Publications by authors named "Rui Wu"

596 Publications

Molecular and functional characterization of HtrA protein in Actinobacillus pleuropneumoniae.

Vet Microbiol 2021 Mar 26;257:109058. Epub 2021 Mar 26.

Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China. Electronic address:

Actinobacillus pleuropneumoniae (A.pleuropneumoniae) causes serious economic loss for the swine industry. A high-temperature requirements A (HtrA)-like protease and its homologs have been reported to be involved in protein quality control and expression of important immunoprotective antigens in many pathogens. In this study, we showed that HtrA of A.pleuropneumoniae exhibited both chaperone and proteolytic activities. Moreover, Outer membrane protein P5 (OmpP5) in A.pleuropneumoniae and Heat shock protein 90 (Hsp90) in porcine lung tissues were first discovered and identified as specific proteolytic substrates for rHtrA. The maximum cleavage activity occurs at 50 ℃ in a time-dependent manner. In addition, rHtrA mainly induced IgG 2a subtype of IgG and Th1 (IFN-γ, IL-2) response in a mice model, and promoted a significant proliferation of spleen lymphocytes compare with negative control (P < 0.05). The survival rates of 37.5 % were observed against A.pleuropneumoniae strain. Together, these data demonstrate that rHtrA plays a multi-functional role in A.pleuropneumoniae.
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http://dx.doi.org/10.1016/j.vetmic.2021.109058DOI Listing
March 2021

Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/β-catenin signaling.

J Cell Biochem 2021 Apr 14. Epub 2021 Apr 14.

Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

LASS2 is a novel tumor-suppressor gene and has been characterized as a ceramide synthase, which synthesizes very-long acyl chain ceramides. However, LASS2 function and pathway-related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes β-catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin-proteasome pathway, phosphorylation of LASS2 is essential for β-catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Furthermore, we find that dephosphorylation of LASS2 at serine residue 248 significantly enhances prostate cancer cell growth and metastasis in vivo, indicating that phosphorylated LASS2 inhibits prostate carcinogenesis through negative regulation of Wnt/β-catenin signaling. Thus, our findings implicate LASS2 as a potential biomarker and therapeutic target of prostate cancer.
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http://dx.doi.org/10.1002/jcb.29926DOI Listing
April 2021

Automatic, dynamic, and nearly optimal learning rate specification via local quadratic approximation.

Neural Netw 2021 Mar 26;141:11-29. Epub 2021 Mar 26.

Guanghua School of Management, Peking University, Beijing, China. Electronic address:

In deep learning tasks, the update step size determined by the learning rate at each iteration plays a critical role in gradient-based optimization. However, determining the appropriate learning rate in practice typically relies on subjective judgment. In this work, we propose a novel optimization method based on local quadratic approximation (LQA). In each update step, we locally approximate the loss function along the gradient direction by using a standard quadratic function of the learning rate. Subsequently, we propose an approximation step to obtain a nearly optimal learning rate in a computationally efficient manner. The proposed LQA method has three important features. First, the learning rate is automatically determined in each update step. Second, it is dynamically adjusted according to the current loss function value and parameter estimates. Third, with the gradient direction fixed, the proposed method attains a nearly maximum reduction in the loss function. Extensive experiments were conducted to prove the effectiveness of the proposed LQA method.
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http://dx.doi.org/10.1016/j.neunet.2021.03.025DOI Listing
March 2021

Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Acta Pharmacol Sin 2021 Apr 8. Epub 2021 Apr 8.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.
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http://dx.doi.org/10.1038/s41401-021-00646-zDOI Listing
April 2021

Oridonin interferes with simple steatosis of liver cells by regulating autophagy.

Tissue Cell 2021 Mar 23;72:101532. Epub 2021 Mar 23.

Departmeng of Hepatology, The Sixth People's Hospital of Hangzhou, Hangzhou, Zhejiang Province, 310000, China. Electronic address:

Oridonin has significant liver-protective effects, but its effect on liver steatosis has not been reported. We investigated the effects of oridonin on liver steatosis by cell cultures. The optimal experimental concentration of oridonin was determined through cytotoxicity experiments. A simple steatosis liver cell model was induced using free fatty acids (FFA). After adding oridonin to the FFA-induced cell model for 24 h, the lipid droplets and triglyceride (TG) content in the cells were measured by Oil Red O staining and TG kits. The expressions of autophagy-related markers (cyclin dependent kinases inhibitor 1a (p21), Beclin-1, microtubule-associated protein light chain 3 (LC3)-I and LC3-II, protein kinase B (AKT), phosphorylated-AKT (p-AKT), AMP-activated protein kinase (AMPK), and phosphorylated-AMPK (p-AMPK)) were detected by Western blot. Based on the results, the cell model was further treated by autophagy inhibitor 3-methyladenine (3-MA) to determine the degree of steatosis and the expressions of autophagy-related factors. Oridonin at a concentration higher than 10 μmol/L caused cytotoxicity to the cells. Adding 10 μmol/L oridonin to the FFA-induced cell model effectively reduced lipid droplets and TG content in the cells. Oridonin up-regulated p21, Beclin-1 and LC3-II expressions, but down-regulated those of p62 and LC3-I. Also, oridonin increased the ratios of LC3-II/LC3-I and p-AMPK/AMPK, but reduced that of p-AKT/AKT. With the addition of 3-MA, the effect of oridonin on reducing steatosis was partially reversed, and the autophagy was inhibited. This study found that oridonin can activate autophagy, thereby preventing simple steatosis of liver cells.
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http://dx.doi.org/10.1016/j.tice.2021.101532DOI Listing
March 2021

ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review.

Eur J Med Res 2021 Mar 31;26(1):30. Epub 2021 Mar 31.

Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No.32 The First Ring Road West 2, Chengdu, 610072, China.

Background: Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV.

Case Presentation: Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge.

Conclusions: AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.
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http://dx.doi.org/10.1186/s40001-021-00500-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011393PMC
March 2021

Genome-Wide Association Study-Based Identification of SNPs and Haplotypes Associated With Goose Reproductive Performance and Egg Quality.

Front Genet 2021 12;12:602583. Epub 2021 Mar 12.

Institute of Poultry Science, Chongqing Academy of Animal Science, Chongqing, China.

Geese are one of the most economically important waterfowl. However, the low reproductive performance and egg quality of geese hinder the development of the goose industry. The identification and application of genetic markers may improve the accuracy of beneficial trait selection. To identify the genetic markers associated with goose reproductive performance and egg quality traits, we performed a genome-wide association study (GWAS) for body weight at birth (BBW), the number of eggs at 48 weeks of age (EN48), the number of eggs at 60 weeks of age (EN60) and egg yolk color (EYC). The GWAS acquired 2.896 Tb of raw sequencing data with an average depth of 12.44× and identified 9,279,339 SNPs. The results of GWAS showed that 26 SNPs were significantly associated with BBW, EN48, EN60, and EYC. Moreover, five of these SNPs significantly associated with EN48 and EN60 were in a haplotype block on chromosome 35 from 4,512,855 to 4,541,709 bp, oriented to and another five SNPs significantly correlated to EYC were constructed in haplotype block on chromosome 5 from 21,069,009 to 21,363,580, which annotated by , , , and . Those genes were enriched in epidermal growth factor-activated receptor activity, regulation of epidermal growth factor receptor signaling pathway. The SNPs, haplotype markers, and candidate genes identified in this study can be used to improve the accuracy of marker-assisted selection for the reproductive performance and egg quality traits of geese. In addition, the candidate genes significantly associated with these traits may provide a foundation for better understanding the mechanisms underlying reproduction and egg quality in geese.
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http://dx.doi.org/10.3389/fgene.2021.602583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994508PMC
March 2021

Total and Sn-2 Fatty Acid Profile in Human Colostrum and Mature Breast Milk of Women Living in Inland and Coastal Areas of China.

Ann Nutr Metab 2021 Mar 17:1-9. Epub 2021 Mar 17.

Department of Nutrition, Food Safety and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Introduction: Although lipid is the major energy source and exerts beneficial effects on infant growth, research on the composition of fatty acid (FA) at the sn-2 position of human milk (HM) in China and abroad is limited.

Objectives: This study aimed to investigate the FA positional distribution in colostrum and mature HM of women living in the inland and coastal areas of China and explore the potential influences of geographical region and lactation stage on the FA profile of Chinese women.

Methods: Colostrum milk (n = 61) and mature milk (n = 56) samples were obtained longitudinally from healthy lactating women in Guangzhou and Chengdu, China. Gas chromatography was used to determine the total and sn-2 FA composition.

Results: Significant differences were observed in the FA profile of HM between different regions and lactation stages, with differences in polyunsaturated FA levels being the most pronounced. Nearly 70% of sn-2 FAs were saturated FAs, of which C16:0 accounted for approximately 75%. C8:0, C10:0, C18:0, C20:0, C22:0, and all of the unsaturated FAs were mainly located at the sn-1 and sn-3 positions, while C14:0, C15:0, and C16:0 were mainly at the sn-2 position. The proportion of C12:0 and C17:0 at sn-2 was approximately equivalent to that at the sn-1, 3 positions.

Conclusions: The results indicate the variability in the FA profile of HM between regions and lactation stages. The contents of polyunsaturated FAs and sn-2 FAs, especially palmitic acid, should be paid more attention when optimizing infant formula.
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http://dx.doi.org/10.1159/000510379DOI Listing
March 2021

Design, synthesis and bioactivity study on 5-phenylfuran derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell.

Eur J Med Chem 2021 Apr 2;216:113336. Epub 2021 Mar 2.

