Publications by authors named "Bing Wu"

686 Publications

Coronal Compensation Mechanism of Pelvic Obliquity in Patients With Developmental Dysplasia of the Hip.

Global Spine J 2021 May 5:21925682211010760. Epub 2021 May 5.

NanKai University School of Medicine, Tianjin, China.

Study Design: Descriptive retrospective study.

Objective: DDH is a common lower limb deformity. It has been reported that this deformity can change the sagittal alignment of spine and pelvis. Sacral obliquity (SO) and iliac obliquity (IO) have been proven simple and reliable pelvic-lower limb coronal parameters to evaluate the coronal balance of the pelvis. To study the spine-pelvic coronal compensation mechanism of pelvic obliquity in patients with developmental dysplasia of the hip (DDH).

Methods: We collected the data of 110 patients with DDH in our hospital from January 2009 to December 2019, who underwent total hip arthroplasty. We used ICC (Intraclass correlation coefficient) to test the reliability of the measurement result of SO and IO in patients with DDH. A paired t-test was used for the statistical analysis.

Results: The intra observer reliability of IO and SO was 0.965 and 0.875 respectively, and the inter observer reliability of IO and SO was 0.887 and 0.889 respectively. The sacroiliac joint and spine can compensate for pelvic obliquity in patients with DDH. We classified the compensatory mechanism into 3 types according to the different imaging performances.

Conclusions: The sacroiliac joint has a considerable compensatory ability to ensure coronal balance. We clarified and classified the compensatory mechanism of pelvic obliquity into 3 types. We differentiated the pelvic obliquity in patients with DDH and in those with scoliosis, which is clinical significant to understand the process of development of the disease.
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http://dx.doi.org/10.1177/21925682211010760DOI Listing
May 2021

Peptide 1018 inhibits swarming and influences Anr-regulated gene expression downstream of the stringent stress response in Pseudomonas aeruginosa.

PLoS One 2021 30;16(4):e0250977. Epub 2021 Apr 30.

Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that causes considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis. P. aeruginosa can adapt to surface growth by undergoing swarming motility, a rapid multicellular movement that occurs on viscous soft surfaces with amino acids as a nitrogen source. Here we tested the small synthetic host defense peptide, innate defense regulator 1018, and found that it inhibited swarming motility at concentrations as low as 0.75 μg/ml, well below the MIC for strain PA14 planktonic cells (64 μg/ml). A screen of the PA14 transposon insertion mutant library revealed 29 mutants that were more tolerant to peptide 1018 during swarming, five of which demonstrated significantly greater swarming than the WT in the presence of peptide. Transcriptional analysis (RNA-Seq) of cells that were inoculated on swarming plates containing 1.0 μg/ml peptide revealed differential expression of 1,190 genes compared to cells swarming on plates without peptide. Furthermore, 1018 treatment distinctly altered the gene expression profile of cells when compared to that untreated cells in the centre of the swarm colonies. Peptide-treated cells exhibited changes in the expression of genes implicated in the stringent stress response including those regulated by anr, which is involved in anaerobic adaptation, indicative of a mechanism by which 1018 might inhibit swarming motility. Overall, this study illustrates potential mechanisms by which peptide 1018 inhibits swarming surface motility, an important bacterial adaptation associated with antibiotic resistance, virulence, and dissemination of P. aeruginosa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250977PLOS
April 2021

Quantitative Analysis of Synthetic Magnetic Resonance Imaging in Alzheimer's Disease.

Front Aging Neurosci 2021 12;13:638731. Epub 2021 Apr 12.

Department of Radiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

The purpose of this study was to evaluate the feasibility and whether synthetic MRI can benefit diagnosis of Alzheimer's disease (AD). Eighteen patients and eighteen age-matched normal controls (NCs) underwent MR examination. The mini-mental state examination (MMSE) scores were obtained from all patients. The whole brain volumetric characteristics, T1, T2, and proton density (PD) values of different cortical and subcortical regions were obtained. The volumetric characteristics and brain regional relaxation values between AD patients and NCs were compared using independent-samples -test. The correlations between these quantitative parameters and MMSE score were assessed by the Pearson correlation in AD patients. Although the larger volume of cerebrospinal fluid (CSF), lower brain parenchymal volume (BPV), and the ratio of brain parenchymal volume to intracranial volume (BPV/ICV) were found in AD patients compared with NCs, there were no significant differences ( > 0.05). T1 values of right insula cortex and T2 values of left hippocampus and right insula cortex were significantly higher in AD patients than in NCs, but T1 values of left caudate showed a reverse trend ( < 0.05). As the MMSE score decreased in AD patients, the BPV and BPV/ICV decreased, while the volume of CSF and T1 values of bilateral insula cortex and bilateral hippocampus as well as T2 values of bilateral hippocampus increased ( < 0.05). Synthetic MRI not only provides more information to differentiate AD patients from normal controls, but also reflects the disease severity of AD.
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http://dx.doi.org/10.3389/fnagi.2021.638731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072384PMC
April 2021

[Radiographic study of effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):414-419

Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen Guangdong, 518000, P.R.China.

Objective: To investigate the mid-term effect of lateral placement of bone graft on shoulder joint degeneration after modified arthroscopic Latarjet surgery with elastic fixation for recurrent anterior shoulder dislocation with an anterior glenoid bone defect.

Methods: According to the inclusion and exclusion criteria, 18 patients with recurrent anterior shoulder dislocation and anterior glenoid bone defect who received the modified arthroscopic Latarjet surgery with elastic fixation between January 2015 and November 2016 were enrolled in this study. There were 12 males and 6 females with an average age of 26.2 years (range, 19-37 years). The number of shoulder dislocation ranged from 4 to 30 times (mean, 8.8 times). The disease duration was 8-49 months (mean, 23.8 months). The mean anterior glenoid bone defect was 25.2% of the glenoid surface (range, 20%-29%). The mean preoperative Instability Severity Index Score (ISIS) was 7.6 (range, 7-10). According to Samilson-Prieto classification, the shoulder joint degeneration was rated as grade 0 in 13 cases, grade Ⅰ in 3 cases, and grade Ⅱ in 2 cases. Before and after operation, the visual analogue scale (VAS) score, American Society of Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, Rowe score, and shoulder mobility were used to evaluate the effectiveness. Imaging examination was performed to observe the shoulder joint degeneration, the position of the bone graft, and the postoperative shaping of the scapular glenoid.

