Publications by authors named "Min Chen"

3,209 Publications

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Enantioselective Formal Vinylogous N-H Insertion of Secondary Aliphatic Amines Catalyzed by a High-Spin Cobalt(II) Complex.

J Am Chem Soc 2021 Jun 21. Epub 2021 Jun 21.

Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.

Vinylcarbene insertion into the nitrogen-hydrogen (N-H) bond of amines allows direct access to α,β-unsaturated γ-amino acid derivatives, meeting a marked challenge in the control of regio- and enantioselectivities. Here, we report a highly γ-selective and enantioselective insertion into N-H bonds of aliphatic or aromatic secondary amines with vinyl substituted α-diazo pyrazoleamides using a high-spin chiral -dioxide/cobalt(II) complex catalyst. The method affords a wide variety of valuable optically active - and -type vinyl γ-amino amides. Calculation reveals a spin state change from the quartet cobalt(II) complex to a doublet Co(II)-carbene species for facile -selective and enantioselective nucleophilic addition.
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http://dx.doi.org/10.1021/jacs.1c04367DOI Listing
June 2021

Tailoring Unsymmetrical-Coordinated Atomic Site in Oxide-Supported Pt Catalysts for Enhanced Surface Activity and Stability.

Small 2021 Jun 21:e2101008. Epub 2021 Jun 21.

Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), School of Chemistry and Materials Science, and National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230026, China.

The catalytic properties of supported metal heterostructures critically depend on the design of metal sites. Although it is well-known that the supports can influence the catalytic activities of metals, precisely regulating the metal-support interactions to achieve highly active and durable catalysts still remain challenging. Here, the authors develop a support effect in the oxide-supported metal monomers (involving Pt, Cu, and Ni) catalysts by means of engineering nitrogen-assisted nanopocket sites. It is found that the nitrogen-permeating process can induce the reconstitution of vacancy interface, resulting in an unsymmetrical atomic arrangement around the vacancy center. The resultant vacancy framework is more beneficial to stabilize Pt monomers and prevent diffusion, which can be further verified by the density functional theory calculations. The final Pt-N/SnO catalysts exhibit superior activity and stability for HCHO response (26.5 to 15 ppm). This higher activity allows the reaction to proceed at a lower operating temperature (100 °C). Incorporated with wireless intelligent-sensing system, the Pt-N/SnO catalysts can further achieve continuous monitoring of HCHO levels and cloud-based terminal data storage.
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http://dx.doi.org/10.1002/smll.202101008DOI Listing
June 2021

The potential of the P2X7 receptor as a therapeutic target in a sub-chronic PCP-induced rodent model of schizophrenia.

J Chem Neuroanat 2021 Jun 17:101993. Epub 2021 Jun 17.

Department of Neurosurgery, Second Affiliation Hospital, Nanchang University, Nanchang, Jiangxi, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi, China. Electronic address:

Objective: We studied the role of the P2 × 7 receptor on cognitive dysfunction in a mouse model of schizophrenia.

Methods: An adult mouse model was established by treatment with phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist. Young mice were divided into three groups: 1) the control (saline-injected) group; 2) experimental 5 mg/kg PCP-injected group; and 3) experimental 10 mg/kg PCP-injected group. The mice were subjected to the open-field and Morris water maze tests at 7 weeks. After intraperitoneal injection of the P2 × 7 receptor antagonist JNJ-47965567, the behaviour tests were performed again. Samples were taken after testing. The P2 × 7 receptor protein and mRNA expression levels were detected by immunohistochemistry, Western blotting and PCR.

Results: This study revealed that the infant sub-chronic PCP mice model showed severe spatial learning and memory impairment in the Morris water maze and schizophrenia-like symptoms (hypermotor behaviour) in the open-field test. The P2 × 7 receptor protein was highly expressed in the sub-chronic PCP mouse model and more highly expressed in the hippocampus than the prefrontal lobe. After the P2 × 7 receptor was blocked with JNJ-47965567, P2 × 7 receptor protein and mRNA expression in the frontal lobe were significantly increased, and the spatial memory impairment and hypermotor behaviour induced by PCP were reversed.

Conclusion: PCP-induced cognitive impairment can be significantly improved by antagonizing the P2 × 7 receptor. Therefore, we believe that the P2 × 7 receptor plays an important role in the cognition of schizophrenic-like mice.
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http://dx.doi.org/10.1016/j.jchemneu.2021.101993DOI Listing
June 2021

Tumor Necrosis Factor-stimulated Gene-6 (TSG-6) Secreted by BMSCs Regulates Activated Astrocytes by Inhibiting NF-κB Signaling Pathway to Ameliorate Blood Brain Barrier Damage After Intracerebral Hemorrhage.

Neurochem Res 2021 Jun 19. Epub 2021 Jun 19.

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, Jiangxi Province, China.

