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1.
Med Sci Monit ; 26: e925179, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052895

RESUMO

BACKGROUND Ankylosing spondylitis (AS) is a disease that causes pathological changes in the spine and sacroiliac joints. Numerous studies have shown that the characteristics of AS differ between males and females. The purpose of this study was to discover the key molecules that contribute to sex-associated differences in AS, which may provide a new molecular target for personalized treatment. MATERIAL AND METHODS The gene expression profile of GSE39340 was downloaded from the Gene Expression Comprehensive database, and 2 groups (AS vs. No-AS groups and male AS vs. female AS groups) of differentially expressed genes (EDGs) were obtained by GEO2R. The DAVID database was used for DEGs function and enrichment analysis. Based on data in the STRING online database, a protein-protein interaction (PPI) network was constructed in Cytoscape. Hub genes were selected from CytoHubba. With the intersection of the top 30 hub genes of 2 sets of EDGs, genes coexisting with the KEGG-related pathway were found. RESULTS We screened 560 genes between the AS and No-AS groups, and screened 710 genes that were differentially expressed between the male and female AS groups. GO analysis showed that DEGs were mainly co-enriched in molecular functions, including structural constituent of muscle. The KEGG pathway mainly included the structural constituent of muscle. Seven hub genes were obtained. Troponin C2 and fast skeletal type (TNNC2) were the key genes participating in the calcium signaling pathway. CONCLUSIONS This study contributes to understanding the molecular biological mechanism underlying sex-associated differences in AS. TNNC2 and calcium signaling pathway may be new targets for the individualized treatment of AS.

2.
Small ; : e2005217, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035390

RESUMO

Optoelectronic-neuromorphic transistors are vital for next-generation nanoscale brain-like computational systems. However, the hardware implementation of optoelectronic-neuromorphic devices, which are based on conventional transistor architecture, faces serious challenges with respect to the synchronous processing of photoelectric information. This is because mono-semiconductor material cannot absorb adequate light to ensure efficient light-matter interactions. In this work, a novel neuromorphic-photoelectric device of vertical van der Waals heterojunction phototransistors based on a colloidal 0D-CsPbBr3 -quantum-dots/2D-MoS2 heterojunction channel is proposed using a polymer ion gel electrolyte as the gate dielectric. A highly efficient photocarrier transport interface is established by introducing colloidal perovskite quantum dots with excellent light absorption capabilities on the 2D-layered MoS2 semiconductor with strong carrier transport abilities. The device exhibits not only high photoresponsivity but also fundamental synaptic characteristics, such as excitatory postsynaptic current, paired-pulse facilitation, dynamic temporal filter, and light-tunable synaptic plasticity. More importantly, efficiency-adjustable photoelectronic Pavlovian conditioning and photoelectronic hybrid neuronal coding behaviors can be successfully implemented using the optical and electrical synergy approach. The results suggest that the proposed device has potential for applications associated with next-generation brain-like photoelectronic human-computer interactions and cognitive systems.

3.
Talanta ; 219: 121348, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887076

RESUMO

In this work, electromagnetic heating was firstly explored as sample introduction approach in portable microplasma-atomic emission spectrometer to achieve the direct, rapid analysis of soil sample. The device primarily consists of an electromagnetic heating unit, a dielectric barrier discharge (DBD) excitation source and an optical signal acquisition unit. A W-boat was used as an electromagnetic heating medium and sample carrier, and copper coil spiraled around the tube was used as magnetic induction coil. With applying a voltage on copper coil, W-boat was electromagnetically heated to vaporize analyte-containing species for sample introduction into the microplasma. The portable battery-powered device is controlled by a miniature touch screen computer with the main advantages of small size (40.5 cm (l) × 30 cm (w) × 15 cm (h).), light weight (less than 7 kg), low-power consumption (the average power consumption is 118 W). By this method, Hg, Cd and Pb in soil were simultaneously analyzed within 4 min. Under the optimal conditions, the limits of detection for Hg, Cd and Pb in soils were 8.0 µg/kg, 17.8 µg/kg and 3.5 mg/kg, respectively, meeting the requirements for environmental quality standards for soils of China. Different types of CRM soils were analyzed, demonstrating good accuracy, stability and utility of this method. This technique could be a promising and powerful tool for on-site, rapid analysis of heavy metals in soil even other solid samples. Electromagnetic heating mode provides a good alternative for solid sampling to develop portable, miniaturized atomic spectrometers for solid sample analysis.

