Publications by authors named "Lu Li"

2,318 Publications

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Brain functional changes in patients with Crohn's disease: A resting-state fMRI study.

Brain Behav 2021 Jun 14. Epub 2021 Jun 14.

Department of Radiology, Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.

Background: Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in-depth.

Objective: To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices.

Methods: A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed.

Results: Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point.

Conclusion: CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive-related functions, which provides more information to further understand the neural mechanisms of the disease.
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http://dx.doi.org/10.1002/brb3.2243DOI Listing
June 2021

Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation.

Chem Sci 2020 Aug 10;11(33):8895-8900. Epub 2020 Aug 10.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy. Although considerable efforts have been directed at drug screening in living cells, performing repeated drug sensitivity analysis using patient-derived primary tumor cells at the single-cell level remains challenging. Here, we present an efficient approach to assess phenotype-related drug sensitivity at the single-cell level using patient-derived circulating tumor cells (CTCs) based on a drug sensitivity microfluidic chip (DS-Chip). The DS-Chip consists of a drug gradient generator and parallel cell traps, achieving continuous single CTC capture, drug gradient distributions, drug stimulation, fluorescent probe labeling and three-color fluorescence imaging. Based on the established DS-Chip, we investigated the drug sensitivity of single cells by simultaneously monitoring epithelial-mesenchymal transition (EMT) biomarkers and apoptosis in living cells, and verified the correlation between EMT gradients and drug sensitivity. Using the new approach, we further tested the optimal drug response dose in individual CTCs isolated from 5 cancer patients through fluorescence analysis of EMT and apoptosis. The DS-Chip allows noninvasive and real-time measurements of the drug sensitivity of a patient's tumor cells during therapy. This developed approach has practical significance and can effectively guide drug selection and therapeutic evaluation for personalized medicine.
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http://dx.doi.org/10.1039/c9sc05566eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163339PMC
August 2020

CoS nanowires grown on TiCT are promising electrodes for supercapacitors: High capacitance and remarkable cycle capability.

J Colloid Interface Sci 2021 Jun 4;602:123-130. Epub 2021 Jun 4.

Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin 150025, People's Republic of China. Electronic address:

Benefitting from the large interlayer spacing, ultrahigh conductivity and abundant surface chemistry, TiCT has been a promising electrode material for supercapacitors (SCs). CoS has attracted much attention due to its low cost, weak Co-S bond and relatively high theoretical capacity. Herein, CoS nanowires were grown on few-layered TiCT by one-step solvothermal method as a SC electrode. Within the composite, TiCT could function as conductive network and buffer matrix to provide ultra-fast electronic transport and relieve volume expansion of CoS nanowires. Simultaneously, the active CoS nanowires with high capacitance act as interlayer spacer to restrain the restacking of TiCT nanosheets. As a result, CoS/TiCT-5 electrode exhibits a remarkable improvement specific capacitance of 528 F g at a current density of 1 A g and ultrahigh capacitance retention of 99.3% after 20 000 cycles at a current density of 10 A g. The attempts and efforts made in this work provide a prototype for achieving excellent electrochemical properties.
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http://dx.doi.org/10.1016/j.jcis.2021.06.011DOI Listing
June 2021

Isolation and characterization of a podovirus infecting the opportunist pathogen Vibrio alginolyticus and Vibrio parahaemolyticus.

Virus Res 2021 Jun 10:198481. Epub 2021 Jun 10.

Beijing University of Chemical Technology, China. Electronic address:

Bacterial infections have a negative impact on both animal husbandry industry and medicine, and increasing bacterial drug resistance exacerbates this adverse impact. Phages show promise as an alternative to drugs against drug-resistant bacteria. In this study, a novel virulent bacteriophage (phage) vB_ValP_IME234 against Vibrio alginolyticus and Vibrio parahaemolyticus was isolated from freshwater in Beijing, China. Phage vB_ValP_IME234 had an isometric head (59 nm in diameter) and a short tail (10 nm long), belonging to Podoviridae family. Its complete genome is liner double-stranded DNA (dsDNA) with a GC content of 41.6% while encoding 61 putative proteins. Three transfer RNA (tRNA) and no lysogenic gene was detected. vB_ValP_IME234 had a polyvalent infectivity, a burst of 390 PFU/cell, and is stable under different temperatures (4°C to 50°C) and pH (6.0 to 10.0) values. Host range test showed that vB_ValP_IME234 has the ability to infect seven strains of Vibrio in total. Phylogenetic analyses based on terminase and capsid suggested that this phage had a close relationship with Vibrio phages. These results indicate that vB_ValP_IME234 could be used as a potential biocontrol agent against V. alginolyticus strains.
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http://dx.doi.org/10.1016/j.virusres.2021.198481DOI Listing
June 2021

Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation.

Sci Rep 2021 Jun 11;11(1):12389. Epub 2021 Jun 11.

Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province, 430060, People's Republic of China.

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1 mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (t = 6.05, t = 2.95, t = 3.67, t = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (t = 5.54, t = 9.82, t = 3.86, t = 7.91, all P < 0.01) and the PPADS topical application group (t = 3.24, t = 5.89, t = 6.75, t = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization.
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http://dx.doi.org/10.1038/s41598-021-91989-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196182PMC
June 2021

Liver-specific Nrf2 deficiency accelerates ethanol-induced lethality and hepatic injury in vivo.

Toxicol Appl Pharmacol 2021 Jun 8:115617. Epub 2021 Jun 8.

Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China. Electronic address:

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality from liver disorders. Various mechanisms, including oxidative stress and impaired lipid metabolism, have been implicated in the pathogenesis of ALD. Our previous studies showed that nuclear factor erythroid-derived 2-like 2 (Nrf2) is a master regulator of adaptive antioxidant response and lipid metabolism by using a liver-specific Nrf2 knockout (Nrf2(L)-KO) mouse model. In the current study, an ALD model was developed by a Lieber-DeCarli liquid-based ethanol diet given to this Nrf2(L)-KO mouse strain. We found that Nrf2(L)-KO mice were quite sensitive to lethality from 6.3% ethanol diet. We thus decreased the ethanol concentration to 4.2% to obtain tissues to analyze the role of hepatic Nrf2 in the development of ALD. We found that mild hepatic steatosis occurred with both liquid control and 4.2% ethanol diet feeding, which contain 35% fat. Both the fatty acid β-oxidation marker peroxisome proliferators-activated receptor α (PPARα), and lipogenesis regulator PPARγ were reduced with ethanol feeding in Nrf2(L)-KO mice, compared to Nrf2 floxed control mice (Nrf2-LoxP). However, Nrf2(L)-KO livers showed more cell injury than the livers of Nrf2-LoxP mice. Consistent with these data, there was increased proportion of apoptotic cells in the liver of ethanol-fed Nrf2(L)-KO mice comparing Nrf2-LoxP controls. Mechanistically, Nrf2 mediated expression of ethanol detoxification enzymes, such as alcohol dehydrogenase 1 and aldehyde dehydrogenase1a1, likely contributed to the sensitivity to ethanol toxicity. In conclusion, hepatic Nrf2 is critical to the development of ALD, particularly the morbidity and liver injury.
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http://dx.doi.org/10.1016/j.taap.2021.115617DOI Listing
June 2021

rs641738 Is Not Associated With the Risk of Hepatocellular Carcinoma or Persistent Hepatitis B Infection.

Front Oncol 2021 25;11:639438. Epub 2021 May 25.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: A hot genetic variant, rs641738 within the and , was recently reported to be associated with several liver diseases. However, the results remain controversial. Therefore, this study aimed to explore the role of rs641738 in the risk of hepatocellular carcinoma (HCC) and persistent hepatitis B virus (HBV) infection.

Methods: We first conducted a case-control study that included 779 HCC cases and 1412 cancer-free controls. Controls consisted of 678 persistent HBV carriers and 734 spontaneously recovered subjects. The gene variant rs641738 was genotyped using the MassARRAY platform. The results were analyzed in five genetic models using multivariate logistic regression analyses. Next, we performed a systematic review and meta-analysis to further explore the role of this variant in HCC risk.

Results: The results suggested no association between rs641738 and HCC risk in most genetic models (all > 0.05). Although a marginally significant association was observed in TT . CC ( = 0.037) and the recessive models ( = 0.044). The meta-analysis of 2135 HCC cases and 4388 controls supported that this variant was not related to HCC risk, even in the TT . CC and recessive models. We also determined that this variant did not influence persistent HBV infection.

Conclusion: Our work highlights that rs641738 is not associated with the risk of HCC or persistent HBV infection. This study provides some clues to identify the "truth" of potential disease-related genetic factors in the post-genome era.
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http://dx.doi.org/10.3389/fonc.2021.639438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185222PMC
May 2021

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats.

Stem Cell Res Ther 2021 Jun 10;12(1):334. Epub 2021 Jun 10.

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian, 116001, Liaoning Province, China.

Background: How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances.

Methods: We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, RESULTS: In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI).

Conclusions: In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.
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http://dx.doi.org/10.1186/s13287-021-02401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193895PMC
June 2021

Pillararene-enriched linear conjugated polymer materials with thiazolo[5,4-]thiazole linkages for photocatalysis.

Chem Commun (Camb) 2021 Jun 10. Epub 2021 Jun 10.

