Publications by authors named "Li Liu"

5,545 Publications

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Shengxuening Extracted from Silkworm Excrement Mitigates Myelosuppression via SCF-Mediated JAK2/STAT3 Signaling.

Chem Biodivers 2021 May 11. Epub 2021 May 11.

Department of Hematology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhang District, Wuhan, 430071, P. R. China.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.
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http://dx.doi.org/10.1002/cbdv.202100139DOI Listing
May 2021

Large-scale network topology reveals brain functional abnormality in Chinese dyslexic children.

Neuropsychologia 2021 May 7:107886. Epub 2021 May 7.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, PR China. Electronic address:

It has been revealed that dyslexic children learning alphabetic languages are characterized by aberrant topological organization of brain networks. However, little is known about the functional organization and the reconfiguration pattern of brain networks in Chinese dyslexic children. Using graph theoretical analysis and functional magnetic resonance images (fMRI), we examined this issue specifically from the perspective of functional integration and segregation. We first compared large-scale topological organizations between dyslexic children and typically developing children during a Chinese phonological rhyming task, and found that dyslexic children showed increased local efficiency and clustering coefficient compared with typically developing children, which were negatively correlated with task performance. Furthermore, dyslexic children and typically developing children could be accurately distinguished at the individual-subject level based on the nodal local efficiency or clustering coefficient. Second, we studied the group difference of network reconfiguration and found that dyslexic children showed more difficulty when shifting from the resting state to the phonological task. Our results suggest an over-segregated brain functional organization and deficits in brain network reconfiguration in Chinese dyslexic children, which helps to advance our knowledge on the neural mechanisms underlying dyslexia.
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http://dx.doi.org/10.1016/j.neuropsychologia.2021.107886DOI Listing
May 2021

Reprogramming Immune Cells for Enhanced Cancer Immunotherapy: Targets and Strategies.

Front Immunol 2021 21;12:609762. Epub 2021 Apr 21.

Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Cancer is one of the leading causes of death and a major public health problem all over the world. Immunotherapy is becoming a revolutionary clinical management for various cancer types. Restoration of aberrant immune surveillance on cancers has achieved markable progress in the past years by either or engineering of the immune cells. Here, we summarized the central roles of immune cells in tumor progression and regression, and the existing and emerging strategies for different immune cell-based immunotherapies. In addition, the current challenges and the potential solutions in translating the immunotherapies into the clinic are also discussed.
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http://dx.doi.org/10.3389/fimmu.2021.609762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097044PMC
April 2021

Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.

Front Pharmacol 2021 21;12:650027. Epub 2021 Apr 21.

Center of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.

Cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) are both greatly important metabolic enzymes in various tissues, including brain. Although expressions of brain CYPs and UGTs and their contributions to drug disposition are much less than liver, both CYPs and UGTs also mediate metabolism of endogenous substances including dopamine and serotonin as well as some drugs such as morphine in brain, demonstrating their important roles in maintenance of brain homeostasis or pharmacological activity of drugs. Some diseases such as epilepsy, Parkinson's disease and Alzheimer's disease are often associated with the alterations of CYPs and UGTs in brain, which may be involved in processes of these diseases via disturbing metabolism of endogenous substances or resisting drugs. This article reviewed the alterations of CYPs and UGTs in brain, the effects on endogenous substances and drugs and their clinical significances. Understanding the roles of CYPs and UGTs in brain provides some new strategies for the treatment of central nervous system diseases.
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http://dx.doi.org/10.3389/fphar.2021.650027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097730PMC
April 2021

Genetic association scan of 32 osteoarthritis susceptibility genes identified TP63 associated with endemic osteoarthritis Kashin-Beck disease.

Bone 2021 May 5:115997. Epub 2021 May 5.

Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, 710061, PR China. Electronic address:

Background: Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The clinical manifestations and radiographic features of KBD were similar to that of osteoarthritis (OA).

Methods: We first performed a genetic association scan of 32 OA susceptibility genes with KBD in 898 Han Chinese subjects. The MassARRAY genotyping system (Agena) was used for SNP genotyping. PLINK 1.9 was used for quality control and association testing. Using articular cartilage specimens from 7 adult KBD patients and 4 healthy control subjects, lentivirus-mediated RNA interference (RNAi), qRT-PCR, Western blot and immunohistochemistry were employed to validate the functional relevance of TP63 in KBD chondrocyte.

