Publications by authors named "Yu Pang"

261 Publications

Mycobacterium tuberculosis protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity.

EMBO Rep 2021 May 2:e52175. Epub 2021 May 2.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing, China.

Upon Mycobacterium tuberculosis (Mtb) infection, protein kinase G (PknG), a eukaryotic-type serine-threonine protein kinase (STPK), is secreted into host macrophages to promote intracellular survival of the pathogen. However, the mechanisms underlying this PknG-host interaction remain unclear. Here, we demonstrate that PknG serves both as a ubiquitin-activating enzyme (E1) and a ubiquitin ligase (E3) to trigger the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-β-activated kinase 1 (TAK1), thereby inhibiting the activation of NF-κB signaling and host innate responses. PknG promotes the attachment of ubiquitin (Ub) to the ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), rather than the usual C86-Ub thiol-ester bond. PknG induces the discharge of Ub from UbcH7 by acting as an isopeptidase, before attaching Ub to its substrates. These results demonstrate that PknG acts as an unusual ubiquitinating enzyme to remove key components of the innate immunity system, thus providing a potential target for tuberculosis treatment.
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http://dx.doi.org/10.15252/embr.202052175DOI Listing
May 2021

Comparative in vitro susceptibility of a novel fluoroquinolone antibiotic candidate WFQ-228, levofloxacin, and moxifloxacin against Mycobacterium tuberculosis.

Int J Infect Dis 2021 Apr 20;106:295-299. Epub 2021 Apr 20.

Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, PR China. Electronic address:

Objective: WFQ-228 is a novel developed fluoroquinolone (FQ) displaying potent antimicrobial activity against various clinical isolates of pathogens, including FQ-resistant isolates. The aim was to comparatively analyze in vitro susceptibilities of WFQ-228, levofloxacin (LFX), and moxifloxacin (MFX) against Mycobacterium tuberculosis (MTB) isolates, especially with gyrA mutations.

Methods: We selected a panel of 75 MTB isolates, consisting of 25 FQ-susceptible and 50 FQ-resistant isolates determined by conventional drug susceptibility testing. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of FQs to MTB isolates were assessed.

Results: MFX exhibited the most potent activity against FQ-susceptible MTB, demonstrating a MIC of 0.031 mg/L, which was lower than that of LFX and WFQ-228. Against FQ-resistant MTB isolates, the MIC of WFQ-228 was higher than that of MFX but lower than that of LFX. For WFQ-228, there was a significant overlap existing in the MIC distributions between the probable susceptible (PS) and probable resistant (PR) groups. Six out of 50 PR isolates were classified as susceptible based on a proposed critical concentration (CC) of 0.5 mg/L, yielding a poor sensitivity of 88.0%. These discordant isolates had GyrA substitution in Ala90Val, Ser91Pro, and Asp94Tyr. Additionally, MFX exhibited bactericidal activity against MTB isolates without gyrA mutations, which was significantly higher than that of isolates with gyrA mutations.

Conclusion: WFQ-228 is more efficacious than LFX in isolates with specific mutations conferring low-level FQ resistance. The bactericidal effect is noted more frequently in FQ-susceptible isolates than FQ-resistant isolates for MFX.
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http://dx.doi.org/10.1016/j.ijid.2021.04.036DOI Listing
April 2021

Urinary metabolomic analysis to identify potential markers for the diagnosis of tuberculosis and latent tuberculosis.

Arch Biochem Biophys 2021 Jun 14;704:108876. Epub 2021 Apr 14.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Electronic address:

Tuberculosis (TB) is a serious infectious disease with high infection and mortality rates. 5%-10% of the latent tuberculosis infections (LTBI) are likely to develop into active TB, and there are currently no clinical biomarkers that can distinguish between LTBI, active TB and other non-tuberculosis populations. Therefore, it is necessary to develop rapid diagnostic methods for active TB and LTBI. In this study, urinary metabolome of 30 active TB samples and the same number of LTBI and non-TB control samples were identified and analyzed by UPLC-Q Exactive MS. In total, 3744 metabolite components were obtained in ESI- mode and 4086 in ESI + mode. Orthogonal partial least square discriminant analysis (OPLS-DA) and hierarchical cluster analysis (HCA) showed that there were significant differences among LTBI, active TB and non-TB. Six differential metabolites were screened in positive and negative mode, 3-hexenoic acid, glutathione (GSH), glycochenodeoxycholate-3-sulfate, N-[4'-hydroxy-(E)-cinnamoyl]-l-aspartic acid, deoxyribose 5-phosphate and histamine. The overlapping pathways differential metabolites involved were mainly related to immune regulation and urea cycle. The results showed that the urine metabolism of TB patients was disordered and many metabolic pathways changed. Multivariate statistical analysis revealed that GSH and histamine were selected as potential molecular markers, with area under curve of receiver operating characteristic curve over 0.75. Among the multiple differential metabolites, GSH and histamine changed to varying degrees in active TB, LTBI and the non-TB control group. The levels of GSH and histamine in 48 urinary samples were measured by ELISA in validation phase, and the result in our study provided the potential for non-invasive biomarkers of TB.
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http://dx.doi.org/10.1016/j.abb.2021.108876DOI Listing
June 2021