4.
Immunotherapy ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32878521

RESUMO

Aim: To evaluate the cost-effectiveness of first-line treatments for advanced renal cell carcinoma with pembrolizumab plus axitinib compared with sunitinib from the US payer perspective. Patients & methods: A Markov model was developed for this purpose. The clinical data were obtained from the KEYNOTE-426 trial. Utility values and direct costs related to the treatments were gathered from the published studies. Results: The incremental cost-effectiveness ratios of pembrolizumab plus axitinib versus sunitinib was $249,704 per quality-adjusted life year, which was higher than a willingness-to-pay threshold of $150,000 per quality-adjusted life year. Conclusion: Pembrolizumab plus axitinib was not considered to be cost-effective versus sunitinib as a first-line treatment for patients with advanced renal cell carcinoma from the US payer perspective.

5.
Ann Noninvasive Electrocardiol ; : e12797, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32896950

RESUMO

In patients with preserved ejection fraction or right bundle branch block (RBBB) pattern requiring a high percentage of ventricular pacing, His-bundle pacing (HBP) might be an alternative to biventricular pacing, although the high threshold occasionally occurs. We provided a case of the intrinsic RBBB correction by capturing intra-Hisian left bundle branch (LBB) or distal His-bundle with different output settings. LBB pacing had the advantage of a much lower threshold while remained most synchrony as HBP. LBB pacing might be a promisingly safe and effective procedure for patients with high-grade atrioventricular (AV) block and RBBB pattern.

6.
Cell Chem Biol ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32916088

RESUMO

MKK4/7 are kinases that phosphorylate JNKs and regulate the MAPK signaling pathway. Their overexpression has been associated with tumorigenesis and aggressiveness in cancers such as breast, prostate, non-small cell lung, and pediatric leukemia, making them a potential target for inhibitor development. Here, we report the discovery, development, and validation of a dual MKK4/7 inhibitor, BSJ-04-122, that covalently targets a conserved cysteine located before the DFG motif and displays excellent kinome selectivity. BSJ-04-122 exhibits potent cellular target engagement and induces robust target-specific downstream effects. The combination of the dual MKK4/7 inhibitor with a selective, covalent JNK inhibitor demonstrated an enhanced antiproliferative activity against triple-negative breast cancer cells. Taken together, the results show that BSJ-04-122 represents a pharmacological probe for MKK4/7 and credential covalent targeting as a way to explore the therapeutic potential of these kinases.

7.
J Mech Behav Biomed Mater ; 112: 104048, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32920276

RESUMO

In this study, two medium Zr-containing Ti-based alloys with commercially pure titanium as control were systematically investigated to assess their potential biomedical application. After samples subjected to TMP and CR, it was found that the Zr addition significantly affected the microstructure, phase constitutions, mechanical properties and cytocompatibility. The microstructural results showed that increasing Zr concentrations resulted in more refined grains. Furthermore, Zr changed the phase constitution: CR Ti-20Zr was formed by the single α-phase while CR Ti-30Zr alloy was formed by the coexistence of α and deformation-induced FCC phases. The P-type FCC phase was dominant and more prone to occur than the B-type one. The mechanical tests demonstrated that the increasing Zr content led to a simultaneous increase in micro-hardness, strength and plasticity of CR samples due to the combined effects of solution strengthening, work hardening and the FCC phase. The SEM fractography indicated that the brittle fracture of CR Ti-20Zr due to deformation twins and ductile fracture of CR Ti-30Zr because of FCC phase. Furthermore, Ti-Zr alloys presented comparable cytocompatibility to the CP-Ti control based on cell viability, proliferation and intracellular O2- content of MSCs. Specifically, alkaline phosphatase activity in BMSCs were significantly higher for grain refined CR Ti-30Zr. Considering all these results, CR Ti-30Zr alloy exhibited the optimal comprehensive performance to be potential dental materials.