Results: All patients were followed up 55-62 months, with an average of 59.6 months. There was no neurovascular injuries, infections, fixation-related and bone graft-related complications. No re-dislocation and revision occurred. All patients returned to normal life, 17 of whom returned to sport. The VAS score was significantly decreased and ASES, Walch-Duplay, and Rowe scores were significantly improved at last follow-up ( <0.05). No significant difference was found in range of motion of forward flexion, abduction, lateral rotation at 90° abduction, internal rotation at 90° abduction, or lateral rotation at 0° between pre- and post-operation ( >0.05). Three-dimensional CT showed that the centers of all bone grafts were between 3∶30 and 4∶30 (right shoulder) or between 7∶40 and 8∶20 (left shoulder) and no bone grafts were positioned superiorly or inferiorly in the glenoid En-face view. All bone grafts were positioned lateral to the scapular glenoid with an average distance of 3.5 mm (range, 2.3-4.6 mm) in cross-sectional imaging by CT. Compared with the preoperative Samilson-Prieto classification results, all cases showed no progression of shoulder joint degeneration at 36, 48 months and last follow-up. All bone grafts remodeled to a steady state within 24 months after operation. The bone graft and glenoid finally remodeled analogous to the shape of the intact glenoid in the En-face view and became flush with the glenoid rim, remodeling to a curved shape congruent to the humeral head in cross-sectional imaging by CT. The shape of the remodeled glenoid at last follow-up was not significantly different from that at 24 months after operation.

Conclusion: The lateral placement of the bone graft during modified arthroscopic Latarjet surgery with elastic fixation do not accelerate the imaging changes of shoulder joint degeneration.
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http://dx.doi.org/10.7507/1002-1892.202011089DOI Listing
April 2021

Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Systemic sclerosis (SSc) is a life-threatening chronic connective tissue disease with the characteristics of skin fibrosis, vascular injury, and inflammatory infiltrations. Though inhibition of phosphodiesterase 4 (PDE4) has been turned out to be an effective strategy in suppressing inflammation through promoting the accumulation of intracellular cyclic adenosine monophosphate (cAMP), little is known about the functional modes of inhibiting PDE4 by apremilast on the process of SSc. The present research aimed to investigate the therapeutic effects and underlying mechanism of apremilast on SSc. Herein, we found that apremilast could markedly ameliorate the pathological manifestations of SSc, including skin dermal thickness, deposition of collagens, and increased expression of α-SMA. Further study demonstrated that apremilast suppressed the recruitment and activation of macrophages and T cells, along with the secretion of inflammatory cytokines, which accounted for the effects of apremilast on modulating the pro-fibrotic processes. Interestingly, apremilast could dose-dependently inhibit the activation of M1 and T cells in vitro through promoting the phosphorylation of CREB. In summary, our research suggested that inhibiting PDE4 by apremilast might provide a novel therapeutic option for clinical treatment of SSc patients.
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http://dx.doi.org/10.1038/s41401-021-00656-xDOI Listing
April 2021

Irradiated whole-cell vaccine suppresses hepatocellular carcinoma growth in mice via Th9 cells.

Oncol Lett 2021 May 22;21(5):409. Epub 2021 Mar 22.

Central Laboratory, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.

Liver cancer is one of the most common malignant tumors with no available satisfactory treatment. The aim of the present study was to investigate the anti-tumor effect of an irradiated hepatocellular carcinoma (HCC) whole-cell vaccine and its underlying mechanisms. Hepa1-6 and H22 HCC cell lines were irradiated in preparation for whole-cell vaccine production. Subsequently, two HCC tumor-bearing mouse models were created by injecting these Hepa1-6 and H22 cells into the abdominal skin of C57BL/6 and ICR mice, respectively. The mice were immunized with the corresponding whole-cell vaccine the next day, and then once a week until the end of the experimental period. Tumor growth, blood T helper (Th)9 cells and plasma interleukin (IL)-9 levels were monitored during the immunization period. Th9 cells were also induced by co-culture of the whole-cell vaccine with lymphocytes from the spleen and lymph nodes of the corresponding mice. Alterations of gene expression in transcription factor (TF) were determined by reverse transcription-quantitative PCR, and Th9 cells were detected using flow cytometry. The whole-cell vaccine effectively suppressed HCC tumor growth, as indicated by slower tumor growth and a smaller tumor size in the immunized group compared with the control. The percentage of blood Th9 cells and the concentration of plasma IL-9 were significantly increased in the immunized group. The whole-cell vaccine also induced Th9 cell differentiation and upregulated the expression of TFs PU.1, interferon regulatory factor 4 and basic leucine zipper transcriptional factor ATF-like. These results suggest that the irradiated HCC whole-cell vaccine inhibited tumor growth by increasing Th9 cell numbers in HCC mice.
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http://dx.doi.org/10.3892/ol.2021.12670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020379PMC
May 2021

[Study on the Antioxidant Activity of Aloe-Emodin Metal Complex].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 Mar;52(2):241-247

Key Laboratory of the Ministry of Education for the Standardization of Traditional Chinese Medicine, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Objective: To synthesize three kinds of metal complexes of aloe-emodin and compare the antioxidant activities of the ligands and the complexes.

Methods: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were synthesized by dissolving and stirring in anhydrous ethanol solvent, and their structures were characterized. The Fe -H O -methylene blue method, the diphenyl bitter hydrazine radical method (DPPH method) and other assays were used to determine the clearance effect of ligands and complexes on superoxide radicals (O •), hydroxyl radicals (•OH) and phenyl bitter hydrazine radical (DPPH•).

Results: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were successfully synthesized. According to the results of structural characterization, we speculated that the aloe-emodin metal complexes were formed at the site between the two molecules of aloe-emodin and one molecule of metal ions (Fe , Mg , Cu ) via the 9 carbonyl and 8 hydroxyl groups of the aloe-emodin molecules. Both the complex and the ligand have clearance effects on three kinds of free radicals, and the complex showed stronger effects than its ligand ( <0.05).

Conclusion: Coordination of aloe-emodin with metal ions, such as Fe , Cu , and Mg , could enhance the antioxidant activity of the ligand itself.
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http://dx.doi.org/10.12182/20201160110DOI Listing
March 2021

Second sacral sacralalar-iliac (S2AI) screw placement in adult degenerative scoliosis (ADS) patients: an imaging study.