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Electrophysiology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ‑CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ‑CCT3 in specimens and cell lines were evaluated by reverse transcription‑quantitative PCR and the relationship between circ‑CCT3 and prognosis was analyzed by Kaplan‑Meier curves. The oncogenic role of circ‑CCT3 was confirmed in HCC cells through a cell counting kit‑8 (CCK‑8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound‑healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ‑CCT3 facilitated HCC progression through the miR‑1287‑5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ‑CCT3, which may be used as a potential therapeutic target for HCC.
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http://dx.doi.org/10.3892/mmr.2021.12014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986040PMC
May 2021

Linking the unique molecular complexity of dissolved organic matter to flood period in the Yangtze River mainstream.

Sci Total Environ 2021 Apr 8;764:142803. Epub 2020 Oct 8.

Key Laboratory of Geoscience Big Data and Deep Resource of Zhejiang Province, School of Earth Sciences, Zhejiang University, Hangzhou, China; State Key Laboratory of Satellite Ocean Environment Dynamics, Second Institute of Oceanography, Ministry of Natural Resources, Hangzhou, China. Electronic address:

Large rivers transport a significant amount of terrestrially derived dissolved organic matter (DOM) to coastal oceans, consisting of a critical component of the global biogeochemical cycle. Although high flow events usually introduce more terrestrial DOM than baseflow, the underlying molecular complexity and lability of DOM during high discharge are not well constrained, especially in large river ecosystems. By combining ultraviolet and fluorescent spectroscopy, and ultrahigh-resolution mass spectrometry, we found that stronger terrestrial DOM signal was detected during high discharge than normal discharge in the Yangtze River mainstream. The averaged DOC concentration was higher during high discharge than normal discharge. Optical properties confirmed higher aromaticity and relatively higher humic-like fluorescent components in DOM during high discharge. The molecular composition showed significantly higher molecular complexity, averaged molecular weight, aromaticity, relative abundances of polyphenols and highly unsaturated compounds of DOM during high discharge than normal discharge. A large set of unique molecular formulae (up to 4927) was only detected during high discharge. These unique molecular formulae were mostly lignin degradation products, likely due to more intensive soil leaching during high discharge. By comparing with incubation experiments and the Yangtze River mouth and East China Sea DOM molecular composition, some of these unique molecular formulae during high discharge are resistant to both bio- and photo-degradation, and persist during their transport to the East China Sea. Therefore, we suggest that high discharge will additionally introduce a relatively recalcitrant pool of DOM into the Yangtze River mainstream and persist during its journey to the ocean. Considering the projected increase of flood frequency, this study provides a preliminary foundation for further studies to better assess the underlying mechanisms how hydrology affect the biogeochemical cycling of DOM in large rivers.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142803DOI Listing
April 2021

Cerebral venous thrombosis in a patient with mild COVID-19 infection.

Ann Acad Med Singap 2021 02;50(2):188-190

Department of General Medicine, Sengkang General Hospital, Singapore.

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February 2021

Social Exclusion Down-Regulates Pain Empathy at the Late Stage of Empathic Responses: Electrophysiological Evidence.

Front Hum Neurosci 2021 1;15:634714. Epub 2021 Mar 1.

Key Laboratory of Brain, Cognition and Education Sciences (South China Normal University), Ministry of Education, Guangzhou, China.

Social exclusion has a significant impact on cognition, emotion, and behavior. Some behavioral studies investigated how social exclusion affects pain empathy. Conclusions were inconsistent, and there is a lack of clarity in identifying which component of pain empathy is more likely to be affected. To investigate these issues, we used a Cyberball task to manipulate feelings of social exclusion. Two groups (social exclusion and social inclusion) participated in the same pain empathy task while we recorded event-related potentials (ERP) when participants viewed static images of body parts in painful and neutral situations. The results showed early N2 differentiation between painful and neutral pictures in the central regions in both groups. The pattern at the late controlled processing stage was different. Parietal P3 amplitudes for painful pictures were significantly smaller than those for neutral pictures in the social exclusion group; they did not differ in the social inclusion group. We observed a parietal late positive potential (LPP) differentiation between painful and neutral pictures in both groups. LPP amplitudes were significantly smaller in the social exclusion group than those in the social inclusion group for painful stimuli. Our results indicate that social exclusion does not affect empathic responses during the early emotional sharing stage. However, it down-regulates empathic responses at the late cognitive controlled stage, and this modulation is attenuated gradually. The current study provides neuroscientific evidence of how social exclusion dynamically influences pain empathy.
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http://dx.doi.org/10.3389/fnhum.2021.634714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956954PMC
March 2021

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients.

