compounds). The average diameter of the inhibitory zone (DIZ) value was 29.10 mm, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OEO against S. aureus were 0.125 and 0.25 mg/mL, respectively. The growth curve assay indicated that the OEO prolonged the lag phase of S. aureus. The decrease in cell viability, changes in the integrity of cell membrane, and abnormal cell morphology further reflected the cell damage of S. aureus caused by the OEO. In addition, a label-free proteomic analysis was applied to analyze the regulatory networks of S. aureus in response to 1/2 MIC OEO-treatment stress. Of the 56 differentially expressed proteins (DEPs) identified, 26 were significantly upregulated and 30 downregulated. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEPs were mainly involved in pathways of ribosomes; valine, leucine, and isoleucine biosynthesis; and phenylalanine, tyrosine, and tryptophan biosynthesis, which suggested that the growth inhibition of S. aureus might be due to the disordered effect of the OEO on protein synthesis and amino acid metabolism. These findings deepened our understanding regarding S. aureus survival and metabolism responses to the OEO treatment and suggested that the carvacrol-rich OEO could be used in food production environments to effectively control S. aureus.

Glioblastoma (GBM) is one of the most common primary and deadliest malignant brain tumor with chemoresistance and poor prognosis. There is a lack of effective chemotherapeutic drug for the treatment of GBM. In this work, we reported the preparation of a histone deacetylase (HDAC) inhibitor, DMC-HA, from the structural modification of natural product curcumin. DMC-HAs were tested in an HDAC inhibition assay and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity. It showed potent inhibition of HDAC1–2 and HDAC6 with IC50 values in the submicromolar concentration range. DMC-HA significantly inhibited the proliferation of human glioblastoma U87 cells and mediated apoptosis of U87 cells in a dose- and time-dependent manner. In addition, DMC-HA elevated the acetylation level of histone H3 in U87 cells. Pharmacokinetic studies showed that DMC-HA possessed acceptable pharmacokinetic profiles, accompanied with certain brain permeability. Lastly, we showed that DMC-HA suppressed the growth of tumor in U87 tumor xenograft model in vivo with no obvious toxicity. These results demonstrate that DMC-HA has the potential to be developed as a chemotherapeutic drug for GBM patients.

Phosphorus (P) is a nonrenewable resource, which is one of the major challenges for sustainable agriculture. Although phosphite (Phi) can be absorbed by the plant cells through the Pi transporters, it cannot be metabolized by plant and unable to use as P fertilizers for crops. However, transgenic plants that overexpressed phosphite dehydrogenase (PtxD) from bacteria can utilize phosphite as the sole P source. In this study, we aimed to improve the catalytic efficiency of PtxD from Ralstonia sp.4506 (PtxDR4506), by directed evolution. Five mutations were generated by saturation mutagenesis at the 139th site of PtxD R4506 and showed higher catalytic efficiency than native PtxDR4506. The PtxDQ showed the highest catalytic efficiency (5.83-fold as compared to PtxDR4506) contributed by the 41.1% decrease in the Km and 2.5-fold increase in the kcat values. Overexpression of PtxDQ in Arabidopsis and rice showed increased efficiency of phosphite utilization and excellent development when phosphite was used as the primary source of P. High-efficiency PtxD transgenic plant is an essential prerequisite for future agricultural production using phosphite as P fertilizers.

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests.Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged.Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

Trichomoniasis gallinae (T. gallinae) is one of the most pathogenic parasites in pigeon, particularly in squabs. Oral cavity is the main site for the host-parasite interaction. Herein, we used RNA-sequencing technology to characterize lncRNA and mRNA profiles and compared transcriptomic dynamics of squabs, including four susceptible birds (S) from infected group, four tolerant birds (T) without parasites after T. gallinae infection, and three birds from uninfected group (N), to understand molecular mechanisms underlying host resistance to this parasite. We identified 29,809 putative lncRNAs and characterized their genomic features subsequently. Differentially expressed (DE) genes, DE-lncRNAs and cis/trans target genes of DE-lncRNAs were further compared among the three groups. The KEGG analysis indicated that specific intergroup DEGs were involved in carbon metabolism (S vs. T), metabolic pathways (N vs. T) and focal adhesion pathway (N vs. S), respectively. Whereas, the cis/trans genes of DE-lncRNAs were enriched in cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, p53 signaling pathway and insulin signaling pathway, which play crucial roles in immune system of the host animal. This suggests T. gallinae invasion in pigeon mouth may modulate lncRNAs expression and their target genes. Moreover, co-expression analysis identified crucial lncRNA-mRNA interaction networks. Several DE-lncRNAs including MSTRG.82272.3, MSTRG.114849.42, MSTRG.39405.36, MSTRG.3338.5, and MSTRG.105872.2 targeted methylation and immune-related genes, such as JCHAIN, IL18BP, ANGPT1, TMRT10C, SAMD9L, and SOCS3. This implied that DE-lncRNAs exert critical influence on T. gallinae infections. The quantitative exploration of host transcriptome changes induced by T. gallinae infection broaden both transcriptomic and epigenetic insights into T. gallinae resistance and its pathological mechanism.

BackgroundHelicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori.MethodWe screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model.ResultsWe identified 115 H. pylori infection–related genes were differentially expressed among H. pylori–infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection–related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters.ConclusionWe successfully constructed a H. pylori–related lncRNA risk signature and nomogram associated with H. pylori–infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.

Crossed beaks have been observed in at least 12 chicken strains around the world, which severely impairs their growth and welfare. To explore the intrinsic factor causing crossed beaks, this study measured the length of bilateral mandibular ramus of affected birds, and investigated the genome-wide DNA methylation profiles of normal and affected sides of mandibular condyle. Results showed that the trait was caused by impaired development of unilateral mandibular ramus, which is extended through calcification of mandibular condyle. The methylation levels in the CG contexts were higher than that of CHG and CHH, with the highest methylation level of gene body region, followed by transcription termination sites and downstream. Subsequently, we identified 1,568 differentially methylated regions and 1,317 differentially methylated genes in CG contexts. Functional annotation analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that these genes were involved in bone mineralization and bone morphogenesis. Furthermore, by combining the WGBS and previous RNA-Seq data, 11 overlapped genes were regulated by both long non-coding RNA and DNA methylation. Among them, FIGNL1 is an important gene in calcification of mandibular condyle. Generally, because the affected genes play key roles in maintaining mandibular calcification, these changes may be pivotal factors of crossed beaks.

Background: The efficacy and safety of peroral endoscopic myotomy (POEM) in the treatment of sigmoid-type achalasia is unknown. This meta-analysis aims to explore the clinical outcomes of POEM for sigmoid-type achalasia.Method: We searched all relevant studies published up to September 2020 in PubMed, Embase, and Cochrane library databases. Meta-analyses for clinical success, Eckardt score, angle of esophageal tortuosity, diameter of esophagus, lower esophageal sphincter (LES) pressure, integrated relaxation pressure (IRP), adverse events, and gastroesophageal reflux diseases were performed based on random or fixed-effects models as needed.Results: We found a total of eight studies that provided data on 248 patients. Overall, the pooled clinical success was achieved in 211 sigmoid-type achalasia patients [90.4%; 95% confidence interval (CI), 85.5%−93.8%]. The pre- and post-POEM Eckardt scores, angle of esophageal tortuosity, diameter of esophageal, LES pressure, and IRP were significantly improved (All p < 0.05). The pooled adverse events rate was 13.0% (95% CI, 3.6%−37.4%). The pooled objective confirmation of reflux rate was 41.5% (95% CI, 26.5%−58.3%), and symptomatic reflux rate was 12.5% (95% CI, 8.3%−18.4%).Conclusions: Our current evidence indicated that POEM is an effective and safe therapeutic modality for the treatment of sigmoid-type achalasia.