Results: SNP genotyping and association analysis identified TP63 (rs12107036, OR = 0.7133, P = 0.005) and OARD1 (rs11280, OR = 1.512, P = 0.004) were significantly associated with KBD. We found that TP63 was significantly up-regulated in KBD articular cartilage in both mRNA and protein level compared to healthy controls (P < 0.05). Lentivirus-mediated RNAi of TP63 suppression notably decreased the abundance of Caspase3 and SOX9 in chondrocytes. Most importantly, compared to the untransfected chondrocytes, the TP63 inhibition increased the production of ACAN. The mRNA expression of chondrocyte marker genes (COL2A1 and ACAN) was partly stable by TP63 knockdown relative to control group.

Conclusion: Our study identifies TP63 as a novel susceptibility gene for KBD, and demonstrates that inhibition of TP63 suppress chondrocyte apoptosis and partly facilitates chondrogenesis. The combination of SNP genotyping and genetic manipulation techniques provides a useful tool for understanding the biological mechanism and differential diagnosis studies of KBD and OA.
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http://dx.doi.org/10.1016/j.bone.2021.115997DOI Listing
May 2021

Visible-light-promoted photocatalyst-free alkylation and acylation of benzothiazoles.

Org Biomol Chem 2021 May 7. Epub 2021 May 7.

Department of Organic Chemistry, College of Chemistry, Beijing University of Chemical Technology (BUCT), Beijing 100029, China.

Herein we report a protocol for the visible-light-mediated alkylation/acylation reaction of benzothiazoles. Alkyl/acyl substituted Hantzsch esters are easily prepared and rationally used as radical precursors. In the presence of BF3·Et2O and Na2S2O8, various benzothiazole derivatives were readily obtained in good yields. Our user-friendly protocol can proceed by simple irradiation with blue LEDs (λ = 465 nm) and without the assistance of external photocatalysts. The reaction is also characterized by mild conditions and scalability, thus offering an alternative and efficient tool for the synthesis of 2-functionalized benzothiazoles.
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http://dx.doi.org/10.1039/d1ob00734cDOI Listing
May 2021

Study on life histroy traits of Stellera chamaejasme provide insights into its control on degraded typical steppe.

J Environ Manage 2021 May 3;291:112716. Epub 2021 May 3.

College of Grassland Science and Technology, China Agricultural University, Beijing, 100193, China; GuYuan National Grassland Ecosystem Field Station, Hebei Province, 076550, China. Electronic address:

The increase of unpalatable Stellera chamaejasme plants has become commonplace in degraded grasslands of China, which can hinder the establishment and growth of palatable plants and have an impact on sustainable development of livestock production. Controlling S. chamaejasme is thus a necessary, yet usually problematic step towards the degraded grassland. Various measures have been implemented to control S. chamaejasme but relatively little is known about the growth and development of S. chamaejasme in degraded grassland. Therefore, focusing on the life history traits of S. chamaejasme can provide theoretical support underpinning its management. In this study, different age classes of S. chamaejasme plants were surveyed and studied from a degraded typical steppe in China, and the variation of the phenotypic traits, biomass increasement, biomass allocation, reserves and nutrient content were described. These analyses could be of great importance in identifying the management practices of S. chamaejasme that are most consistent with the development of S. chamaejasme in degraded grasslands. We found that most of the phenotypic traits and biomass of all organs increased by different patterns with age class. Like many other species, there has been three developmental phases in S. chamaejasme, however, previous researches only focus on the S. chamaejasme in the adult reproductive phase, therefore leading to a delay between the time of S. chamaejasme's seedling and the time when it begins to establish. Our findings demonstrate that S. chamaejasme mainly distributes the biomass to belowground part (RMF and SMF), which is conducive to the survival of S. chamaejasme on degraded grasslands, making mowing fail to eradicate S. chamaejasme in practice. Partial least squares path modeling suggested that nutrient content (N) played a key role in flowering of S. chamaejasme, but the indirect effect was greater than direct effect. The results from this study highlight that control efforts and the management of S. chamaejasme should not only focus on the S. chamaejasme individual in unreproductive phase, but also on the belowground part of plant in reproductive phase.
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http://dx.doi.org/10.1016/j.jenvman.2021.112716DOI Listing
May 2021

Crystal structures of NAD-linked isocitrate dehydrogenase from the green alga Ostreococcus tauri and its evolutionary relationship with eukaryotic NADP-linked homologs.

Arch Biochem Biophys 2021 May 3:108898. Epub 2021 May 3.

Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases and Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, No.1 Beijing East Road, College of Life Sciences, Anhui Normal University, Wuhu, Anhui, 241000, China. Electronic address:

NAD-linked isocitrate dehydrogenases (NAD-IDHs) catalyze the oxidative decarboxylation of isocitrate into α-ketoglutarate. Previously, we identified a novel phylogenetic clade including NAD-IDHs from several algae in the type II subfamily, represented by homodimeric NAD-IDH from Ostreococcus tauri (OtIDH). However, due to its lack of a crystalline structure, the molecular mechanisms of the ligand binding and catalysis of OtIDH are little known. Here, we elucidate four high-resolution crystal structures of OtIDH in a ligand-free and various ligand-bound forms that capture at least three states in the catalytic cycle: open, semi-closed, and fully closed. Our results indicate that OtIDH shows several novel interactions with NAD, unlike type I NAD-IDHs, as well as a strictly conserved substrate binding mode that is similar to other homologs. The central roles of Lys283' in dual coenzyme recognition and Lys234 in catalysis were also revealed. In addition, the crystal structures obtained here also allow us to understand the catalytic mechanism. As expected, structural comparisons reveal that OtIDH has a very high structural similarity to eukaryotic NADP-linked IDHs (NADP-IDHs) within the type II subfamily rather than with the previously reported NAD-IDHs within the type I subfamily. It has also been demonstrated that OtIDH exhibits substantial conformation changes upon ligand binding, similar to eukaryotic NADP-IDHs. These results unambiguously support our hypothesis that OtIDH and OtIDH-like homologs are possible evolutionary ancestors of eukaryotic NADP-IDHs in type II subfamily.
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http://dx.doi.org/10.1016/j.abb.2021.108898DOI Listing
May 2021

A nomogram prediction of overall survival based on lymph node ratio, AJCC 8th staging system, and other factors for primary pancreatic cancer.

PLoS One 2021 5;16(5):e0249911. Epub 2021 May 5.

Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

Background: As a malignant tumor with poor prognosis, accurate and effective prediction of the prognosis of pancreatic cancer (PC) is crucial.

Methods: A total of 12,909 patients diagnosed with pancreatic cancer were selected from the Surveillance, Epidemiology, and End Results program between 2004 and 2016. The sex, age, ethnicity, marital status, metastasis status, radiotherapy, chemotherapy, tumor size, regional nodes examined, regional nodes positive of each patient were recorded. Univariate and multivariate Cox regression analyses were used to identify prognostic factors with a threshold of P<0.05, and a nomogram was constructed. Harrell's concordance indexes and calibration plots were used to verify the predictive power of the model. The risk groups were also stratified by quartile of the total score. Survival rates were estimated by the Kaplan-Meier method.

Results: Age, year of diagnosis, sex, grade, histologic, marital, TNM stage, surgery of the primary site, tumor size, regional nodes positive and regional nodes examined ratio (LNR), lymph node dissection, radiotherapy, and chemotherapy were identified as prognostic factors for the construction of the nomogram. The nomogram exhibited a clinical predictive ability of 0.675(95% CI, 0.669~0.681) in the internal verification. The predicted calibration curve was similar to the standard curve. Decision curve analysis showed that the nomogram had value in terms of clinical application. Besides, the nomogram was able to divide the patients into different groups according to total points.

Conclusions: Hence, our nomogram was highly effective in predicting overall survival in patients with PC, which may provide a reference tool for clinicians to guide individualized treatment and follow-ups for patients with PC, accurately determine the 1-,3- and 5-year overall survival of patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249911PLOS
May 2021

Phenotypic Recapitulation and Correction of Desmoglein-2-deficient Cardiomyopathy using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes.

Hum Mol Genet 2021 May 5. Epub 2021 May 5.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintains the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disc structures in the myocardium. Induced pluripotent stem cells were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes (iPSC-CMs). Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not HDR-iPSC-CMs. Micro force testing of 3-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provides evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.
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http://dx.doi.org/10.1093/hmg/ddab127DOI Listing
May 2021

Cognitive control and emotional response in attention-deficit/ hyperactivity disorder comorbidity with disruptive, impulse-control, and conduct disorders.

BMC Psychiatry 2021 05 4;21(1):232. Epub 2021 May 4.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

Background: This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD).

Methods: Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden's Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively.

Results: For Golden's interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden's Stroop RT disappeared, but differences in Golden's Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group.

Conclusions: Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.
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http://dx.doi.org/10.1186/s12888-021-03221-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094501PMC
May 2021

Diabetic Hepatosclerosis in a Woman with Maturity-Onset Diabetes of the Young Type 3.

Dig Dis Sci 2021 May 3. Epub 2021 May 3.

Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, USA.

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http://dx.doi.org/10.1007/s10620-021-07005-2DOI Listing
May 2021

Imaging and analysis on the interaction between human antigen-pulsed Vδ2 T cells and antigen-specific CD4 T cells.