College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region, Zhejiang University of Technology, Hangzhou, 310014, China. Electronic address:

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a phenomenon in which cells become resistant to structurally and mechanistically unrelated drugs resulting in low intracellular drug concentrations. It is one of the noteworthy problems in malignant tumor clinical therapeutics. So P-gp protein is one of the ideal targets to solve MDR. Based on the lead compound 5m obtained from our previous work, a series of furan derivatives featuring alkyl-substituted phenols and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline were designed and synthesized as reversal agents against P-gp in this paper. Compound 16 containing isopropoxy possessed good potency against P-gp mediated MDR in MCF-7/ADR (IC (doxorubicin) = 0.73 μM, RF = 69.6 with 5 μM 16 treated). Western blot results and Rh123 accumulation assays showed that 16 effectively inhibited P-gp efflux function but not its expression. The preliminary structure-activity relationship and docking studies demonstrated that compound 16 would be a potential P-gp inhibitor. Most worthy of mention is that compound 16 has achieved satisfactory results in combination with a variety of anti-tumor drugs, such as doxorubicin, paclitaxel, and vincristine. This study forwards a hopeful P-gp inhibitor for withstanding malignant tumor cell with multidrug resistance setting the basis for further studies.
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http://dx.doi.org/10.1016/j.ejmech.2021.113336DOI Listing
April 2021

Discovery of novel HBV capsid assembly modulators by structure-based virtual screening and bioassays.

Bioorg Med Chem 2021 Apr 4;36:116096. Epub 2021 Mar 4.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. Electronic address:

HBV capsid assembly has been regarded as an attractive potential target for anti-HBV therapy. In this study, we discovery the Novel HBV capsid assembly modulators (CAMs) through structure-based virtual screening and bioassays. A total of 16 structurally diverse compounds were purchased and assayed, including three compounds with inhibition rate > 50% at 20 μM. Further lead optimization based on the most potent compound II-1-7 (EC = 5.6 ± 0.1 µM) were performed by using substructure searching strategy, resulting in compound II-2-9 with an EC value of 1.8 ± 0.6 μM. In bimolecular fluorescence complementation (BiFC) assay, compound II-2-9 inhibited the HBV by disrupting the HBV capsid interactions. In summary, this study provides a highly efficient way to discover novel CAMs, and 2-aryl-4-quinolyl amide derivatives could serve as the starting point for development of novel anti-HBV drugs.
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http://dx.doi.org/10.1016/j.bmc.2021.116096DOI Listing
April 2021

Appropriate duration of endoscopic dilation for postoperative benign esophageal strictures.

Surg Endosc 2021 Mar 10. Epub 2021 Mar 10.

Digestive Endoscopy Department and General Surgery Department, The First Affiliated Hospital With Nanjing Medical University and Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Background: Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.

Methods: Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups.

Results: Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80-12.00) months in the 1-min group, 6.60 (range, 1.80-12.00) months in the 3-min group and 6.25 (range, 2.40-12.00) months in the 5-min group (P < 0.05). For patients who developed stricture recurrence, the mean dysphagia-free periods were 2.26  ±  1.27 months, 4.00  ±  1.76 months and 4.23  ±  1.63 months, respectively (P < 0.05). The dysphagia-free periods were comparable between the 3- and 5-min groups and were longer than those in the 1-min group. Muscle layer damage occurred in two patients (11.11%) in the 5-min group and in no patients in the other two groups.

Conclusion: Three minutes was considered a safe and effective dilation duration for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.
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http://dx.doi.org/10.1007/s00464-021-08400-6DOI Listing
March 2021

Brentuximab Vedotin in Combination with Chemotherapy for Pediatric Patients with ALK+ALCL: Results of COG Trial ANHL12P1.

Blood 2021 Mar 8. Epub 2021 Mar 8.

Children's National Health System, Washington, District of Columbia, United States.

Approximately 30% of pediatric patients with ALCL relapse. While brentuximab vendotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed, non-localized, ALK+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin (Arm BV). All patients received five-day prophase followed by six cycles of chemotherapy at 21-day intervals. Brentuximab vedotin was given on day 1 of each of the six cycles. Of the 67 eligible patients for toxicity evaluation, 66 completed all six cycles of chemotherapy resulting in 399 cycles evaluable. There were no toxic deaths, no cases of progressive multifocal leukoencephalopathy syndrome, and no cases of grade 3 or 4 neuropathy. The two-year EFS is 79.1% (95% CI, 67.2% to 87.1%). The two-year OS is 97.0% (95% CI, 88.1% to 99.2%). Fourteen patients relapsed and were the only events contributing to EFS. 11 of 14 (79%) relapses occurred within ten months of initial diagnosis, with only one patient (1.5%) having relapsed during therapy. Quantitative RT-PCR for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value and impacted 2-year EFS (P=0.0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity, nor does it alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy and the overall and event-free survival estimates compare favorably with results obtained using conventional chemotherapy.
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http://dx.doi.org/10.1182/blood.2020009806DOI Listing
March 2021

Clinical Benefit of Antiviral Agents for Hepatocellular Carcinoma Patients With Low Preoperative HBV-DNA Loads Undergoing Curative Resection: A Meta-Analysis.