Plant root angle determines the vertical and horizontal distribution of roots in the soil layer, which further influences the acquisition of phosphorus (P) in topsoil. Large genetic variability for the lateral root angle (root angle) was observed in a linkage mapping population (BnaTNDH population) and an association panel ofBrassica napuswhether at a low P (LP) or at an optimal P (OP). At LP, the average root angle of both populations became smaller. Nine quantitative trait loci (QTLs) at LP and three QTLs at OP for the root angle and five QTLs for the relative root angle (RRA) were identified by the linkage mapping analysis in theBnaTNDH population. Genome-wide association studies (GWASs) revealed 11 single-nucleotide polymorphisms (SNPs) significantly associated with the root angle at LP (LPRA). The interval of a QTL for LPRA on A06 (qLPRA-A06c) overlapped with the confidence region of the leading SNP (Bn-A06-p14439400) significantly associated with LPRA. In addition, a QTL cluster on chromosome C01 associated with the root angle and the primary root length (PRL) in the “pouch and wick” high-throughput phenotyping (HTP) system, the root P concentration in the agar system, and the seed yield in the field was identified in theBnaTNDH population at LP. A total of 87 genes on A06 and 192 genes on C01 were identified within the confidence interval, and 14 genes related to auxin asymmetric redistribution and root developmental process were predicted to be candidate genes. The identification and functional analyses of these genes affecting LPRA are of benefit to the cultivar selection with optimal root system architecture (RSA) under P deficiency inBrassica napus.

The analysis of polymorphic variations in the human major histocompatibility complex (MHC) class II genomic region on the short-arm of chromosome 6 is a scientific enquiry to better understand the diversity in population structure and the effects of evolutionary processes such as recombination, mutation, genetic drift, demographic history, and natural selection. In order to investigate associations between the polymorphisms of HLA-DRB1 gene and recent Alu insertions (POALINs) in the HLA class II region, we genotyped HLA-DRB1 and five Alu loci (AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10), and determined their allele frequencies and haplotypic associations in 12 minority ethnic populations in China. There were 42 different HLA-DRB1 alleles for ethnic Chinese ranging from 12 alleles in the Jinuo to 28 in the Yugur with only DRB1∗08:03, DRB1∗09:01, DRB1∗12:02, DRB1∗14:01, DRB1∗15:01, and DRB1∗15:02 present in all ethnic groups. The POALINs varied in frequency between 0.279 and 0.514 for AluDPB2, 0 and 0.127 for AluDQA2, 0.777 and 0.995 for AluDQA1, 0.1 and 0.455 for AluDRB1 and 0.084 and 0.368 for AluORF10. By comparing the data of the five-loci POALIN in 13 Chinese ethnic populations (including Han-Yunnan published data) against Japanese and Caucasian published data, marked differences were observed between the populations at the allelic or haplotypic levels. Five POALIN loci were in significant linkage disequilibrium with HLA-DRB1 in different populations and AluDQA1 had the highest percentage association with most of the HLA-DRB1 alleles, whereas the nearby AluDRB1 indel was strongly haplotypic for only DRB1∗01, DRB1∗10, DRB1∗15 and DRB1∗16. There were 30 five-locus POALIN haplotypes inferred in all populations with H5 (no Alu insertions except for AluDQA1) and H21 (only AluDPB2 and AluDQA1 insertions) as the two predominant haplotypes. Neighbor joining trees and principal component analyses of the Alu and HLA-DRB1 polymorphisms showed that genetic diversity of these genomic markers is associated strongly with the population characteristics of language family, migration and sociality. This comparative study of HLA-DRB1 alleles and multilocus, lineage POALIN frequencies of Chinese ethnic populations confirmed that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic and evolutionary markers for the identification of allele and haplotype lineages and genetic variations within the same and/or different populations.

Purpose: Accurate prediction of the progression to severe stroke in initially diagnosed nonsevere patients with acute–subacute anterior circulation nonlacuna ischemic infarction (ASACNLII) is important in making clinical decision. This study aimed to apply a machine learning method to predict if the initially diagnosed nonsevere patients with ASACNLII would progress to severe stroke by using diffusion-weighted images and clinical information on admission.Methods: This retrospective study enrolled 344 patients with ASACNLII from June 2017 to August 2020 on admission, and 108 cases progressed to severe stroke during hospitalization within 3–21 days. The entire data were randomized into a training set (n = 271) and an independent test set (n = 73). A U-Net neural network was employed for automatic segmentation and volume measurement of the ischemic lesions. Predictive models were developed and used for evaluating the progression to severe stroke using different feature sets (the volume data, the clinical data, and the combination) and machine learning methods (random forest, support vector machine, and logistic regression).Results: The U-Net showed high correlation with manual segmentation in terms of Dice coefficient of 0.806 and R2 value of the volume measurements of 0.960 in the test set. The random forest classifier of the volume + clinical combination achieved the best area under the receiver operating characteristic curve of 0.8358 (95% CI 0.7321–0.9269), and the accuracy, sensitivity, and specificity were 0.7780 (0.7397–0.7945), 0.7695 (0.6102–0.9074), and 0.8686 (0.6923–1.0), respectively. The Shapley additive explanation diagram showed the volume variable as the most important predictor.Conclusion: The U-Net was fully automatic and showed a high correlation with manual segmentation. An integrated approach combining clinical variables and stroke lesion volumes that were derived from the advanced machine learning algorithms had high accuracy in predicting the progression to severe stroke in ASACNLII patients.

Leukemia is the most common malignancy affecting children. The morphologic analysis of bone marrow smears is an important initial step for diagnosis. Recent publications demonstrated that artificial intelligence is able to classify blood cells but a long way from clinical use. A total of 1,732 bone marrow images were used for the training of a convolutional neural network (CNN). New techniques of deep learning were integrated and an end-to-end leukemia diagnosis system was developed by using raw images without pre-processing. The system creatively imitated the workflow of a hematologist by detecting and excluding uncountable and crushed cells, then classifying and counting the remain cells to make a diagnosis. The performance of the CNN in classifying WBCs achieved an accuracy of 82.93%, precision of 86.07% and F1 score of 82.02%. And the performance in diagnosing acute lymphoid leukemia achieved an accuracy of 89%, sensitivity of 86% and specificity of 95%. The system also performs well at detecting the bone marrow metastasis of lymphoma and neuroblastoma, achieving an average accuracy of 82.93%. This is the first study which included a wider variety of cell types in leukemia diagnosis, and achieved a relatively high performance in real clinical scenarios.