Medicine (Baltimore) 2021 Feb;100(8):e24615

Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing.

Abstract: The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results.Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens.The agreement rate of 84.98% (82.85%-86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results.ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.
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http://dx.doi.org/10.1097/MD.0000000000024615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909155PMC
February 2021

Bipolar Distribution of Minimum Inhibitory Concentration of Q203 Across Mycobacterial Species.

Microb Drug Resist 2021 Feb 26. Epub 2021 Feb 26.

Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.

In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A total of 344 nonduplicate mycobacterium isolates were randomly selected for susceptibility testing. Overall, Q203 exhibited excellent activity against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates, whereas it showed high minimum inhibitory concentration (MIC) values for all nontuberculous mycobacteria (NTM) isolates tested. The MIC and MIC values were both 0.008 mg/L for MDR- and XDR-TB isolates, respectively. In contrast, the MIC and MIC values of four NTM species were all >16 mg/L. QcrB of , a component of the CytBC1 complex of the respiratory chain targeted by Q230, shared 89.7% amino acid sequence identity with QcrB, 87.9% with that of , and 84.0% with that of , whereas with low sequence identity observed in QcrB sequence of . Notably, the QcrBs of and contained a 10-amino acid insertion in the linker between the eighth and ninth helical region. In conclusion, our data demonstrate the bipolar distribution of Q203 MICs across mycobacterial species. Compared with the high MICs in four clinically relevant mycobacterial species, MDR- and XDR-TB isolates have extremely low MICs, indicating that Q203 is a particularly promising candidate for TB treatment. In addition, the 10-amino acid insertion within QcrBs of and may be a plausible explanation for the natural resistance to Q203 among these two species.
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http://dx.doi.org/10.1089/mdr.2020.0239DOI Listing
February 2021

Stepwise selection of mutation conferring fluroquinolone resistance: multisite MDR-TB cohort study.

Eur J Clin Microbiol Infect Dis 2021 Feb 18. Epub 2021 Feb 18.

Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No 9, Beiguan Street, Tongzhou District, Beijing, 101149, People's Republic of China.

In this study, we demonstrate that fluroquinolone (FQ) is at risk of acquired drug resistance after continuous exposure. The reduced susceptibility is observed in subsequent Mycobacterium tuberculosis isolates from patients without FQ exposure. The stepwise selection of mutation of increasing FQ resistance highlights the urgent need for monitoring FQ resistance in multidrug-resistant tuberculosis patients throughout the entire treatment course.
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http://dx.doi.org/10.1007/s10096-021-04187-5DOI Listing
February 2021

Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang.

Front Pharmacol 2020 27;11:606689. Epub 2021 Jan 27.

Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.
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http://dx.doi.org/10.3389/fphar.2020.606689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872959PMC
January 2021

Transcriptomic analysis reveals that the small protein MgtS contributes to the virulence of uropathogenic Escherichia coli.

Microb Pathog 2021 Mar 29;152:104765. Epub 2021 Jan 29.

Tianjin Key Laboratory of Microbial Functional Genomics, TEDA College, Nankai University, Tianjin, 300457, China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, 300457, China. Electronic address:

Uropathogenic Escherichia coli (UPEC) is the most common pathogen causing urinary tract infections (UTIs). The pathogenesis of UPEC relies on the formation of intracellular bacterial communities (IBCs) after invading bladder epithelial cells (BECs). In this study, the gene expression profiles of UPEC after invading BECs were comprehensively analyzed using RNA sequencing to reveal potential virulence-related genes. The small protein MgtS, which is transcriptionally upregulated in BECs, was further investigated. It was found that MgtS contributed positively to UPEC invasion of BECs and colonization in murine bladders. A two-component regulatory system, PhoPQ was confirmed as a direct activator of mgtS expression in BECs, and magnesium limitation is proposed as a host cue for the activation. This study provides the first comprehensive analysis of the transcriptome profile of UPEC during its intra-BECs life, revealing a new virulence-associated gene and its regulatory mechanism.
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http://dx.doi.org/10.1016/j.micpath.2021.104765DOI Listing
March 2021

Occurrence of N-nitrosamines and their precursors in the middle and lower reaches of Yangtze River water.

Environ Res 2021 04 27;195:110673. Epub 2021 Jan 27.