8.
Int J Mol Med ; 46(5): 1783-1793, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901861

RESUMO

Phosphorus reduction can prevent against vascular calcification (VC) in chronic kidney disease (CKD), but the mechanisms underlying its actions remain unclear. The aim of the present study was to determine the effect of a fortified phosphorus­lowing treatment on VC in CKD. Serum levels of creatinine, blood urea nitrogen (BUN), fibroblast growth factor 23 (FGF23), calcium and phosphorus, and the plasma levels of parathyroid hormone (PTH) were determined in an animal model of CKD treated with or without lanthanum. Haematoxylin and eosin (H&E) staining was performed to examine the structure of kidney tissues. Western blot analysis was performed to compare the levels of total­ (t­) extracellular signal­related kinase (ERK) and phospho­ (p­)ERK among the different experimental groups to investigate the effect of FGF23 on p­ERK expression. In the animal model, administration of adenine increased the serum levels of creatinine, BUN, FGF23 and phosphorus but decreased the serum levels of calcium. In addition, adenine treatment increased the plasma levels of PTH. H&E staining showed that lanthanum treatment did not alter the severity of renal cortex injury. Furthermore, the levels of t­ERK levels did not notably differ between the Adenine­free, Adenine­vehicle and Adenine­lanthanum groups, whereas the levels of p­ERK and aortic calcium in the Adenine­vehicle group were significantly upregulated. In addition, ectopic overexpression of FGF23 increased the levels of p­ERK, Msx2 and Osx in a dose­dependent manner. Furthermore, a total of 48 patients were enrolled in the present study. In the fortified group, the serum levels of FGF23, phosphorus and PTH were significantly reduced, whereas the serum levels of calcium were significantly increased, indicating an enhanced preventative effect in the fortified group. The results of the present study suggest that FGF23 may be used as a therapeutic target in the management and prevention of VC in CKD.

9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(6): 673-677, 2020 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879124

RESUMO

OBJECTIVES: To provide clues for further study of the relationship between miRNAs and Kawasaki disease (KD) development, and to provide molecular markers for ultimately improve the rate of early diagnosis for KD. METHODS: We collected acute, recovery KD children's plasma and normal samples, then used the miRNAs Assay Chip to screen the differentially expressed miRNAs in the plasma from KD children. Subsequently, miR-455-5p, which had identified via miRNAs assay chip, was validated by quantitative real-time PCR via independent cohort. RESULTS: According to the results of miRNAs Assay chip, we identified a miRNAs panel including 5 miRNAs significantly up-regulated and 5 miRNAs remarkably down-regulated in the plasma from KD children compared to the normal control; miR-455-5p in both of acute and recovery KD children's plasma was remarkably lower than that in the normal control (P<0.001, P=0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children (P=0.007) by independent cohort validation. CONCLUSIONS: There are significantly differentially expressed circulating miRNAs between the KD children and normal control. We identified 10 miRNAs dysregulation in the KD children's plasma compared with the normal group. Circulating miR-455-5p in both of acute and recovery KD children's plasma is remarkably lower than that in the normal control, and miR-455-5p may considered as a marker to show the recovery process of KD children. Plasma specific circulating miRNAs play an important role in the early diagnosis of KD and become the new molecular marker of KD in the future.


Assuntos
MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/genética , Biomarcadores , Criança , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real
10.
J Phys Chem Lett ; : 8477-8482, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32966084

RESUMO

Organometal halide perovskites (OHPs) have been considered as promising materials for light-emission devices. However, the factors influencing the luminescent property of OHPs are intricate. It is not only affected by the intrinsic crystalline quality but also depends on the surrounding environment. Here we demonstrate that the luminescence of CH3NH3PbI3 (MAPbI3) is governed by light-irradiation-induced oxygen curing and vacancy-mediated ion migration. The luminescence increases under continuous irradiation because of the curing of iodine vacancies (VI) by oxygen. While, it decreases with enhanced ion migration, which would induce excess trap states. The existence of VI is proved by low-temperature photoluminescence (PL) spectra, the hysteresis effect in J-V curves, and the excitation density dependence of the PL lifetime. Different oxygen environments and applied biases are employed to control the degree of oxygen curving and ion migration. These results provide a perception of the correlation of the complicated influencing factors affecting the luminescence of OHPs.