Safety is an important issue in human–robot interaction (HRI) applications. Various research works have focused on different levels of safety in HRI. If a human/obstacle is detected, a repulsive action can be taken to avoid the collision. Common repulsive actions include distance methods, potential field methods, and safety field methods. Approaches based on machine learning are less explored regarding the selection of the repulsive action. Few research works focus on the uncertainty of the data-based approaches and consider the efficiency of the executing task during collision avoidance. In this study, we describe a system that can avoid collision with human hands while the robot is executing an image-based visual servoing (IBVS) task. We use Monte Carlo dropout (MC dropout) to transform a deep neural network (DNN) to a Bayesian DNN, and learn the repulsive position for hand avoidance. The Bayesian DNN allows IBVS to converge faster than the opposite repulsive pose. Furthermore, it allows the robot to avoid undesired poses that the DNN cannot avoid. The experimental results show that Bayesian DNN has adequate accuracy and can generalize well on unseen data. The predictive interval coverage probability (PICP) of the predictions along x, y, and z directions are 0.84, 0.94, and 0.95, respectively. In the space which is unseen in the training data, the Bayesian DNN is also more robust than a DNN. We further implement the system on a UR10 robot, and test the robustness of the Bayesian DNN and the IBVS convergence speed. Results show that the Bayesian DNN can avoid the poses out of the reach range of the robot and it lets the IBVS task converge faster than the opposite repulsive pose.1

Aims: The aim of this study was to determine whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters might be prognostic markers for patients with differentiated thyroid carcinoma (DTC).Methods: We searched for eligible articles in PubMed, EMBASE (Ovid), Cochrane Library, and ClinicalTrials.gov from inception to February 2021. We included studies addressing the association between 18F-FDG PET/CT parameters and clinical outcomes among patients with DTC. Quality assessment was performed using the Quality in Prognosis Studies (QUIPS) tool.Results: A total of 25 studies including 2,954 patients (1,994 females, 67.5%) were included; 2,416 patients (81.8%) had papillary thyroid carcinoma (PTC), and the mean or median follow-up time ranged from 19.1 months to 17.1 years. Thirteen (52.0%) studies were assessed as “unclear” for the domain of study participation. The most common timing of PET/CT scans was after thyroidectomy (in 20 of 25 studies, 80%), especially in patients with an elevated thyroglobulin (Tg) and a negative radioiodine whole-body scan (WBS). The most common PET parameter was FDG uptake. Twelve of 17 (70.6%) and 12 of 12 (100%) studies showed an association between PET/CT parameters and disease progression and survival in patients with DTC, respectively.Conclusion:18F-FDG PET/CT parameters alone or combined with other variables can serve as prognostic markers to identify DTC patients with poor outcomes, especially in the setting of an elevated Tg and a negative WBS. Future research is needed to confirm these findings and to examine the prognostic value of PET/CT parameters for DTC patients, considering the heterogeneity in PET/CT parameters, unclear information of patients, and PET/CT-adapted treatment modifications.

Three-dimensional (3D) graphene-based macrostructures are being developed to combat the issues associated with two-dimensional (2D) graphene materials in practical applications. The 3D macrostructures (3DMs), for example, membranes, fibres, sponges, beads, and mats, can be formed by the self-assembly of 2D graphene-based precursors with exceptional surface area and unique chemistry. With rational design, the 3D macrostructures can then possess outstanding properties and exclusive structures. Thanks to various advantages, these macrostructures are competing in a variety of applications with promising performances unlike the traditional activated carbons, biochars and hydrochars, which have less flexibilities for modifications towards versatile applications. However, despite having such a wide range of applications, 3DMs remain applicable on laboratory scale due to the associated factors like cost and extensive research. This perspective provides an overview of available graphene-based macrostructures and their diverse synthesis protocols. In the synthesis, hydrothermal route, chemical vapor deposition (CVD), wet spinning, 3D printing, vacuum filtration, spray drying and emulsion methods are highlighted. In addition, the physio-chemical properties of these macrostructures are discussed with the relationship among the porosity, surface area and the bulk density. The perspective also highlights the versatile potentials of different 3DMs in wastewater remediation by adsorption, desalination, and catalytic oxidation, etc. Following the concluding remarks, future outlooks on commercial applications of 3DMs are also provided.

Extended-spectrum β-lactamases (ESBLs) production and (fluoro)quinolone (FQ) resistance among Salmonella pose a public health threat. The objective of this study was the phenotypic and genotypic characterization of an ESBL-producing and nalidixic acid-resistant Salmonella enterica serovar Gloucester isolate (serotype 4:i:l,w) of sequence type 34 (ST34) from ready-to-eat (RTE) meat products in China. Whole-genome short and long read sequencing (HiSeq and MinION) results showed that it contained blaCTX–M–55, qnrS1, and tetB genes, with blaCTX–M–55 and qnrS1 located in chromosomal IS26-mediated composite transposon (IS26–qnrS1–IS3–Tn3–orf–blaCTX–M–55–ISEcp1–IS26). The same genetic structure was found in the chromosome of S. enterica subsp. enterica serovar Typhimurium strain and in several plasmids of Escherichia coli, indicating that the IS26-mediated composite transposon in the chromosome of S. Gloucester may originate from plasmids of E. coli and possess the ability to disseminate to Salmonella and other bacterial species. Besides, the structural unit qnrS1–IS3–Tn3–orf–blaCTX–M–55 was also observed to be linked with ISKpn19 in both the chromosomes and plasmids of various bacteria species, highlighting the contribution of the insertion sequences (IS26 and ISKpn19) to the co-dissemination of blaCTX–M–55 and qnrS1. To our knowledge, this is the first description of chromosomal blaCTX–M–55 and qnrS in S. Gloucester from RTE meat products. Our work expands the host range and provides additional evidence of the co-transfer of blaCTX–M–55 and qnrS1 among different species of Salmonella through the food chain.

Understanding phosphorylation-mediated regulation of metabolic enzymes, pathways, and cell phenotypes under metabolic shifts represents a major challenge. The kinases associated with most phosphorylation sites and the link between phosphorylation and enzyme activity remain unknown. In this study, we performed stable isotope labeling by amino acids in cell culture (SILAC)-based proteome and phosphoproteome analysis of Escherichia coli ΔyeaG, a strain lacking a poorly characterized serine/threonine kinase YeaG, to decipher kinase-substrate interactions and the effects on metabolic phenotype during shifts from glucose to malate. The starting point of our analysis was the identification of physiological conditions under which ΔyeaG exhibits a clear phenotype. By metabolic profiling, we discovered that ΔyeaG strain has a significantly shorter lag phase than the wild type during metabolic shift from glucose to malate. Under those conditions, our SILAC analysis revealed several proteins that were differentially phosphorylated in the ΔyeaG strain. By focusing on metabolic enzymes potentially involved in central carbon metabolism, we narrowed down our search for putative YeaG substrates and identified isocitrate lyase AceA as the direct substrate of YeaG. YeaG was capable of phosphorylating AceA in vitro only in the presence of malate, suggesting that this phosphorylation event is indeed relevant for glucose to malate shift. There is currently not enough evidence to firmly establish the exact mechanism of this newly observed regulatory phenomenon. However, our study clearly exemplifies the usefulness of SILAC-based approaches in identifying proteins kinase substrates, when applied in physiological conditions relevant for the activity of the protein kinase in question.

The prevalence of ossification of the posterior longitudinal ligament (OPLL) is increasing, and currently there is no effective medical treatment for OPLL. Methyltransferase like 3 (METTL3), one of the components of the N6-methyladenosine (m6A) methyltransferase complex, regulates gene expression via modification of mRNA. Although METTL3 has been implicated in a variety of diseases, its role in OPLL remains to be elucidated. Primary ligament fibroblasts were used in this study. To investigate the role of METTL3 in OPLL, METTL3 was silenced or overexpressed. m6A RNA methylation was measured by commercially available kits. Luciferase reporter assay was performed to investigate the binding of miR-302a-3p and METTL3, and the binding of miR-302a-3p and USP8. Quantitative RT-PCR and western blots were used to evaluate mRNA and protein expression, respectively. OPLL increases METTL3 and its m6A modification. Overexpressing METTL3 significantly promoted osteogenic differentiation of primary ligament fibroblasts. Mechanism study showed that METTL3 increased m6A methylation of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST). Further study showed that lncRNA XIST regulates osteogenic differentiation of primary ligament fibroblasts via miR-302a-3p, which targets ubiquitin-specific protease 8 (USP8). METTL3 enhanced osteogenic differentiation of primary ligament fibroblasts via the lncRNA XIST/miR-302a-3p/USP8 axis. The findings highlight the importance of METTL3-mediated m6A methylation of XIST in OPLL and provide new insights into therapeutic strategies for OPLL.