State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan, 430074, China; School of Environmental Studies, China University of Geosciences, Wuhan, 430074, China. Electronic address:

The presence of some types of N-nitrosamines in water bodies is of great concern worldwide due to their carcinogenic risks and harmful mutagenic effects on human health. In the present study, eight N-nitrosamines and their formation potentials (FPs) were primarily investigated in Yangtze River surface water to evaluate their spatial distribution, mass loads, and ecological risks. The results showed that of the eight N-nitrosamines investigated, NDMA (<1.5-17 ng/L), NDEA (<1.4-9.5 ng/L), NDPA (1.0 ng/L), NMOR (<1.0-1.3 ng/L), NPIP (<2.1-3.7 ng/L), and NDBA (<3.6-30 ng/L) were detected. The FPs of NDMA (<27-130 ng/L), NDEA (<0.9-2.3 ng/L), NDPA (<1.2-1.9 ng/L), NPYR (<1.4-2.9 ng/L), NMOR (<1.0 ng/L), and NDBA (<1.1-14 ng/L) were significantly identified. NDBA was predominantly observed in surface water, while NDMA was noticeably detected in chloraminated water samples. It was estimated that approximately 5.4 t/y of N-nitrosamines were carried by the Yangtze River to the East China Sea, whereas the input flux of N-nitrosamine precursors was estimated to be approximately 69.5 t/y. Spatial variations were observed due to the input of N-nitrosamines from the upstream dams and lakes. The origin of N-nitrosamine precursors was not associated with the presence of sediment in river water. NDEA could be introduced into river water by the discharge of wastewater. NDBA and its precursors could originate from industrial and aquaculture activities. NDMA and its precursors could result from both of the aforementioned sources. Moreover, the wastewater discharge from small cities, pH value, wastewater treatment ratio, and dilution could be the key factors that influence the occurrence of N-nitrosamines along the Yangtze River. More attention should be paid to the cancer risks posed by N-nitrosamines. The ecological risks posed by N-nitrosamines in the Yangtze River can be ignored.
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http://dx.doi.org/10.1016/j.envres.2020.110673DOI Listing
April 2021

Diagnostic Yield of Oral Swab Testing by TB-LAMP for Diagnosis of Pulmonary Tuberculosis.

Infect Drug Resist 2021 12;14:89-95. Epub 2021 Jan 12.

Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People's Republic of China.

Objective: A prospective study was conducted to ascertain the accuracy of oral swab specimens collected in the early morning, spot and at night for detecting pulmonary tuberculosis (TB).

Methods: We prospectively enrolled patients with symptoms suggestive of pulmonary TB in Beijing Chest Hospital. An early morning sputum specimen was collected from each patient for GeneXpert MTB/RIF (Xpert) and mycobacterial culture. In addition, three oral swabs were collected for TB-LAMP testing.

Results: With the combined results of three oral swab specimens, the proportion of (MTB)-positive cases achieved 40.6%, which was comparable to results for Xpert and MGIT (=0.603). Using Xpert plus MGIT as reference, the sensitivity of OS-LAMP on a single specimen ranged from 32.6% on the night oral swab to 50.0% on the morning swab. The combination of three oral swab specimens correctly identified 38 MTB-positive cases, indicating an overall sensitivity of 82.6%, which was significantly higher than that of a single oral swab specimen (<0.001, =0.001).

Conclusion: Oral swab can be used as an alternative specimen for diagnosis of pulmonary TB using TB-LAMP. Morning oral swab exhibits the highest sensitivity, and the inclusion of more specimens at different time points provides compensation in diagnostic sensitivity with single oral swab.
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http://dx.doi.org/10.2147/IDR.S284157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811440PMC
January 2021

Optimal delivery timing for twin pregnancies: A population-based retrospective cohort study.

Int J Clin Pract 2021 May 27;75(5):e14014. Epub 2021 Jan 27.

MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims: The optimal timing of delivery for twin pregnancies remains controversial. This study examined the risks of adverse neonatal outcomes and neonatal deaths according to gestational age at delivery in order to determine the optimal gestational age of delivery for twin pregnancies.

Methods: This is a retrospective study of twin pregnancies delivered between 34 and 40 weeks of gestation from 1995 to 2000 in the United States. The primary outcomes evaluated were neonatal morbidity and mortality. The composite outcome of neonatal morbidity included the following variables: Apgar score lower than 7 at 5 minutes, assisted ventilation <30 minutes, assisted ventilation ≥30 minutes, hyaline membrane disease, meconium aspiration syndrome, neonatal seizures, birth injury, anaemia, and congenital malformations. Logistic regressions were applied to calculate adjusted odds ratios of the adverse outcomes according to the gestational week at delivery, with either individual twins or twin pairs as the unit of analysis.

Results: A total of 466 038 twins from 233 019 pregnancies from the US National Center for Health Statistics matched the multiple birth data set included in the study. The composite neonatal morbidity and mortality risks declined from 34 to 38 weeks of gestation and increased thereafter in both individual and pair twins stratified analyses. Amongst neonatal adverse outcomes, the risk of low Apgar score and hyaline membrane disease decreased progressively towards 38 weeks of gestation, only to increase again towards 40 weeks. The risk of meconium aspiration syndrome increased after 38 weeks, in both individual and pair twins. There were no differences in the risk of birth injury and neonatal seizures when stratified by gestational age.