11.
Clin Ther ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32900534

RESUMO

PURPOSE: There are many anticoagulant test indexes available for direct oral anticoagulants (DOACs), but how to select the appropriate index and the index cutoff values are still controversial. This is the first study, to our knowledge, to assess the association of different coagulation indicators with clinical outcomes among DOACs using a meta-analysis of observational studies. METHODS: A medical literature search was conducted using PubMed, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Library from inception to February 2020. Studies that reported relationships between coagulation indexes and clinical outcomes or the diagnostic value of coagulation assays were included in the analysis. FINDINGS: A total of 17 articles (7 meta-analyses and 10 systematic reviews) from 8904 citations were included in the analysis. In the analysis of bleeding events with coagulation indexes for DOACs, for peak prothrombin time level (cutoff value of 19-25 s), the pooled results found a sensitivity of 0.61 (95% CI, 0.44-0.75) and a specificity of 0.71 (95% CI, 0.49-0.86). For rivaroxaban, the trough anti-factor Xa concentration (AXA-C) (cutoff value of 400-500 ng/mL) had a sensitivity of 0.53 (95% CI, 0.16-0.87) and a specificity of 0.87 (95% CI, 0.71-0.94), with a diagnostic odds ratio of 7 (95% CI, 2-32). For apixaban, trough AXA-C had a sensitivity of 0.85 (95% CI, 0.60-0.96) and a specificity of 0.83 (95% CI, 0.52-0.95). The AUC of the AXA-C peak was higher than that of the trough AXA-C for apixaban, with a higher sensitivity and specificity. Compared with trough concentration of anti-factor IIa for dabigatran, the peak concentration had a higher specificity (98%) at the cutoff value of 484 ng/mL. In the analysis of thromboembolic events with coagulation indexes for DOACs, peak and trough prothrombin time values were not typically correlated with subsequent symptomatic venous thromboembolism, without a sensitivity or specificity higher than 90%. Trough AXA-C had a sensitivity of 100% and but a low specificity (<50%) for rivaroxaban-apixaban. Trough AXA-C had a sensitivity of 100% and a specificity of 32% with a cutoff value of 108 ng/mL for dabigatran. IMPLICATION: Peak prothrombin time (19-25 s) and AXA-C had a better predictive value on bleeding outcomes for rivaroxaban and apixaban, whereas peak concentration of anti-factor IIa activity can be an indicator for dabigatran. Coagulation indexes might not be a good indicator of thromboembolic events of DOACs. Because the limited studies focused on association of coagulation indicators and clinical outcomes, more studies are needed to verify this in the future.

12.
Nat Commun ; 11(1): 4810, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968061

RESUMO

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.


Assuntos
Basigina/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos Quiméricos/efeitos dos fármacos , Animais , Basigina/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Células Hep G2 , Humanos , Células Matadoras Naturais , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
FASEB J ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780898

RESUMO

Potential underlying molecular mechanisms for uric acid-induced lipid metabolic disturbances had not been elucidated clearly. This study investigated the effects and underlying mechanisms of uric acid on the development of lipid metabolic disorders. We collected blood samples from 100 healthy people and 100 patients with hyperuricemia for whom serum lipid analysis was performed. Meanwhile, a mouse model of hyperuricemia was generated, and lipidomics was performed on liver tissues, comparing control and hyperuricemia groups, to analyze lipid profiles and key metabolic enzymes. Uric acid directly induced serum lipid metabolic disorders in both humans and mice based on triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Through lipidomic analysis, 46 lipids were differentially expressed in hyperuricemic mouse livers, and the phosphatidylcholine composition was altered, which was mediated by LPCAT3 upregulation. High-uric acid levels-induced p-STAT3 inhibition and SREBP-1c activation in vivo and in vitro. Moreover, LPCAT3-knockdown significantly attenuated uric acid-induced p-STAT3 inhibition, SREBP-1c activation, and lipid metabolic disorders in L02 cells. In conclusion, uric acid induces lipid metabolic disturbances through LPCAT3-mediated p-STAT3 inhibition and SREBP-1c activation. LPCAT3 could be a key regulatory factor linking hyperuricemia and lipid metabolic disorders. These results might provide novel insights into the clinical treatment of hyperuricemia.