College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

A heteroatom-doped conjugated polymer with tunable bandgap is synthesized using pillararenes as the electron-rich C2 symmetric nodes and thiazolo[5,4-d]thiazole as the electron-deficient linkage. The influence of pillararenes in regulating the band structure and photogenerated charge carrier transportation for photocatalytic environmental contaminant degradation has been revealed.
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http://dx.doi.org/10.1039/d1cc02373jDOI Listing
June 2021

Two-dose varicella vaccine effectiveness in China: a meta-analysis and evidence quality assessment.

BMC Infect Dis 2021 Jun 9;21(1):543. Epub 2021 Jun 9.

Department of Immunization and Prevention, Beijing Center for Disease Prevention and Control, Beijing Research Center for Preventive Medicine, He Ping Li Zhong Jie No.16, Dongcheng District, Beijing, 100013, China.

Background: The objectives of this review were to evaluate the vaccine effectiveness (VE) of the two-dose varicella vaccine for healthy children in China and explore the application of the approach of Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in observational studies on VE.

Methods: We searched for observational studies on two-dose varicella VE for children in China aged 1-12 years that were published from 1997 to 2019, and assessed the quality of each study using the Newcastle Ottawa Scale (NOS). We used meta-analysis models to obtain the pooled two-dose VE, and the studies were divided into subgroups and analysed according to whether or not it was an outbreak investigation and its NOS score. The quality of evidence of VEs were rated by approach of the GRADE system.

Results: A total of 12 studies and 87,196 individuals were included. The pooled two-dose VE was 90% (95% confidence interval [CI]: 69-97%). The VE of outbreak studies (87% [95% CI: 76-93%]) was lower than non-outbreak studies (99% [95% CI: 98-99%]). There was no significant difference in VEs by different NOS quality. The quality of the evidence assessment of pooled two-dose VE was "low", which was rated down by one category in limitations and publication bias respectively and rated up by two category in large effect. The quality of evidence assessment in subgroup of NOS score ≥ 7 was "moderate".

Conclusions: The VE of two-dose varicella vaccine is relatively high in preventing varicella, and is recommended for countries which need further control for varicella. However, higher quality evidence is needed as a supplement for stronger recommendations. The approach of GRADE could be applied for rating the quality of evidence in observational study.
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http://dx.doi.org/10.1186/s12879-021-06217-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188742PMC
June 2021

Association of lipoproteins and thyroid hormones with cognitive dysfunction in patients with systemic lupus erythematosus.

BMC Rheumatol 2021 Jun 9;5(1):18. Epub 2021 Jun 9.

Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China.

Background: Neuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances. This study aimed to investigate whether cognitive dysfunction in patients with SLE was related to the expression of serum thyroid hormone and lipoprotein levels.

Methods: A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, and 81 SLE patients were divided into a high-cognition (n = 33) group and a low-cognition group (n = 48). The clinical and laboratory characteristics of the patients were compared; moreover, correlations between serum HDL-C, LDL-C, F-T3 and F-T4 levels and cognitive function were analysed. Serum levels of APOE, APOA1, IGF-1, and IGFBP7 in 81 patients were detected by ELISA, and the correlation between these four proteins and cognition was analysed separately.

Results: The patients with SLE with abnormal cognitive function were less educated than the HCs. For low-cognition patients, the levels of albumin, F-T3 (P <  0.05) and F-T4 decreased, while D-dimer, anti-dsDNA antibody, and IgM levels increased. Serum F-T3 and F-T4 levels positively correlated with cognition. Furthermore, serum protein levels of APOE and APOA1 showed no difference between the high- and low-cognition groups. However, the serum APOE levels were negatively correlated with line orientation scores, and APOA1 levels were positively correlated with coding scores.

Conclusions: Serum F-T3 and F-T4 levels were both positively correlated with four indexes of cognition (language was the exception), while serum APOE levels were negatively correlated with line orientation scores, APOA1 levels were positively correlated with coding scores, and IGFBP7 levels were negatively correlated with figure copy scores. These results demonstrated that F-T3 and F-T4 might be clinical biomarkers of cognitive dysfunction in SLE.
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http://dx.doi.org/10.1186/s41927-021-00190-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188676PMC
June 2021

A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response.

Theranostics 2021 8;11(14):6936-6949. Epub 2021 May 8.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.