Conclusions: The optimal timing for twin delivery appears to be at 38 weeks of gestation, although individual maternal, foetal, and pregnancy characteristics should be considered when determining the best timing for delivery.
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http://dx.doi.org/10.1111/ijcp.14014DOI Listing
May 2021

The ubiquitin proteasome system is necessary for efficient proliferation of porcine reproductive and respiratory syndrome virus.

Vet Microbiol 2021 Feb 8;253:108947. Epub 2020 Dec 8.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. Electronic address:

The ubiquitin-proteasome system (UPS) plays a vital role in cellular protein homeostasis by ensuring protein quality control and maintaining a critical level of important regulatory proteins. Thus, it is not surprising that the functional UPS is manipulated by viruses to assist in viral propagation. Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant swine disease that has been devastating the swine industry worldwide. However, the role of UPS in PRRSV infection is unknown. In this study, we found that treatment with the proteasome inhibitor MG132 significantly inhibited PRRSV proliferation in a dose-dependent manner. The anti-PRRSV effect of MG132 was most significant in the middle stage of the PRRSV lifecycle, which is achieved via inhibition of viral attachment and replication. Interestingly, the expression of poly-ubiquitin was drastically decreased and the accumulation of free-ubiquitin was obviously elevated in the middle stage of PRRSV infection. Furthermore, the ectopic expression of ubiquitin in MG132-treated cells partially reversed the inhibitory effect of MG132 on PRRSV proliferation. Taken together, these results suggest that PRRSV manipulates UPS to promote self-proliferation by cheating or taking advantage of the host proteasome, degrading intracellular poly-ubiquitin and increasing the accumulation of free ubiquitin.
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http://dx.doi.org/10.1016/j.vetmic.2020.108947DOI Listing
February 2021

Fault Diagnosis for Rotating Machinery Using Multiscale Permutation Entropy and Convolutional Neural Networks.

Entropy (Basel) 2020 Jul 31;22(8). Epub 2020 Jul 31.

School of Mechanical Engineering, North University of China, Taiyuan 030051, China.

In view of the limitations of existing rotating machine fault diagnosis methods in single-scale signal analysis, a fault diagnosis method based on multi-scale permutation entropy (MPE) and multi-channel fusion convolutional neural networks (MCFCNN) is proposed. First, MPE quantitatively analyzes the vibration signals of rotating machine at different scales, and obtains permutation entropy (PE) to construct feature vector sets. Then, considering the structure and spatial information between different sensor measurement points, MCFCNN constructs multiple channels in the input layer according to the number of sensors, and each channel corresponds to the MPE feature sets of different monitored points. MCFCNN uses convolutional kernels to learn the features of each channel in an unsupervised way, and fuses the features of each channel into a new feature map. At last, multi-layer perceptron is applied to fuse multi-channel features and identify faults. Through the health monitoring experiment of planetary gearbox and rolling bearing, and compared with single channel convolutional neural networks (CNN) and existing CNN based fusion methods, the proposed method based on MPE and MCFCNN model can diagnose faults with high accuracy, stability, and speed.
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http://dx.doi.org/10.3390/e22080851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517452PMC
July 2020

Genotypes of Mycobacterium tuberculosis isolates circulating in Shaanxi Province, China.

PLoS One 2020 3;15(12):e0242971. Epub 2020 Dec 3.

Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

Objectives: The prevalence of drug-resistant TB in Shaanxi Province is higher than other areas. This study was aimed to investigate the genetic diversity and epidemiology of Mycobacterium tuberculosis clinical strains in Shaanxi Province, China.

Methods: From January to December 2016, a total of 298 Mycobacterium tuberculosis clinical isolates from smear-positive pulmonary tuberculosis patients were genotyped by Mcspoligotyping and 15-locus VNTR.

Results: We found that the Beijing family strains was the most prominent family(81.54%, 243/298). Other family strains included T family(9.06%, 27/298), U family(0.67%, 2/298), LAM9 family(0.34%, 1/298) and Manu family(0.34%, 1/298). The rates of multidrug-resistant (MDR) M.Tuberculosis, age, type of case and education between Beijing and non-Beijing family strains were not statistically different, while the distribution in the three different regions among these was statistically significant. VNTR results showed that strains were classified into 280 genotypes, and 33 (11.07%) strains could be grouped into 14 clusters. 11 of the 15-VNTR loci were highly or moderately discriminative according to the Hunter-Gaston discriminatory index.

Conclusions: We concluded that the Beijing family genotype was the most prevalent genotype and 15-locus VNTR typing might be suitable for genotyping of M. tuberculosis in Shaanxi Province. There was less association between Beijing family genotypes and drug resistance in our study area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242971PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714122PMC
January 2021

sp. nov. and sp. nov., isolated from a glacier on the Tibetan Plateau.