BMC Surg 2021 Apr 6;21(1):181. Epub 2021 Apr 6.

Department of Orthopedics, the Fourth Medical Centre, Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, 100048, Beijing, China.

Background: The imaging characteristics of sacral sacralalar-iliac (S2AI) screw trajectory in adult degenerative scoliosis (ADS) patients will be determined.

Methods: S2AI screw trajectories were mapped on three-dimensional computed tomography (3DCT) reconstructions of 40 ADS patients. The starting point, placement plane, screw template, and a circle centered at the lowest point of the ilium inner cortex were set on these images. A tangent line from the starting point to the outer diameter of the circle was selected as the axis of the screw trajectory. The related parameters in different populations were analyzed and compared.

Results: The trajectory length of S2AI screws in ADS patients was 12.00 ± 0.99 cm, the lateral angle was 41.24 ± 3.92°, the caudal angle was 27.73 ± 6.45°, the distance from the axis of the screw trajectory to the iliosciatic notch was 1.05 ± 0.81 cm, the distance from the axis of the screw trajectory to the upper edge of the acetabulum was 1.85 ± 0.33 cm, and the iliac width was 2.12 ± 1.65 cm. Compared with females, the lateral angle of male ADS patients was decreased, but the trajectory length was increased (P < 0.05). Compared to patients without ADS in previous studies, the lateral angle of male patients was larger, the lateral angle of female patients was increased, and the caudal angle was decreased (P < 0.05).

Conclusions: There is an ideal trajectory of S2AI screws in ADS patients. A different direction should be noticed in the placement of S2AI screws, especially in female patients.
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http://dx.doi.org/10.1186/s12893-021-01139-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025332PMC
April 2021

Case Report: Primary NK/T Cell Lymphoma Nasal Type of the Colon With Multiple Intestinal Perforations.

Front Oncol 2021 17;11:577939. Epub 2021 Mar 17.

Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

Extranodal NK/T cell lymphoma is a rare non-Hodgkin lymphoma mainly involving the upper aerodigestive tract, even rarer is primary extranasal disease involving the intestine. We present a case of primary intestinal NK/T cell lymphoma with diagnostic challenge, which eventually developed into multiple intestinal perforations. A 35-year-old man presented with diarrhea and recurrent fever. Abdominal CT revealed multi-segmental intestinal wall thickening. Colonoscopy showed multiple irregular ulcers in colon. During the hospitalization, the patient developed intestinal perforation and an emergency surgery was performed. The resected specimen showed multiple perforations of the colon. The surgical samples underwent pathological analysis, and a diagnosis of extranodal NK/T cell lymphoma nasal type was confirmed. After recovering from surgery, the patient started receiving chemotherapy and PD-1 monoclonal antibody. Fortunately, he was discharged after significant improvement in his general condition. Eleven months follow-up was uneventful. Early diagnosis of primary intestinal NK/T cell lymphoma is frequently difficult. Most patients were definitely diagnosed only after surgical resection following complications, resulting in a poor prognosis. Therefore, doctors should maintain high suspicion of this malignancy for early diagnosis at an early stage clinically.
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http://dx.doi.org/10.3389/fonc.2021.577939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010170PMC
March 2021

Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

medRxiv 2021 Mar 26. Epub 2021 Mar 26.

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections. Critically ill patients with coronavirus disease 2019 (COVID-19) face an elevated risk of VAP, although susceptibility varies widely. Because mechanisms underlying VAP predisposition remained unknown, we assessed lower respiratory tract host immune responses and microbiome dynamics in 36 patients, including 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill controls. We employed a combination of tracheal aspirate bulk and single cell RNA sequencing (scRNA-seq). Two days before VAP onset, a lower respiratory transcriptional signature of bacterial infection was observed, characterized by increased expression of neutrophil degranulation, toll-like receptor and cytokine signaling pathways. When assessed at an earlier time point following endotracheal intubation, more than two weeks prior to VAP onset, we observed a striking early impairment in antibacterial innate and adaptive immune signaling that markedly differed from COVID-19 patients who did not develop VAP. scRNA-seq further demonstrated suppressed immune signaling across monocytes/macrophages, neutrophils and T cells. While viral load did not differ at an early post-intubation timepoint, impaired SARS-CoV-2 clearance and persistent interferon signaling characterized the patients who later developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients who developed VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. Together, these findings demonstrate that COVID-19 patients who develop VAP have impaired antibacterial immune defense weeks before secondary infection onset.

One Sentence Summary: COVID-19 patients with secondary bacterial pneumonia have impaired immune signaling and lung microbiome changes weeks before onset.
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http://dx.doi.org/10.1101/2021.03.23.21253487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010763PMC
March 2021

Mitigation of emerging pollutants and pathogens in decentralized wastewater treatment processes: A review.

Authors:
Selina Hube Bing Wu

Sci Total Environ 2021 Mar 18;779:146545. Epub 2021 Mar 18.

Faculty of Civil and Environmental Engineering, University of Iceland, Hjardarhagi 2-6, IS-107 Reykjavik, Iceland. Electronic address:

Emerging pollutants (such as micropollutants, microplastics) and pathogens present in wastewater are of rising concern because their release can affect the natural environment and drinking water resources. In this decade, with increasing numbers of small-scale decentralized wastewater systems globally, the status of emerging pollutant and pathogen mitigation in the decentralized wastewater treatment processes has received more attention. This state-of-the-art review aims to discuss the mitigation efficiencies and mechanisms of micropollutants, microplastics, and pathogens in single-stage and hybrid decentralized wastewater treatment processes. The reviewed results revealed that hybrid wastewater treatment facilities could display better performance compared to stand-alone facilities. This is because the multiple treatment steps could offer various microenvironments, allowing incorporating several mitigation mechanisms (such as sorption, degradation, filtration, etc.) to remove complicated emerging pollutants and pathogens. The factors (such as system operation conditions, environmental conditions, wastewater matrix) influencing the removals of emerging pollutants from wastewater in these systems have been further identified. Nevertheless, it was found that very limited research work focused on synergised or conflicted effects of operation conditions on various emerging pollutants naturally present in the wastewater. Meanwhile, effective, reliable, and rapid analysis of the emerging pollutants and pathogens in the complicated wastewater matrix is still a major challenge.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146545DOI Listing
March 2021

miR-666-3p mediates the protective effects of mesenchymal stem cell-derived exosomes against oxygen-glucose deprivation and reoxygenation-induced cell injury in brain microvascular endothelial cells via mitogen-activated protein kinase pathway.