14.
BMC Genomics ; 21(1): 580, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831016

RESUMO

BACKGROUND: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed. RESULTS: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events. CONCLUSIONS: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

15.
Cell Commun Signal ; 18(1): 134, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843053

RESUMO

Chimeric Antigen Receptor (CAR) immunotherapy utilizes genetically-engineered immune cells that express a unique cell surface receptor that combines tumor antigen specificity with immune cell activation. In recent clinical trials, the adoptive transfer of CAR-modified immune cells (including CAR-T and CAR-NK cells) into patients has been remarkably successful in treating multiple refractory blood cancers. To improve safety and efficacy, and expand potential applicability to other cancer types, CARs with different target specificities and sequence modifications are being developed and tested by many laboratories. Despite the overall progress in CAR immunotherapy, conventional tools to design and evaluate the efficacy and safety of CAR immunotherapies can be inaccurate, time-consuming, costly, and labor-intensive. Furthermore, existing tools cannot always determine how responsive individual patients will be to a particular CAR immunotherapy. Recent work in our laboratory suggests that the quality of the immunological synapse (IS) can accurately predict CAR-modified cell efficacy (and toxicity) that can correlate with clinical outcomes. Here we review current efforts to develop a Synapse Predicts Efficacy (SPE) system for easy, rapid and cost-effective evaluation of CAR-modified immune cell immunotherapy. Ultimately, we hypothesize the conceptual basis and clinical application of SPE will serve as an important parameter in evaluating CAR immunotherapy and significantly advance precision cancer immunotherapy. Video abstract Graphic abstract for manuscript CCAS-D-20-00136 by Liu, D., et al., 'The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy". The various branches of evaluating cancer immunotherapy metaphorically represented as a Rubik's cube. The development of a novel approach to predict the effectiveness of Chimeric Antigen Receptor (CAR)-modified cells by quantifying the quality of CAR IS will introduce a new parameter to the rapidly expanding field of cancer immunotherapy. Currently, no single parameter can predict the clinical outcome or efficacy of a specific type of CAR-modified cell. IS quality will serve as a quantifiable measure to evaluate CAR products and can be used in conjunction with other conventional parameters to form a composite clinical predictor. Much like a Rubik's cube has countless configurations, several methods and combinations of clinical metrics have arisen for evaluating the ability of a given immunotherapeutic strategy to treat cancer. The quality of IS depicting cancer immunotherapy is metaphorically expressed as a Rubik's cube. Each face/color represents one aspect of cancer therapy. Each grid in one face indicates one factor within that aspect of cancer therapy. For example, the green color represents the tumor microenvironment, and one out of the nine grids in the green color indicates suppressor cells (suppressors in green). Changes in one factor may completely alter the entire strategy of cancer therapy. However, the quality of IS (illuminated center red grid) makes the effectiveness of CAR immunotherapy predictable.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32819837

RESUMO

BACKGROUND: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. METHODS: This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. RESULTS: OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton-Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. CONCLUSION: This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.

17.
Emerg Microbes Infect ; 9(1): 1881-1891, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779526

RESUMO

Occult hepatitis B virus (HBV) infection (OBI) has been observed among infants born to hepatitis B surface antigen (HBsAg)-positive mothers despite successful immunoprophylaxis. This study enrolled 549 infants [349 infants received a 10µg/dose of hepatitis B vaccine (HepB), and 200 infants received 20µg/dose HepB] born to HBsAg-positive mothers with HBV DNA load >6log10IU/mL. The anti-HBs levels in the 10µg group were significantly lower than that in the 20µg group both at 7 [652.48 (564.05-754.82) vs. 1541.72 (1268.69-1873.51) mIU/mL, P<0.001] and 12 months old [257.44 (220.29-300.88) vs. 1073.41 (839.27-1372.78) mIU/mL, P<0.001]. The OBI incidence in the 10µg group was significantly higher than that in the 20µg group at both 7 [21.55% (25/116) vs. 7.56% (9/119), P=0.002] and 12 months old [17.07% (14/82) vs. 6.90% (6/87), P=0.041]. OBI incidence in infants with anti-HBs levels <100mIU/mL was higher than that of those with anti-HBs ≥100mIU/mL [35.71% (5/14) vs. 13.12% (29/221), P=0.036]. This study showed that increasing the immunisation dose from 10µg to 20µg significantly improved anti-HBs levels and decreased OBI incidence in infants with a high maternal viral load. We recommend 20µg HepB to treat this high-risk population.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32745005