Int J Syst Evol Microbiol 2021 Jan 3;71(1). Epub 2020 Dec 3.

China General Microbiological Culture Collection Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.

Two Gram-stain-negative, aerobic, rod-shaped, non-motile, bacterial strains, designated as ZB1P21 and ZT4R22, were isolated from ice and cryoconite samples collected from Zepu glacier on the Tibetan Plateau, PR China. The phylogenetic analysis of 16S rRNA gene showed that the two strains belong to the genus . Strain ZB1P21 showed the highest similarity to WPCB133 (97.35 %), while strain ZT4R22 showed the highest similarity to F01003 (99.11 %). The average nucleotide identity values between the two novel strains and their closest relatives were 79.42 and 85.72 % respectively. The two novel strains contained MK-7 as the major menaquinone, and summed feature 3 (comprising C7 and/or C6), iso-C, iso-C3-OH and C5 as the major fatty acids. The major polar lipid of the two novel strains were phosphatidylethanolamine. Based on these data, we propose two novel species, sp. nov. (ZB1P21=CGMCC 1.23981=NBRC 113932) and sp. nov. (ZT4R22=CGMCC 1.23487=NBRC 113931).
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http://dx.doi.org/10.1099/ijsem.0.004585DOI Listing
January 2021

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

J Stroke Cerebrovasc Dis 2020 Dec 6;29(12):105379. Epub 2020 Oct 6.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Neurology, Department of Medicine, National University Health System, Singapore. Electronic address:

Background: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology.

Objective: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature.

Methods: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included.

Results: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%.

Conclusions: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538072PMC
December 2020

Acquisition of clofazimine resistance following bedaquiline treatment for multidrug-resistant tuberculosis.

Int J Infect Dis 2021 Jan 29;102:392-396. Epub 2020 Oct 29.

National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, P.R. China. Electronic address:

Objectives: We described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort in China. We also aimed to identify dynamic changes in CFZ susceptibility and its molecular mechanism after exposure to bedaquiline (BDQ) and/or CFZ.

Methods: The experimental settings were conducted based on our MDR-TB cohort receiving BDQ-containing regimens. Sequential isolates were obtained from patients. CFZ and BDQ susceptibility of isolates were determined using the minimum inhibitory concentration (MIC) method. The fragments of Rv0678 and pepQ were sequenced.

Results: A total of 277 patients infected with MDR-TB were included in our study. CFZ resistance was noted in 23 (23/277, 8.3%) isolates. The rate of acquired CFZ resistance (12/189, 6.3%) was significantly greater than that of primary resistance (11/88, 12.5%, P = 0.028). Out of 23 CFZ-resistant isolates, five (5/23) were BDQ-resistant, and the other 18 (18/23) were susceptible to BDQ. Of note, nine 9/23) out of 23 CFZ-resistant isolates had mutations within either target genes. Kaplan-Meier analysis demonstrated that the baseline CFZ resistance had no influence on time to culture conversion in our cohort (P = 0.828). Acquired CFZ resistance emerged in eight (8/94, 8.5%) patients during treatment for MDR-TB, including three patients receiving regimens without CFZ.

Conclusions: Our results demonstrate the high rate of CFZ resistance among MDR-TB patients in China. Patients treated with BDQ-containing regimens achieve comparative culture conversion rate regardless of baseline CFZ susceptibility. The presence of acquired CFZ-resistance following BDQ treatment without known mutation indicates that other mechanisms conferring cross resistance to these two compounds may exist.
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http://dx.doi.org/10.1016/j.ijid.2020.10.081DOI Listing
January 2021

Effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti-tuberculosis drugs in Chinese population.

Medicine (Baltimore) 2020 Oct;99(44):e22258

Tuberculosis Department.

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120  minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30  minutes interval and 120  minutes interval were 21.8 ± 2.0 and 19.2 ± 2.0 μg/mL for rifampin, 1.6 ± 0.2 and 2.1 ± 0.2 μg/mL for isoniazid (INH), 1.5 ± 0.1and 1.5 ± 0.2 μg/mL for ethambutol (EMB), and 49.2 ± 3.7 and 41.5 ± 3.9 μg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ± 0.4 μg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ± 1.0 μg/mL), and slow acetylator (2.5 ± 1.0 μg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).
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http://dx.doi.org/10.1097/MD.0000000000022258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598834PMC
October 2020

Rapid Detection of Ethambutol-Resistant from Sputum by High-Resolution Melting Analysis in Beijing, China.

Infect Drug Resist 2020 20;13:3707-3713. Epub 2020 Oct 20.

National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, People's Republic of China.

Objective: We conducted a retrospective study to evaluate the performance of MeltPro assay for detecting ethambutol (EMB) susceptibility of (MTB) isolates in sputum specimens in Beijing, China.