Background: Little is known about the function of tumor suppressor gene Forkhead box 1 (FOXO1) in myelodysplastic syndromes (MDS). The aim of this study was to elucidate the role of FOXO1 through decitabine (DAC) treatment. Methods: Microarray analysis was used to identify differentially expressed genes (DEGs) from 2 MDS cell lines by DAC treatment. WebGestalt was used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) for constructing protein–protein interaction (PPI) network analysis. Cell apoptosis, cycle arrest, differentiation, and immunoregulation were performed to validate the function of FOXO1 by silencing its expression prior to DAC treatment in MDS. Results: The results showed that the FOXO signaling pathway was one of the most promising. FOXO1 exists in a hyperphosphorylated, inactive form in MDS-L cells. DAC treatment both induces FOXO1 expression and reactivates the protein through reducing its phosphorylation level. Furthermore, we showed that this FOXO1 activation is responsible for the DAC-induced apoptosis, cell cycle arrest, antigen differentiation, and immunoregulation in MDS-L cells. The results also demonstrated that DAC-induced FOXO1 activation upregulated anti-tumor immune response in higher risk MDS specimens.Conclusions: These results suggest that DAC induces FOXO1 activation, which plays an important role in anti-MDS tumors.

Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase (ERAP1 and ERAP2) genes are associated with the pathogenesis of bacterial and viral infections. To search for the variations in the ERAP1 and ERAP2 genes associated with tuberculosis (TB), 449 TB cases and 435 healthy individuals of the Han population in the Yunnan province of China were included in the present study. Eleven SNPs of ERAPs were genotyped using the SNaPshot SNP assay. Allelic, genotypic, and haplotypic association analyses were performed between the TB and control groups. Furthermore, stratification analyses among pulmonary TB (PTB), extrapulmonary TB (EPTB), and healthy controls; and initial treatment TB (ITTB), retreatment TB (RTB), and healthy controls were also performed. The TT genotype of rs26618 in ERAP1 exhibited a protective factor for TB, compared with the role of the CC/CT genotype (P = 0.003; OR = 1.490, 95% CI: 1.140-1.940). In ERAP2, the frequency of the G allele of rs2549782 was higher in the case group than in the control group (0.491 vs. 0.417, P = 0.002, OR = 1.350, 95% CI: 1.118-1.631), and the TT genotype exhibited a protective factor for TB, compared with the role of the GG/GT genotype (P = 0.001; OR = 1.650, 95% CI: 1.230-2.220). The frequency of the C allele of rs1056893 was higher in the case group than in the control group (0.468 vs. 0.394, P = 0.002, OR = 1.350, 95% CI: 1.118-1.631), and the genotype exhibited a difference in the log-additive model (P = 0.002; OR = 1.350, 95% CI: 1.120-1.630). The frequencies of the haplotype rs27037-rs27044-s30187-rs26618-rs26653-rs3734016-GCCCGC in ERAP1 (0.290 vs. 0.240, P-adj = 0.028, OR = 1.320, 95% CI: 1.063-1.638) and the haplotypes rs2549782-rs2248374-rs2287988-rs1056893-GTAGC in ERAP2 (0.446 vs. 0.348, P-adj = 4.80E-05, OR = 1.510, 95% CI: 1.246-1.829) was higher in the TB groups, while the frequencies of the haplotypes rs2549782-rs2248374-rs2287988-rs1056893-TAGAT (0.478 vs. 0.539, P-adj = 0.020, OR = 0.782, 95% CI: 0.649-0.943) were lower in the TB groups. The allelic and genotypic associations were also investigated in the subsequent stratification between the PTB, EPTB and control groups as well as between the ITTB, RTB, and control groups. In conclusion, variations in ERAP1 and ERAP2 genes were identified to be associated with TB in the Han Chinese population.

Background Lung immune prognostic index (LIPI) status was recently developed to predict responses to immune checkpoint inhibitor (ICI) treatments. However, it is unclear whether LIPI is a prognostic index for both patients treated with ICI monotherapy and patients treated with ICIs combined with chemotherapy (ICIs CC). Methods This retrospective study established the patterns of LIPI in Chinese patients with advanced non-small cell lung cancer. Lung immune prognostic index based on the derived neutrophil-to-lymphocyte ratio greater than 3 and lactate dehydrogenase greater than the upper limit of normal was developed to characterize good, intermediate, or poor LIPI status. Associations between LIPI status and progression-free survival (PFS) and overall survival (OS) were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine survival differences. Results Three hundred thirty patients were included in this study. Of these patients, 216 received ICI monotherapy and 114 received ICIs CC. A good LIPI status was associated with better PFS (6.1 months vs. 2.3 months vs. 2.1 months, P = 0.023) and OS (24.2 months vs. 14.5 months vs. 9.3 months, P < 0.001) in ICI monotherapy compared to intermediate or poor LIPI status. No differences in PFS (17.9 vs. 9.9 months vs. 7.6 months, P = 0.355, respectively) and OS (P = 0.346) were observed in patients who received ICIs CC. Moreover, we found that patients who had an improved LIPI status compared with the baseline value had a longer PFS with ICI monotherapy and LIPI intermediate status (8.4 months vs. 2.1 months vs. 1.4 months, P < 0.001). However, in patients treated with ICIs CC, these dynamic changes were not observed (P = 0.444). Conclusions Lung immune prognostic index status and dynamic changes in LIPI could be prognostic markers of treatment response to ICI monotherapy, but not to ICIs CC. In particular, good LIPI status was associated with a better clinical outcome compared with intermediate and poor LIPI status in ICI monotherapy treatment.

Pathogenic autoantibodies can cause inflammation and tissue injury in systemic lupus erythematosus (SLE). Although IgG4 is considered non-inflammatory owing to the unique structure of its hinge region, the role of IgG4 autoantibodies in SLE remains largely unknown. The titers of serum anti-nuclear-IgG antibodies (ANA-IgG) and anti-nuclear-IgG4 antibodies (ANA-IgG4) in newly diagnosed SLE patients were detected. The effects of IgG4 purified from SLE patients (SLE IgG4) and healthy controls on complement consumption and inflammatory cytokine production were evaluated in vitro. The therapeutic effects of mouse IgG1 (functionally resembles human IgG4) purified from lupus-prone MRL-lpr/lpr mice (lupus IgG1) and control mice on disease progression were examined in MRL-lpr/lpr mice. The results showed that SLE patients with equal titers of total serum ANA-IgG (1:3,200) were divided into group I with lower ANA-IgG4 titers (≤ 1:10) and group II with higher ANA-IgG4 titers (≥ 1:100), and disease activity, inflammatory cytokine production, complement consumption, and renal-function parameters in group I SLE patients were more severe than those in group II. Further, compared with control IgG4, SLE IgG4 inhibited complement consumption by autoantibody-autoantigen immune complexes, and also inhibited inflammatory cytokines production by SLE PBMCs in vitro. Moreover, compared with control IgG1, lupus IgG1 exhibited a therapeutic effect on lupus by attenuating disease progression in MRL-lpr/lpr mice. These findings, for the first time, suggest that IgG4 autoantibodies can attenuate SLE progression by suppressing complement consumption and inflammatory cytokine production. Hence, this study may provide novel therapeutic strategies against SLE and other autoimmune diseases.