Curr Neurovasc Res 2021 Mar 19. Epub 2021 Mar 19.

Department of Cardiothoracic Surgery, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000. China.

Background: Previous studies have reported that mesenchymal stem cell (MSC)-derived exosomes can protect rat primary brain microvascular endothelial cells (BMECs) against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury.

Objective: To identify the key factors mediating the protective effects of MSC-derived exosomes.

Methods: Rat primary BMECs were either pretreated or not pretreated with MSC-derived exosomes before exposure to OGD/R. Naïve cells were used as a control. After performing small RNA deep sequencing, quantitative reverse transcription polymerase chain reaction was performed to validate microRNA (miRNA) expression. The effects of rno-miR-666-3p on cell viability, apoptosis, and inflammation in OGD/R-exposed cells were assessed by performing the Cell Counting Kit 8 assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Moreover, the role of rno-miR-666-3p in regulating gene expression in OGD/R-exposed cells was studied using mRNA deep sequencing. Lastly, to evaluate whether mitogen-activated protein kinase 1 (MAPK1) was the target of rno-miR-666-3p, western blotting and the dual-luciferase assay were performed.

Results: MSC-derived exosomes altered the miRNA expression patterns in OGD/R-exposed BMECs. In particular, the expression levels of rno-miR-666-3p, rno-miR-92a-2-5p, and rno-miR-219a-2-3p decreased in OGD/R-exposed cells compared with those in the control; however, MSC-derived exosomes restored the expression levels of these miRNAs under OGD/R conditions. rno-miR-666-3p overexpression enhanced cell viability and alleviated the apoptosis of OGD/R-exposed cells. Moreover, rno-miR-666-3p suppressed OGD/R-induced inflammation. mRNA deep sequencing revealed that rno-miR-666-3p is closely associated with the MAPK signaling pathway. Western blotting and the dual-luciferase assay confirmed that MAPK1 is the target of rno-miR-666-3p.

Conclusion: MSC-derived exosomes restore rno-miR-666-3p expression in OGD/R-exposed BMECs. Moreover, this specific miRNA exerts protective effects against OGD/R by suppressing the MAPK signaling pathway.
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http://dx.doi.org/10.2174/1567202618666210319152534DOI Listing
March 2021

Combined effects of arsenic and palmitic acid on oxidative stress and lipid metabolism disorder in human hepatoma HepG2 cells.

Sci Total Environ 2021 May 19;769:144849. Epub 2021 Jan 19.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China. Electronic address:

The toxicity of arsenic (As) can be influenced by many nutrients in food. However, the combined effects and underlying mechanisms of As and palmitic acid (PA) are still unclear. Here, cell viability, oxidative stress, lipids accumulation, gene expression profiles, and metabolome profiles of human hepatoma HepG2 cells exposed to As, PA, and As + PA were analyzed and compared. Results showed that co-exposure of 100 μM PA and 2 μM As induced lower cell viability, higher intracellular reactive oxygen species level, more lipid droplet accumulation, and more intracellular triglyceride contents than As alone or PA alone exposure. High-throughput quantitative PCR and H NMR-based metabolomics analysis showed that co-exposure of As and PA caused all toxic effects on gene expression and metabolome profiles induced by As alone or PA alone exposure, and showed higher toxicities. Gene expression profiles in the As + PA group had higher similarity with those in the As group than the PA group. However, PA played a more important role in metabolism disorder than As in their interactive effects. Oxidative stress and lipid metabolism disorder were found to be the main toxic effects in the As + PA group. Several differentially expressed genes (such as OXR1, OXSR1, INSR, and PPARA) and changed metabolites (such as pyruvate, acetate, and L-phenylalanine) were involved in the combined toxicity of As and PA. This study provides basic information on the interactive effects of As and PA, which is useful for the health risk assessment of As and FFA.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144849DOI Listing
May 2021

DNA Nanosieve-Based Regenerative Electrochemical Biosensor Utilizing Nucleic Acid Flexibility for Accurate Allele Typing in Clinical Samples.

ACS Sens 2021 03 3;6(3):1348-1356. Epub 2021 Mar 3.

Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.

Herein, an interface-based DNA nanosieve that has the ability to differentiate ssDNA from dsDNA has been demonstrated for the first time. The DNA nanosieve could be readily built through thiol-DNA's self-assembly on the gold electrode surface, and its cavity size was tunable by varying the concentration of thiol-DNAs. Electrochemical chronocoulometry using [Ru(NH)] as redox revealed that the average probe-to-probe separation in the 1 μM thiol-DNA-modified gold electrode was 10.6 ± 0.3 nm so that the rigid dsDNA with a length of ∼17 nm could not permeate the nanosieve, whereas the randomly coiled ssDNA could enter it due to its high flexibility, which has been demonstrated by square wave voltammetry and methylene blue labels through an upside-down hybridization format. After combining the transiently binding characteristic of a short DNA duplex and introducing a regenerative probe (the counterpart of ssDNA), a highly reproducible nanosieve-based E-DNA model was obtained with a relative standard deviation (RSD) as low as 2.7% over seven cycles. Finally, we built a regenerative nanosieve-based E-DNA sensor using a ligation cycle reaction as an ssDNA amplification strategy and realized one-sensor-based continuous measurement to multiple clinical samples with excellent allele-typing performance. This work holds great potential in low-cost and high-throughput analysis between biosensors and biochips and also opens up a new avenue in nucleic acid flexibility-based DNA materials for future applications in DNA origami and molecular logic gates.
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http://dx.doi.org/10.1021/acssensors.0c02720DOI Listing
March 2021

Severe lumbar spinal stenosis combined with Guillain-Barré syndrome: A case report.

World J Clin Cases 2021 Feb;9(5):1096-1102

Department of Orthopedic Surgery, Shaoxing Central Hospital, Shaoxing 312000, Zhejiang Province, China.

Background: Guillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS.

Case Summary: A 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up.

Conclusion: GBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms.
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http://dx.doi.org/10.12998/wjcc.v9.i5.1096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896650PMC
February 2021

Heme supplementation ameliorates lupus nephritis through rectifying the disorder of splenocytes and alleviating renal inflammation and oxidative damage.