Methods: Smear-positive TB patients undergoing MeltPro assay in the Beijing Chest Hospital between January 2019 and December 2019 were included. Phenotypic drug susceptibility testing (DST) was used as the reference standard to calculate the diagnostic accuracy of MeltPro assay for EMB resistance. Sanger sequencing of gene was conducted to resolve the discrepancies between MeltPro assay and phenotypic DST.

Results: A total of 222 smear-positive patients were included in our analysis. The overall agreement rate between the two assays was 91.4%, with a kappa value of 0.78. Among 59 EMB-resistant TB cases diagnosed by DST, 49 were identified by MeltPro assay, demonstrating a sensitivity of 83.1%. In addition, 154 out of 163 EMB-susceptible patients diagnosed by DST were correctly detected with MeltPro assay, yielding a specificity of 93.9%. The probe frequency associated with the observed EMB-resistance was as follows: A (45/58), B (7/58), and D (6/58), and no EMB-resistance was associated with probe C. The presence of amino acid substitution was observed among all 9 cases with potentially "false-negative" results, including 7 with Met306Ile, 1 with Met306Val, 1 with Gly406Asp, respectively.

Conclusion: MeltPro assay is a promising diagnostic tool for the detection of EMB resistance in China. The specific amino acid substitution in gene is the major reason for discrepancies between MeltPro assay and phenotypic DST.
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http://dx.doi.org/10.2147/IDR.S270542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586015PMC
October 2020

The Distribution and Localization of Collagen Triple Helix Repeat Containing-1 in Naturally and Experimentally Avian Leukosis Virus Subgroup J-Infected Chickens.

Front Vet Sci 2020 25;7:565773. Epub 2020 Sep 25.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

Collagen triple helix repeat containing-1 (CTHRC1) has recently been identified as avian leukosis virus subgroup J (ALV-J) replication-dependent factor that remarkably facilitates ALV-J replication via interaction with the envelope glycoprotein (SU) of ALV-J. However, the dynamic distribution and localization of CTHRC1 in various tissues upon ALV-J infection are still unknown. In this study, data revealed that the levels of CTHRC1 were significantly increased in various tissues and that the protein was mainly located in the cytoplasm and nucleus of parenchymal cells in tissues of chickens that were infected by ALV-J naturally and experimentally. Interestingly, CTHRC1 was also observed in leukocytes other than erythrocytes in congested veins of ALV-J-infected tissues. Consequently, the positive cells in these veins were confirmed as lymphocytes by laser confocal microscopy. Taken together, these results conclude that the CTHRC1 is an inducible protein and exhibited ubiquitous expression in ALV-J-infected chickens, which may provide basic information for in-depth study of ALV-J infection and replication mechanisms.
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http://dx.doi.org/10.3389/fvets.2020.565773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546020PMC
September 2020

Lung gene expression signatures suggest pathogenic links and molecular markers for pulmonary tuberculosis, adenocarcinoma and sarcoidosis.

Commun Biol 2020 Oct 23;3(1):604. Epub 2020 Oct 23.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, 100101, Beijing, China.

Previous reports have suggested a link between pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), and the development of lung adenocarcinoma (LUAD) and sarcoidosis. Furthermore, these lung diseases share certain clinical similarities that can challenge differential diagnosis in some cases. Here, through comparison of lung transcriptome-derived molecular signatures of TB, LUAD and sarcoidosis patients, we identify certain shared disease-related expression patterns. We also demonstrate that MKI67, an over-expressed gene shared by TB and LUAD, is a key mediator in Mtb-promoted tumor cell proliferation, migration, and invasion. Moreover, we reveal a distinct ossification-related TB lung signature, which may be associated with the activation of the BMP/SMAD/RUNX2 pathway in Mtb-infected macrophages that can restrain mycobacterial survival and promote osteogenic differentiation of mesenchymal stem cells. Taken together, these findings provide novel pathogenic links and potential molecular markers for better understanding and differential diagnosis of pulmonary TB, LUAD and sarcoidosis.
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http://dx.doi.org/10.1038/s42003-020-01318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584606PMC
October 2020

Metagenomic Next-Generation Sequencing Improves Diagnosis of Osteoarticular Infections From Abscess Specimens: A Multicenter Retrospective Study.

Front Microbiol 2020 15;11:2034. Epub 2020 Sep 15.

