Publications by authors named "Yijun Zhu"

27 Publications

  • Page 1 of 1

IRF1 as a potential biomarker in Mycobacterium tuberculosis infection.

J Cell Mol Med 2021 Jul 2. Epub 2021 Jul 2.

Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Pulmonary tuberculosis (PTB) is a major global public health problem. The purpose of this study was to find biomarkers that can be used to diagnose tuberculosis. We used four NCBI GEO data sets to conduct analysis. Among the four data sets, GSE139825 is lung tissue microarray, and GSE83456, GSE19491 and GSE50834 are blood microarray. The differential genes of GSE139825 and GSE83456 were 68 and 226, and intersection genes were 11. Gene ontology (GO) analyses of 11 intersection genes revealed that the changes were mostly enriched in regulation of leucocyte cell-cell adhesion and regulation of T-cell activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs revealed that the host response in TB strongly involves cytokine-cytokine receptor interactions and folate biosynthesis. In order to further narrow the range of biomarkers, we used protein-protein interaction to establish a hub gene network of two data sets and a network of 11 candidate genes. Eventually, IRF1 was selected as a biomarker. As validation, IRF1 levels were shown to be up-regulated in patients with TB relative to healthy controls in data sets GSE19491 and GSE50834. Additionally, IRF1 levels were measured in the new patient samples using ELISA. IRF1 was seen to be significantly up-regulated in patients with TB compared with healthy controls with an AUC of 0.801. These results collectively indicate that IRF1 could serve as a new biomarker for the diagnosis of pulmonary tuberculosis.
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http://dx.doi.org/10.1111/jcmm.16756DOI Listing
July 2021

Index-Based Dietary Patterns and Inflammatory Bowel Disease: A Systematic Review of Observational Studies.

Adv Nutr 2021 Jun 22. Epub 2021 Jun 22.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Diet is one of the most critical factors for inflammatory bowel disease (IBD). A whole dietary pattern should be considered when doing nutrient-based research to preserve the potential for synergism between nutrients. Dietary indices are important tools to evaluate diet quality, and we investigated the associations of it with IBD. Fourteen studies on the relation between index-based dietary patterns and IBD were included. 6 studies showed the relation between index-based dietary patterns and IBD risk, 7 studies explored the dietary indices and progression of IBD, and 1 study investigated the relationship between index and all-cause mortality in IBD patients. These results implied that a high score on the Mediterranean diet was negatively associated with risk and progression of IBD. However, a diet with high inflammatory potential could increase risk and aggravate disease activity in IBD. Dietary scores have the potential to evaluate the association between overall diet quality and risk and progression of IBD. Future randomized controlled trials are required to confirm the effect of the change in dietary score. This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020220926.
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http://dx.doi.org/10.1093/advances/nmab069DOI Listing
June 2021

Cholesterol-Modified Oligonucleotides as Internal Reaction Controls during DNA-Encoded Chemical Library Synthesis.

Bioconjug Chem 2021 04 9;32(4):667-671. Epub 2021 Mar 9.

HitGen Inc., Building 6, No. 8 Huigu 1st East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu 610200, Sichuan, P. R. China.

We report two cholesterol-modified oligonucleotides for use as internal controls for on-DNA reactions during the pooled stages of a DNA-encoded chemical library (DECL) synthesis. As these cholesterol-tagged oligonucleotides are chromatographically separable from normal DECL intermediates, they can be directly monitored by mass spectrometry to track reaction progression within a complex pool of DNA. We observed similar product conversions for reactions on substrates linked to a standard DECL DNA headpiece, to the cholesterol-modified oligonucleotides, and to the cholesterol-modified oligonucleotides while in the presence of pooled DECL synthetic intermediates-validating their use as a representative control. We also highlight an example from a DECL production in which the use of the cholesterol-modified oligonucleotides provided quality control information that guided synthetic decisions. We conclude that the use of cholesterol-modified oligonucleotides as a regular control will significantly improve the quality of DECL productions.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00045DOI Listing
April 2021

Long non-coding RNAs and are associated with metabolic activity in tuberculosis lesions of sputum-negative tuberculosis patients.

Aging (Albany NY) 2021 03 3;13(6):8228-8247. Epub 2021 Mar 3.

Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Accurate diagnosis of complete inactivation of tuberculosis lesions is still a challenge with respect to sputum-negative tuberculosis. RNA-sequencing was conducted to uncover potential lncRNA indicators of metabolic activity in tuberculosis lesions. Lung tissues with high metabolic activity and low metabolic activity demonstrated by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography were collected from five sputum-negative tuberculosis patients for RNA-sequencing. Differentially-expressed mRNAs and lncRNAs were identified. Their correlations were evaluated to construct lncRNA-mRNA co-expression network, in which lncRNAs and mRNAs with high degrees were confirmed by quantitative real-time PCR using samples collected from 11 patients. Prediction efficiencies of lncRNA indicators were assessed by receiver operating characteristic curve analysis. Bioinformatics analysis was performed for potential lncRNAs. 386 mRNAs and 44 lncRNAs were identified to be differentially expressed. Differentially-expressed mRNAs in lncRNA-mRNA co-expression network were significantly associated with fibrillar collagen, platelet-derived growth factor binding, and leukocyte migration involved in inflammatory response. Seven mRNAs (, , , , , , and ) and two lncRNAs ( and ) were validated to be significantly up-regulated. The area under the curve of and was 0.750 and 0.813, respectively. Two lncRNAs and might be considered as potential indicators of metabolic activity in tuberculosis lesions for sputum-negative tuberculosis.
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http://dx.doi.org/10.18632/aging.202634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034958PMC
March 2021