Substantial progress has been made with cancer immunotherapeutic strategies in recent years, most of which mainly rely on enhancing the T cell response. However, sufficient tumor antigen information often cannot be presented to T cells, resulting in a failed effector T cell response. The innate immune system can effectively recognize tumor antigens and then initiate an adaptive immune response. Here, we developed a spontaneous multifunctional hydrogel (NOCC-CpG/OX-M, Ncom Gel) vaccine to amplify the innate immune response and harness innate immunity to launch and maintain a powerful adaptive immune response. Ncom Gel was formed by a Schiff base reaction between CpG-modified carboxymethyl chitosan (NOCC-CpG) and partially oxidized mannan (OX-M). The effects of the Ncom Gel vaccine on DCs and macrophages and antigen-specific humoral immunity and cellular immunity were studied. Furthermore, the antitumor immune response of the Ncom Gel vaccine and its effect on the tumor microenvironment were evaluated. The Ncom Gel vaccine enhanced antigen presentation to T cells by facilitating DC uptake and maturation and inducing macrophages to a proinflammatory subtype, further leading to a T cell-mediated adaptive immune response. Moreover, the innate immune response could be amplified via the promotion of antigen-specific antibody production. The Ncom Gel vaccine reversed the tumor immune microenvironment to an inflamed phenotype and showed a significant antitumor response in a melanoma model. Our research implies the potential application of injectable hydrogels as a platform for tumor immunotherapy. The strategy also opens up a new avenue for multilayered cancer immunotherapy.
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http://dx.doi.org/10.7150/thno.58173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171104PMC
May 2021

Myxomavirus serpin alters macrophage function and prevents diffuse alveolar hemorrhage in pristane-induced lupus.

Clin Immunol 2021 Jun 2;229:108764. Epub 2021 Jun 2.

Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, FL 32610, United States of America.

C57BL/6 mice with pristane-induced lupus develop macrophage-dependent diffuse alveolar hemorrhage (DAH), which is blocked by treatment with liver X receptor (LXR) agonists and is exacerbated by low IL-10 levels. Serp-1, a myxomavirus-encoded serpin that impairs macrophage activation and plasminogen activation, blocks DAH caused by MHV68 infection. We investigated whether Serp-1 also could block DAH in pristane-induced lupus. Pristane-induced DAH was prevented by treatment with recombinant Serp-1 and macrophages from Serp1-treated mice exhibited an anti-inflammatory M2-like phenotype. Therapy activated LXR, promoting M2 polarization and expression of Kruppel-like factor-4 (KLH4), which upregulates IL-10. In contrast, deficiency of tissue plasminogen activator or plasminogen activator inhibitor had little effect on DAH. We conclude that Serp-1 blocks pristane-induced lung hemorrhage by enhancing LXR-regulated M2 macrophage polarization and KLH4-regulated IL-10 production. In view of the similarities between DAH in pristane-treated mice and SLE patients, Serp-1 may represent a potential new therapy for this severe complication of SLE.
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http://dx.doi.org/10.1016/j.clim.2021.108764DOI Listing
June 2021

Simultaneous enhancement of power generation and chlorophenol degradation in nonmodified microbial fuel cells using an electroactive biofilm carbon felt anode.

Sci Total Environ 2021 Aug 19;783:147045. Epub 2021 Apr 19.

School of Environment, Northeast Normal University, Changchun 130117, PR China. Electronic address:

Microbial fuel cells (MFCs) are an emerging technique presenting remarkable potential. In the current MFC, an electroactive biofilm anode was inoculated with activated sludge from a local municipal sewage treatment plant. The output voltage peaked at 0.60 V and 0.56 V in MFCs cultured with 2-chlorophenol (MFC-2-CP) and 2,4-dichlorophenol (MFC-2,4-DCP), respectively. The degradation and mineralization efficiency in MFC-2-CP were 100.0% and 82.0%, respectively. Based on the bacterial 16S rRNA gene sequence analysis, abundant Acinetobacter and Azospirillum existed during both the bioelectricity and biodegradation stages in MFC-2-CP, but different patterns were exhibited in MFC-2,4-DCP. The electrogenic bacteria relied on the electron transfer pathway of nicotinamide adenine dinucleotide dehydrogenase, succinate dehydrogenase and terminal oxidase, while the electrons were transferred to the extracellular electrode by cytochrome C, riboflavin, degradation products of CPs and flagella. 2-CP and 2,4-DCP were biodegraded into less toxic cyclohexanol via dichlorination, hydroxylation, and hydrogenation; hereafter, the ring was opened to generate long-chain hydrocarbons, and finally mineralized into CO and HO. This work provided a new strategy for MFCs in power generation and contaminant treatment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147045DOI Listing
August 2021

Intrinsic low sodium/NASICON interfacial resistance paving the way for room temperature sodium-metal battery.

J Colloid Interface Sci 2021 May 25;601:418-426. Epub 2021 May 25.