STAR Protoc 2021 Jun 14;2(2):100453. Epub 2021 Apr 14.

AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

This protocol describes how to visualize surface protein-protein co-localization across a cell-cell interface between antigen-presenting γδ-T cells and CD4 T cells. By consolidating immunofluorescence assay, confocal microscopy and 3D imaging analysis, it enables assessment of interaction between cell surface proteins such as Δ42PD1 and TLR4 between co-cultured γδ-T and CD4 T cells. This protocol can be applied to study a surface protein of interest and its potential interaction with a target cell/protein at the cell-cell interface. For complete details on the use and execution of this profile, please refer to Mo et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2021.100453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076705PMC
June 2021

The consumption of wholegrain is related to depressive symptoms among Chinese adults: a cross-sectional study.

Eur J Clin Nutr 2021 Apr 30. Epub 2021 Apr 30.

Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Wholegrains contribute a range of beneficial nutrients, such as dietary fiber and several minerals and vitamins, that are beneficial to depressive symptoms. However, there are a few studies aimed at exploring whether a wholegrain diet is related to depressive symptoms. We conducted this study to investigate the relationship between wholegrains consumption and depressive symptoms.

Methods: This cross-sectional study included a total of 24,776 (mean age: 39.9 years, age range: 18.1-91.3 years; males, 54.1%) inhabitants living in Tianjin, China. Wholegrains consumption was assessed using a valid self-administered food frequency questionnaire. Depressive symptoms were evaluated using the Chinese version of Zung Self-Rating Depression Scale (SDS) and the cutoff point was set at 45. Multiple logistic regression analysis was used to estimate the relationship between wholegrains consumption and depressive symptoms.

Results: The prevalence of depressive symptoms was 19.1% and 22.4% in males and females, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence intervals) of depressive symptoms across wholegrains consumption were 0.77 (0.65-0.91) for <1 time/week, 0.73 (0.62-0.86) for 1 time/week and 0.68 (0.59-0.79) for ≥2 time/week in males compared with the control group (almost never). In females, the odds ratios (95% confidence intervals) were 0.86 (0.71-1.04) for <1 time/week, 0.94 (0.78-1.13) for 1 time/week, and 0.76 (0.65-0.91) for ≥2 time/week. Similar results were observed when we use other cut-offs (SDS ≥ 40 and 50) to define depressive symptoms.

Conclusion: This study first demonstrated that the higher consumption of wholegrains might have effects on the prevention and improvement of depressive symptoms. Prospective or intervention studies are needed to confirm these findings.
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http://dx.doi.org/10.1038/s41430-021-00917-2DOI Listing
April 2021

Skin effect of facial cleansing: Should not be overemphasized compared with the long-term potential risk.

J Cosmet Dermatol 2021 Apr 30. Epub 2021 Apr 30.

Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, China.

We read with interest the study by Aiello and colleagues published online on Feb. 22. In this study, the effect of physiological properties was revealed through comparing a cleansing process with cosmetic product applied manually to cleansing with cosmetic product associated with the use of an electric sonic device and result the sonic device did not cause a significant hydration reduction with better preservation of skin homeostasis.
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http://dx.doi.org/10.1111/jocd.14190DOI Listing
April 2021

Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment.

Carcinogenesis 2021 Apr 30. Epub 2021 Apr 30.

The State Key Lab of Respiratory Disease, Institute of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China.

A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-Seq analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve (AUC) values as 0.662 (95% confidence interval [CI]= 0.614-0.711) and 0.624 (95%CI= 0.522-0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio [HR] = 1.58, 95%CI = 1.01-2.49). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate TNFAIP3 expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE leads to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC.
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http://dx.doi.org/10.1093/carcin/bgab034DOI Listing
April 2021

Hesperidin alleviates insulin resistance by improving HG-induced oxidative stress and mitochondrial dysfunction by restoring miR-149.

Diabetol Metab Syndr 2021 Apr 29;13(1):50. Epub 2021 Apr 29.

School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, 150040, Heilongjiang, People's Republic of China.

Background: Hesperidin, a natural flavanone, has been proven to have multiple protective effects in diabetic rats, such as antioxidant, anti-inflammatory and anti-apoptotic effects. However, the molecular mechanisms underlying the effects of hesperidin are not well elucidated.

Methods: LO2 cells were stimulated with high glucose (HG, 33 mM) for 24 h to establish a model of oxidative stress. Then, cell viability was determined using the MTT assay. The antioxidant activities, including the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, mitochondrial membrane potential (MMP) and adenosine-triphosphate (ATP) production, were measured with the corresponding kits. The levels of gene expression, protein expression and methylation were detected using qRT-PCR, western blotting and methylation-specific PCR (MSP) assays, respectively.