Prognostic nomogram for surgery of lung cancer in HIV-infected patients.

J Thorac Dis 2021 Jan;13(1):76-81

Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University Shanghai, China.

Background: This study aimed to establish an effective prognostic nomogram for surgery of lung cancer in HIV-infected patients.

Methods: The nomogram is based on a retrospective study of 51 patients who underwent lung cancer surgery at the Shanghai Public Health Clinical Center from July 2012 to November 2019. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve analysis. Internal validity was assessed using bootstrapping validation.

Results: Predictors contained in the prognostic nomogram included age, CD4+ cell count, surgery method, and pathological stage. The model displayed good discrimination with a C-index of 0.755 (95% CI: 0.715-0.795) and good calibration. A high C-index value of 0.844 was reached after internal validation.

Conclusions: The proposed nomogram may result in more-accurate prognostic predictions for surgery of lung cancer in HIV-infected patients.
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http://dx.doi.org/10.21037/jtd-20-2268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867813PMC
January 2021

Clinical value of the detection of gene mutations in pleural effusion cell blocks among patients with non-small-cell lung cancer.

Indian J Pathol Microbiol 2021 Jan-Mar;64(1):107-110

Department of Clinical Laboratory, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.

Objective: To evaluate the clinical value of epidermal growth factor receptor (EGFR) detection in pleural effusion cell blocks among patients with non-small-cell lung cancer (NSCLC).

Methods: From July 2016 to September 2018, EGFR gene mutations in 40 lung tumor tissue samples and pleural fluid samples from NSCLC patients in Jinhua Municipal Central Hospital were assessed by the amplification refractory mutation system method. The EGFR results of the two types of samples were compared using the paired Chi-square test, and the mutation positive rates in EGFR exons 18, 19, 20 and 21 were compared between the two types of specimens using the four-grid Chi-square test.

Results: Among the 40 tissue samples and pleural effusion samples, 21 and 18 cases of EGFR mutations were detected, respectively, and the mutation positive rates were 52.5% and 45%, respectively. The κ value of the consistency test of the two specimens was 0.851. There were no significant differences in the mutation positive rates in EGFR exons 18, 19, 20, and 21 between the two types of specimens.

Conclusion: The EGFR results of pleural fluid and tissue samples were in good agreement. Therefore, we can use pleural fluid samples to detect EGFR mutations to guide tyrosine kinase inhibitor treatment for NSCLC patients in whom tumor tissue samples cannot be obtained.
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http://dx.doi.org/10.4103/IJPM.IJPM_360_20DOI Listing
July 2021

Tri-layer gradient and polarization-selective vertical couplers for interlayer transition.

Opt Express 2020 Jul;28(15):23048-23059

We demonstrate and optimize a tri-layer vertical coupler for a silicon nitride (SiN) multilayer platform operating at a 2 µm band. The large spacing between the topmost and bottommost layers of a gradient structure enables ultra-low crossing loss and interlayer crosstalk without affecting the efficiency interlayer transition. We achieve a 0.31 dB transition loss, ultra-low multi-layer crosstalk of -59.3 dB at a crossing angle of 90° with an interlayer gap of 2300 nm at 1950nm. With width optimization of this structure, the fabrication tolerances toward lateral misalignment of two stages in this coupler have increased 61% and 56%, respectively. We also propose a vertical coupler, based on this design, with mode selectivity and achieve an extinction ratio of < 15 dB for wavelengths in the 1910-1990 range. Meanwhile, a multi-layer interlaced AWGs centered at 1950nm and based on vertical coupler has been demonstrated. The proposed vertical couplers exhibit potential for application in large-scale photonic-integrated circuits and broadly in photonic devices.
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http://dx.doi.org/10.1364/OE.397543DOI Listing
July 2020

Lung cancer surgery in HIV-infected patients: An analysis of postoperative complications and long-term survival.

Thorac Cancer 2020 08 5;11(8):2146-2154. Epub 2020 Jul 5.

Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Shanghai, China.

Background: The purpose of this study was to investigate the risk factors of postoperative complications and reliable prognostic factors of long-term survival in HIV-infected patients with non-small cell lung cancer (NSCLC).