Department of Mechanical Engineering, National University of Singapore, Singapore 117575, Singapore; National University of Singapore (Suzhou) Research Institute, Suzhou 215123, PR China; National University of Singapore (Chongqing) Research Institute, Chongqing 401123, P.R. China. Electronic address:

Sodium-metal batteries have strong potential to be utilized as stationary high energy density storage devices. Owing to its high ionic conductivity, low electronic conductivity and relatively easy fabrication, NASICON-structure electrolyte (NaZrSiPO) is one of the potential candidates to be considered in the solid-state sodium-metal batteries at room temperature. However, the large interfacial resistance between the solid-state electrolyte and the metallic sodium is known to limit the critical current density (CCD) of the cell. In this study, a simple and cost-effective annealing process is introduced to the electrolyte preparation to improves its interface with metallic sodium. X-ray photoelectron spectroscopy and scanning probe microscopy show that Si forms bonds with the surface functional groups when exposed to the ambient condition. With the removal of surface contamination as well as a partially reduced electrolyte surface, the annealed electrolyte shows an extremely small interfacial resistance of 11 Ω cm and a high CCD of 0.9 mA cm. This study provides an insight on the electrolyte surface preparation and its significant in a sodium-metal solid-state battery.
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http://dx.doi.org/10.1016/j.jcis.2021.05.123DOI Listing
May 2021

Precise Engineering of Acorn-Like Janus Nanoparticles for Cancer Theranostics.

Acta Biomater 2021 Jun 1. Epub 2021 Jun 1.

Institute of Catalysis for Energy and Environment, College of Chemistry and Chemical Engineering, Shenyang Normal University, Shenyang, 110034, P. R. China; State Key Laboratory of Heavy Oil Processing, College of Science, China University of Petroleum, Beijing, 102249, P. R. China. Electronic address:

The anisotropic Janus nanoparticles (JNPs) provide synergistic effects by concentrating multiple properties on a single carrier. Herein, we reported a novel and simple approach to fabricate acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine (PAA-mCaP/PDA) JNPs, which were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain superior stability, while the other mCaP sides served as a storage space and passage for the anti-cancer drug of doxorubicin (DOX). The unique acorn-like PAA-mCaP/PDA-PEG JNPs were utilized as novel theranostic agents for photoacoustic (PA) imaging-guided synergistic cancer chemo-phototherapy. More importantly, this synthetic strategy can be applied to synthesize various mesoporous Janus nanocarriers, paving the way toward designed synthesis of acorn-like JNPs in nanomedicine, biosensing and catalysis.
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http://dx.doi.org/10.1016/j.actbio.2021.05.037DOI Listing
June 2021

Extracellular Vesicles: An Emerging Regenerative Treatment for Oral Disease.

Front Cell Dev Biol 2021 17;9:669011. Epub 2021 May 17.

Department of Periodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

Extracellular Vesicles (EVs) are small lipid-enclosed particles containing biological molecules such as RNA and proteins that have emerged as vital modulators of intercellular communication. Increasingly, studies have shown that EVs play an essential role in the occurrence and prognosis of oral diseases. EVs are increasingly considered a research hotspot of oral diseases. In addition, the characteristics of carrying active molecules have also been studied in oral tissue regeneration. Evidence has shown that EVs regulate the homeostasis of the inflammatory microenvironment, promote angiogenesis, and repair damaged tissues. In this review, we summarized the characteristics of EVs and highlighted the role of EVs in oral tissue regeneration, including dental pulp, periodontal tissue, cartilage, and bone. We also discussed their deficiencies and prospects as a potential therapeutic role in the regeneration treatment of oral disease.
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http://dx.doi.org/10.3389/fcell.2021.669011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165191PMC
May 2021

Magnesium Isoglycyrrhizinate Reduces Hepatic Lipotoxicity through Regulating Metabolic Abnormalities.

Int J Mol Sci 2021 May 30;22(11). Epub 2021 May 30.

Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.
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http://dx.doi.org/10.3390/ijms22115884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198484PMC
May 2021

Will COVID-19 Vaccinations End Discrimination against COVID-19 Patients in China? New Evidence on Recovered COVID-19 Patients.

Vaccines (Basel) 2021 May 11;9(5). Epub 2021 May 11.

School of Health Policy & Management, Nanjing Medical University, Nanjing 211166, China.

(1) Background: By April 2021, over 160 million Chinese have been vaccinated against coronavirus disease 2019 (COVID-19). This study analyzed the impact of vaccination on discrimination against recovered COVID-19 patients and the determinants of discrimination among intended vaccinated people. (2) Methods: A self-designed questionnaire was used to collect data on COVID-19 associated discrimination from nine provinces in China. Pearson chi-square tests and a multivariate ordered logistic regression analyzed the determinants of COVID-19-related discrimination. (3) Results: People who intended to be COVID-19 vaccinated displayed a high level of discrimination against recovered COVID-19 patients, with only 37.74% of the intended vaccinated without any prejudice and 34.11% displaying severe discrimination. However, vaccinations reduced COVID-19-related discrimination against recovered COVID-19 patients from 79.76% to 62.26%. Sex, age, education level, occupation, geographical region, respondents' awareness of vaccine effectiveness and infection risk, and COVID-19 knowledge score had a significant influence on the COVID-19 related discrimination ( < 0.05). (4) Conclusions: Vaccination significantly reduced COVID-19 associated discrimination, but discrimination rates remained high. Among the intended vaccinated respondents, females, the older aged, people with high school and above education level, retirees, migrant workers, and residents in central China were identified as key targets for information campaigns to reduce COVID-19 related discrimination.
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http://dx.doi.org/10.3390/vaccines9050490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150813PMC
May 2021

The Intention to Receive the COVID-19 Vaccine in China: Insights from Protection Motivation Theory.