Int Immunopharmacol 2021 May 24;94:107482. Epub 2021 Feb 24.

Laboratory of Anti-inflammation, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Heme is an important iron-containing porphyrin molecule expressed ubiquitously in organisms. Recently, this endogenous molecule has been widely reported to be involved in the pathogenesis of numerous diseases such as sepsis, atherosclerosis and inflammatory bowel disease. However, the role of heme during systemic lupus erythematosus (SLE) pathogenesis has not been previously evaluated. Herein, we have measured the levels of heme in lupus-prone mice and explored the influence of heme on the pathogenesis of lupus. We revealed that heme levels in serum, kidney and spleen lymphocytes are all negatively associated with the levels of proteinuria in lupus-prone mice. Heme supplementation at 15 mg/kg could significantly ameliorate the syndromes of lupus in MRL/lpr mice, extending lifespan, reducing the level of proteinuria and alleviating splenomegaly and lymphadenopathy. Further study demonstrated that heme replenishment corrected the abnormal compartment of T cell subsets, plasma cells and macrophages in the spleen and alleviates inflammation and oxidative damage in kidney of MRL/lpr mice. Our study well defined heme as a relevant endogenous molecule in the etiology of SLE, as well as a potential therapeutic target for treating this autoimmune disease. Meanwhile, heme replenishment might be a new choice to therapeutically modulate immune homeostasis and prevent SLE.
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http://dx.doi.org/10.1016/j.intimp.2021.107482DOI Listing
May 2021

Highly Efficient Hydrated Electron Utilization and Reductive Destruction of Perfluoroalkyl Substances Induced by Intermolecular Interaction.

Environ Sci Technol 2021 03 26;55(6):3996-4006. Epub 2021 Feb 26.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, P. R. China.

Perfluoroalkyl substances (PFASs) are highly toxic synthetic chemicals, which are considered the most persistent organic contaminants in the environment. Previous studies have demonstrated that hydrated electron based techniques could completely destruct these compounds. However, in the reactions, alkaline and anaerobic conditions are generally required or surfactants are involved. Herein, we developed a simple binary composite, only including PFAS and hydrated electron source chemical. The system exhibited high efficiency for the utilization of hydrated electrons to decompose PFASs. By comparing the degradation processes of perfluorooctanoic acid (PFOA) in the presence of seven indole derivatives with different chemical properties, we could conclude that the reaction efficiency was dependent on not only the yield of hydrated electrons but also the interaction between PFOA and indole derivative. Among these derivatives, indole showed the highest degradation performance due to its relatively high ability to generate hydrated electrons, and more importantly, indole could form a hydrogen bonding with PFOA to accelerate the electron transfer. Moreover, the novel composite demonstrated high reaction efficiency even with coexisting humic substance and in a wide pH range (4-10). This study would deepen our understanding of the design of hydrated electron based techniques to treat PFAS-containing wastewater.
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http://dx.doi.org/10.1021/acs.est.0c07927DOI Listing
March 2021

SARS-CoV-2 viral shedding characteristics and potential evidence for the priority for faecal specimen testing in diagnosis.

PLoS One 2021 22;16(2):e0247367. Epub 2021 Feb 22.

Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhejiang Province, People's Republic of China.

This study aimed to identify the specimen type that has high positivity and its proper sampling time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to promote diagnostic efficiency. All SARS-CoV-2-infected patients with a laboratory-confirmed diagnosis in Zhoushan City were followed up for viral shedding in respiratory tract specimens and faecal samples. Positivity was analysed both qualitatively and quantitatively by proper statistical approaches with strong testing power. Viral shedding in respiratory tract and faecal specimens was prolonged to 45 and 40 days after the last exposure, respectively. The overall positive rate in respiratory tract specimens was low and relatively unstable, being higher in the early-to-mid stage than in the mid-to-late stage of the disease course. Compared with respiratory tract specimens, faecal samples had a higher viral load, higher overall positive rate, and more stable positivity in different disease courses and varied symptomatic status. Faecal specimens have the potential ability to surpass respiratory tract specimens in virus detection. Testing of faecal specimens in diagnosis, especially for identifying asymptomatic carriers, is recommended. Simultaneously, testing respiratory tract specimens at the early-to-mid stage is better than testing at the mid-to-late stage of the disease course. A relatively small sample size was noted, and statistical approaches were used to address it. Information was missing for both specimen types at different stages of the disease course due to censored data. Our research extends the observed viral shedding in both specimen types and highlights the importance of faecal specimen testing in SARS-CoV-2 diagnosis. Healthcare workers, patients, and the general public may all benefit from our study findings. Disposal of sewage from hospitals and residential areas should be performed cautiously because the virus sheds in faeces and can last for a long time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247367PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899334PMC
March 2021

Interbundle Impingement Pressure in Individualized and Nonindividualized Double-Bundle Anterior Cruciate Ligament Reconstruction: A Cadaveric Study.

Orthop J Sports Med 2021 Feb 2;9(2):2325967120958487. Epub 2021 Feb 2.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Graft impingement is one of the main concerns in double-bundle anterior cruciate ligament reconstruction (DB-ACLR). Impingement between the anteromedial (AM) and posterolateral (PL) bundles has been postulated to cause graft deterioration or rerupture, but this has not been thoroughly investigated, and the interbundle impingement pressure (IIP) has not been well researched.

Purpose: To determine the IIP between the AM and PL bundles in the native anterior cruciate ligament (ACL) and in DB-ACLR with individualized and nonindividualized double-tunnel placement.

Study Design: Controlled laboratory study.

Methods: A total of 30 fresh-frozen, nonpaired, human cadaveric knees were randomly divided into 3 groups of 10 knees: native intact ACL (NI group), DB-ACLR tunnel placement using the preserved remnant procedure (individualized reconstruction) (PR group), and DB-ACLR tunnel placement using the bony landmark procedure (nonindividualized reconstruction) (BL group). Pressure sensors were inserted between the AM and PL bundles. The knee was moved passively from full extension to full flexion, and the IIP between the 2 ACL bundles was measured every 15°. Similarly, the impingement pressure was measured between the ACL and intercondylar roof and between the ACL and posterior cruciate ligament (PCL).