Theoretical have shown that cooperation can be promoted by the so-called "network reciprocity", where cooperation can coexist with defection via the compact cooperative clusters. However, this mechanism has one assumption interpreted as players have no chance to exit from the game even the situation is extremely bad, which is in sharp contrast with real-life situations. Here, we relax this assumption in the spatial prisoner's dilemma game by giving players the right to choose one of their state between active (participate in the game) and inactive (exit from the game) in each round of the game determined by win-stay-lose-leave rule. This new rule attracts a winner whose payoff is larger than the average payoff of its neighbors to stay in its current state, thus retains its current advantage to its neighbors. Conversely, a loser is pushed to leave from its current state and thus increase its chance to obtain a higher payoff. Specifically, we incorporate exit costs into consideration by assuming anyone who decides to exit from the game must pay a cost $\gamma$. Extensively numerical simulation shows that for the requirement of exit cost is neither too high or too small, a full cooperation plateau is achieved, where cooperation evolves with the support of enhanced network reciprocity. In fact, inactive players can only exist at the boundary of cooperative clusters during its evolution dynamics, which create a crucial buffer area for the endangered cooperators. Finally, the joint effect of this protective film composed of inactive players and cooperative clusters forming the foundation of enhanced network reciprocity. Our findings may provide new insight into network reciprocity.

In this study, we found miR-362-5p was upregulated in bladder cancer tissues and we predicted that QKI is potential a target of miR-362-5p and MBNL1-AS1 might be able to directly target to miR-362-5p. We attempted to evaluate whether miR-362-5p could play its roles in bladder cancer through regulating QKI (quaking) and whether the expression and function of miR-362-5p could be mediated by lncRNA MBNL1-AS1. We performed the gain- and loss-function experiments to explore the association between miR-362-5p expression and bladder cancer proliferation. In vivo, the nude mice were injected with miR-362-5p knockdown SW780 cells to assess the effects of miR-362-5p on tumor growth. The results showed upregulation of miR-362-5p promoted cell proliferation of bladder cancer cells. MBNL1-AS1 and QKI could directly bind with miR-362-5p, and knockdown of MBNL1-AS1 or QKI could abrogate the regulatory effects of miR-362-5p on bladder cancer cell proliferation. Furthermore, downregulation of miR-362-5p inhibited bladder tumor growth and increased QKI expression. Our data unveiled that miR-362-5p may play an oncogenic role in bladder cancer through QKI and MBNL1-AS1 might function as a sponge to mediate the miR-362-5p expression and function.

Hemagglutination inhibition (HI) and virus neutralization antibody (nAb) do not always correlate with the protection of H7 avian influenza vaccines in mammals and humans. The contribution of different classes of antibodies induced by H7N9 vaccines to protection is poorly characterized in chickens. In this study, antibody responses induced by both inactivated and viral-vectored H7N9 vaccines in chickens were dissected. Chickens immunized with inactivated H7N9 vaccine showed 50% seroconversion rate and low HI and nAb titers at week 3 post immunization. However, inactivated H7N9 vaccine elicited 100% seroconversion rate in terms of high levels of HA-binding IgG antibody determined by ELISA. Despite inducing low levels of nAb, inactivated H7N9 vaccine conferred full protection against H7N9 challenge in chickens and markedly inhibited virus shedding. Similarly, Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and nAb titers but high level of IgG antibody against H7N9 virus. In addition, NDV-H7N9 vaccine also provided complete protection against H7N9 challenge. Chicken antisera had a high IgG/VN ratio, indicating that a larger proportion of serum antibodies were non-neutralizing antibody (non-nAb). More importantly, passive transfer challenge experiment showed that non-neutralizing antisera provided partial protection (37.5%) of chickens against H7N9 challenge, without significant difference from that provided by neutralizing antisera. In conclusion, our results suggest that antibodies measured by the traditional HI and virus neutralization assays do not correlate with the protection of inactivated and viral-vectored H7N9 vaccines in chickens, and HA-binding non-nAb also contributes to the protection against H7N9 infection. Total binding antibody can be used as a key correlate to the protection of H7N9 vaccine.

Na and cyano-group co-modified g-C3N4 was easily synthesized and its physicochemical property was completely analyzed. The results manifested that Na and cyano-group modification could heighten visible light absorbed ability and accelerate photoinduced charge separation. When resultant Na and cyano-group co-modified g-C3N4 was splitting water H2 evolution, its H2 evolution rate was obviously improved. Furthermore, it also kept excellent stable capacity of H2 evolution and stability of chemical structure. Hence, this present study does not only develop an efficient strategy to boost photocatalytic property of g-C3N4 based catalysts, but also provides useful guidance for designing more effective photocatalysts.

Background and Purpose: This study aimed to investigate the association between insulin resistance (IR) and the overall cerebral small vessel disease (CSVD) burden.Methods: We recruited elderly, nondiabetic, healthy subjects prospectively. The overall effect of CSVD on the brain was described by a validated CSVD score. The homeostasis model assessment–estimated insulin resistance index (HOMA-IR) was used for IR estimation, and HOMA-IR ≥2.80 was defined as IR. We evaluated the association between IR and the increasing severity of CSVD score by ordinal regression models adjusting for demographics and cardiovascular risk factors.Results: A total of 156 healthy participants were recruited. The mean age was older in the IR group than in the non-IR group (70.03 vs. 67.45, p = 0.04), and the prevalence of hypertension was significantly higher in the IR group than in the non-IR group (82.35% vs. 53.28%, p < 0.01). In ordinal regression analysis, IR was positively associated with increasing severity of the total CSVD score (adjusted odds ratio, 3.74; 95% confidence interval, 1.63–5.08; p < 0.01) after adjusting traditional risk factors. Furthermore, HOMA-IR levels showed a positive dose-dependent correlation with the total CSVD score (p < 0.01, p for trend

Aim: The objective of this study was to evaluate the association of the human leukocyte antigen (HLA) class II genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 with the humoral immune response elicited by inactivated Japanese encephalitis (JE) vaccine (IJEV). Methods: A total of 373 individuals aged 3-12 years in the Inner Mongolia Autonomous Region in China, who received two doses of IJEV at 0 and 7 days, were enrolled in the current study. Based on the individuals' specific JE virus (JEV)-neutralizing antibodies (NAbs), they were divided into a seropositive and a seronegative group. HLA-DRB1, HLA-DPB1, and HLA-DQB1 were genotyped using a sequencing-based typing method. Next, the association of the HLA class II genes and their haplotypes with antibody response was evaluated. Results: Based on NAbs, a total of 161 individuals were classified as seropositive and 212 as seronegative. DQB1 * 02:01 was significantly associated with JEV seropositivity (P < 0.001, OR = 0.364, 95% CI: 0.221-0.600), while DQB1 * 02:02 was significantly associated with JEV seronegativity (P = 5.03 × 10-6, OR = 7.341, 95% CI: 2.876-18.736). The haplotypes DRB1 * 07:01-DPB1 * 04:01-DQB1 * 02:01, DRB1 * 15:01-DPB1 * 02:01-DQB1 * 06:02, DRB1 * 07:01-DQB1 * 02:01, and DPB1 * 02:01-DQB1 * 06:02 were very frequent in the seropositive group, while DRB1 * 07:01-DPB1 * 17:01-DQB1 * 02:02, DRB1 * 07:01-DQB1 * 02:02, and DPB1 * 17:01-DQB1 * 02:02 were very frequent in the seronegative group. The presence of DRB1 * 01:01, DRB1 * 04:05, DRB1 * 09:01, DRB1 * 12:02, DRB1 * 13:02, and DRB1 * 14:01 was associated with a higher geometric mean titer (GMT) of NAbs than that of DRB1 * 11:01 at the DRB1 locus (P < 0.05). At the DPB1 locus, the presence of DPB1 * 05:01 was associated with higher GMTs than that of DPB1 * 02:01 and DPB1 * 13:01 (P < 0.05), and the presence of DPB1 * 04:01 and DPB1 * 09:01 was associated with higher GMTs than that of DPB1 * 13:01 (P < 0.05). Conclusions: The present study suggests that HLA class II genes may influence the antibody response to IJEV.