Front Oncol 2021 19;11:605648. Epub 2021 Feb 19.

Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China.

Background And Aims: The clinical benefit of adjuvant antiviral therapy after curative therapy for HCC in patients with high preoperative HBV-DNA loads has been studied widely but that in patients with low preoperative HBV-DNA loads remains controversial. The purpose of this study was to determine the effect of antiviral treatment prophylaxis on HBV reactivation, overall survival (OS), and postoperative liver function in patients with low preoperative HBV-DNA levels undergoing curative resection.

Methods: A meta-analysis was conducted by searching Web of Science, PubMed, Embase, and Cochrane Library until May 2020. We used REVMAN for data analysis and completed the study under the PRISMA guidelines.

Results: Three randomized trials and seven cohort studies, comprising of 1,131 individuals, were included in the meta-analysis. Antiviral treatment significantly reduced the rate of HBV reactivation after curative treatment of HCC, with a pooled risk ratio of 0.12 (95% c.i. 0.07 to 0.21; P < 0.00001). The trials were consistently favorable for the antiviral group, with a pooled hazard ratio of 0.52 (95% c.i. 0.37 to 0.74; P = 0.0002) in respect of OS rate. However, by pooling the data from studies that reported ALT on the 30th day postoperatively, the result didn't reach statistical significance (mean difference -4.38, 95% c.i. -13.83 to 5.07; P = 0.36). The I² values of the heterogeneity test for the above three comparisons are zero.

Conclusion: Antiviral therapy during curative resection is effective in reducing HBV reactivation and improving OS rate in HCC patients with low viral load.
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http://dx.doi.org/10.3389/fonc.2021.605648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933452PMC
February 2021

Multiparametric MRI-based machine learning models for preoperatively predicting rectal adenoma with canceration.

MAGMA 2021 Mar 1. Epub 2021 Mar 1.

Department of Radiology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, People's Republic of China.

Objectives: To propose multiparametric MRI-based machine learning models and assess their ability to preoperatively predict rectal adenoma with canceration.

Materials And Methods: A total of 53 patients with postoperative pathology confirming rectal adenoma (n = 29) and adenoma with canceration (n = 24) were enrolled in this retrospective study. All patients were divided into a training cohort (n = 42) and a test cohort (n = 11). All patients underwent preoperative pelvic MR examination, including high-resolution T2-weighted imaging (HR-T2WI) and diffusion-weighted imaging (DWI). A total of 1396 radiomics features were extracted from the HR-T2WI and DWI sequences, respectively. The least absolute shrinkage and selection operator (LASSO) was utilized for feature selection from the radiomics feature sets from the HR-T2WI and DWI sequences and from the combined feature set with 2792 radiomics features incorporating two sequences. Five-fold cross-validation and two machine learning algorithms (logistic regression, LR; support vector machine, SVM) were utilized for model construction in the training cohort. The diagnostic performance of the models was evaluated by sensitivity, specificity and area under the curve (AUC) and compared with the Delong's test.

Results: Ten, 8, and 25 optimal features were selected from 1396 HR-T2WI, 1396 DWI and 2792 combined features, respectively. Three group models were constructed using the selected features from HR-T2WI (Model), DWI (Model) and the two sequences combined (Model). Model showed better prediction performance than Model and Model. In Model, there was no significant difference between the LR and SVM algorithms (p = 0.4795), with AUCs in the test cohort of 0.867 and 0.900, respectively.

Conclusions: Multiparametric MRI-based machine learning models have the potential to predict rectal adenoma with canceration. Compared with Model and Model, Model showed the best performance. Moreover, both LR and SVM have equal excellent performance for model construction.
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http://dx.doi.org/10.1007/s10334-021-00915-2DOI Listing
March 2021

[Analysis of animal models of chronic skin ulcers based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(4):782-785

Henan University of Chinese Medicine Zhengzhou 450046,China.

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200918.601DOI Listing
February 2021

Systematic identification of key functional modules and genes in esophageal cancer.

Cancer Cell Int 2021 Feb 25;21(1):134. Epub 2021 Feb 25.

Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Background: Esophageal cancer is associated with high incidence and mortality worldwide. Differential expression genes (DEGs) and weighted gene co-expression network analysis (WGCNA) are important methods to screen the core genes as bioinformatics methods.

Methods: The DEGs and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the hub module in the WGCNA. The CCNB1 was identified as the hub gene based on the intersection between DEGs and the greenyellow module in WGCNA. Expression levels and prognostic values of CCNB1 were verified in UALCAN, GEPIA2, HCMDB, Kaplan-Meier plotter, and TIMER databases.