Vaccines (Basel) 2021 May 2;9(5). Epub 2021 May 2.

School of Health Policy & Management, Nanjing Medical University, Nanjing 211166, China.

(1) Background: More coronavirus disease 2019 (COVID-19) vaccines are gradually being developed and marketed. Improving the vaccination intention will be the key to increasing the vaccination rate in the future; (2) Methods: A self-designed questionnaire was used to collect data on COVID-19 vaccination intentions, protection motivation and control variables. Pearson Chi-square test and multivariate ordered logistic regression models were specified to analyze the determinants of intention to receive COVID-19 vaccine; (3) Results: Although the vaccine was free, 17.75% of the 2377 respondents did not want, or were hesitant, to receive the COVID-19 vaccine. Respondents' cognition of vaccine safety, external reward and response efficacy were positively related to COVID-19 vaccination intention, while age, income and response cost were negatively related to the intention to receive the COVID-19 vaccine. Professionals and people without medical insurance had the lowest intention to vaccinate; (4) Conclusions: The older aged, people without health insurance, those with higher incomes and professionals should be treated as the key intervention targets. Strengthening publicity and education about the safety and efficacy of COVID-19 vaccines, training vaccinated people and community leaders as propagandists for the vaccine, and improving the accessibility to the COVID-19 vaccine are recommended to improve COVID-19 vaccination intention.
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http://dx.doi.org/10.3390/vaccines9050445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147465PMC
May 2021

AtWAKL10, a Cell Wall Associated Receptor-Like Kinase, Negatively Regulates Leaf Senescence in .

Int J Mol Sci 2021 May 5;22(9). Epub 2021 May 5.

Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Qingdao 266101, China.

Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing showed an opposite trend. Additionally, some defense and senescence related WRKY transcription factors could bind to the promoter of . In addition, deletion and overexpression of AtWAKL10 caused several specific transcriptional alterations, including genes involved in cell extension, cell wall modification, defense response and senescence related WRKYs, which may be implicated in regulatory mechanisms adopted by AtWAKL10 in controlling leaf senescence. Taken together, these results revealed that AtWAKL10 negatively regulated leaf senescence.
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http://dx.doi.org/10.3390/ijms22094885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124439PMC
May 2021

Hippocampal microglia CD40 mediates NPSLE cognitive dysfunction in mice.

J Neuroimmunol 2021 May 27;357:577620. Epub 2021 May 27.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address:

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the most serious and complicated clinical manifestation of lupus erythematosus. Cognitive dysfunction is the most common symptom of NPSLE. A variety of potential mechanisms or mediators related to the pathogenesis of NPSLE cognitive dysfunction have been proposed. However, the involvement of microglia CD40 has not been reported yet. This study aimed to investigate whether hippocampal microglia CD40 of MRL/MpJ-Fas (MRL/lpr) mice was involved in NPSLE cognitive dysfunction. This study found, using quantitative polymerase chain reaction, western blotting and immunohistochemistry, that hippocampal CD40 was aberrantly overexpressed in the MRL/lpr lupus mice. It also determined using flow cytometry and immunofluorescence that the aberrantly overexpressed CD40 was mainly derived from hippocampal microglia. The adeno-associated virus was used to inhibit microglia CD40 expression, and the brain damage and cognitive dysfunction of MRL/lpr mice improved. Also, imiquimod (IMQ)-induced lupus mice had the same NPSLE cognitive dysfunction, brain damage, and overexpressed hippocampal microglia CD40 as MRL/lpr mice. Therefore, IMQ-induced lupus mouse was proposed as one of the mouse models for studying NPSLE cognitive dysfunction for the first time in this study. The findings indicated that hippocampal microglia CD40 was involved in the development of NPSLE cognitive dysfunction, thus providing a novel research direction for the study of the pathogenesis of NPSLE.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577620DOI Listing
May 2021

Sex differences in the factors associated with sleep duration in university students: A cross-sectional study.

J Affect Disord 2021 Jul 21;290:345-352. Epub 2021 Apr 21.

Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, China.. Electronic address:

Background: Insufficient sleep duration among university students was commonly associated with many detrimental effects. University students experience substantial environmental and psychological changes. Female and male university students may differ in many spheres. However, most research on sleep duration of university students is based on an aggregate sample rather than digging the sex-specific profiles. The objective of this study is to examine potential sex differences in the correlates of sleep duration and explore the underlying mechanism of correlations.

Methods: This is a large-scale university-based mental health survey, which was conducted in university students in Qinghai Province in Northwest China in December 2019. A multi-stage logistic regression was separately fitted by sex to examine the factors associated with short sleep duration in university students.