Methods: HIV-infected patients with NSCLC who underwent surgical treatment were retrospectively studied; a single-institutional analysis was conducted from November 2011 to August 2018. Pre- and postoperative clinical data, including age, gender, smoking history, highly active antiretroviral therapy (HAART), CD4+ T cell count, HIV viral load, cancer histology, clinical and pathological stage (p-stage), surgical result, Glasgow Prognostic Score (GPS), the Charlson comorbidity index (CCI), survival time and postoperative complications were collected.

Results: A total of 33 HIV-infected patients with NSCLC were enrolled of which 18 (54.7%) had preoperative comorbidities and postoperative complications were observed in 22 (66.7%) patients. Thirty-day mortality was not observed in these patients. Median survival time after surgery was 65 months: the MST of p-stage I patients was 65 months; p-stage II MST was unestimable; p-stage III MST was 21 months. Univariate analyses showed that postoperative complications were associated with HIV viral load (P = 0.002), CCI (P = 0.027), HAART (P = 0.028) and CD4+ T cell count (P = 0.045). However, multiple logistic regression analysis showed no correlation between HAART and postoperative complications. The p-stage was an independent prognostic factor for survival time.

Conclusions: In our single-arm retrospective analysis, the risk factors for postoperative complications in HIV-infected patients with NSCLC were HIV viral load, CCI and CD4+ T cell counts. The p-stage was a predictive factor for long-term survival.
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http://dx.doi.org/10.1111/1759-7714.13519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396368PMC
August 2020

Ultrasound measurement of laryngeal structures in the parasagittal plane for the prediction of difficult laryngoscopies in Chinese adults.

BMC Anesthesiol 2020 06 2;20(1):134. Epub 2020 Jun 2.

Department of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine& Health Sciences, 1 Chengbei Road, Shanghai, 201800, P.R. China.

Background: Abnormal laryngeal structures are likely to be associated with a difficult laryngoscopy procedure. Currently, laryngeal structures can be measured by ultrasonography, however, little research has been performed on the potential role of ultrasound on the evaluation of a difficult laryngoscopy. The present study investigated the value of laryngeal structure measurements for predicting a difficult laryngoscopy.

Objective: The main objective of this study was to explore the value of laryngeal structure measurements for predicting a difficult laryngoscopy.

Methods: Two hundred and eleven adult patients (over 18 years old) were recruited to undergo elective surgery under general anesthesia via endotracheal intubation. Ultrasound was utilized to measure the distance between the skin and thyroid cartilage (DST), the distance between the thyroid cartilage and epiglottis (DTE), and the distance between the skin and epiglottis (DSE) in the parasagittal plane. These metrics were then investigated as predictors for classifying a laryngoscopy as difficult vs easy, as defined by the Cormack and Lehane grading scale.

Results: Multivariate logistic regression showed that the DSE, but not DST or DTE, was significantly related to difficult laryngoscopies. Specifically, a DSE ≥ 2.36 cm predicted difficult laryngoscopies with a sensitivity and specificity of 0.818 (95% CI: 0.766-0.870) and 0.856 (95% CI: 0.809-0.904). Furthermore, when combining the best model constructed of other indicators (i.e. sex, body mass index, modified Mallampati test) to predict the difficult laryngoscopy, the AUC reached 93.28%.

Conclusion: DSE is an independent predictor of a difficult laryngoscopy; a DSE cutoff value of 2.36 cm is a better predictor of a difficult laryngoscope than other ultrasound or physiological measurements for predicting a difficult laryngoscope. Nevertheless, it's more valuable to apply the best model of this study, composed of various physiological measurements, for this prediction purpose.
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http://dx.doi.org/10.1186/s12871-020-01053-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265219PMC
June 2020

The role of cytokine and immune responses in intestinal fibrosis.

J Dig Dis 2020 Jun 23;21(6):308-314. Epub 2020 Jun 23.

School of Laboratory Medicine, Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China.

The rapidly increasing incidence of inflammatory bowel disease (IBD) in South America, eastern Europe, Asia, and Africa has resulted in a global public health challenge. Intestinal fibrosis is a common complication in patients with long-term IBD, which may develop into stenosis and subsequent obstruction. Hitherto, the origin of IBD is unclear and several factors may be involved, including genetic, immune, environmental and microbial influences. Little is known about how the recurrent inflammation in patients with IBD develops into intestinal fibrosis and currently, there is no suitable treatment to reverse intestinal fibrosis in these patients. Here, we review the role of immune components in the pathogenesis of IBD and intestinal fibrosis, including cytokine networks, host-microbiome interactions, and immune cell trafficking.
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http://dx.doi.org/10.1111/1751-2980.12879DOI Listing
June 2020

Highly Robust Non-Noble Alkaline Hydrogen-Evolving Electrocatalyst from Se-Doped Molybdenum Disulfide Particles on Interwoven CoSe Nanowire Arrays.

Small 2020 Apr 4;16(13):e1906629. Epub 2020 Mar 4.