To investigate the influence of tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by bone mesenchymal stem cells (BMSCs) on blood brain barrier (BBB) after intracerebral hemorrhage (ICH) and its related mechanisms. BMSCs and astrocytes were isolated and induced by TNF-α and LPS respectively. The effect of TSG-6 secreted by BMSCs on the proliferation and apoptosis of astrocytes and inflammatory response were assessed by CCK8, flow cytometry, and ELISA respectively. Then we studied the effects of TSG-6 secreted by BMSCs through the paracrine mechanism on the integrity of BBB after ICH via NF-κB signaling pathway in vitro and in vivo. We successfully isolated BMSCs and astrocytes. After LPS treatment of astrocytes, IL-1β, IL-6, and TNF-α showed an upward trend. TSG-6 secreted by TNF-α-activated BMSCs could antagonize the inflammatory response in activated astrocytes. Through the co-culture of astrocytes and BMSCs and the ICH animal model, we found that TSG-6 regulates activated astrocytes by inhibiting the NF-κB signaling pathway and ameliorates BBB damage. Furthermore, we found that TNF-α-activated BMSCs secreted exosomes containing TSG-6 and played an anti-inflammatory effect. TSG-6 secreted by BMSCs regulates activated astrocytes by inhibiting the NF-κB signaling pathway, thereby ameliorating BBB damage.
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http://dx.doi.org/10.1007/s11064-021-03375-1DOI Listing
June 2021

Hemodynamic Status During Endovascular Stroke Treatment: Association of Blood Pressure with Functional Outcome.

Neurocrit Care 2021 Jun 17. Epub 2021 Jun 17.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Background: Optimal blood pressure (BP) management during endovascular stroke treatment in patients with large-vessel occlusion is not well established. We aimed to investigate associations of BP during different phases of endovascular therapy with reperfusion and functional outcome.

Methods: We performed a post hoc analysis of a single-center prospective study that evaluated a new simplified procedural sedation standard during endovascular therapy (Keep Evaluating Protocol Simplification in Managing Periinterventional Light Sedation for Endovascular Stroke Treatment). BP during endovascular therapy in patients was managed according to protocol. Data from four different phases (baseline, pre-recanalization, post recanalization, and post intervention) were obtained, and mean BP values, as well as changes in BP between different phases and reductions in systolic BP (SBP) and mean arterial pressure (MAP) from baseline to pre-recanalization, were used as exposure variables. The main outcome was a modified Rankin Scale score of 0-2 three months after admission. Secondary outcomes were successful reperfusion and change in the National Institutes of Health Stroke Scale score after 24 h. Multivariable linear and logistic regression models were used for statistical analysis.

Results: Functional outcomes were analyzed in 139 patients with successful reperfusion (defined as thrombolysis in cerebral infarction grade 2b-3). The mean (standard deviation) age was 76 (10.9) years, the mean (standard deviation) National Institutes of Health Stroke Scale score was 14.3 (7.5), and 70 (43.5%) patients had a left-sided vessel occlusion. Favorable functional outcome (modified Rankin Scale score 0-2) was less likely with every 10-mm Hg increase in baseline (odds ratio [OR] 0.76, P = 0.04) and pre-recanalization (OR 0.65, P = 0.011) SBP. This was also found for baseline (OR 0.76, P = 0.05) and pre-recanalization MAP (OR 0.66, P = 0.03). The maximum Youden index in a receiver operating characteristics analysis revealed an SBP of 163 mm Hg and MAP of 117 mm Hg as discriminatory thresholds during the pre-recanalization phase to predict functional outcome.

Conclusions: In our protocol-based setting, intraprocedural pre-recanalization BP reductions during endovascular therapy were not associated with functional outcome. However, higher intraprocedural pre-recanalization SBP and MAP were associated with worse functional outcome. Prospective randomized controlled studies are needed to determine whether BP is a feasible treatment target for the modification of outcomes.
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http://dx.doi.org/10.1007/s12028-021-01229-wDOI Listing
June 2021

A novel miRNA-disease association prediction model using dual random walk with restart and space projection federated method.

PLoS One 2021 17;16(6):e0252971. Epub 2021 Jun 17.

Hunan Institute of Technology, School of Computer Science and Technology, Hengyang, China.

A large number of studies have shown that the variation and disorder of miRNAs are important causes of diseases. The recognition of disease-related miRNAs has become an important topic in the field of biological research. However, the identification of disease-related miRNAs by biological experiments is expensive and time consuming. Thus, computational prediction models that predict disease-related miRNAs must be developed. A novel network projection-based dual random walk with restart (NPRWR) was used to predict potential disease-related miRNAs. The NPRWR model aims to estimate and accurately predict miRNA-disease associations by using dual random walk with restart and network projection technology, respectively. The leave-one-out cross validation (LOOCV) was adopted to evaluate the prediction performance of NPRWR. The results show that the area under the receiver operating characteristic curve(AUC) of NPRWR was 0.9029, which is superior to that of other advanced miRNA-disease associated prediction methods. In addition, lung and kidney neoplasms were selected to present a case study. Among the first 50 miRNAs predicted, 50 and 49 miRNAs have been proven by in databases or relevant literature. Moreover, NPRWR can be used to predict isolated diseases and new miRNAs. LOOCV and the case study achieved good prediction results. Thus, NPRWR will become an effective and accurate disease-miRNA association prediction model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252971PLOS
June 2021

Arsenic and Cadmium in Soils from a Typical Mining City in Huainan, China: Spatial Distribution, Ecological Risk Assessment and Health Risk Assessment.