Results: Compared to the NG treatment, hesperidin treatment increased the viability and improved the oxidative stress, mitochondrial dysfunction and insulin resistance of HG-treated LO2 cells, and these effects were correlated with heightened SOD and GPx activities, increased MMP level and ATP generation, reduced MDA, ROS and glucose levels, and activated GSK3β/AKT and inactivated IRS1 signals. Mechanistically, hesperidin treatment enhanced the miR-149 expression level by reducing its promoter methylation by inhibiting DNMT1. Importantly, knockdown of miR-149 obviously abolished the biological roles of hesperidin.

Conclusions: Our findings demonstrated that hesperidin treatment ameliorated HG-induced insulin resistance by reducing oxidative stress and mitochondrial dysfunction partly by suppressing DNMT1-mediated miR-149 silencing.
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http://dx.doi.org/10.1186/s13098-021-00664-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082863PMC
April 2021

A novel pseudovirus-based mouse model of SARS-CoV-2 infection to test COVID-19 interventions.

J Biomed Sci 2021 Apr 30;28(1):34. Epub 2021 Apr 30.

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities. Here we describe the development of a preclinical animal model using intranasal administration of ACE2 followed by non-infectious SARS-CoV-2 pseudovirus (PsV) challenge.

Methods: To specifically generate our SARS-CoV-2 PsV, we used a lentivirus system. Following co-transfection with a packaging plasmid containing HIV Gag and Pol, luciferase-expressing lentiviruses, and a plasmid carrying the SARS-CoV-2 spike protein, SARS-CoV-2 PsVs can be isolated and purified. To better understand and maximize the infectivity of SARS-CoV-2 PsV, we generated PsV carrying spike protein variants known to have varying human ACE2 binding properties, including 19 deletion (19del) and 19del + D614G.

Results: Our system demonstrated the ability of PsVs to infect the respiratory passage of mice following intranasal hACE2 transduction. Additionally, we demonstrate in vitro and in vivo manipulability of our system using recombinant receptor-binding domain protein to prevent PsV infection.

Conclusions: Our PsV system is able to model SARS-CoV-2 infections in a preclinical mouse model and can be used to test interventions or preventative treatments. We believe that this method can be extended to work in various mouse strains or to model infection with different coronaviruses. A simple in vivo system such as our model is crucial for rapidly and effectively responding to the current COVID-19 pandemic in addition to preparing for future potential coronavirus outbreaks.
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http://dx.doi.org/10.1186/s12929-021-00729-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084690PMC
April 2021

Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.

Molecules 2021 Apr 27;26(9). Epub 2021 Apr 27.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage generates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular microscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations particularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.
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http://dx.doi.org/10.3390/molecules26092551DOI Listing
April 2021

The p23 of Citrus Tristeza Virus Interacts with Host FKBP-Type Peptidyl-Prolylcis-Trans Isomerase 17-2 and Is Involved in the Intracellular Movement of the Viral Coat Protein.

Cells 2021 Apr 17;10(4). Epub 2021 Apr 17.

Key Lab of Plant Pathology of Hubei Province, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

is a member of the genus in the family . The p23 of citrus tristeza virus (CTV) is a multifunctional protein and RNA silencing suppressor. In this study, we identified a p23 interacting partner, FK506-binding protein (FKBP) 17-2, from (CaFKBP17-2), a susceptible host, and (NbFKBP17-2), an experimental host for CTV. The interaction of p23 with CaFKBP17-2 and NbFKBP17-2 were individually confirmed by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Subcellular localization tests showed that the viral p23 translocated FKBP17-2 from chloroplasts to the plasmodesmata of epidermal cell of leaves. The knocked-down expression level of NbFKBP17-2 mRNA resulted in a decreased CTV titer in plants. Further, BiFC and Y2H assays showed that NbFKBP17-2 also interacted with the coat protein (CP) of CTV, and the complexes of CP/NbFKBP17-2 rapidly moved in the cytoplasm. Moreover, p23 guided the CP/NbFKBP17-2 complexes to move along the cell wall. To the best of our knowledge, this is the first report of viral proteins interacting with FKBP17-2 encoded by plants. Our results provide insights for further revealing the mechanism of the CTV CP protein movement.
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http://dx.doi.org/10.3390/cells10040934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073322PMC
April 2021

Sulfur nanoparticles/TiCT MXene with an optimum sulfur content as a cathode for highly stable lithium-sulfur batteries.