Synergetic Innovation Center for Quantum Effects and Applications, Key Laboratory of Low-Dimensional Quantum Structures and Quantum Control of Ministry of Education, School of Physics and Electronics, Hunan Normal University, Changsha, 410081, Hunan, China.

Developing efficient non-noble and earth-abundant hydrogen-evolving electrocatalysts is highly desirable for improving the energy efficiency of water splitting in base. Molybdenum disulfide (MoS ) is a promising candidate, but its catalytic activity is kinetically retarded in alkaline media due to the unfavorable water adsorption and dissociation feature. A heterogeneous electrocatalyst is reported that is constructed by selenium-doped MoS (Se-MoS ) particles on 3D interwoven cobalt diselenide (CoSe ) nanowire arrays that drives the hydrogen evolution reaction (HER) with fast reaction kinetics in base. The resultant Se-MoS /CoSe hybrid exhibits an outstanding catalytic HER performance with extremely low overpotentials of 30 and 93 mV at 10 and 100 mA cm in base, respectively, which outperforms most of the inexpensive alkaline HER catalysts, and is among the best alkaline catalytic activity reported so far. Moreover, this hybrid catalyst shows exceptional catalytic performance with very low overpotentials of 84 and 95 mV at 10 mA cm in acidic and neutral electrolytes, respectively, implying robust pH universality of this hybrid catalyst. This work may provide new inspirations for the development of high-performance MoS -based HER electrocatalysts in unfavorable basic media for promising catalytic applications.
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http://dx.doi.org/10.1002/smll.201906629DOI Listing
April 2020

Validating the surgical indication value of the LTB-S classification system for drug resistant tuberculosis.

Int J Infect Dis 2020 Jun 20;95:67-73. Epub 2020 Feb 20.

Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Fudan University, Shanghai, China. Electronic address:

Background: Currently there is no guideline based on preoperative clinical parameters for assessing the prognosis of the adjunctive surgery for drug-resistant tuberculosis.

Methods: We retrospectively analyzed 138 patients who had undergone surgical resection as a treatment for drug- resistant tuberculosis after 24 months. Four clinical parameters on lesion type, treatment history, body physiological status, and surgery approach were evaluated. Categorical preoperative clinical parameters were analyzed by ordinal logistic regression model when considering postoperative complications as outcomes ordered in terms of severity. Statistically significant parameters were then combined in a single classification system for predicting the outcomes of the adjunctive surgery.

Findings: Diffused, progressive bilateral lesions, or active/progressive extra pulmonary tuberculosis (L3), and history of less than 2 months treatment before surgery (T3) were the strongest predicative parameters for postoperative complications and for surgery failure. Classification systems based on the four parameters were found to have a statistically significant effect on postoperative complications and postoperative efficacy. 24- month follow up indicated a high cure rate (above 95.5%) among patients without T3, L3, or severe physiological complications (B3).

Interpretation: A classification system based on objective clinical parameters showed predicative value for the prognosis of the adjunctive surgery and could guide management of drug-resistant Tuberculosis.
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http://dx.doi.org/10.1016/j.ijid.2020.02.030DOI Listing
June 2020

Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340.

Drug Des Devel Ther 2019 3;13:3465-3475. Epub 2019 Oct 3.

Department of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai 201800, People's Republic of China.

Background: Dexmedetomidine (Dex) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which Dex exhibits anti-inflammation effects on LPS-stimulated BV2 microglia cells remains unclear. Thus, this study aimed to investigate the role of Dex in LPS-stimulated BV2 cells.

Methods: The BV2 cells were stimulated by lipopolysaccharides (LPS). BV2 cells were infected with short-hairpin RNAs targeting NF-κB (NF-κB-shRNAs) and NF-κB overexpression lentivirus, respectively. In addition, miR-340 mimics or miR-340 inhibitor was transfected into BV2 cells, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of miR-340 and NF-κB in BV2 cells. CCK-8 was used to detect the viability of BV2 cells. In addition, Western blotting was used to detect the level of NF-κB in LPS-stimulated BV2 cells. The levels of TNF-α, IL-6, IL-1β, IL-2, IL-12, IL-10 and MCP-1 in LPS-stimulated BV2 cells were measured with ELISA.

Results: The level of miR-340 was significantly upregulated in Dex-treated BV2 cells. Meanwhile, the level of NF-κB was significantly increased in BV2 cells following infection with lenti-NF-κB, which was markedly reversed by Dex. LPS markedly increased the expression of NF-κB and proinflammatory cytokines in BV2 cells, which were reversed in the presence of Dex. Moreover, miR-340 mimics enhanced the anti-inflammatory effects of Dex in LPS-stimulated BV2 cells via inhibiting NF-κB and proinflammatory cytokines. Furthermore, Dex obviously inhibited LPS-induced phagocytosis in BV2 cells.