RESUMO

In this article, we propose a Dual Relation-aware Attention Network (DRANet) to handle the task of scene segmentation. How to efficiently exploit context is essential for pixel-level recognition. To address the issue, we adaptively capture contextual information based on the relation-aware attention mechanism. Especially, we append two types of attention modules on the top of the dilated fully convolutional network (FCN), which model the contextual dependencies in spatial and channel dimensions, respectively. In the attention modules, we adopt a self-attention mechanism to model semantic associations between any two pixels or channels. Each pixel or channel can adaptively aggregate context from all pixels or channels according to their correlations. To reduce the high cost of computation and memory caused by the abovementioned pairwise association computation, we further design two types of compact attention modules. In the compact attention modules, each pixel or channel is built into association only with a few numbers of gathering centers and obtains corresponding context aggregation over these gathering centers. Meanwhile, we add a cross-level gating decoder to selectively enhance spatial details that boost the performance of the network. We conduct extensive experiments to validate the effectiveness of our network and achieve new state-of-the-art segmentation performance on four challenging scene segmentation data sets, i.e., Cityscapes, ADE20K, PASCAL Context, and COCO Stuff data sets. In particular, a Mean IoU score of 82.9% on the Cityscapes test set is achieved without using extra coarse annotated data.

19.
Bioresour Technol ; 316: 123925, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758921

RESUMO

An anoxic/oxic membrane bioreactor (AO) and three pilot-scale anaerobic side stream reactors (ASSR) coupled MBRs (ASSR-MBRs), packed with 0%, 25% and 50% carriers in ASSRs, were continuously operated to study the mechanisms for sludge reduction. Four systems showed efficient COD and NH4+-N removal, while packing carriers significantly enhanced nitrogen removal. 25% filling fraction (AP25) achieved the highest sludge reduction efficiency of 50.5% compared to 0% (21.7%) and 50% (39.7%). Compared to ASSR-MBR, carriers enhanced the release of dissolved organic matters, and accelerated the secretion of enzyme for cell lysis and hydrolysis. In AP25, the presence of carriers prompted the formation of environment propitious to sludge reduction in bulk sludge. AP25 tended to enrich hydrolytic, fermentative and denitrifying bacteria to accelerate hydrolysis process, while excessive carriers had negative effect on biomass stability and movement of carriers.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Anaerobiose , Reatores Biológicos , Nitrogênio
20.
Int J Mol Sci ; 21(17)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842656

RESUMO

Bacterial fruit blotch (BFB), caused by Acidovorax citrulli, seriously affects watermelon and other cucurbit crops, resulting in significant economic losses. However, the pathogenicity mechanism of A. citrulli is not well understood. Plant pathogenic bacteria often suppress the plant immune response by secreting effector proteins. Thus, identifying A. citrulli effector proteins and determining their functions may improve our understanding of the underlying pathogenetic mechanisms. In this study, a novel effector, AopN, which is localized on the cell membrane of Nicotiana benthamiana, was identified. The functional analysis revealed that AopN significantly inhibited the flg22-induced reactive oxygen species burst. AopN induced a programmed cell death (PCD) response. Unlike its homologous protein, the ability of AopN to induce PCD was dependent on two motifs of unknown functions (including DUP4129 and Cpta_toxin), but was not dependent on LXXLL domain. More importantly, the virulence of the aopN mutant of A. citrulli in N. benthamiana significantly decreased, indicating that it was a core effector. Further analysis revealed that AopN interacted with watermelon ClHIPP and ClLTP, which responds to A. citrulli strain Aac5 infection at the transcription level. Collectively, these findings indicate that AopN suppresses plant immunity and activates the effector-triggered immunity pathway.

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