Results: We identified 1,044 DEGs from dataset GSE20347, 1,904 from GSE29001, and 2,722 from GSE111044, and 32 modules were revealed by WGCNA. The greenyellow module was identified as the hub module in the WGCNA. CCNB1 gene was identified as the hub gene, which was upregulated in tumour tissues. Moreover, esophageal cancer patients with higher expression of CCNB1 showed a worse prognosis. However, CCNB1 'might not play an important role in immune cell infiltration.

Conclusions: Based on DEGs and key modules related to esophageal cancer, CCNB1 was identified as the hub gene, which offered novel insights into the development and treatment of esophageal cancer.
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http://dx.doi.org/10.1186/s12935-021-01826-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905886PMC
February 2021

A synergetic effect of BARD1 mutations on tumorigenesis.

Nat Commun 2021 02 23;12(1):1243. Epub 2021 Feb 23.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

To date, a large number of mutations have been screened from breast and ovarian cancer patients. However, most of them are classified into benign or unidentified alterations due to their undetectable phenotypes. Whether and how they could cause tumors remains unknown, and this significantly limits diagnosis and therapy. Here, in a study of a family with hereditary breast and ovarian cancer, we find that two BARD1 mutations, P24S and R378S, simultaneously exist in cis in surviving cancer patients. Neither of the single mutations causes a functional change, but together they synergetically impair the DNA damage response and lead to tumors in vitro and in vivo. Thus, our report not only demonstrates that BARD1 defects account for tumorigenesis but also uncovers the potential risk of synergetic effects between the large number of cis mutations in individual genes in the human genome.
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http://dx.doi.org/10.1038/s41467-021-21519-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902612PMC
February 2021

Potential of bacteriophages as disinfectants to control of Staphylococcus aureus biofilms.

BMC Microbiol 2021 Feb 20;21(1):57. Epub 2021 Feb 20.

Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Daqing, 163319, P. R. China.

Background: Staphylococcus aureus is the causative agent of chronic mastitis, and can form a biofilm that is difficult to completely remove once formed. Disinfectants are effective against S. aureus, but their activity is easily affected by environmental factors and they are corrosive to equipment and chemically toxic to livestock and humans. Therefore, we investigated the potential utility of a bacteriophage as a narrow-spectrum disinfectant against biofilms formed by S. aureus. In this study, we isolated and characterized bacteriophage vB_SauM_SDQ (abbreviated to SDQ) to determine its efficacy in removing S. aureus biofilms.

Results: SDQ belongs to the family Myoviridae and consists of a hexagonal head, long neck, and short tail. This phage can sterilize a 10 CFU/mL culture of S. aureus in 12 h and multiply itself 1000-fold in that time. Biofilms formed on polystyrene, milk, and mammary-gland tissue were significantly reduced after SDQ treatment. Fluorescence microscopy and scanning electron microscopy showed that SDQ destroyed the biofilm structure. Moreover, the titer of SDQ remained relatively high after the lysis of the bacteria and the removal of the biofilm, exerting a continuous bacteriostatic effect. SDQ also retained its full activity under conditions that mimic common environments, i.e., in the presence of nonionic detergents, tap water, or organic materials. A nonionic detergent (Triton X-100) enhanced the removal of biofilm by SDQ.

Conclusions: Our results suggest that SDQ, a specific lytic S. aureus phage, can be used to control biofilm infections. SDQ maintains its full activity in the presence of nonionic detergents, tap water, metal chelators, and organic materials, and can be used in combination with detergents. We propose this phage as a narrow-spectrum disinfectant against S. aureus, to augment or supplement the use of broad-spectrum disinfectants in the prevention and control of the mastitis and dairy industry contamination caused by S. aureus.
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http://dx.doi.org/10.1186/s12866-021-02117-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896381PMC
February 2021

Creating Ferromagnetic Insulating LaBaMnO Thin Films by Tuning Lateral Coherence Length.

ACS Appl Mater Interfaces 2021 Feb 15;13(7):8863-8870. Epub 2021 Feb 15.

Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, United Kingdom.

In this work, heteroepitaxial vertically aligned nanocomposite (VAN) LaBaMnO (LBMO)-CeO films are engineered to produce ferromagnetic insulating (FMI) films. From combined X-ray photoelectron spectroscopy, X-ray diffraction, and electron microscopy, the elimination of the insulator-metal (I-M) transition is shown to result from the creation of very small lateral coherence lengths (with the corresponding lateral size ∼ 3 nm (∼7 u.c.)) in the LBMO matrix, achieved by engineering a high density of CeO nanocolumns in the matrix. The small lateral coherence length leads to a shift in the valence band maximum and reduction of the double exchange (DE) coupling. There is no "dead layer" effect at the smallest achieved lateral coherence length of ∼3 nm. The FMI behavior obtained by lateral dimensional tuning is independent of substrate interactions, thus intrinsic to the film itself and hence not related to film thickness. The unique properties of VAN films give the possibility for multilayer spintronic devices that can be made without interface degradation effects between the layers.
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http://dx.doi.org/10.1021/acsami.1c00607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023513PMC
February 2021

Does dual red imaging work better?