Bull Environ Contam Toxicol 2021 Jun 14. Epub 2021 Jun 14.

School of Earth and Environment, Anhui University of Science and Technology, Huainan, 232001, China.

In order to determine the ecological risk and health risk of Arsenic (As) and Cadmium (Cd) in soils from a typical mining city in Huainan, a total of 99 soil samples were collected and analyzed. The results showed that the concentrations of As and Cd ranged from 3.2 to 39.50 and 0.01 to 0.19 mg/kg, respectively, which exceeded the soil background values by 6.06 and 14.14%, respectively. The soil pH and content of organic carbon demonstrated no significant (P > 0.05) correlation with the As and Cd concentrations, while the land use types significantly (P < 0.05) affected the As and Cd distribution. According to the Nemero synthesis pollution index, three spot areas were identified as moderately to strongly polluted. The potential ecological risk index ranged from 4.34 to 108.64, which represented that the potential ecological risk was low. In addition, children faced more carcinogenic risk of As. Consequently, mining has increased the concentrations of As and Cd in soils, and the carcinogenic risk of As to children should be paid more attention.
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http://dx.doi.org/10.1007/s00128-021-03278-5DOI Listing
June 2021

Incidence and impact of community respiratory viral infections in post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis and haploidentical stem cell transplantation.

Br J Haematol 2021 Jun 14. Epub 2021 Jun 14.

Department of Medicine, City of Hope, Duarte, CA, USA.

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P = 0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.
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http://dx.doi.org/10.1111/bjh.17563DOI Listing
June 2021

Type-I ROP18 Targeting Human E3 Ligase TRIM21 for Immune Escape.

Front Cell Dev Biol 2021 26;9:685913. Epub 2021 May 26.

Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China.

is an intracellular pathogen that exerts its virulence through inhibiting host's innate immune responses, which is mainly related to the type II interferon (IFN-γ) response. IFN-γ inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that virulence factor ROP18 of the type I RH strain (ROP18) interacted with human TRIM21, and promoted the latter's phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-γ in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of IκB-α with p65 to activate the IFN-γ-inducible NF-κB pathway, which might be resulted by TRIM21-IκB-α interaction. In brief, our research identified that in human cells, IFN-γ-inducible TRIM21 functioned in the innate immune responses against type III infection; however, ROP18 promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.
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http://dx.doi.org/10.3389/fcell.2021.685913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187923PMC
May 2021

Total Cerebral Small Vessel Score Association With Hoehn and Yahr Stage in Parkinson's Disease.

Front Aging Neurosci 2021 28;13:682776. Epub 2021 May 28.

Department of Neurology, Parkinson's Disease and Extra Pyramidal Disease Diagnosis and Treatment Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

: This study aimed to evaluate the total cerebral small vessel disease (CSVD) score in patients with Parkinson's disease (PD) at different stages and related factors. : A 100 and seven patients with idiopathic PD and 62 normal controls (NCs) who underwent brain magnetic resonance imaging (MRI) were enrolled. PD patients were divided into two groups: early PD [(Hoehn and Yahr (H&Y) 1-1.5, = 36)] and advanced PD (H&Y 2-4, = 71) groups. We calculated the total CSVD score for each participant based on lacunes, high-grade white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs). Differences in total CSVD score between the PD and NCs and between the two subgroups were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between CSVD markers and clinical variables in PD. : Lacunes were found in 9.3% of patients with PD, periventricular WMH (PVWMH) in 89.7%, deep WMH (DWMH) in 81.3%, EPVS in 85%, and CMBs in 2.8%. Compared with NCs, patients with PD showed higher PVWMH and DWMH scores. Advanced PD patients exhibited greater PVWMH ( = 0.041), DWMH ( = 0.046), and total CSVD score ( = 0.044) than the early PD group. After adjusting for multiple variables, higher H&Y stage was independently correlated with increased total CSVD score (OR = 2.667, 95% CI 1.154-2.266) and PVWMH score (OR = 2.237, 95% CI 1.084-1.696). : CSVD may play a critical role in patients with PD. The total CSVD score is a potential neuroimaging marker for monitoring the progression of PD.
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http://dx.doi.org/10.3389/fnagi.2021.682776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192831PMC
May 2021

PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Expression via Modulation of Lysine Histone Modifications.