Conclusion: Taken together, our results suggested that Dex might exert anti-inflammatory effects in LPS-stimulated BV2 cells via upregulation of miR-340. Therefore, Dex might serve as a potential agent for the treatment of neuroinflammation.
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http://dx.doi.org/10.2147/DDDT.S210511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781164PMC
April 2020

[Data analysis of non-invasive prenatal testing based on special loci in cell-free fetal DNA].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2018 Feb;35(1):56-59

Cyagen Health Research Center (Taicang) Co., Ltd., Suzhou, Jiangsu 215000, China. Email:

OBJECTIVE To analyze the data of non-invasive prenatal testing based on specific loci of circulating cell-free fetal DNA (cffDNA). METHODS Selected loci of target chromosomes were analyzed by sequence capture and sequencing. Meanwhile, 600 loci were selected from other chromosomes for determining the concentration of cffDNA. RESULTS A total of 768 specific loci were captured on chromosomes 21 and 18, and used to determine whether the two were abnormal. When the minimum concentration of detected cffDNA was set at 3% and the threshold of Z score was set to [-6,6], the specificity of the analysis was 99.37% and the sensitivity was 100%. CONCLUSION A reliable, convenient and low-cost analytical method has been developed. The method requires less sequencing data for non-invasive prenatal testing, and can accurately detect abnormalities of fetal chromosomes 21 and 18, and simultaneously determine the concentration of cffDNA.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2018.01.012DOI Listing
February 2018

Pulmonary resection in the treatment of multidrug-resistant tuberculosis: A case series.

Medicine (Baltimore) 2017 Dec;96(50):e9109

Department of Thoracic Surgery, Shanghai Public Health Clinical Center Department of Tuberculosis, The Eighty-Fifth Hospital of PLA Scientific Research, Shanghai Public Health Clinical Center Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Shanghai Department of Surgery, Suzhou Fifth People's Hospital, Suzhou Department of Surgery, Anhui Chest Hospital (Henan), Zhengzhou Department of Surgery, Anhui Chest Hospital (Anhui), Hefei, China.

Multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis (TB) are significant health problems throughout the world. Although the main treatment is medical, adjunctive surgical resection may increase the chance of cure in selected patients with MDR-TB or XDR-TB. This study aimed to present a case series of patients who underwent surgical resection for MDR-TB.Between March 2008 and November 2011, surgical resection was performed on 54 patients including 34 with MDR-TB and 20 with XDR-TB at the Departments of Surgery of Shanghai Public Health Clinical Center (Shanghai), Henan Chest Hospital (Henan), and Anhui Chest Hospital (Henan). Preoperative sputum smear samples were positive for 28 patients and sputum quantitative polymerase chain reaction was positive for 32. Patients were treated according to a standard therapy protocol for a mean of 4.2 months before the operation. The variables that affected treatment outcomes were identified through multivariate regression analysis.Fifty-four patients were operated for MDR-TB with localized disease usually complicated by cavity formation or destroyed lung. Thirty-seven were males and 17 were females. Median age was 37.8 (range, 20-75) years. Lobectomy was performed in 46 patients and pneumonectomy in 8. Muscle flaps were used in 36 of the patients with lobectomy and 8 with pneumonectomy. Various complications occurred in 6 (11.1%) patients, including bronchopleural fistula in 1 patient, bleeding in 2 patients, and prolonged air leak in 2 patients. A favorable outcome was achieved in 47 patients (87%) who underwent surgical resection. Higher body mass index (BMI) was associated with better outcome (odds ratio = 0.537, 95% confidence interval: 0.310-0.928, P = .026).Patients with MDR-TB had good treatment outcomes after adjunctive pulmonary resection, and with few complications. Higher BMI was related to a favorable outcome.
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http://dx.doi.org/10.1097/MD.0000000000009109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815719PMC
December 2017

Convex relaxation for illumination control of multi-color multiple-input-multiple-output visible light communications with linear minimum mean square error detection.

Appl Opt 2017 Aug;56(23):6587-6595

Visible light communications (VLC) using multi-color light-emitting diodes (LEDs) can support simultaneous high-speed data rate and high-quality lighting. However, since the radiation spectrum of LEDs has a limited width, spectral overlapping will result in multi-color cross talk even when optical filters are applied at the receivers. Moreover, since LEDs are used for illumination and wireless data transmission in the meantime, both lighting quality and communication performance must be considered in VLC systems. In this paper, we consider a multiple-input-multiple-output with low-complexity linear minimum mean square error detection to collaboratively manage the cross talk by maximizing the minimum signal-to-interference-plus-noise ratio (SINR) subject to chromaticity constraint based on MacAdam ellipse, luminance constraint, and signal range constraint. A sub-optimal convex relaxation is proposed to attack the SINR maximization problem. Extensive simulations indicate that the proposed method provides very efficient solutions and outperforms the conventional wave-division multiplexing scheme under the illumination constraint.
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http://dx.doi.org/10.1364/AO.56.006587DOI Listing
August 2017

Investigation of Respiratory Syncytial Virus Outbreak on an Adult Stem Cell Transplant Unit by Use of Whole-Genome Sequencing.