Gastrointest Endosc 2021 Mar;93(3):775-776

Digestive Endoscopy Department, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1016/j.gie.2020.09.047DOI Listing
March 2021

Aberrant promoter methylation of T-cadherin in sera is associated with a poor prognosis in oral squamous cell carcinoma.

Neoplasma 2021 Feb 11. Epub 2021 Feb 11.

Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Liwan, Guangzhou, China.

T-cadherin functions as a suppressor gene, which is frequently inactivated by aberrant promoter methylation in several human cancers, but its methylation status in oral squamous cell carcinoma (OSCC) has been scarcely studied. Thus this study aimed at exploring the clinical significance and prognostic value of T-cadherin methylation in sera of patients with OSCC. Methylation-specific PCR (MSP) and bisulfate sequencing PCR (BSP) was performed to examine the methylation status of T-cadherin. Then, the associations between methylation status of T-cadherin and various clinicopathological variables or patient survival were investigated in 202 patients with OSCC and 68 controls. T-cadherin methylation was detected in 62 out of 202 (30.7%) patients with OSCC, and the methylation status of T-cadherin in corresponding tissues was confirmed by BSP. Methylation of T-cadherin was significantly associated with advanced tumor T-stage (P < 0.001) and N-stage (P = 0.003), positive lymphatic metastasis (P = 0.004) and tumor recurrence (P = 0.001). In addition, patients with methylation of T-cadherin had worse overall survival (P = 0.018) and progression-free survival (P < 0.001) than patients without, and methylation of T-cadherin in sera was an independent prognostic factor for worse overall survival (HR: 3.626, 95% CI: 1.112-9.624, P = 0.007) and progression-free survival (HR: 4.201, 95% CI: 1.562-10.038, P < 0.001) of patients with OSCC. These results demonstrated that methylation of T-cadherin was frequently detected in sera of patients with OSCC, which was associated with risk factors of poor outcomes, and may act as a potential independent prognostic marker for patients with OSCC.
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http://dx.doi.org/10.4149/neo_2021_201110N1203DOI Listing
February 2021

MiRNA-107 contributes to inflammatory pain by down-regulating GLT-1 expression in rat spinal dorsal horn.

Eur J Pain 2021 Feb 8. Epub 2021 Feb 8.

Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.

Background: Inflammatory pain is a severe clinical problem that affects the quality of life in patients. However, the currently available treatments for inflammatory pain have limited effect and even causes severe side effects. The aim of this study was to investigate the roles of miRNA-107 and glutamate transporter 1 (GLT-1) in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA).

Methods: Paw withdrawal threshold (PWT) of rats was measured by von Frey Filaments. The expressions of miRNA-107 and GLT-1 in the lumbar spinal dorsal horn (L4-L6) were measured with real-time quantitative PCR and western blotting analysis. Fluorescent in situ hybridization and fluorescent-immunohistochemistry were employed to detect the expression of miRNA-107, GLT-1 and co-location of miRNA-107 with GLT-1.

Results: Injection of CFA significantly reduced PWT of rats. The miRNA-107 expression level was obviously up-regulated while the GLT-1 expression level was decreased in the spinal dorsal horn of CFA rats. miRNA-107 and GLT-1 were co-expressed in the same cells of the spinal dorsal horn in CFA rats. Ceftriaxone, a selective activator of GLT-1, obviously increased the PWT of CFA rats. Furthermore, antagomir of miRNA-107 reversed the down-regulation of GLT-1 and alleviated CFA-induced mechanical allodynia of CFA rats.

Conclusions: These results suggest that an increase of miR-107 contributes to inflammatory pain through downregulating GLT-1 expression, implying a promising strategy for pain therapy.

Significance: The currently available treatments for inflammatory pain has limited effect even causes severe side effects. MiRNAs may have important diagnostic and therapeutic potential in inflammatory pain. In present study, we show a potential spinal mechanism of allodynia in rat inflammatory pain model induced by CFA. Increased miR-107 contribute to inflammatory pain by targeting and downregulating GLT-1 expression, implying a promising strategy for inflammatory pain.
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http://dx.doi.org/10.1002/ejp.1745DOI Listing
February 2021

Deletion of Polyamine Transport Protein PotD Exacerbates Virulence in Glaesserella (Haemophilus) parasuis in the Form of Non-biofilm-generated Bacteria in a Murine Acute Infection Model.

Virulence 2021 12;12(1):520-546

Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University , Chengdu, China.