Front Cell Dev Biol 2021 21;9:673258. Epub 2021 May 21.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of mono- or symmetric dimethylarginine residues on histones and non-histone substrates and has been demonstrated to play important roles in many biological processes. In the present study, we observed that PRMT5 is abundantly expressed in spermatogonial stem cells (SSCs) and that deletion results in a progressive loss of SSCs and male infertility. The proliferation of -deficient SSCs cultured exhibited abnormal proliferation, cell cycle arrest in G0/G1 phase and a significant increase in apoptosis. Furthermore, PLZF expression was dramatically reduced in -deficient SSCs, and the levels of H3K9me2 and H3K27me2 were increased in the proximal promoter region of the gene in -deficient SSCs. Further study revealed that the expression of lysine demethylases (JMJD1A, JMJD1B, JMJD1C, and KDM6B) was significantly reduced in -deficient SSCs and that the level of permissive arginine methylation H3R2me2s was significantly decreased at the upstream promoter region of these genes in -deficient SSCs. Our results demonstrate that PRMT5 regulates spermatogonial stem cell development by modulating histone H3 lysine modifications.
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http://dx.doi.org/10.3389/fcell.2021.673258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185031PMC
May 2021

Preparation of magnetic zeolitic imidazolate framework-8 for magnetic solid-phase extraction of strobilurin fungicides from environmental water samples.

Anal Methods 2021 Jun 10. Epub 2021 Jun 10.

College of Life Science, Yantai University, Yantai 264005, P. R. China.

In this paper, magnetic zeolitic imidazolate framework-8 composites were synthesized by a simple in situ method and then used for the first time as an adsorbent in magnetic solid-phase extraction for extracting multiple strobilurin fungicides. The magnetic composites were characterized in detail. The results showed that Fe3O4 nanoparticles were attached on the surface of zeolitic imidazolate framework-8 with a uniform particle size of 150-200 nm and that the magnetic composites possessed a perfect molecular transfer rate towards strobilurin fungicides. The parameters of the magnetic solid-phase extraction process, including solution pH, adsorption time, solution volume, elution solvent, and elution volume, were investigated. Under the optimum conditions, the recoveries of all five fungicides fell within the range 80.8-109.0% with spiking levels of 10, 20 and 50 ng mL-1. A magnetic solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry method based on the magnetic composites was established and confirmed to be simple, time-efficient and highly sensitive.
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http://dx.doi.org/10.1039/d1ay00645bDOI Listing
June 2021

Pharmacokinetics-Based Chronoefficacy of and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis.

Front Pharmacol 2021 24;12:673263. Epub 2021 May 24.

Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, China.

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT timed delivery.
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http://dx.doi.org/10.3389/fphar.2021.673263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181759PMC
May 2021

USP28 promotes aerobic glycolysis of colorectal cancer by increasing stability of FOXC1.

Acta Biochim Pol 2021 Jun 9. Epub 2021 Jun 9.

Department of Anorectal Surgery, First People's Hospital of Yuhang District, Hangzhou, Hangzhou City, Zhejiang Province, 311100, P.R. China.

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Our data showed that USP28 mRNA and protein expressions were enhanced in colorectal cancer tissues and cells. Functional assays demonstrated that overexpression of USP28 promoted cell proliferation and aerobic glycolysis of colorectal cancer, while USP28 inhibition could reverse these effects. Protein expression of Forkhead Box C1 (FOXC1) was increased by USP28 over-expression, whereas knockdown of USP28 aggravated cycloheximide (CHX; protein synthesis inhibitor) stimulated decrease of FOXC1. Moreover, proteasome inhibitor, MG132, could rescue USP28 silence-induced degradation of FOXC1. Overexpression of FOXC1 counteracted the suppressive effects of USP28 interference on colorectal cancer cell viability and aerobic glycolysis. In conclusion, USP28 enhanced cell viability and aerobic glycolysis of colorectal cancer by stabilizing FOXC1, suggesting that USP28-FOXC1 might be a novel therapeutic avenue for colorectal cancer.
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http://dx.doi.org/10.18388/abp.2020_5504DOI Listing
June 2021

[Establishment and Usage of Leukemia-Lymphoma Cell Lines--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):1007-1010

Department of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China,E-mail:

Cancer cell lines are an indispensable tool in the cancer research. Since the first human cell line, HeLa was established in the 1950s, thousands of cancer cell lines have been established, including 637 characterized leukemia-lymphoma cell lines. The probability to successfully establish cancer cell lines is a low by traditional methods, and the addition of regulatory factors is often required. However, a novel "conditional reprogramming" technology can improve this situction. The establishment and description of a new cell line should be consistent with international guidelines. Cancer cell lines are mainly used in the research of tumor pathogenesis and drug development. Scientists have developed many kinds of cell line panels which can be used for the high-throughput screening of anticancer drugs. Mycoplasma contamination and/or cross-contamination from other cells should be avoided during the use of cell lines. The establishment of a cell model passport database can prevent those misidentifications. In this review, the types, establishment and usage of leukemia-lymphoma cell lines as well as points of attention when using them are summarized briefly.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.057DOI Listing
June 2021

Chinese expert consensus on gastroesophageal reflux disease in 2020.

J Dig Dis 2021 Jun 8. Epub 2021 Jun 8.

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

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http://dx.doi.org/10.1111/1751-2980.13028DOI Listing
June 2021

The attenuation of diabetic nephropathy by annexin A1 regulation of lipid metabolism through AMPK/PPARα/CPT1b pathway.

Diabetes 2021 Jun 8. Epub 2021 Jun 8.

Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China.