Dalton Trans 2021 Apr;50(16):5574-5581

Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), Nanjing Tech University, Nanjing 211816, Jiangsu Province, China. and School of Energy Sciences and Engineering, Nanjing Tech University, Nanjing 211816, China.

Lithium-sulfur batteries have a high theoretical energy density but they need better sulfur host materials to retain the lithium polysulfide shuttle effect, which results in the batteries' capacity fading. Titanium carbide MXene (Ti3C2Tx MXene) is an excellent host for the sulfur cathode because of its layered-stacked structure and many surface termination groups. The sulfur content in S/Ti3C2Tx MXene composites is an important factor affecting the cathodes' electrochemical performance. In this work, S/Ti3C2Tx MXene composites with different sulfur contents are prepared by a one-step hydrothermal process, and the influence of the sulfur content in the S/Ti3C2Tx MXene composite on the S/Ti3C2Tx MXene cathode's electrochemical performance is studied. When the mass ratio of sulfur to MXene in the reactant is 4 : 1, the sulfur nanoparticles are uniformly filled in the layered-stacked structure. The layered-stacked structure can buffer the volume expansion of sulfur during cycling and the surface termination groups exhibit strong adsorption of LiPSn. Thus, the S/MXene composite with an optimum sulfur content (67.0 wt%) demonstrates an excellent electrochemical performance, including a high initial reversible capacity (1277 mA h g-1 at 0.5 C) and the best cycling performance (1059 mA h g-1 at 0.5 C after 100 cycles). This work offers a guide to developing advanced S-based cathode materials with an appropriate S content for lithium sulfur batteries.
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http://dx.doi.org/10.1039/d1dt00381jDOI Listing
April 2021

Transmission dynamics of the rubella virus circulating in China during 2010-2019: two lineage switches between genotypes 1E and 2B.

Clin Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Yunnan Provincial Center for Disease Control and Prevention, Kunming, China.

Background: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019.

Methods: Total 4895 strains were obtained from 29 out of the 31 provinces in mainland of China during 2010-2019. The genotyping region of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and previously reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship.

Results: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that two switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses in this study.

Conclusions: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 and 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.
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http://dx.doi.org/10.1093/cid/ciab339DOI Listing
April 2021

Wnt5a up-regulates Periostin through CaMKII pathway to influence periodontal tissue destruction in early periodontitis.

J Mol Histol 2021 Apr 26. Epub 2021 Apr 26.

Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

Periostin is essential for periodontal tissue integrity and homeostasis and also associated with periodontitis and periodontitis healing. This study aims to investigate the temporal and spatial expression of Periostin and Wnt5a/CaMKII in periodontitis and how the Wnt5a regulates Periostin through CaMKII signaling pathway in PDLCs in inflammatory environment. The experimental periodontitis mice were adopted to clarify the temporal and spatial expression of Wnt5a, CaMKII and Periostin during early periodontitis. And the Wnt5a, CaMKII and Periostin expression pattern and regulation mechanism in PDLCs were clarified in Porphyromonas gingivalis Lipopolysaccharide (P.g. LPS) induced inflammatory condition. Along with the periodontitis development, Wnt5a, CaMKII and Periostin significantly increased in periodontal ligament and partially increased in gingiva during 0 to 6 day (P < 0.05). They were involved in early periodontitis homeostasis especially in periodontal ligament tissue. Meanwhile, Wnt5a, CaMKII and Periostin were significantly decreased at 12 h (P < 0.05) and increased at 48 h (P < 0.05) in PDLCs after induced by P.g. LPS. Besides, Wnt5a significantly enhanced total CaMKII protein (P < 0.05), pCaMKII (P < 0.001) and Periostin (P < 0.001), and this could be blocked by CaMKII inhibitor KN93 (P < 0.05). In conclusions, in early periodontitis, Wnt5a/CaMKII and Periostin should be involved in maintaining periodontal homeostasis and Wnt5a could up-regulate Periostin via CaMKII pathway in inflammation, which would provide new clues for us to understand the pathogenesis of periodontitis and develop better therapeutic strategies.
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http://dx.doi.org/10.1007/s10735-021-09975-zDOI Listing
April 2021

N-Enriched Porous Carbon/SiO2 Composites Derived from Biomass Rice Husks for Boosting Li-Ion Storage: Insight into the Effect of N-Doping.

Chemistry 2021 Apr 26. Epub 2021 Apr 26.

Chemistry, Qianjin Street 2699, 130012, Changchun, CHINA.