Polyamines are small, polycationic molecules with a hydrocarbon backbone and multiple amino groups required for optimal cell growth. The gene, belonging to the ABC (ATP-binding cassette) transport system , encodes the bacterial substrate-binding subunit of the polyamine transport system, playing a pivotal role in bacterial metabolism and growth. The swine pathogen possesses an intact operon, and the studies presented here mainly examined the involvement of PotD in pathogenesis. A -deficient mutant was constructed using a virulent strain SC1401 by natural transformation; immuno-electron microscopy was used to identify the subcellular location of native PotD protein; an electron microscope was adopted to inspect biofilm and bacterial morphology; immunofluorescence technique was employed to study cellular adhesion, the levels of inflammation and apoptosis. The TSA++-pre-cultured mutant strain showed a significantly reduced adhesion capacity to PK-15 and MLE-12 cells. Likewise, we also found attenuation in virulence using murine models focusing on the clinical sign, H&E, and IFA for inflammation and apoptosis. However, when the mutant was grown in TSB++, virulence recovered to normal levels, along with a high level of radical oxygen species formation in the host. The expression of PotD could actively stimulate the production of ROS in Raw 264.7. Our data suggested that PotD from has a high binding potential to polyamine, and is essential for the full bacterial virulence within mouse models. However, the virulence of the mutant is highly dependent on its TSA++ culture conditions rather than on biofilm-formation.
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http://dx.doi.org/10.1080/21505594.2021.1878673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872090PMC
December 2021

Templating Synthesis of Metal-Organic Framework Nanofiber Aerogels and Their Derived Hollow Porous Carbon Nanofibers for Energy Storage and Conversion.

Small 2021 Feb 1:e2004140. Epub 2021 Feb 1.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, Hefei Science Center of CAS, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.

A kind of metal-organic framework (MOF) aerogels are synthesized by the self-assembly of uniform and monodisperse MOF nanofibers. Such MOF nanofiber aerogels as carbon precursors can effectively avoid the aggregation of nanofibers during calcination, resulting in the formation of well-dispersed hollow porous carbon nanofibers (HPCNs). Moreover, HPCNs with well-dispersion are investigated as sulfur host materials for Li-S batteries and electrocatalysts for cathode oxygen reduction reaction (ORR). On the one hand, HPCNs act as hosts for the encapsulation of sulfur into their hierarchical micro- and mesopores as well as hollow nanostructures. The obtained sulfur cathode exhibits excellent electrochemical features, good cycling stability and high coulombic efficiency. On the other hand, HPCNs exhibit better electrocatalytic activity than aggregated counterparts for ORR. Furthermore, a highly active single atom electrocatalyst can be prepared by the carbonization of bimetallic MOF nanofiber aerogels. The results indicate that well-dispersed HPCNs show enhanced electrochemical properties in contrast to their aggregated counterparts, suggesting that the dispersion situation of nanomaterials significantly influence their final performance. The present concept of employing MOF nanofiber aerogels as precursors will provide a new strategy to the design of MOF-derived nanomaterials with well-dispersion for their applications in energy storage and conversion.
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http://dx.doi.org/10.1002/smll.202004140DOI Listing
February 2021

Immunosuppressive activity of daphnetin on the humoral immune responses in ovalbumin-sensitized BALB/c mice.

Immunopharmacol Immunotoxicol 2021 Apr 24;43(2):171-175. Epub 2021 Jan 24.

Department of Biological Science, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, P. R. China.

Introduction: Most of the immunosuppressive drugs are used for the treatment of autoimmune disease, allergic diseases, and transplant rejection, but toxicity is the major obstacle for the potent drugs in the wide use of these immunosuppressive drugs. Daphnetin, a Chinese herbal product, has been reported that daphnetin possesses antimicrobial, anticoagulation, antimalarial, anticancer, and antioxidant activity. In a previous study, we found that daphnetin exhibited a potential immunosuppressive effect on LPS-induced B lymphocyte cells , therefore, in this research, we investigated the immunosuppressive effects of daphnetin in BALB/c mice use OVA as a prototype antigen.

Methods: Sixty BALB/c mice were divided into six groups. The emulsion (100 μL containing 100 μg OVA) was injected subcutaneously with OVA + CFA into the shaved backs of the BALB/c mice on day 1, and a boosting injection was administered in OVA + IFA 2 weeks later. Beginning on the day of immunization, the immunized mice were administered intraperitoneally with daphnetin at a dose of 5, 10, and 20 mg/kg in saline solution for 28 consecutive days. We measured the effect of daphnetin on OVA-specific antibody, cytokine production, and Splenocyte proliferation .

Results: The results revealed that daphnetin significantly suppressed serum immunoglobulin G levels (IgG), and the OVA-specific IgG subclasses IgG1 and IgG2b, daphnetin was also significantly decreased the Th1 and Th2 cytokine productions, inhibited the splenocytes proliferation rate .