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated ThrAMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.
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http://dx.doi.org/10.2337/db21-0050DOI Listing
June 2021

Myeloid-specific SIRT1 deletion exacerbates airway inflammatory response in a mouse model of allergic asthma.

Aging (Albany NY) 2021 Jun 7;13(11):15479-15490. Epub 2021 Jun 7.

Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

Sirtuin 1 (SIRT1) is a class III histone deacetylase that exerts an anti-inflammatory effect in airway diseases. Activated macrophages play an important role in asthma. However, the roles of SIRT1 on allergic airway inflammation in macrophages remain largely unexplored. In this study, we aimed to determine the roles of SIRT1 on allergic airway inflammation in macrophages. The effect of myeloid-specific SIRT1 deletion (-) on airway inflammation was assessed by using models of asthma following allergen exposure and culture of primary bone marrow-derived macrophages (BMDMs) exposed to house dust mite (HDM). We observed that - mice substantially enhanced airway inflammation and mucus production in response to allergen exposure. Expression of chemokine ligand (CXCL) 2, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were reduced in BMDMs with myeloid-specific deletion of after stimulation of HDM. Moreover, SIRT1 suppressed the inflammatory cytokines expression in BMDMs partially via the ERK/p38 MAPK pathways. Our study demonstrated that SIRT1 suppresses the allergic airway inflammation in macrophages, and suggested that activation of SIRT1 in macrophages may represent therapeutic strategy for asthma.
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http://dx.doi.org/10.18632/aging.203104DOI Listing
June 2021

Sea turtle demand in China threatens the survival of wild populations.

iScience 2021 Jun 6;24(6):102517. Epub 2021 May 6.

Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou 571158, China.

Sea turtles are an important umbrella species in marine ecosystems. The populations of all five species of sea turtles in China have dropped sharply due to massive illegal trade and habitat loss. The fast-growing demand for sea turtle displays from Chinese aquariums and private individuals has led to a large-scale illegal trade domestically and internationally. Captive sea turtles are also frequently kept in harsh environments with severe injuries and high mortality rates. Sea turtles have only recently been upgraded from level II to level I on the "List of Wildlife under Special State Protection", this protection level has therefore not matched the real status of sea turtles over the past three decades. The additional collusion between the government and business corporations encourages illegal trade. We argue that the commercial use of sea turtles must be completely prohibited to guarantee their future survival in Chinese waters.
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http://dx.doi.org/10.1016/j.isci.2021.102517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163976PMC
June 2021

Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis.

Front Pharmacol 2021 19;12:671845. Epub 2021 May 19.

The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. We included 10 trials ( = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI -1.24 to -0.63); fremanezumab showed similar findings (SMD, -0.55, 95%CI -0.85 to -0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.
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http://dx.doi.org/10.3389/fphar.2021.671845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170150PMC
May 2021

Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction.

Chin J Nat Med 2021 Jun;19(6):454-463

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or αβ nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.
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http://dx.doi.org/10.1016/S1875-5364(21)60044-4DOI Listing
June 2021

Dolomiaea souliei ethyl acetate extract protected against α-naphthylisothiocyanate-induced acute intrahepatic cholestasis through regulation of farnesoid x receptor-mediated bile acid metabolism.

Phytomedicine 2021 Jul 3;87:153588. Epub 2021 Jun 3.

College of Pharmaceutical Sciences, Key Laboratory of Luminescence Analysis and Molecular Sensing (Ministry of Education), Southwest University, No. 2 Tiansheng Road, Chongqing 400715, P.R. China. Electronic address:

Background: Cholestasis is characterized by accumulation of bile components in liver and systemic circulation. Restoration of bile acid homeostasis via activating farnesoid x receptor (FXR) is a promising strategy for the treatment of cholestasis. FXR-SHP (small heterodimer partner) axis plays an important role in maintaining bile acid homeostasis.

Purpose: To investigate the anti-cholestasis effect of Dolomiaea souliei (Franch.) C.Shih (D. souliei) and clarify its underlying mechanism against α-naphthylisothiocyanate (ANIT) induced acute intrahepatic cholestasis.

Methods: ANIT-induced Sprague-Dawley rats were employed to investigate the anti-cholestasis effect of D. souliei ethyl acetate extract (DSE). Ursodeoxycholic acid (UDCA) was used as positive control. Bile flow and blood biochemical parameters were measured. Liver histopathological examination was conducted via hematoxylin-eosin staining. Western blot analysis was carried out to evaluate the protein levels related to bile acids metabolism and inflammation. The interactions between FXR and costunolide or dehydrocostus lactone, were conducted by molecular docking experiments. The effect of costunolide and dehydrocostus lactone on aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and FXR expression were also evaluated using guggulsterone-induced L02 cells.

Results: DSE could promote bile excretions and protect against ANIT-induced liver damage in cholestasis rats. Protein levels of FXR, SHP, Na/taurocholate cotransporter (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) were increased and the expressions of cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) were decreased by DSE. Meanwhile, the anti-inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were also significantly increased, and the pro-inflammatory factor, interleukin-10 (IL-10), was significantly decreased in rats of DSE groups. Molecular docking revealed that costunolide and dehydrocostus lactone could be well docked into the FXR protein molecule, and hydrophobic interactions played the main function. Costunolide could reverse the increased AST and ALT levels and increase the FXR expression in guggulsterone-induced L02 cells.