N-enriched porous carbon/SiO 2 (SiO 2 /NC) composite from rice husks was prepared by ball mill and tested as stable anode for lithium ion batteries (LIBs), in which the homogeneous dispersion of SiO 2 nanoparticles and carbon matrix, and high level of N-doping can be realized simultaneously. The N-doping influence on a series of SiO 2 /NC has been systematically studied, which proves that the porosity, N-doping content and electronic conductivity of SiO 2 /NC can be controlled by adjusting common nitrogen sources (urea and melamine) and doping routes including dry and wet mill to reach a desirable balance of high capacity, long-term cyclability and rate property. The optimized SiO 2 /NC composite delivers stably reversible capacity of 581 mA h g -1 at high current load of 1.0 A g -1 at 1000 th . The novel Li-storage mechanism of active silica in composite has been firstly proposed upon N-doping effect that redox reaction between SiO 2 and Li + is accelerated to transform into alloying reaction of Si generated and Li + , enhancing reversible capacity. Besides, kinetics analysis confirms that there is combined Li-storage mechanism of battery-capacitive pattern in composite, which contributes to fast charge transfer and ion diffusion during cycle.
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http://dx.doi.org/10.1002/chem.202100727DOI Listing
April 2021

Highly efficient and genotype-independent barley gene editing based on anther culture.

Plant Commun 2021 Mar 5;2(2):100082. Epub 2020 Jun 5.

Western Barley Genetics Alliance, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA 6150, Australia.

Recalcitrance to tissue culture and genetic transformation is the major bottleneck for gene manipulation in crops. In barley, immature embryos of Golden Promise have typically been used as explants for transformation. However, the genotype dependence of this approach limits the genetic modification of commercial varieties. Here, we developed an anther culture-based system that permits the effective creation of transgenic and gene-edited plants from commercial barley varieties. The protocol was tested in Golden Promise and four Australian varieties, which differed in phenology, callus induction, and green plant regeneration responses. -mediated transformation was performed on microspore-derived callus to target the gene, and T0 albinos with targeted mutations were successfully obtained from commercial varieties. Further editing of three targets was achieved with an average mutation rate of 53% in the five varieties. In 51 analyzed T0 individuals, Cas9 induced a large proportion (69%) of single-base indels and two-base deletions in the target sites, with variable mutation rates among targets and varieties. Both on-target and off-target activities were detected in T1 progenies. Compared with immature embryo protocols, this genotype-independent platform can deliver a high editing efficiency and more regenerant plants within a similar time frame. It shows promise for functional genomics and the application of CRISPR technologies for the precise improvement of commercial varieties.
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http://dx.doi.org/10.1016/j.xplc.2020.100082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060703PMC
March 2021

Myeloid MKL1 Disseminates Cues to Promote Cardiac Hypertrophy in Mice.

Front Cell Dev Biol 2021 9;9:583492. Epub 2021 Apr 9.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Cardiac hypertrophy is a key pathophysiological process in the heart in response to stress cues. Although taking place in cardiomyocytes, the hypertrophic response is influenced by other cell types, both within the heart and derived from circulation. In the present study we investigated the myeloid-specific role of megakaryocytic leukemia 1 (MKL1) in cardiac hypertrophy. Following transverse aortic constriction (TAC), myeloid MKL1 conditional knockout (MFCKO) mice exhibit an attenuated phenotype of cardiac hypertrophy compared to the WT mice. In accordance, the MFCKO mice were protected from excessive cardiac inflammation and fibrosis as opposed to the WT mice. Conditioned media collected from macrophages enhanced the pro-hypertrophic response in cardiomyocytes exposed to endothelin in an MKL1-dependent manner. Of interest, expression levels of macrophage derived miR-155, known to promote cardiac hypertrophy, were down-regulated in the MFCKO mice compared to the WT mice. MKL1 depletion or inhibition repressed miR-155 expression in macrophages. Mechanistically, MKL1 interacted with NF-κB to activate miR-155 transcription in macrophages. In conclusion, our data suggest that MKL1 may contribute to pathological hypertrophy via regulating macrophage-derived miR-155 transcription.
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http://dx.doi.org/10.3389/fcell.2021.583492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063155PMC
April 2021

Identification of Gradient Promoters of and Their Applications in the Biosynthesis of 2-Keto-L-Gulonic Acid.

Front Bioeng Biotechnol 2021 9;9:673844. Epub 2021 Apr 9.

Key Laboratory of Industrial Biotechnology, Ministry of Education and School of Biotechnology, Jiangnan University, Wuxi, China.