J Clin Microbiol 2017 10 26;55(10):2956-2963. Epub 2017 Jul 26.

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

A viral whole-genome sequencing (WGS) strategy, based on PCR amplification followed by next-generation sequencing, was used to investigate a nosocomial respiratory syncytial virus-B (RSV-B) outbreak in a hematology-oncology and stem cell transplant unit. RSV-B genomes from 16 patients and health care workers (HCWs) suspected to be involved in the outbreak were compared to RSV-B genomes that were acquired from outpatients during the same time period but epidemiologically unrelated to the outbreak. Phylogenetic analysis of the whole genome identified a cluster of 11 patients and HCWs who had an identical RSV-B strain which was clearly distinct from strains recovered from individuals unrelated to the outbreak. Sequence variation of the glycoprotein (G) gene alone was insufficient to distinguish the outbreak strains from the outbreak-unrelated strains, thereby demonstrating that WGS is valuable for local outbreak investigation.
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http://dx.doi.org/10.1128/JCM.00360-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625381PMC
October 2017

O -independent demethylation of trimethylamine N-oxide by Tdm of Methylocella silvestris.

FEBS J 2016 11 20;283(21):3979-3993. Epub 2016 Oct 20.

School of Life Sciences, University of Warwick, Coventry, UK.

Bacterial trimethylamine N-oxide (TMAO) demethylase, Tdm, carries out an unusual oxygen-independent demethylation reaction, resulting in the formation of dimethylamine and formaldehyde. In this study, site-directed mutagenesis, homology modelling and metal analyses by inorganic mass spectrometry have been applied to gain insight into metal stoichiometry and underlying catalytic mechanism of Tdm of Methylocella silvestris BL2. Herein, we demonstrate that active Tdm has 1 molar equivalent of Zn and 1 molar equivalent of non-haem Fe . We further investigated Zn - and Fe -binding sites through homology modelling and site-directed mutagenesis and found that Zn is coordinated by a 3-sulfur-1-O motif. An aspartate residue (D198) likely bridges Fe and Zn centres, either directly or indirectly via H-bonding through a neighbouring H O molecule. H276 contributes to Fe binding, mutation of which results in an inactive enzyme, and the loss of iron, but not zinc. Site-directed mutagenesis of Tdm also led to the identification of three hydrophobic aromatic residues likely involved in substrate coordination (F259, Y305, W321), potentially through a cation-π interaction. Furthermore, a crossover experiment using a substrate analogue gave direct evidence that a trimethylamine-alike intermediate was produced during the Tdm catalytic cycle, suggesting TMAO has a dual role of being both a substrate and an oxygen donor for formaldehyde formation. Together, our results provide novel insight into the role of Zn and Fe in the catalysis of TMAO demethylation by this unique oxygen-independent enzyme.
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http://dx.doi.org/10.1111/febs.13902DOI Listing
November 2016

An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

PLoS One 2016 21;11(7):e0159648. Epub 2016 Jul 21.

Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159648PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956272PMC
July 2017

A mechanism for bacterial transformation of dimethylsulfide to dimethylsulfoxide: a missing link in the marine organic sulfur cycle.

Environ Microbiol 2016 09 27;18(8):2754-66. Epub 2016 Jun 27.

School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry, CV4 7AL, UK.

The volatile organosulfur compound, dimethylsulfide (DMS), plays an important role in climate regulation and global sulfur biogeochemical cycles. Microbial oxidation of DMS to dimethylsulfoxide (DMSO) represents a major sink of DMS in surface seawater, yet the underlying molecular mechanisms and key microbial taxa involved are not known. Here, we reveal that Ruegeria pomeroyi, a model marine heterotrophic bacterium, can oxidize DMS to DMSO using trimethylamine monooxygenase (Tmm). Purified Tmm oxidizes DMS to DMSO at a 1:1 ratio. Mutagenesis of the tmm gene in R. pomeroyi completely abolished DMS oxidation and subsequent DMSO formation. Expression of Tmm and DMS oxidation in R. pomeroyi is methylamine-dependent and regulated at the post-transcriptional level. Considering that Tmm is present in approximately 20% of bacterial cells inhabiting marine surface waters, particularly the marine Roseobacter clade and the SAR11 clade, our observations contribute to a mechanistic understanding of biological DMSO production in surface seawater.
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http://dx.doi.org/10.1111/1462-2920.13354DOI Listing
September 2016

A novel and practical asymmetric synthesis of dapoxetine hydrochloride.

Beilstein J Org Chem 2015 17;11:2641-5. Epub 2015 Dec 17.

State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, State Institute of Pharmaceutical Industry, No. 285, Gebaini Rd., Shanghai 201203, China.

A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent.
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http://dx.doi.org/10.3762/bjoc.11.283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685759PMC
January 2016

Identification and characterization of trimethylamine N-oxide (TMAO) demethylase and TMAO permease in Methylocella silvestris BL2.

Environ Microbiol 2014 Oct 17;16(10):3318-30. Epub 2014 Sep 17.