Conclusion: DSE had an anti-cholestasis effect by activating FXR-SHP axis, inhibiting synthesis of bile acid, and increasing bile secretion, together with inflammatory response and improving liver injury. Costunolide may be the main active component. This study provided a potential therapeutic mechanism for D. souliei as an anti-cholestasis medicine in the treatment of cholestasis liver diseases.
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http://dx.doi.org/10.1016/j.phymed.2021.153588DOI Listing
July 2021

Associations between brain volumetry and relaxometry signatures and the Edmonton Frail Scale in frailty.

Quant Imaging Med Surg 2021 Jun;11(6):2560-2571

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

Background: Frailty is a geriatric condition characterized by a decreased reserve. The Edmonton frailty scale (EFS) has been widely used as an assessment tool in clinical practice. However, the brain's underlying pathophysiological changes in frailty and their associations with the EFS remain unclear. This study aimed to explore the associations between brain volumetry and relaxometry signatures and the EFS (and each domain score of the EFS) in frailty.

Methods: A total of 40 non-demented subjects were enrolled in this prospective study. Frailty assessment was performed for each subject according to the EFS. All subjects underwent synthetic magnetic resonance imaging (MRI) (MAGnetic resonance image Compilation, MAGiC) and three-dimensional fast spoiled gradient-recalled echo (3D-FSPGR) T1-weighted structural image acquisitions on a 3.0 T MR scanner. Brain segmentation was performed based on quantitative values obtained from the MAGiC and 3D-FSPGR images. Volumetry and relaxometry of the global brain and regional gray matter (GM) were also obtained. The associations between the total EFS score (and the score of each domain) and the brain's volumetry and relaxometry were investigated by partial correlation while eliminating the effects of age. Multiple comparisons of regional GM volumetry and relaxometry analyses were controlled by false discovery rate (FDR) correction. All data were analyzed using the SPSS 13.0 statistical package (IBM, Armonk, NY, USA) and MATLAB (MathWorks, Natick, MA, USA).

Results: For global volumetry, significant correlations were found between multiple global volumetry parameters and the EFS, as well as the cognition score, functional independence score, nutrition score, and functional performance score (P<0.05). For global relaxometry, notable positive correlations were found between the T2 values of gray and white matter (WM) and the EFS (r=0.357, P=0.026; r=0.357, P=0.026, respectively). Significant correlations were also identified between the T2 value of GM, the T1, T2, and PD values of WM, and the cognition score (r=0.426, P=0.007; r=0.456, P=0.003; r=0.377, P=0.018; r=0.424, P=0.007, respectively), functional independence score (r=-0.392, P=0.014; r=-0.611, P<0.001; r=-0.367, P=0.022; r=-0.569, P<0.001, respectively), and functional performance score (r=0.337, P=0.036; r=0.472, P=0.002; r=0.354, P=0.027; r=0.376, P=0.018, respectively). For regional GM volumetry, multiple regions showed significant negative correlations with the EFS (P<0.05). Notable negative correlations were found between multiple regional GM volume and the functional independence score (P<0.05). For regional GM relaxometry, the T1 and T2 values of several regions showed significant negative correlations with the functional independence score (T1 value of caudate, r=-0.617, P<0.001; T2 value of insula, r=-0.510, P=0.015; T2 value of caudate, r=-0.633, P<0.001, respectively). No significant correlation was found between the domain scores of the EFS and regional GM PD values (P>0.05).

Conclusions: In conclusion, brain volumetry and relaxometry signatures showed strong associations with the EFS and some EFS domain scores in frailty. These associations may reveal the possible underlying pathophysiology of the EFS and different domains of the EFS.
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http://dx.doi.org/10.21037/qims-20-852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107325PMC
June 2021

Effect of adaptive statistical iterative reconstruction-V (ASiR-V) levels on ultra-low-dose CT radiomics quantification in pulmonary nodules.

Quant Imaging Med Surg 2021 Jun;11(6):2344-2353

Department of Radiology, Peking University Third Hospital, Beijing, China.

Background: The weightings of iterative reconstruction algorithm can affect CT radiomic quantification. But, the effect of ASiR-V levels on the reproducibility of CT radiomic features between ultra-low-dose computed tomography (ULDCT) and low-dose computed tomography (LDCT) is still unknown. The purpose of study is to investigate whether adaptive statistical iterative reconstruction-V (ASiR-V) levels affect radiomic feature quantification using ULDCT and to assess the reproducibility of radiomic features between ULDCT and LDCT.

Methods: Sixty-three patients with pulmonary nodules underwent LDCT (0.70±0.16 mSv) and ULDCT (0.15±0.02 mSv). LDCT was reconstructed with ASiR-V 50%, and ULDCT with ASiR-V 50%, 70%, and 90%. Radiomics analysis was applied, and 107 features were extracted. The concordance correlation coefficient (CCC) was calculated to describe agreement among ULDCTs and between ULDCT and LDCT for each feature. The proportion of features with CCC >0.9 among ULDCTs and between ULDCT and LDCT, and the mean CCC for all features between ULDCT and LDCT were also compared.