Results: No significant differences were found in the maximum, mean, or minimum ACL-roof and ACL-PCL impingement pressures among the 3 groups. The IIP significantly increased when the knee joint was flexed >120° in all 3 groups ( < .001). Compared with the other 2 groups, the BL group had significantly higher maximum and mean IIP throughout the range of knee movement ( < .001) and from maximum extension to 120° of flexion ( < .001). The BL group also had significantly higher minimum IIP than the other 2 groups when knee flexion was >120° ( < .001). No significant differences were seen in maximum, minimum, or mean IIP between the NI and PR groups.

Conclusion: The PR procedure (individualized DB-ACLR) was more consistent with the interbundle biomechanical conditions of the native ACL, whereas the BL procedure (nonindividualized DB-ACLR) had higher maximum and mean IIP. The IIP was higher than the ACL-intercondylar roof or ACL-PCL pressures, and it increased significantly when knee flexion was >120°.

Clinical Relevance: These data suggest that surgeons can perform individualized DB-ACLR using preserved remnants for tunnel placement as impingement-free DB-ACLR.
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http://dx.doi.org/10.1177/2325967120958487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869155PMC
February 2021

AHLs-mediated quorum sensing threshold and its response towards initial adhesion of wastewater biofilms.

Water Res 2021 Apr 13;194:116925. Epub 2021 Feb 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, Jiangsu, P.R. China. Electronic address:

Quorum sensing (QS) plays a crucial role during initial biofilm formation, however the QS threshold and the response of biofilm formation towards N-acyl-homoserine lactones (AHLs) remains largely unknown due to the limitation of nondestructive online methods for monitoring bacterial adherence and the complexity of QS system, which limits the application of QS signal reagents in biofilm reactors. In this study, bacterial QS threshold and its response of biofilm formation to AHLs in purely cultured Sphingomonas rubra biofilm as well as in three different wastewater biofilms #1-3 were investigated via real time cell analysis (RTCA). The main perspective was to study the biomass adherence in response to 12 different forms of AHLs at different concentrations. Results showed that bacterial adhesion was significantly improved by exogenous AHLs with the maximum increase of 2.26-, 2.36-, 2.52-, and 2.80- times biomass production in the four respective biofilms. Although the preferred form of AHL differed for various biofilms, the long-chain AHLs (12-14 carbons) resulted in an overall improvement of bacterial adhesion due to their stronger hydrophobicity and hydrolysis resistance. In addition, bacterial QS threshold of AHLs was observed to have a wide range of concentration from 10 ng/L to 10 μg/L. Meanwhile, QS response time to AHLs also showed a significant difference in different biofilms. Biofilm #2 inoculated with bulking sludge had lower QS threshold of 10 ng/L and faster response to most AHLs that is less than 6 h. Thus, considering the improvement of biofilm adhesion by AHLs, 10 ng/L of C12-HSL, 10 ng/L of C12-HSL, and 10 ng/L of C6-HSL were preferentially selected for wastewater biofilms #1-3 respectively. Unexpectedly, adding high-concentration of AHLs detected in sludges did not significantly improved the bacterial adhesion. Infact the addition of these AHLs at low concentrations or even undetected concentrations substantially improved bacterial adhesion, which could be explained by bacterial communities composition. According to the Pearson correlation analysis, 62% of the top 50 most abundant genera in bacterial communities were significantly negatively related to the response time of multiple AHLs, representing their fast QS response. The QS bacteria, Dechloromonas and Nitrospira have fast QS response for C4-HSL and C8-HSL while, Comamonadaceae has fast QS response for 3OC8-HSL, 3OC10-HSL, 3OC12-HSL, and 3OC14-HSL. In contrast, the rest 38% of the top most abundant genera, such as Ferruginibacter, Hyphomicrobium, and Terrimonas quickly responded to only one AHL, showing significant negative relationship with the response time of C6-HSL. Overall, this study provides an effective and convenient means to select appropriate AHL reagents to promote bacterial adhesion in biofilm systems. Moreover, it also suggests that exogenous AHLs may be useful in improving the settling property of bulking sludge.
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http://dx.doi.org/10.1016/j.watres.2021.116925DOI Listing
April 2021

LncRNA RNCR3 promotes endothelial cell proliferation and inflammatory cytokine secretion via regulating miR-185-5p/cyclin D2 axis.

Environ Sci Pollut Res Int 2021 Jan 26. Epub 2021 Jan 26.

Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China.

Endothelial cell is one critical structure of blood vessels, and irregular migration and proliferation of endothelial cell might cause progression of several vascular diseases such as atherosclerosis and restenosis. We showed that TNF-α, PDGF-bb, and IL-1β promote RNCR3 expression in a dose-dependent manner inhuman endothelial cell. RNCR3 level is higher in serum of atherosclerosis patients compared with those in control volunteers. Overexpression of RNCR3 promotes cell proliferation and three inflammatory cytokine secretion including IL-6, IL-1β, and TNF-α in endothelial cell. We illustrated that overexpression of RNCR3 inhibits miR-185-5p expression in endothelial cell. Furthermore, we indicated that miR-185-5p level is lower in the serum of patients with atherosclerosis compared with those in control volunteers. There is a negative correlation between miR-185-5p and RNCR3 expression in serum of patients with atherosclerosis. Using Targetscan, it predicted that miR-185-5p may bind to cyclin D2 and miR-185-5p is one potential target of miR-185-5p. Luciferase reporter data indicated that miR-185-5p suppresses luciferase value of wild-type cyclin D2 while it has no influence of cyclin D2 mutant. Overexpression of RNCR3 enhances cyclin D2 expression in endothelial cell. Moreover, RNCR3 induces cell growth and enhances inflammatory cytokine secretion through modulating cyclin D2 expression in endothelial cell. These results suggested that RNCR3 may serve as one new target for the treatment of atherosclerosis.
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http://dx.doi.org/10.1007/s11356-020-12117-9DOI Listing
January 2021

Human organoid biofilm model for assessing antibiofilm activity of novel agents.

NPJ Biofilms Microbiomes 2021 01 25;7(1). Epub 2021 Jan 25.

Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.

Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.
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http://dx.doi.org/10.1038/s41522-020-00182-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835231PMC
January 2021

Smoking cessation in late life is associated with increased risk of all-cause mortality amongst oldest old people: a community-based prospective cohort study.

Age Ageing 2021 Jan 23. Epub 2021 Jan 23.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Objective: we aimed to investigate the association of smoking cessation with risk of all-cause mortality amongst oldest old people (aged ≥ 80 years).

Design: this was a prospective cohort study.