Results: A total of 5,552 university students with an average sleep duration of 6.88 h (SD = 1.04) were included, among which 35.0% of the participants may currently be sleeping less than the optimal duration. Female students (6.84 h, SD = 1.00) slept shorter than males (6.94 h, SD = 1.09). The only parallel between sexes was that both female and male students with 3-5 times weekly breakfast were less likely to have short sleep duration. Adjusting for depressive symptoms in the following step eliminated the association between anxiety symptoms and short sleep duration in the model for female students. Female-specific associated factors with short sleep duration were age, grade, academic pressure, weekly physical exercise, depressive symptoms. Male-specific characteristics were current smoking tobacco cigarette, self-perceived health, duration of daily Internet use.

Conclusion: Characteristic profiles of sleep duration differed between female and male university students; only a few male-specific factors were identified. Psychological guidance and education courses as well as other interventions to improve university students' sleep and related health should be designed and implemented based on sex differences.
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http://dx.doi.org/10.1016/j.jad.2021.04.025DOI Listing
July 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

Combined cesarean delivery and repair of acute aortic dissection at 34 weeks of pregnancy during COVID-19 outbreak: A case report.

World J Clin Cases 2021 May;9(15):3644-3648

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the exclusion of a patient from COVID-19 should be performed before surgery. However, patients with type A acute aortic dissection (AAD) during pregnancy can seriously endanger the health of either the mother or fetus that requires emergency surgical treatment without the test for COVID-19.

Case Summary: A 38-year-old woman without Marfan syndrome was admitted to the hospital because of chest pain in the 34 week of gestation. She has diagnosed as having a Stanford type-A AAD involving an aortic arch and descending aorta aortic computed tomographic angiography. The patient was transferred to the isolated negative pressure operating room in one hour and underwent cesarean delivery and ascending aorta replacement. All medical staff adopted third-level medical protection measures throughout the patient transfer and surgical procedure. After surgery, the patient was transferred to the isolated negative pressure intensive care unit ward. The nucleic acid test and anti-COVID-19 immunoglobulin (Ig) G and IgM were performed and were negative. The patient and infant were discharged without complication nine days later and recovered uneventfully.

Conclusion: The results indicated that the procedure that we used is feasible in patients with a combined cesarean delivery and surgery for Stanford type-A AAD during the COVID-19 outbreak, which was mainly attributed to rapid multidisciplinary consultation, collaboration, and quick decision-making.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130093PMC
May 2021

Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.

Signal Transduct Target Ther 2021 May 28;6(1):188. Epub 2021 May 28.

Department of the Second Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.
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http://dx.doi.org/10.1038/s41392-021-00581-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160199PMC
May 2021

Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway.

Phytomedicine 2021 Jul 24;87:153585. Epub 2021 May 24.

Guangdong Provincial Key Laboratory of Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address:

Background: Hyperuricemia (HUA) is characterized by abnormal serum uric acid (UA) levels and demonstrated to be involved in renal injury leading to hyperuricemic nephropathy (HN). Apigenin (API), a flavonoid naturally present in tea, berries, fruits, and vegetables, exhibits various biological functions, such as antioxidant and anti-inflammatory activity.

Purpose: To investigate the effect of API treatment in HN and to reveal its underlying mechanisms.

Methods: The mice with HN were induced by potassium oxonate intraperitoneally and orally administered for two weeks. The effects of API on renal function, inflammation, fibrosis, and uric acid (UA) metabolism in mice with HN were evaluated. The effects of API on urate transporters were further examined in vitro.

Results: The mice with HN exhibited abnormal renal urate excretion and renal dysfunction accompanied by increased renal inflammation and fibrosis. In contrast, API reduced the levels of serum UA, serum creatinine (CRE), blood urea nitrogen (BUN) and renal inflammatory factors in mice with HN. Besides, API ameliorated the renal fibrosis via Wnt/β-catenin pathway suppression. Furthermore, API potently promoted urinary UA excretion and inhibited renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mice with HN. In vitro, API competitively inhibited URAT1 and GLUT9 in a dose-dependent manner, with IC values of 0.64 ± 0.14 μM and 2.63 ± 0.69 μM, respectively.

Conclusions: API could effectively attenuate HN through co-inhibiting UA reabsorption and Wnt/β-catenin pathway, and thus it might be a potential therapy to HN.
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http://dx.doi.org/10.1016/j.phymed.2021.153585DOI Listing
July 2021

Tonifying spleen and replenishing kidney method of traditional Chinese medicine for myasthenia gravis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 May;100(21):e25966

Chengdu Eighth People's Hospital (Geriatric Hospital of Chengdu Medical College).