Results: Sixty-three solid nodules (SNs) and 48 pure ground-glass nodules (pGGNs) were analyzed. There was no difference for the proportion of features in SNs among ULDCTs and between ULDCT and LDCT (P>0.05). The proportion of features in pGGNs were highest for ULDCT (78.5%) and ULDCT LDCT (50.5%). In SNs, the mean CCC for ULDCT LDCT was 0.67±0.26, not different with that for ULDCT LDCT (0.68±0.24) and ULDCT LDCT (0.64±0.21) (P>0.05). In pGGNs, the mean CCC for ULDCT LDCT was 0.79±0.19, higher than that for ULDCT LDCT (0.61±0.28) and ULDCT LDCT (0.76±0.24) (P<0.05).

Conclusions: ASiR-V levels significantly affected ULDCT radiomic feature quantification in pulmonary nodules, with stronger effects in pGGNs than in SNs. The reproducibility of radiomic features was highest between ULDCT and LDCT.
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http://dx.doi.org/10.21037/qims-20-932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107324PMC
June 2021

A long short-term memory-fully connected (LSTM-FC) neural network for predicting the incidence of bronchopneumonia in children.

Environ Sci Pollut Res Int 2021 Jun 2. Epub 2021 Jun 2.

Chongqing Jinfo Mountain Karst Ecosystem National Observation and Research Station, School of Geographical Sciences, Southwest University, Chongqing, 400715, China.

Bronchopneumonia is the most common infectious disease in children, and it seriously endangers children's health. In this paper, a deep neural network combining long short-term memory (LSTM) layers and fully connected layers was proposed to predict the prevalence of bronchopneumonia in children in Chengdu based on environmental factors and previous prevalence rates. The mean square error (MSE), mean absolute error (MAE), and Pearson correlation coefficient (R) were used to detect the performance of the deep learning model. The values of MSE, MAE, and R in the test dataset are 0.0051, 0.053, and 0.846, respectively. The results show that the proposed model can accurately predict the prevalence of bronchopneumonia in children. We also compared the proposed model with three other models, namely, a fully connected (FC) layer neural network, a random forest model, and a support vector machine. The results show that the proposed model achieves better performance than the three other models by capturing time series and mitigating the lag effect.
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http://dx.doi.org/10.1007/s11356-021-14632-9DOI Listing
June 2021

Tree shrew cells transduced with human CD4 and CCR5 support early steps of HIV-1 replication, but viral infectivity is restricted by APOBEC3.

J Virol 2021 Jun 2:JVI0002021. Epub 2021 Jun 2.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Bio-safety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

The host range of human immunodeficiency virus type 1 (HIV-1) is narrow. Therefore, using ordinary animal models to study HIV-1 replication, pathogenesis, and therapy is impractical. The lack of applicable animal models for HIV-1 research spurred our investigation on whether tree shrews (), which are susceptible to many types of human viruses, can act as an animal model for HIV-1. Here, we report that tree shrew primary cells are refractory to wild-type HIV-1 but support the early replication steps of HIV-1 pseudotyped with the vesicular stomatitis virus glycoprotein envelope (VSV-G), which can bypass entry receptors. The exogenous expression of human CD4 renders the tree shrew cell line infectable to X4-tropic HIV-1, suggesting that tree shrew CXCR4 is a functional HIV-1 co-receptor. However, tree shrew cells did not produce infectious HIV-1 progeny virions, even with the human CD4 receptor. Subsequently, we identified tree shrew (ts) apolipoprotein B editing catalytic polypeptide 3 (tsAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity, with virus infectivity reduced 10-1 000-fold. Unlike human APOBEC3G, the tsA3Z2c-Z1b protein was not degraded by the HIV-1 viral infectivity factor (Vif), but markedly restricted HIV-1 replication through mutagenicity and reverse transcription inhibition. The pooled knockout of tsA3Z2c-Z1b partially restored the infectivity of the HIV-1 progeny. This work suggests that tsAPOBEC3 proteins serve as an additional barrier to the development of HIV-1 tree shrew models, even when virus entry is overcome by exogenous expression of human CD4. The development of animal models is critical for studying human diseases and their pathogenesis and for evaluating drug and vaccine efficacy. For improved AIDS research, the ideal animal model of HIV-1 infection should be a small laboratory mammal that closely mimics virus replication in humans. Tree shrews exhibit considerable potential as animal models for the study of human diseases and therapeutic responses. Here, we report that human-CD4-expressing tree shrew cells support the early steps of HIV-1 replication and that tree shrew CXCR4 is a functional co-receptor of HIV-1. However, tree shrew cells harbor additional restrictions that lead to the production of HIV-1 virions with low infectivity. Thus, the tsAPOBEC3 proteins are partial barriers to developing tree shrews as an HIV-1 model. Our results provide insight into the genetic basis of HIV inhibition in tree shrews and build a foundation for the establishment of gene-edited tree shrew HIV-1-infected models.
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http://dx.doi.org/10.1128/JVI.00020-21DOI Listing
June 2021

Real-Time and Label-Free Measurement of Deubiquitinase Activity with a MspA Nanopore.