Setting: the Chinese Longitudinal Healthy Longevity Survey, implemented in 23 provinces of China.

Participants: a total of 28,643 community-dwelling oldest old people (mean age, 92.9 ± 7.5 years) were included.

Methods: in this community-based cohort study, Cox proportional hazards models were used to examine the association of smoking cessation with risk of all-cause mortality.

Results: during 136,585 person-years of follow-up from baseline to 1 September 2014, compared with never smokers, hazard ratios and 95% confidence intervals for all-cause mortality were 1.06 (1.02-1.10) for current smokers, 1.23 (1.09-1.39) for transient quitters (≤1 consecutive years since smoking cessation), 1.22 (1.12-1.32) for recent quitters (2-6 consecutive years since smoking cessation) and 1.11 (1.02-1.22) for long-term quitters (>6 consecutive years since smoking cessation). Cox models with penalised splines revealed an increased risk of all-cause mortality after smoking cessation; the highest mortality risk was observed within 2-4 years after smoking cessation and the risk gradually decreased with duration of smoking cessation. We further conducted subgroup analyses and sensitivity analyses to reduce the impact of reverse causation.

Conclusions: smoking is harmful to health in all populations. Our study findings indicated smoking cessation in late life to be associated with increased risk of all-cause mortality amongst oldest old people who have smoked for a long time.
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http://dx.doi.org/10.1093/ageing/afaa280DOI Listing
January 2021

An investigation on gastric cancer staging using CT structured report.

Eur J Radiol 2021 Mar 13;136:109550. Epub 2021 Jan 13.

Department of Radiology, Peking University First Hospital, Beijing, China. Electronic address:

Objective: To evaluate the clinical performance of structured report (SR) for CT in patients with pre-operative staging of gastric cancer, compared to non-SR.

Methods: Retrospectively, 51 consecutive cases with primary gastric cancer staging were enrolled. Every SR or non-SR was performed by two GI radiologists (1 junior and 1 senior). Interobserver agreement was conducted between the junior and senior groups for both SR and non-SR. 10 key features required for lesion description and staging were assessed between SR and non-SR. Diagnostic content between SR and non-SR was also compared. Accuracy of SR and non-SR on T staging was measured. Subjective evaluation of SR vs. non-SR was also conducted in form of survey by 20 radiologists and 3 GI surgeons.

Results: Interobserver agreement showed excellent in SR (Kappa = 1, P < 0.001), but poor in non-SR (Kappa = 0.036, P = 0.455). For the 10 key features required for lesion assessment, non-SR showed 6.84 ± 0.83 while SR reported all of them (P < 0.001). Statistically significant improvement was observed in the SR for parts of key features, especially for assessment of adjacent organs and vessels (P < 0.001). Accuracy comparison of T staging showed higher in SR for cohort of T4a (P = 0.028<0.05). The scores of subjective evaluation were higher (P < 0.05) in SR than in non-SR by both radiologists and surgeons. Meanwhile, the inter-observer agreement among surgeons was good in SR with significance (w=0.53, P = 0.005 for efficiency; w=0.638, P < 0.001 for integrity) but poor in non-SR.

Conclusions: SR of gastric multiphasic CT ensured reliable detection of all relevant key features for staging along with reproducible documentation, which was not always the case for non-SR. In addition, SR has the potential in improving diagnostical accuracy of T staging and was welcomed by clinicians.
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http://dx.doi.org/10.1016/j.ejrad.2021.109550DOI Listing
March 2021

The value of intravoxel incoherent motion and diffusion kurtosis imaging in the assessment of tumor regression grade and T stages after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

Eur J Radiol 2021 Mar 25;136:109504. Epub 2020 Dec 25.

From the Departments of Radiology, West China Hospital, Sichuan University, Guoxue Xiang No. 37, Chengdu, Sichuan, 610041, PR China. Electronic address:

Purpose: To evaluate the role of IVIM and diffusion kurtosis imaging (DKI) in identifying pathologic complete response (pCR) and T stages after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).

Method: Forty-two patients with biopsy-proven rectal adenocarcinoma, who underwent both pre-and post-CRT MRI with IVIM and DKI sequences on a 3 T scanner, were enrolled prospectively. According to the pathologic ypTNM stages and tumor regression grade (TRG), patients were grouped into pCR (TRG0) and non-pCR (TRG1-3) groups and low T stage (ypT0-2) and high T stage (ypT3-4) groups. IVIM parameters (the slow diffusion coefficient [D], fast diffusion coefficient [D*], perfusion fraction [f]), DKI parameters (mean diffusivity [MD] and mean kurtosis [MK]), and mono-exponential ADC were calculated and analyzed between groups.

Results: The pCR group had significantly higher post-CRT ADC, D*, f, and MD values than non-pCR group, and higher percent changes in the ADC, f, and MD values (all P < 0.05). The post-CRT MD values yielded the highest AUC (0.788) with higher sensitivity than post-ADC values (82.9 % vs. 77.1 %, respectively). Post-CRT ADC and MD values and the percent changes in the ADC and MD values were also negatively correlated with TRG (all P < 0.05). Besides, negative correlations were found among the pre-CRT MD, post-CRT ADC, D, f, and MD values and the ypT stages (all P < 0.05).

Conclusions: Both IVIM and DKI parameters could provide more information when evaluating pCR and T stages after nCRT. In particular, the diagnostic performance of the MD values was more valuable than ADC values in being able to determine pCR.
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http://dx.doi.org/10.1016/j.ejrad.2020.109504DOI Listing
March 2021

The TGF-β superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation.

Immunity 2021 Feb 8;54(2):308-323.e6. Epub 2021 Jan 8.

Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Th17 cells are known to exert pathogenic and non-pathogenic functions. Although the cytokine transforming growth factor β1 (TGF-β1) is instrumental for Th17 cell differentiation, it is dispensable for generation of pathogenic Th17 cells. Here, we examined the T cell-intrinsic role of Activin-A, a TGF-β superfamily member closely related to TGF-β1, in pathogenic Th17 cell differentiation. Activin-A expression was increased in individuals with relapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. Stimulation with interleukin-6 and Activin-A induced a molecular program that mirrored that of pathogenic Th17 cells and was inhibited by blocking Activin-A signaling. Genetic disruption of Activin-A and its receptor ALK4 in T cells impaired pathogenic Th17 cell differentiation in vitro and in vivo. Mechanistically, extracellular-signal-regulated kinase (ERK) phosphorylation, which was essential for pathogenic Th17 cell differentiation, was suppressed by TGF-β1-ALK5 but not Activin-A-ALK4 signaling. Thus, Activin-A drives pathogenic Th17 cell differentiation, implicating the Activin-A-ALK4-ERK axis as a therapeutic target for Th17 cell-related diseases.
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http://dx.doi.org/10.1016/j.immuni.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878438PMC
February 2021

The protective effects of trelagliptin on high-fat diet-induced nonalcoholic fatty liver disease in mice.