School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.

Methylocella silvestris, an alphaproteobacterium isolated from a forest soil, can grow on trimethylamine N-oxide (TMAO) as a sole nitrogen source; however, the molecular and biochemical mechanisms underpinning its growth remain unknown. Marker-exchange mutagenesis enabled the identification of several genes involved in TMAO metabolism, including Msil_3606, a permease of the amino acids-polyamine (APC) superfamily, and Msil_3603, consisting of an N-terminal domain of unknown function (DUF1989) and a C-terminal tetrahydrofolate-binding domain. Null mutants of Msil_3603 and Msil_3606 can no longer grow on TMAO. Purified Msil_3603 from recombinant Escherichia coli can convert TMAO to dimethylamine and formaldehyde (1 TMAO → 1 dimethylamine + 1 formaldehyde), confirming that it encodes a bona fide TMAO demethylase (Tdm). Tdm of M. silvestris and eukaryotic Tdms have no sequence homology and contrasting characteristics. Recombinant Tdm of M. silvestris appears to be hexameric, has a high affinity for TMAO (Km = 3.3 mM; Vmax = 21.7 nmol min(-1)  mg(-1) ) and only catalyses demethylation of TMAO and a structural homologue, dimethyldodecylamine N-oxide. Our study has contributed to the understanding of the genetic and biochemical mechanisms for TMAO degradation in M. silvestris.
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http://dx.doi.org/10.1111/1462-2920.12585DOI Listing
October 2014

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota.

Proc Natl Acad Sci U S A 2014 Mar 3;111(11):4268-73. Epub 2014 Mar 3.

School of Life Sciences and Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.

Dietary intake of L-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual "bridging" glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual "bridging glutamate" residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism.
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http://dx.doi.org/10.1073/pnas.1316569111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964110PMC
March 2014

Sustained activation of PPARα by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice.

FASEB J 2012 Feb 18;26(2):628-38. Epub 2011 Oct 18.

Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Obesity, a major health concern, results from an imbalance between energy intake and expenditure. Leptin-deficient ob/ob mice are paradigmatic of obesity, resulting from excess energy intake and storage. Mice lacking acyl-CoA oxidase 1 (Acox1), the first enzyme of the peroxisomal fatty acid β-oxidation system, are characterized by increased energy expenditure and a lean body phenotype caused by sustained activation of peroxisome proliferator-activated receptor α (PPARα) by endogenous ligands in liver that remain unmetabolized in the absence of Acox1. We generated ob/ob mice deficient in Acox1 (Acox1(-/-)) to determine how the activation of PPARα by endogenous ligands might affect the obesity of ob/ob mice. In contrast to Acox1(-/-) (14.3±1.2 g at 6 mo) and the Acox1-deficient (ob/ob) double-mutant mice (23.8±4.6 g at 6 mo), the ob/ob mice are severely obese (54.3±3.2 g at 6 mo) and had significantly more (P<0.01) epididymal fat content. The resistance of Acox1(-/-)/ob/ob mice to obesity is due to increased PPARα-mediated up-regulation of genes involved in fatty acid oxidation in liver. Activation of PPARα in Acox1-deficient ob/ob mice also reduces serum glucose and insulin (P<0.05) and improves glucose tolerance and insulin sensitivity. Further, PPARα activation reduces hepatic steatosis and increases hepatocellular regenerative response in Acox1(-/-)/ob/ob mice at a more accelerated pace than in mice lacking only Acox1. However, Acox1(-/-)/ob/ob mice manifest hepatic endoplasmic reticulum (ER) stress and also develop hepatocellular carcinomas (8 of 8 mice) similar to those observed in Acox1(-/-) mice (10 of 10 mice), but unlike in ob/ob (0 of 14 mice) and OB/OB (0 of 6 mice) mice, suggesting that superimposed ER stress and PPARα activation contribute to carcinogenesis in a fatty liver. Finally, absence of Acox1 in ob/ob mice can impart resistance to high-fat diet (60% fat)-induced obesity, and their liver had significantly (P<0.01) more cell proliferation. These studies with Acox1(-/-)/ob/ob mice indicate that sustained activation of lipid-sensing nuclear receptor PPARα attenuates obesity and restores glucose homeostasis by ameliorating insulin resistance but increases the risk for liver cancer development, in part related to excess energy combustion.
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http://dx.doi.org/10.1096/fj.11-194019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290446PMC
February 2012

Influence of fertilisation regimes on a nosZ-containing denitrifying community in a rice paddy soil.

J Sci Food Agric 2012 Mar 27;92(5):1064-72. Epub 2011 Jul 27.

Key Laboratory of Agro-ecological Processes in Subtropical Regions and Taoyuan Station of Agro-ecology Research, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Mapoling, ChangSha, China.