Chembiochem 2021 May 31. Epub 2021 May 31.

Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA.

Covalently attaching ubiquitin (Ub) to cellular proteins as a post-translational modification can result in altered function of modified proteins. Enzymes regulating Ub as a post-translational modification, such as ligases and deubiquitinases, are challenging to characterize in part due to the low throughput of in-vitro assays. Single-molecule nanopore based assays have the advantage of detecting proteins with high specificity and resolution, and in a label-free, real-time fashion. Here we demonstrate the use of a MspA nanopore for discriminating and quantifying Ub proteins. We further applied the MspA pore to measure the Ub-chain disassembly activity of UCH37, a proteasome associated deubiquitinase. The implementation of this MspA system into nanopore arrays could enable high throughput characterizations of unknown deubiquitinases as well as drug screening against disease related enzymes.
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http://dx.doi.org/10.1002/cbic.202100092DOI Listing
May 2021

Motor Symptom Lateralization Influences Cortico-Striatal Functional Connectivity in Parkinson's Disease.

Front Neurol 2021 14;12:619631. Epub 2021 May 14.

Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Disease, Qilu Hospital of Shandong University, Jinan, China.

The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI). Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation. Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients. Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.
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http://dx.doi.org/10.3389/fneur.2021.619631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160303PMC
May 2021

sp. nov., a novel bacterium isolated from wormcast of .

Int J Syst Evol Microbiol 2021 May;71(5)

Guizhou Academy of Tobacco Science, Guiyang, 550081, PR China.

A novel Gram-stain-negative, rod-shaped, non-motile, yellowish bacterium, designated strain 1.3611, was isolated from the wormcast of . The strain grew optimally at 30-37 ℃, at pH 7.0 and with 0-1.0 % (w/v) NaCl. Based on the results of 16S rRNA gene sequence and phylogenetic analyses, strain 1.3611 showed the highest degree of 16S rRNA gene sequence similarity to HAL-9 (97.0 %), followed by Y3L14 (95.8 %). The respiratory quinone of strain 1.3611 was menaquinone-7 (MK-7) and its major cellular fatty acids were iso-C (41.3 %), summed feature 3 (C7 and/or C6, 22.1 %) and iso-C 3-OH (16.2 %). The major polar lipids were sphingophospholipid, phosphatidylethanolamine, four unidentified glycolipids, two unidentified phospholipids and five unidentified polar lipids. The genomic DNA G+C content was 39.0 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between the genomes of strain 1.3611 and HAL-9 were 37.9 and 88.9 %, respectively. According to the phenotypic and chemotaxonomic phylogenetic results, strain 1.3611 should represent a novel species of the genus , for which the name sp. nov. is proposed, with strain 1.3611 (=KCTC 62980=CCTCC AB 2018349) as the type strain.
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http://dx.doi.org/10.1099/ijsem.0.004823DOI Listing
May 2021

COMMD10 inhibits tumor progression and induces apoptosis by blocking NF-κB signal and values up BCLC staging in predicting overall survival in hepatocellular carcinoma.

Clin Transl Med 2021 May;11(5):e403

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Currently, there is limited knowledge of dysregulation of cellular proliferation and apoptosis that contribute to the malignant phenotype in HCC. Copper metabolism gene MURR1 domain 10 (COMMD10) is initially identified as a suppressor gene in the pathogenesis of HCC in our observations. Here we aimed to explore its function and prognostic value in the progression of HCC.

Methods: Functional experiments were performed to explore the role of COMMD10 in HCC. The molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, and immunoprecipitation. The nomogram was based on a retrospective and multicenter study of 516 patients who were pathologically diagnosed with HCC from three Chinese hospitals. The predictive accuracy and discriminative ability of the nomogram were determined by a C-index and calibration curve and were compared with COMMD10 and the Barcelona Clinic Liver Cancer (BCLC) staging system. The primary endpoint was overall survival (OS).

Results: COMMD10 expression was significantly lower in HCC than that in normal liver tissues. In vitro and in vivo experiments revealed that COMMD10 suppressed cell proliferation and induced apoptosis in HCC. Mechanistically, COMMD10 inhibits TNFα mediated ubiquitination of IκBα and p65 nuclear translocation through the combination of COMMD10-N terminal to the Rel homology domain of p65, which inhibited NF-κB activity and increased expression of cleaved caspase9/3 in HCC. Clinically, COMMD10 stratifies early-stage HCC patients into two risk groups with significantly different OS. Additionally, the nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in three cohorts.

Conclusions: COMMD10 suppresses proliferation and promotes apoptosis by inhibiting NF-κB signaling and values up BCLC staging in predicting OS, which provides evidence for the identification of potential therapeutic targets and the accurate prediction of prognosis for patients with HCC.
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http://dx.doi.org/10.1002/ctm2.403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093973PMC
May 2021