Conclusions: It proved that daphnetin could suppress humoral response activity on OVA-sensitized mice, suggesting a potential role on daphnetin as a new immunosuppressive drug.
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http://dx.doi.org/10.1080/08923973.2021.1872618DOI Listing
April 2021

Circular RNA hsa_circ_0000554 promotes progression and elevates radioresistance through the miR-485-5p/fermitin family members 1 axis in esophageal cancer.

Anticancer Drugs 2021 Apr;32(4):405-416

Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China.

Esophageal cancer is one of the most aggressive malignant cancers in the world. Circular RNA hsa_circ_0000554 (circ_0000554) and Fermitin family members 1 (FERMT1) are rated to the advancement of esophageal cancer. Nevertheless, the regulatory mechanisms between circ_0000554 and FERMT1 in the radioresistance of esophageal cancer are unclear. Quantitative real-time PCR (qRT-PCR) was applied to examine the expression of circ_0000554, FERMT1 mRNA, and miR-485-5p. Western blot analysis was employed to assess the protein expression levels of FERMT1, Ki-67, matrix metalloproteinase (MMP)-9 and MMP-2. Cell colony formation, migration, invasion, radiosensitivity and apoptosis were evaluated by cell colony formation, transwell or flow cytometry assays. The relationship between circ_0000554 or FERMT1 and miR-485-5p was verified with dual-luciferase reporter assay. Circ_0000554 and FERMT1 expression was enhanced in esophageal cancer tissues and radioresistant esophageal cancer tissues. Both circ_0000554 and FERMT1 repression blocked cell colony formation, migration, invasion and elevated cell radiosensitivity and apoptosis in esophageal cancer cells. Importantly, circ_0000554 served as a sponge for miR-485-5p in esophageal cancer cells. And FERMT1 acted as a downstream target for miR-485-5p. Additionally, circ_0000554 modulated FERMT1 expression via miR-485-5p. Furthermore, FERMT1 enhancement reversed circ_0000554 inhibition-mediated effects on the colony formation, migration, invasion, radiosensitivity and apoptosis of esophageal cancer cells. Circ_0000554 silencing repressed EC progression and enhanced cell radiosensitivity through downregulating FERMT1 via sponging miR-485-5p, which provided a possible method for improving the radioresistence of esophageal cancer.
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http://dx.doi.org/10.1097/CAD.0000000000001007DOI Listing
April 2021

Purification, characterization and immunostimulatory effects of polysaccharides from Anemarrhena asphodeloides rhizomes.

Int J Biol Macromol 2021 Mar 16;172:550-559. Epub 2021 Jan 16.

Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneung Daehangno, Gangneung, Gangwon 210-702, South Korea. Electronic address:

The crude polysaccharide was extracted from A. asphodeloides rhizomes and further purified to produce two fractions F (50.0%) and F (19.6%). The chemical constitutions of the polysaccharides were neutral sugars (51.4%-89.7%), uronic acids (1.0%-30.2%) and sulfate esters (3.4%-8.1%), with various ratios of monosaccharides including rhamnose (1.4%-6.1%), arabinose (7.1%-21.2%), xylose (0.2%-4.8%), mannose (39.9%-79.0%), glucose (6.0%-11.1%) and galactose (2.6%-22.0%). The molecular properties of the polysaccharides were investigated by the HPSEC-UV-MALLS-RI system, revealing the M 130.0 × 10-576.5 × 10 g/moL, R 87.6-382.6 nm and SV 0.3-54.3 cm/g. The polysaccharides stimulated RAW264.7 cells to produce considerable amounts of NO and up-regulate the expression of TNF-α, IL-1 and COX-2 genes. Polysaccharides exhibited the growth inhibitory effects on cancer cells lines of AGS, MKN-28 and MKN-45, in which F fraction exhibited prominent bioactivities. The AGS cells treated with F experienced condensed cytoplasm, shrinkage of nucleus and chromatin marginalization with the highest number of cells at early-stage apoptosis reaching 54.6%. The inhibitory effect of F polysaccharide on AGS cells was through MAPKs and STAT3 signaling pathways. The backbone of the F was mainly linked by (1 → 4)-linked mannopyranosyl and (1 → 3)-linked galactopyranosyl. Taken together, the polysaccharide from A. asphodeloides rhizomes could be utilized as medicinal, pharmacological and functional food ingredients.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.088DOI Listing
March 2021

Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model.

Sci Rep 2021 Jan 13;11(1):909. Epub 2021 Jan 13.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

Cladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.
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http://dx.doi.org/10.1038/s41598-020-79642-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806624PMC
January 2021

An Efficient Turing-Type Ag Se-CoSe Multi-Interfacial Oxygen-Evolving Electrocatalyst*.

Angew Chem Int Ed Engl 2021 Mar 12;60(12):6553-6560. Epub 2021 Feb 12.

Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, China.

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag Se on CoSe nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag Se-CoSe material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5 % anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag Se-CoSe interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces.
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http://dx.doi.org/10.1002/anie.202017016DOI Listing
March 2021