Colorectal cancer (CRC) has emerged as a major public health concern in China during the last decade. In this study, we investigated the disease burden posed by CRC and analyzed temporal trends in CRC incidence and mortality rates in this country. We collected CRC incidence data from the Cancer Incidence in Five Continents, Volume XI dataset and the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CRC by sex and age, from the 2016 Global Burden of Diseases Study. We used the average annual percentage change (AAPC) to quantify temporal trends in CRC incidence and mortality from 1990 to 2016 and found the ASIR of CRC increased from 14.25 per 100,000 in 1990 to 25.27 per 100,000 in 2016 (AAPC = 2.34, 95% confidence interval [CI] 2.29, 2.39). Cancer cases increased from 104.3 thousand to 392.8 thousand during the same period. The ASIR increased by 2.76% (95% CI 2.66%, 2.85%) and 1.70% (95% CI 1.64%, 1.76%) per year in males and females, respectively. The highest AAPC was found in people aged 15-49 years (2.76, 95% CI 2.59, 2.94). Cancer deaths increased from 81.1 thousand in 1990 to 167.1 thousand in 2016, while the ASMR remained stable (-0.04, 95% CI -0.13, 0.05), A mild increase (AAPC = 0.42, 95% CI 0.34, 0.51) was found among males and a significant decrease (AAPC = -0.75, 95% CI -0.90, -0.60) was found among females. Between 2016 and 2025, cancer cases and deaths are expected to increase from 392.8 and 167.1 thousand in 2016 to 642.3 (95% CI 498.4, 732.1) and 221.1 thousand (95% CI 122.5, 314.8) in 2025, respectively. Our study showed a steady increase in the CRC incidence in China over the past three decades and predicted a further increase in the near future. To combat this health concern, the prevention and management of known risk factors should be promoted through national polices. Greater priority should be given to CRC prevention in younger adults, and CRC screening should be widely adopted for this population.

Human adenovirus type 55 (HAdV-55) is considered a highly virulent pathogen causing severe and even deadly pneumonia in immunocompetent people. The mechanisms of HAdV-55-induced initiation and progression of severe pneumonia remain ambiguous. In the current study, we endeavored to identify novel immune response genes which are substantially involved in the pathogenesis of severe inflammation in HAdV-55-infected patients. HAdV-55-infected patients with upper respiratory tract symptoms (minor patients) and pneumonia (severe patients) were enrolled. Through transcriptome sequencing and quantitative real-time PCR, the peripheral blood mononuclear cells of the patients were analyzed. We found that the expression of eight genes, including Il18, Il36b, Il17rc, Tnfsf10, Tnfsf11, Tnfsf14, Tnfsf15, and Il1a, were closely correlated with the severity of HAdV-55 infection. Most of these genes belong to interleukin-1 family or tumor necrosis factor (TNF) superfamily, respectively. The changes in gene expression were confirmed by Western blot assay. Our data will be crucial for deepening the understanding of the pathogenic mechanisms of severe pneumonia in HAdV-55 infection.

Porcine respiratory disease (PRD) is responsible for severe economic losses in the swine industry worldwide. Our objective was to characterize the oropharyngeal microbiota of suckling piglets and compare the microbiota of healthy piglets and piglets with PRD. Oropharyngeal swabs were collected from healthy (Healthy_A, n = 6; Healthy_B, n = 4) and diseased (PRD_A, n = 18; PRD_B, n = 5) piglets at 2–3 weeks of age from two swine farms in Guangdong province, China. Total DNA was extracted from each sample and the V3-V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. No statistically significant differences were observed in bacterial diversity and richness between the healthy and PRD groups in the two farms except for Shannon index in farm A. Principal coordinates analysis (PCoA) showed structural segregation between diseased and healthy groups and between groups of different farms. Among all samples, the phyla Firmicutes, Proteobacteria, and Bacteroidetes were predominant. At the genus level, Streptococcus, Lactobacillus, and Actinobacillus were the core genera in the oropharynx of healthy piglets from the two farms. Significant differences in bacterial taxa were found when the microbiota was compared regarding the health status. In farm A, the percentages of Moraxella and Veillonella were higher in the PRD group, while only Porphyromonas was significantly increased in the PRD group in farm B (p < 0.05). Compared to PRD groups, statistically significant predominance of Lactobacillus was observed in the healthy groups from both farms (p < 0.05). Our findings revealed that Moraxella, Veillonella, and Porphyromonas may play a potential role in PRD and Lactobacillus may have a protective role against respiratory diseases.

Efflux is a primary fluoroquinolone resistance mechanism in Listeria monocytogenes. In the present study, ciprofloxacin resistant strains were selected by exposure of sensitive strain to progressively increasing concentrations of ciprofloxacin and then the roles of efflux pumps Lde and MdrL in the development of resistance to ciprofloxacin were also investigated in L. monocytogenes. Ciprofloxacin sensitive strain of L. monocytogenes exhibited reduced susceptibility to this antibiotic after induction. Cross-resistance to ethidium bromide (EtBr) was observed in ciprofloxacin-induced strains. However, cross-resistance to benzalkonium chloride (BC) did not occur in this study. Compared to the wild-type strain HL06, the expression levels of lde were increased in four ciprofloxacin-induced strains. The single-gene deletion mutants of lde and mdrL from the ciprofloxacin-induced resistant strain HL06CIP4 were constructed. However, decreased minimum inhibitory concentration (MIC) of ciprofloxacin was observed only in HL06CIP4Δlde compared to that of the parental strain HL06CIP4. Ciprofloxacin uptake appeared to be obviously increased in HL06CIP4Δlde in relative to HL06CIP4. These evidences suggested that efflux pump Lde is involved in ciprofloxacin resistance in L. monocytogenes HL06CIP4. The deletion of lexA had no effect on the expression levels of lde in HL06CIP4 in the absence or presence of ciprofloxacin, indicating that LexA was not involved in the regulation of efflux pump Lde in L. monocytogenes.

Livestock-associated Staphylococcus aureus colonization and/or infections exist in pigs and people in frequent contact with pigs. In this study, a total of 130 S. aureus isolates obtained from different stages of pork production were subjected to antimicrobial susceptibility, biofilm formation, as well as PCR screening to identify virulence genes, and the accessory gene regulator alleles (agr). Among all 130 S. aureus isolates, 109 (83.8%, 109/130) isolates were positive for agr. All swine farms isolates belonged to agr IV, whereas S. aureus isolated from slaughterhouse and retail indicated diverse agr types. All isolates exhibited biofilm formation ability, and raw meat isolates (belonging to agr I) exhibited a greater ability to form strong biofilms than swine farms isolates (belonging to agr IV). agr-positive isolates were associated with more virulence genes than agr-negative isolates. Most biofilm-producing isolates were positive for microbial surface component recognizing adhesive matrix molecule (MSCRAMM), capsule type and ica group genes. The results illustrate a significant association between the prevalence rate of MSCRAMM, capsule type and ica group genes among isolates producing weak, moderate and strong biofilms. The high prevalence of resistance to ciprofloxacin, gentamicin, tetracycline, clarithromycin, clindamycin, and trimethoprim-sulfamethoxazole were mainly observed in moderate and weak biofilm producers. Our findings indicate that S. aureus isolates from pork production displayed diverse molecular ecology.