National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

: We conducted this retrospective study to reveal the accuracy of metagenomic next-generation sequencing (mNGS) for diagnosing osteoarticular infections from fresh abscess specimens obtained from patients in an HIV-naive population. : We retrospectively analyzed hospital records at three participating TB-specialized hospitals for patients admitted with suggestive diagnoses of osteoarticular tuberculosis between January 2018 and August 2019. Abscess specimens obtained from each patient were tested pathogen culture, GeneXpert (MTB)/rifampicin (RIF), and mNGS assay. : A total of 82 abscess samples were collected from patients with osteoarticular infections, including 53 cases with (64.6%) bacterial, 21 (25.6%) with mycobacterial, 7 (8.5%) with fungal, and 1 (1.2%) with actinomycetal organisms detected. Analysis of mNGS assay results identified potential pathogens in all cases, with complex (MTBC) most frequently isolated, followed by and . Conventional culture testing identified causative pathogens in only 48.4% of samples, a significantly lower rate than the mNGS pathogen identification rate (100%, < 0.01). Culture-positive group specimens yielded significantly greater numbers of sequence reads than did culture-negative group specimens ( < 0.01). Of patients receiving surgical interventions and mNGS-guided treatment, 76 (92.7%) experienced favorable outcomes by the time of follow-up assessment at 3 months post-treatment. Notably, MTBC detection in two patients experiencing treatment failure suggests that they had mixed infections with MTBC and other pathogens. : Results presented here demonstrate that mNGS has a greater pathogen detection rate in osteoarticular infections than conventional culture-based methods.
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http://dx.doi.org/10.3389/fmicb.2020.02034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523410PMC
September 2020

Andrade-Oliveira Salvianolic Acid B Modulates Caspase-1-Mediated Pyroptosis in Renal Ischemia-Reperfusion Injury Nrf2 Pathway.

Front Pharmacol 2020 3;11:541426. Epub 2020 Sep 3.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Acute kidney injury (AKI) is a serious disease characterized by a rapid decline in kidney function. Oxidative stress is the primary pathogenesis of AKI. Salvianolic acid B (SalB), a water-soluble compound extracted from , possesses a potent antioxidant activity. Here, we investigated the protective effect of SalB against renal ischemia-reperfusion injury (I/R) in mice. Briefly, by analyzing renal function, oxidative stress markers and inflammatory biomarkers, we found that SalB could improve kidney damage, reduce oxidative stress and inflammatory factor levels. Interestingly, the expression of the NLR family pyrin domain-containing 3 (NLRP3), caspase-1, pyroptosis related proteins gasdermin D (GSDMD) and interleukin (IL)-1β, which were significantly upregulated in the kidney tissues of I/R group, was effectively reversed by SalB. Meanwhile, renal tubular epithelial cells hypoxia and reoxygenation model was used to explore pyroptosis of caspase-1-dependent. Further mechanism study showed that the SalB pretreatment could promote the increase of nuclear factor erythroid-2 related factor 2 (Nrf2) nuclear accumulation, which significantly suppressed oxidative stress, proinflammatory cytokines, NLRP3 inflammasome activation and pyroptosis. These results indicate that SalB can inhibit caspase-1/GSDMD-mediated pyroptosis by activating Nrf2/NLRP3 signaling pathway, resulting in alleviating I/R injury in mice.
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http://dx.doi.org/10.3389/fphar.2020.541426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495093PMC
September 2020

Hydrological management constraints on the chemistry of dissolved organic matter in the Three Gorges Reservoir.

Water Res 2020 Dec 19;187:116413. Epub 2020 Sep 19.

Organic Geochemistry Unit, School of Earth Sciences, Zhejiang University, Hangzhou 310027, China. Electronic address:

Reservoirs are well known as a far-reaching human modification on the functions of natural river networks. However, changes in the chemistry and reactivity of dissolved organic matter (DOM) responding to hydrological management for water retention structures, and its influence on the river carbon cycle, remain poorly understood. Here we show that hydrological management does shape the molecular composition of DOM in the world's largest Three Gorges Reservoir, as revealed by optical spectroscopy and ultrahigh-resolution mass spectrometry. Relatively higher terrestrial input, molecular complexity, isomeric complexity, and environmental stability of DOM were observed during the storage period, whereas the inverse occurred during the drainage period. The results demonstrate that the hydrodynamic processes, which are mainly controlled by water intrusion from mainstream to tributaries, are likely the underlying mechanism controlling DOM chemistry. Integrated with observations from worldwide river reservoirs, the DOM degradation experiments suggest that reservoir hydrological management would enhance DOM mineralization, thereby increase CO emission and change the river carbon cycle.
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http://dx.doi.org/10.1016/j.watres.2020.116413DOI Listing
December 2020

Neurology of COVID-19 in Singapore.

J Neurol Sci 2020 Nov 3;418:117118. Epub 2020 Sep 3.

Department of Neurology, National Neuroscience Institute (Tan Tock Seng Hospital campus), Singapore. Electronic address:

Purpose: To describe the spectrum of COVID-19 neurology in Singapore.

Method: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions.

Results: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases.

Conclusion: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.
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http://dx.doi.org/10.1016/j.jns.2020.117118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470792PMC
November 2020