Background: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder caused by dysfunction at the neuromuscular junction spreads. The main clinical features of this disease are fluctuating fatigue, and weakness of the skeletal muscles of the eyes and limbs. At present, the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine has been widely used for MG. The present study was conducted to evaluate the efficacy and safety of the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine for MG.

Methods: The following 10 databases were searched from inception to March 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, China National Knowledge Infrastructure (CNKI), Wan fang, VIP Chinese Science and Technique Journals Database, the Chinese Bio Medical Database (CBM), and Baidu Scholar. The language was limited to the Chinese and English language. Merely randomized controlled trials (RCTs) were included. The Cochrane Collaboration risk-of-bias tool was used for the methodological quality assessment and risk of bias. The meta-analysis was assessed using the Cochrane RevMan 5.3 software.

Results: In the present study, a meta-analysis was conducted, and RCTs that met the eligibility criteria were included. Furthermore, the different outcome indicators of different methods were objectively compared. The main outcome indicators included the effective rate, quantitative myasthenia gravis (QMG) scores, adverse events, and quality of life (QOL). The secondary outcome indicators included AchRAb, serum-related immune cells (such as CD3+CD4+cells and CD4+/CD8+cells), the traditional Chinese medicine syndrome score scale (TCMSSS), the serum interleukin-6 level, the level of IFN-γ and its mRNA, and the clinical score that contains the clinical absolute score (CAS) and clinical relative score (CRS).

Conclusion: This study would provide credible evidence to determine whether the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine is an effective treatment method for MG.

Trial Registration Number: INPLASY202110097.
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http://dx.doi.org/10.1097/MD.0000000000025966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154406PMC
May 2021

Transcriptome landscape of the late-stage alcohol-induced osteonecrosis of the human femoral head.

Bone 2021 May 18;150:116012. Epub 2021 May 18.

Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China; Laboratory of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China; National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China. Electronic address:

Osteonecrosis resulting from heavy ethanol consumption is one of the major causes of nontraumatic osteonecrosis of the femoral head (ONFH). The underlying pathological and molecular mechanisms remain elusive. In this study, we performed deep RNA sequencing from femoral heads of patients diagnosed with late-stage alcohol-induced ONFH (AIONFH), other types of ONFH and traumatic injury (bone fracture). Genome-wide gene expression analyses identified 690 differentially expressed mRNAs in AIONFH. Gene annotation and pathway analyses revealed significant dysregulated genes involved in hemostasis, angiogenesis and bone remodeling processes from the late-stage AIONFH. Notably, ADH1B, which codes for one of the major alcohol dehydrogenases, is significantly upregulated in AIONFH samples. Further, we found that the ADH1B protein was primarily expressed in smooth muscle cells of the blood vessels, stromal cells and adipocytes of the femoral heads of AIONFH patients; but was absent in other ONFH samples. Our analyses also revealed unique long non-coding RNA (lncRNA) expression profiles and identified novel lncRNAs in AIONFH. In addition, we observed a close co-expression correlation between lncRNAs and mRNAs in AIONFH suggesting that cis-gene regulation represents a major mechanism of action of human femoral lncRNAs. Further, the expression signature of lncRNAs, but not mRNAs, distinguishes AIONFH from other types of ONFH. Taken together, our studies uncovered novel molecular signatures associated with late-stage AIONFH in which the dysregulation of several key signaling pathways within the femoral head may be involved in AIONFH. Subsequently, lncRNAs may serve as potential biomarkers for diagnosis and therapeutic treatment of AIONFH. Further studies are needed to confirm that ADH1B is specifically upregulated in AIONFH and not generally upregulated in patients who consume alcohol excessively.
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http://dx.doi.org/10.1016/j.bone.2021.116012DOI Listing
May 2021

Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease.

iScience 2021 May 1;24(5):102457. Epub 2021 May 1.

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.

Translocator protein (TSPO, 18 kDa) levels increase in parallel with the evolution of simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD). However, TSPO function in SS and NASH is unknown. Loss of TSPO in hepatocytes downregulated acetyl-CoA acetyltransferase 2 and increased free cholesterol (FC). FC accumulation induced endoplasmic reticulum stress via IRE1A and protein kinase RNA-like ER kinase/ATF4/CCAAT-enhancer-binding protein homologous protein pathways and autophagy. TSPO deficiency activated cellular adaptive antioxidant protection; this adaptation was lost upon excessive FC accumulation. A TSPO ligand 19-Atriol blocked cholesterol binding and recapitulated many of the alterations seen in TSPO-deficient cells. These data suggest that TSPO deficiency accelerated the progression of SS. In NASH, however, loss of TSPO ameliorated liver fibrosis through downregulation of bile acid synthesis by reducing CYP7A1 and CYP27A1 levels and increasing farnesoid X receptor expression. These studies indicate a dynamic and complex role for TSPO in the evolution of NAFLD.
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http://dx.doi.org/10.1016/j.isci.2021.102457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113880PMC
May 2021