Background: Denitrification is a microbial process that has received considerable attention during the past decade since it can result in losses of added nitrogen fertilisers from agricultural soils. Paddy soil has been known to have strong denitrifying activity, but the denitrifying microorganisms responsible for fertilisers in paddy soil are not well known. The objective of this study was to explore the impacts of 17-year application of inorganic and organic fertiliser (rice straw) on the abundance and composition of a nosZ-denitrifier community in paddy soil. Soil samples were collected from CK plots (no fertiliser), N (nitrogen fertiliser), NPK (nitrogen, phosphorus and potassium fertilisers) and NPK + OM (NPK plus organic matter). The nitrous oxide reductase gene (nosZ) community composition was analysed using terminal restriction fragment length polymorphism, and the abundance was determined by quantitative PCR.

Results: Both the largest abundance of nosZ-denitrifier and the highest potential denitrifying activity (PDA) occurred in the NPK + OM treatment with about four times higher than that in the CK and two times higher than that in the N and NPK treatments (no significant difference). Denitrifying community composition differed significantly among fertilisation treatments except for the comparison between CK and N treatments. Of the measured abiotic factors, total organic carbon was significantly correlated with the observed differences in community composition and abundance (P < 0.01 by Monte Carlo permutation).

Conclusion: This study shows that the addition of different fertilisers affects the size and composition of the nosZ-denitrifier community in paddy soil.
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http://dx.doi.org/10.1002/jsfa.4533DOI Listing
March 2012

Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation.

J Biol Chem 2002 May 23;277(22):20011-9. Epub 2002 Mar 23.

Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008, USA.

PIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function. We now report that PIMT strongly interacts with transcriptional coactivators, CBP, p300, and PBP but not with SRC-1 and PGC-1alpha under in vitro and in vivo conditions. The PIMT binding sites on CBP and p300 are located in the cysteine-histidine-rich C/H1 and C/H3 domains, and the PIMT binding site on PBP is in the region encompassing amino acids 1101-1560. The N-terminal of PIMT (residues 1-369) containing the RNA binding domain interacts with both C/H1 and C/H3 domains of CBP and p300 and with the C-terminal portion of PBP that encompasses amino acids 1371-1560. The C-terminal of PIMT (residues 611-852), which binds S-adenosyl-l-methionine, interacts respectively with the C/H3 domain of CBP/p300 and with a region encompassing amino acids 1101-1370 of PBP. Immunoprecipitation data showed that PIMT forms a complex in vivo with CBP, p300, PBP, and PRIP. PIMT appeared to be co-localized in the nucleus with CBP, p300, and PBP. PIMT enhanced PBP-mediated transcriptional activity of the PPARgamma, as it did for PRIP, indicating synergism between PIMT and PBP. In contrast, PIMT functioned as a repressor of CBP/p300-mediated transactivation of PPARgamma. Based on these observations, we suggest that PIMT bridges the CBP/p300-anchored coactivator complex with the PBP-anchored coactivator complex but differentially modulates coactivator function such that inhibition of the CBP/p300 effect may be designed to enhance the activity of PBP and PRIP.
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http://dx.doi.org/10.1074/jbc.M201739200DOI Listing
May 2002

Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors.

J Biol Chem 2002 Feb 27;277(5):3585-92. Epub 2001 Nov 27.

Department of Pathology, Northwestern University School of Medicine, Chicago, Illinois 60611-3008, USA.

Peroxisome proliferator activator receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARgamma and other nuclear receptors. It has been identified as an integral component of a multiprotein thyroid hormone receptor-associated protein/vitamin D(3) receptor-interacting protein/activator-recruited cofactor complexes required for transcriptional activity. Here, we show that PBP is critical for the development of placenta and for the normal embryonic development of the heart, eye, vascular, and hematopoietic systems. The primary functional cause of embryonic lethality at embryonic day11.5 observed with PBP null mutation was cardiac failure because of noncompaction of the ventricular myocardium and resultant ventricular dilatation. There was a paucity of retinal pigment, defective lens formation, excessive systemic angiogenesis, a deficiency in the number of megakaryocytes, and an arrest in erythrocytic differentiation. Some of these defects involve PPARgamma and retinoid-sensitive sites, whereas others have not been recognized in the PPAR-signaling pathway. Phenotypic changes in four organ systems observed in PBP null mice overlapped with those in mice deficient in members of GATA, a family of transcription factors known to regulate differentiation of megakaryocytes, erythrocytes, and adipocytes. We demonstrate that PBP interacts with all five GATA factors analyzed, GATA-1, GATA-2, GATA-3, GATA-4, and GATA-6, and show that the binding of GATA-1, GATA-4, and GATA-6 to PBP is not dependent on the nuclear receptor recognition sequence motif LXXLL (where L is leucine and X is any amino acid) in PBP. Coexpression of PBP with GATA-3 markedly enhanced transcriptional activity of GATA-3 in nonhematopoietic cells. These observations identify the GATA family of transcription factors as a new interacting partner of PBP and demonstrate that PBP is essential for normal development of vital organ systems.
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http://dx.doi.org/10.1074/jbc.M107995200DOI Listing
February 2002
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