J Biochem Mol Toxicol 2021 Apr 9;35(4):e22696. Epub 2021 Jan 9.

Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China.

Nonalcoholic fatty liver disease (NAFLD) occurs in patients with type 2 diabetes mellitus (T2DM). Trelagliptin is an important member of the Gliptins family, which has been recently licensed for the treatment of T2DM. However, the pharmacological function of trelagliptin in NAFLD has not been previously reported. In this study, we aimed to investigate the roles of trelagliptin in the development of NAFLD in a mouse model. To induce NAFLD disease, C57BL/6 mice were fed a high-fat diet for 10 weeks. Our results indicate that trelagliptin reduced plasma lipid levels in NAFLD mice by reducing triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Treatment with trelagliptin exhibited an improvement in insulin resistance. More important, trelagliptin improved liver function by reducing alanine transaminase, aspartate transaminase, lactate dehydrogenase, and total bile acid. In addition, trelagliptin ameliorated oxidative stress in the liver of NAFLD mice by reducing malondialdehyde and increasing the levels of reduced glutathione and superoxide dismutase activity. Also, the enzyme-linked immunosorbent assay results indicate that trelagliptin-treated mice displayed anti-inflammatory properties by reducing the levels of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α. Hematoxylin and eosin and Oil red O staining show that trelagliptin treatment ameliorates liver tissue damage and hepatic lipid deposition. Mechanistically, we found that the administration of trelagliptin reduced the activity of hepatic nuclear factor-κB but increased the activity of AMP-activated protein kinase. These findings suggest that trelagliptin might become a promising therapeutic agent for the treatment of NAFLD.
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http://dx.doi.org/10.1002/jbt.22696DOI Listing
April 2021

Ameliorative effect of graphene nanosheets against arsenic-induced toxicity in mice by oral exposure.

Environ Sci Pollut Res Int 2021 Jan 7. Epub 2021 Jan 7.

Department of Environmental Science, School of Engineering, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, People's Republic of China.

Arsenic is a highly toxic environmental pollutant that is abundant in waters around the world. Previous studies have indicated that the toxicity of arsenic can be affected by co-exposure to chemicals. As a promising two-dimensional nanomaterial, graphene has received extensive attention in recent years. Owing to the wide application of graphene, its co-exposure with arsenic increases significantly. However, little information is available on the combined toxicity of graphene and arsenic. This study aimed to investigate the effects of graphene on arsenic-induced toxicity by oral exposure in mice. The results showed that the addition of graphene significantly reduced the toxicity of arsenic in the intestine and liver of mice, and the high-concentration graphene exhibited greater toxicity reduction effects. Graphene significantly decreased the bioavailability of arsenic because of its adsorption capability and spatial structure. In addition, graphene adhered to the intestinal tract may also prevent arsenic from passing through the intestinal epithelium freely. Moreover, graphene also affected arsenic toxicity through enhanced metabolism transformation by changing the gut microbiota. This study provides a comprehensive understanding of the combined toxicity of graphene and arsenic.
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http://dx.doi.org/10.1007/s11356-020-12082-3DOI Listing
January 2021

Enhancing performance of biocarriers facilitated gravity-driven membrane (GDM) reactor for decentralized wastewater treatment: Effect of internal recirculation and membrane packing density.

Sci Total Environ 2021 Mar 15;762:144104. Epub 2020 Dec 15.

Singapore Membrane Technology Centre, Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, Clean Tech One 06-08, Singapore 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. Electronic address:

This study aims to investigate the effect of internal recirculation and membrane packing density on the performance (water quality, membrane performance, and microbial community) of a biocarriers facilitated gravity-driven membrane (GDM) reactor under intermittent aeration condition. The results revealed that the presence of internal recirculation in the GDM reactors could effectively improve water quality (especially increasing nitrogen removal) and membrane performance (especially reducing cake layer resistance) compared to those without internal recirculation. In addition, compared to a high packing density membrane module (1150 m/m), a lower packing density membrane module (290 m/m) benefited to improve 15% of nitrogen removal and 44% of permeate flux due to the effective aeration scouring effect and less-limited eukaryotic activity, as well as reduce 20% of total treatment cost. In addition, the presence and absence of internal recirculation could lead to dissimilar microbial community compositions of the biofilms in the GAC layers and on the membrane surfaces. However, the membrane packing density could play an insignificant effect on the microbial community compositions of the biofilms in the GDM reactors with internal recirculation.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144104DOI Listing
March 2021

Vaccine targeting TNF epitope 1-14 do not suppress host defense against Mycobacterium bovis Bacillus Calmette-Guérin infection.

Int J Biol Macromol 2021 Feb 19;169:371-383. Epub 2020 Dec 19.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China; Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China. Electronic address:

Anti-TNF inhibitors are efficacious in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). However, more and more clinical case reports revealed that anti-TNF inhibitors could increase the risk of viral, fungal, and bacterial (especially intracellular) infection. In this study, based on Immune Epitope Database (IEDB) online B cell epitope prediction and the knowledge of TNF three dimensional (3D) structure we developed a novel vaccine (DTNF114-TNF114) that targeting TNF epitope 1-14, which produced antibodies only partially binding to trans-membrane TNF (tmTNF), therefore partially sparing tmTNF-TNFR1/2 interaction. Immunization with DTNF114-TNF114 significantly protected and prolonged the survival rate of mice challenged with lipopolysaccharide (LPS); and in the mCherry expressing Mycobacterium bovis Bacillus Calmette-Guérin (mCherry-BCG) infection model, DTNF114-TNF114 immunization significantly decreased soluble TNF (solTNF) level in serum, meanwhile did not suppress host immunity against infection. Thus, this novel and infection concern-free vaccine provides a potential alternative or supplement to currently clinically used anti-TNF inhibitors.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.131DOI Listing
February 2021