The plant cuticle, which consists of cutin and waxes, forms a hydrophobic coating covering the aerial surfaces of all plants. It acts as an interface between plants and their surrounding environment whilst also protecting them against biotic and abiotic stresses. In this research, we have investigated the biodiversity and cuticle properties of aquatic plant duckweed, using samples isolated from four different locations around Hongze lake in Jiangsu province, China. The samples were genotyped using two chloroplast markers and nuclear ribosomal DNA markers, which revealed them as ecotypes of the larger duckweed, Spirodela polyrhiza. Duckweed cuticle properties were investigated by compositional analysis using Gas Chromatography coupled with Mass Spectroscopy (GC-MS) Flame Ionization Detector (GC-FID), and ultrastructural observation by cryo-Scanning Electron Microscopy (cryo-SEM). Cuticle compositional analysis indicated that fatty acids and primary alcohols, the two typical constituents found in many land plant cuticle, are the major duckweed wax components. A large portion of the duckweed wax fraction is composed of phytosterols, represented by campesterol, stigmasterol, sitosterol and their common precursor squalene. The cryo-SEM observation uncovered significant differences between the surface structures of the top air-facing and bottom water-facing sides of the plant fronds. The top side of the fronds, containing multiple stomata complexes, appeared to be represented by a rather flat waxy film sporadically covered with wax crystals. Underneath the waxy film was detected a barely distinguished nanoridge net, which became distinctly noticeable after chloroform treatment. On the bottom side of the fronds, the large epidermal cells were covered by the well-structured net, whose sections became narrower and sharper under cryo-SEM following chloroform treatment. These structural differences between the abaxial and adaxial sides of the fronds evidently relate to their distinct physiological roles in interacting with the contrasting environments of sunlight/air and nutrients/water. The unique structural and biochemical features of Spirodela frond surfaces with their rapid reproductive cycle and readily availability genome sequence, make duckweed an attractive monocot model for studying the fundamental processes related to plant protection against ultraviolet irradiation, pathogens and other environmental stresses.

To assess the diversity of actinobacterial taxa in desert sands and obtain the novel microbial resources, 79 and 50 samples were collected from the Badain Jaran (BJD) and Tengger Deserts (TGD) of China, respectively. High-throughput sequencing (HTS) of environmental 16S rRNA genes within these samples was conducted on an Illumina Miseq platform, using universal bacterial primers targeting the V3–V4 hypervariable region. Based on the HTS analyses, cultivation-dependent (CULD) techniques were optimized to identify the cultivable Actinobacteria members. A total of 346,766 16S rRNA gene reads comprising 3,365 operational taxonomic units (OTUs) were obtained from the BJD sands using HTS, while 170,583 reads comprising 1,250 OTUs were detected in the TGD sands. Taxonomic classification indicated that Actinobacteria was the predominant phylum, comprising 35.0 and 29.4% of the communities in BJD and TGD sands, respectively. Among the Actinobacteria, members of the Geodermatophilaceae were considerably abundant in both deserts, indicating that they represent ubiquitous populations within the deserts. At the genus level, Arthrobacter spp. and Kocuria spp. were dominant, and corresponded to 21.2 and 5.3% of the actinobacterial communities in BJD and TGD deserts, respectively. A total of 786 and 376 actinobacterial strains were isolated and identified from BJD and TGD samples, respectively. The isolates comprised 73 genera of 30 families within the phylum Actinobacteria. In addition to the Geodermatophilaceae, Streptomyces spp. were a prominent component of the isolates, comprising 25% of the isolates from BJD and 17.5% of those from TGD. Comparison of the actinobacterial community structure in other ecosystems indicated that Geodermatophilaceae was the main actinobacterial group in desert sands, which is consistent with our results. Additionally, in these desert habits, Geodermatophilaceae and some other core groups may promote or inhabit the subsequent members' occurrence or prosper to shape the bacteria community structure. However, it should be noted that a number of other low-abundance bacteria appear to be specific to desert sands, which are worth further investigation. In antimicrobial activity assays, 10.36 % of the tested isolates showed antimicrobial activities in one or more screens. Importantly, 37 of the newly isolated strains reported here represent novel taxa that could be valuable resources for further research of novel secondary metabolites and their ecological significance in deserts.

Developing therapeutic approaches that target neuronal differentiation will be greatly beneficial for the regeneration of neurons and synaptic networks in neurological diseases. Protein synthesis (mRNA translation) has recently been shown to regulate neurogenesis of neural stem/progenitor cells (NSPCs). However, it has remained unknown whether engineering translational machinery is a valid approach for manipulating neuronal differentiation. The present study identifies that a bivalent securinine compound SN3-L6, previously designed and synthesized by our group, induces potent neuronal differentiation through a novel translation-dependent mechanism. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis in Neuro-2a progenitor cells revealed that SN3-L6 upregulated a group of neurogenic transcription regulators, and also upregulated proteins involved in RNA processing, translation, and protein metabolism. Notably, puromycylation and metabolic labeling of newly synthesized proteins demonstrated that SN3-L6 induced rapid and robust activation of general mRNA translation. Importantly, mRNAs of the proneural transcription factors Foxp1, Foxp4, Hsf1, and Erf were among the targets that were translationally upregulated by SN3-L6. Either inhibition of translation or knockdown of these transcription factors blocked SN3-L6 activity. We finally confirmed that protein synthesis of a same set of transcription factors was upregulated in primary cortical NPCs. These findings together identify a new compound for translational activation and neuronal differentiation, and provide compelling evidence that reprogramming transcriptional regulation network at translational levels is a promising strategy for engineering NSPCs.

Aquaporins (AQPs) are an abundant protein family and play important roles to facilitate small neutral molecule transport across membranes. Oilseed rape (Brassica napus L.) is an important oil crop in China as well as in the world, and is very sensitive to low boron (B) stress. Several AQP family genes have been reported to be involved in B transport across plasma membranes in plants. In this study, a total of 121 full-length AQPs were identified and characterized in B. napus (AC genome), and could be classified into four sub-families, including 43 PIPs (plasma membrane intrinsic proteins), 35 TIPs (tonoplast intrinsic proteins), 32 NIPs (NOD26-like intrinsic proteins) and 11 SIPs (small basic intrinsic proteins). The gene characteristics of BnaAQPs were similar to that of BraAQPs (A genome) and BolAQPs (C genome) including the composition of each sub-family, gene structure, and substrate selectivity filters. The BnaNIP was the most complex of AQP sub-family, reflecting the composition of substrate selectivity filter structures which affect the permeation of solution molecules. In this study, the seedlings of both B-efficient (QY10) and B-inefficient (W10) cultivars were treated with two boron (B) levels, the deficient (0.25 μM B) and the sufficient (25 μM B). Then the transcription of AQP genes in root (R), juvenile leaf (JL) and old leaf (OL) tissues of both cultivars was investigated under B deficient and sufficient conditions. Transcription of most BnaPIPs and BnaTIPs was significantly increased compared with other BnaAQPs in all the three tissues, especially in the roots, of both B-efficient and B-inefficient cultivars under both B conditions. With B deprivation, the expression of the majority of the BnaPIPs and BnaTIPs was down-regulated in the roots. However, the BnaNIPs were up-regulated. In addition, the BnaCnn_randomPIP1;4b, BnaPIP2;4s, BnaC04.TIP4;1a, BnaAnn_randomTIP1;1b and BnaNIP5;1s (except for BnaA07.NIP5;1c and BnaC06.NIP5;1c) exhibited obvious differences at low B between B-efficient and B-inefficient cultivars. These will help us to understand the boron homeostasis in B. napus.

Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries. Recent investigations of the transient cortical layer known as subplate, especially regarding subplate’s secretory role, opens up a novel set of potential molecular modulators of neonatal HI injury. This review examines the biological mechanisms of human neonatal HI, discusses evidence for the relevance of subplate-secreted molecules to this condition, and evaluates available animal models. Neuroserpin, a neuronally released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post-ischaemic injury.

Vibrio alginolyticus is one of the most common pathogenic marine Vibrio species, and has been found to cause serious seafood-poisoning or fatal extra-intestinal infections in humans, such as necrotizing soft-tissue infections, bacteremia, septic shock and multiple organ failures. Delayed accurate diagnosis and treatment of most Vibrio infections usually result to high mortality rates. The objective of this study was to establish a rapid diagnostic method to detect and identify the presence of V. alginolyticus in different samples, so as to facilitate timely treatment. The widely employed conventional methods for detection of V. alginolyticus include biochemical identification and a variety of PCR methods. The former is of low specificity and time-consuming (2-3 days), while the latter has improved accuracy and processing time. Despite such advancements, these methods are still complicated, time-consuming, expensive, require expertise and advanced laboratory systems, and are not optimal for field use. With the goal of providing a simple and efficient way to detect V. alginolyticus, we established a rapid diagnostic method based on Loop-mediated Isothermal Amplification (LAMP) technology that is feasible to use in both experimental and field environments. Three primer pairs targeting the toxR gene of V. alginolyticus were designed, and amplification was carried out in an ESE tube scanner and Real-Time PCR device. We successfully identified 93 V. alginolyticus strains from a total of 105 different bacterial isolates and confirmed their identity by 16s rDNA sequencing. We also applied this method on infected mouse blood and contaminated scallop samples, and accurate results were both easily and rapidly (20-60min) obtained. Therefore, the RT-LAMP assay we developed can be conveniently used to detect the presence of V. alginolyticus in different samples. Furthermore, this method will also fulfill the gap for real-time screening of V. alginolyticus infections especially while on field. Keywords: Vibrio alginolyticus; toxR gene; Real-Time LAMP; 16s rDNA sequencing; rapid detection

Background Bifrontal contusion is a common clinical brain injury. In the early stage, it is often mild, but it progresses rapidly and frequently worsens suddenly. This condition can become life threatening and therefore requires surgery. Conventional decompression craniectomy is the commonly used treatment method. In this study, the effect of ICP monitored stepwise intracranial decompression surgery on the prognosis of patients with acute severe bifrontal contusion was investigated. Method A total of 136 patients with severe bifrontal contusion combined with deteriorated intracranial hypertension admitted from March 2001 to March 2014 in our hospital were selected and randomly divided into two groups, i.e., a conventional decompression group and an intracranial pressure (ICP) monitored stepwise intracranial decompression group (68 patients each), to conduct a retrospective study. The incidence rates of acute intraoperative encephalocele, delayed hematomas, and postoperative cerebral infarctions and the Glasgow outcome scores (GOSs) 6 months after the surgery were compared between the two groups. Results (1) The incidence rates of acute encephalocele and contralateral delayed epidural hematoma in the stepwise decompression surgery group were significantly lower than those in the conventional decompression group; the differences were statistically significant (P < 0.05); (2) 6 months after the surgery, the incidence of vegetative state and mortality in the stepwise decompression group were significantly lower than those in the conventional decompression group (P < 0.05); the rate of favorable prognosis in the stepwise decompression group was also significantly higher than that in the conventional decompression group (P < 0.05). Conclusions The ICP monitored stepwise intracranial decompression technique reduced the perioperative complications of traumatic brain injury through the gradual release of intracranial pressure and was beneficial to the prognosis of severe traumatic brain injury treatment.

In order to screen for cellular substrates of the Bacillus subtilis BY-kinase PtkA, and its cognate phosphotyrosine-protein phosphatase PtpZ, we performed a triple Stable Isotope Labeling by Amino acids in Cell culture-based quantitative phosphoproteome analysis. Detected tyrosine phosphorylation sites for which the phosphorylation level decreased in the ΔptkA strain and increased in the ΔptpZ strain, compared to the wild type (WT), were considered as potential substrates of PtkA/PtpZ. One of those sites was the residue tyrosine 601 of the molecular chaperone DnaK. We confirmed that DnaK is a substrate of PtkA and PtpZ by in vitro phosphorylation and dephosphorylation assays. In vitro, DnaK Y601F mutant exhibited impaired interaction with its co-chaperones DnaJ and GrpE, along with diminished capacity to hydrolyze ATP and assist the re-folding of denatured proteins. In vivo, loss of DnaK phosphorylation in the mutant strain dnaK Y601F, or in the strain overexpressing the phosphatase PtpZ, led to diminished survival upon heat shock, consistent with the in vitro results. The decreased survival of the mutant dnaK Y601F at an elevated temperature could be rescued by complementing with the WT dnaK allele expressed ectopically. We concluded that the residue tyrosine 601 of DnaK can be phosphorylated and dephosphorylated by PtkA and PtpZ, respectively. Furthermore, Y601 is important for DnaK chaperone activity and heat shock survival of B. subtilis.

WOS: 000431478700002, PubMed ID: 29868558, It is known that iron is one of the most widely used metals in industrial production. In this work, the inhibition performances of three thiophene derivatives on the corrosion of iron were investigated in the light of several theoretical approaches. In the section including DFT calculations, several global reactivity descriptors such as E-HOMO, E-LUMO, ionization energy (I), electron affinity (A), HOMO-LUMO energy gap (Delta E), chemical hardness (eta), softness (sigma), as well as local reactivity descriptors like Fukui indices, local softness, and local electrophilicity were considered and discussed. The adsorption behaviors of considered thiophene derivatives on Fe(110) surface were investigated using molecular dynamics simulation approach. To determine the most active corrosion inhibitor among studied thiophene derivatives, we used the principle component analysis (PCA) and agglomerative hierarchical cluster analysis (AHCA). Accordingly, all data obtained using various theoretical calculation techniques are consistent with experiments., National Natural Science Foundation of China [21706195]; Cumhuriyet University Scientific Research Project Commission [F495]; Guizhou Province Science Fund for Excellent Young Scholars [QKHTC2017-5604]; Science and Technology Program of Guizhou Province [QKHJC2016-1149]; Provincial Key Disciplines of Chemical Engineering and Technology in Guizhou Province [ZDXK2017-8]; Guizhou Provincial Department of Education Foundation [QJHKYZ2016-105], This work was financially supported by the National Natural Science Foundation of China (21706195), the Cumhuriyet University Scientific Research Project Commission as a research project with F495 code, the Guizhou Province Science Fund for Excellent Young Scholars (QKHTC2017-5604), the Science and Technology Program of Guizhou Province (QKHJC2016-1149), the Provincial Key Disciplines of Chemical Engineering and Technology in Guizhou Province (ZDXK2017-8), and the Guizhou Provincial Department of Education Foundation (QJHKYZ2016-105).