The acetic acid bacterium is known for its unique incomplete oxidation and therefore widely applied in the industrial production of many compounds, e.g., 2-keto-L-gulonic acid (2-KLG), the direct precursor of vitamin C. However, few molecular tools are available for metabolically engineering , which greatly limit the strain development. Promoters are one of vital components to control and regulate gene expression at the transcriptional level for boosting production. In this study, the low activity of SDH was found to hamper the high yield of 2-KLG, and enhancing the expression of SDH was achieved by screening the suitable promoters based on RNA sequencing data. We obtained 97 promoters from 's genome, including two strong shuttle promoters and six strongest promoters. Among these promoters, P and P revealed strong activities in both and , and the activity of the strongest promoter (P) was about threefold that of the other reported strong promoters of . These promoters were used to overexpress SDH in WSH-003. The titer of 2-KLG reached 3.7 g/L when SDH was under the control of strong promoters P and P. This study obtained a series of gradient promoters, including two strong shuttle promoters, and expanded the toolbox of available promoters for the application in metabolic engineering of for high-value products.
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http://dx.doi.org/10.3389/fbioe.2021.673844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064726PMC
April 2021

Genetic variants in STAT4 and their interactions with environmental factors for the incidence of hepatocellular carcinoma.

Cancer Biomark 2021 Apr 22. Epub 2021 Apr 22.

Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

Background: A recent genome-wide association study (GWAS) has posed STAT4 as a promising susceptibility gene for hepatocellular carcinoma (HCC). However, the most significant variant in this GWAS, rs7574865, yielded inconsistent results.

Objective: This study, in a Southern Chinese population, was aimed to clarify the roles in HCC incidence of the rs7574865 and other two potentially functional variants, rs897200 and rs1031507 in STAT4.

Methods: This study enrolled 631 new HCC cases and 631 cancer-free controls. The genetic association was estimated using the multivariate logistic regression model. The pairwise gene-environment interactions were assessed using the multiplicative term in regression model and the "Delta" method for the additive scale.

Results: In the multivariate analysis, the rs7574865 TT genotype conferred a decreased risk of HCC compared to the GG genotype (adjusted OR = 0.62, 95%CI = 0.38∼0.99). The significant association of rs7574865 was also observed under the additive genetic model, with an adjusted OR of 0.81 (95%CI = 0.65∼0.99). Nevertheless, other two variants alone showed no significant association, as well as the haplotypes and genetic risk scores. Further analysis indicated a potential interaction between the rs897200 and alcohol drinking (P= 0.048 and 0.072 for additive and multiplicative interactions, respectively). Drinkers with the rs897200 CT+CC genotypes presented an increased disease-risk, as compared with non-drinkers carrying the TT genotype (adjusted OR = 1.68, 95%CI = 1.11∼2.54).

Conclusions: The variant in STAT4, rs7574865, serves as a potential marker for predicting incidence of HCC. The rs897200 variant possibly interplays with alcohol drinking to alter HCC risk in the Southern Chinese, but warrants further investigation.
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http://dx.doi.org/10.3233/CBM-203162DOI Listing
April 2021

Clinical usefulness of metagenomic next generation sequencing for the diagnosis of central nervous system infections in people living with HIV.

Int J Infect Dis 2021 Apr 20. Epub 2021 Apr 20.

Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Infectious Diseases and Immunology, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China. Electronic address:

Objectives: To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system (CNS) infections in people living with HIV (PLWH) in real-world situation.

Methods: We send CSF to mNGS for PLWH who tested negative by all the conventional tests, but still suspected of CNS infections. We performed a retrospective analysis of the results and their clinical effect of mNGS on this cohort. The final diagnosis was adjudicated by a panel discussion after patient's discharge when the results of all the tests and patients' response to the empiric therapy were available.

Results: Eighty-eight eligible PLWH, including 58.0%(51/88) suspected of encephalitis and 46.7%(34/88) suspected of meningitis were included in the analysis. 77.3% (68/88) were diagnosed with CNS infections, among which 50 were based on the pathogens identified by mNGS. The most common diseases that mNGS missed were clinically suspected tuberculosis meningitis, followed by clinically suspected nontuberculous mycobacterial meningitis. The results from mNGS led to the modification of treatment in 23.9% (21/88) patients, while they increased confidence in maintaining original therapy in 34.1% (30/88). During hospitalization, total mortality was 2.3% (2/88) while 75% (66/88) of patients improved.

Conclusions: The CSF clinical mNGS is a useful tool in diagnosing CNS infections among PLWH. Further investigations are warranted to improve its sensitivity.
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http://dx.doi.org/10.1016/j.ijid.2021.04.057DOI Listing
April 2021