Publications by authors named "Qin Han"

207 Publications

Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF‑κB signaling.

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

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

Cigarette smoke (CS) exposure is a risk factor for dyslipidemia and atherosclerosis. Reduced expression of low‑density lipoprotein receptor (LDLR) in hepatocytes may be one of the underlying mechanisms for these disorders. The aim of the present study was to investigate the molecular mechanism underlying the regulatory effect of CS extract (CSE) on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low LDLR expression in HepG2 cells. PCSK9 and LDLR mRNA and protein expression levels in HepG2 cells were evaluated after CSE treatment via reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, total intracellular reactive oxygen species (ROS) production was determined via 2,7‑dichlorofluorescein diacetate fluorescence. CSE significantly increased PCSK9 expression and inhibited LDLR expression in a time‑ and concentration‑dependent manner. Furthermore, CSE significantly induced ROS production and nuclear factor κB (NF‑κB) activation. However, pretreatment with a ROS scavenger or an NF‑κB inhibitor significantly attenuated the CSE‑induced changes in PCSK9 and LDLR expression. In addition, pretreatment with melatonin markedly reduced ROS production, NF‑κB activation and PCSK9 expression, and increased LDLR expression in the CSE‑treated cells. These data suggest that melatonin inhibits CSE‑regulated PCSK9 and LDLR production in HepG2 cells via ROS/NF‑κB signaling.
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http://dx.doi.org/10.3892/mmr.2021.11970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974406PMC
May 2021

Screening of Key Genes of Sepsis and Septic Shock Using Bioinformatics Analysis.

J Inflamm Res 2021 11;14:829-841. Epub 2021 Mar 11.

Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People's Republic of China.

Objective: Sepsis is a disease associated with high mortality. We performed bioinformatic analysis to identify key biomarkers associated with sepsis and septic shock.

Methods: The top 20% of genes showing the greatest variance between sepsis and controls in the GSE13904 dataset (children) were screened by co-expression network analysis. The differentially expressed genes (DEGs) were identified through analyzing differential gene expression between sepsis patients and control in the GSE13904 (children) and GSE154918 (adult) data sets. Intersection analysis of module genes and DEGs was performed to identify common DEGs for enrichment analysis, protein-protein interaction network (PPI network) analysis, and Short Time-series Expression Miner (STEM) analysis. The PPI network genes were ranked by degree of connectivity, and the top 100 sepsis-associated genes were identified based on the area under the receiver operating characteristic curve (AUC). In addition, we evaluated differences in immune cell infiltration between sepsis patients and controls in children (GSE13904, GSE25504) and adults (GSE9960, GSE154918). Finally, we analyzed differences in DNA methylation levels between sepsis patients and controls in GSE138074 (adults).

Results: The common genes were associated mainly with up-regulated inflammatory and metabolic responses, as well as down-regulated immune responses. Sepsis patients showed lower infiltration by most types of immune cells. Genes in the PPI network with AUC values greater than 0.9 in both GSE13904 (children) and GSE154918 (adults) were screened as key genes for diagnosis. These key genes (MAPK14, FGR, RHOG, LAT, PRKACB, UBE2Q2, ITK, IL2RB, and CD247) were also identified in STEM analysis to be progressively dysregulated across controls, sepsis patients and patients with septic shock. In addition, the expression of MAPK14, FGR, and CD247 was modified by methylation.

Conclusion: This study identified several potential diagnostic genes and inflammatory and metabolic responses mechanisms associated with the development of sepsis.
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http://dx.doi.org/10.2147/JIR.S301663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962593PMC
March 2021

The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts.

Cell Death Dis 2021 Mar 17;12(4):291. Epub 2021 Mar 17.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No. BZO381), 100005, Beijing, China.

Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression by regulating tumor cell proliferation, angiogenesis, and metastasis. Recent studies demonstrated that CAFs induce inhibitory immune cell infiltration and chemotherapy resistance in gastric cancer by activating the NF-κB signaling pathway to secrete IL6, IL8, and other inflammatory factors. Inhibition of the NF-κB signaling pathway in CAFs might be a potential therapeutic strategy in gastric cancer. However, how the NF-κB pathway is activated in CAFs remains unclear. We showed that mesenchymal stem cells (MSCs) differentiated into CAFs, induced by the exosomes derived from gastric cancer cells. During the process of differentiation from MSCs into CAFs, we showed that nuclear PKM2 expression was continuously upregulated and associated with NF-κB P65 acetylation, contributing to P65 nuclear retention in CAFs and constant transcription of IL-6, IL-8, and other inflammatory factors, thus promoting gastric cancer cell proliferation. We showed that NF-κB P65 acetylation was induced by P300. We showed that nuclear PKM2 was derived from exosomes of gastric cancer cell lines and the positive feedback loop induced by PKM2-P65 combination. It is also proved that P300 inhibitors can inhibit tumor proliferation in an AGS subcutaneous xenograft tumor model. Our study showed that gastric cancer cells influence the continuous activation of the NF-κB signaling pathway in CAFs by secreting gastric cancer exosomes containing PKM2, thus inducing abnormal metabolism and inflammation activation. This study provides a new therapeutic target for CAF normalization or deactivation strategies.
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http://dx.doi.org/10.1038/s41419-021-03579-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969736PMC
March 2021

Research on control effectiveness of fluidic thrust vectoring.

Sci Prog 2021 Jan-Mar;104(1):36850421998137

China Academy of Aerospace Aerodynamics, Beijing, China.

In view of the control effects of fluidic thrust vector technology for low-speed aircraft at high altitude/low density and low altitude/high density are studied. The S-A model of FLUENT software is used to simulate the flow field inside and outside the nozzle with variable control surface parameters, and the relationship between the area of control surface and the deflection effect of main flow at different altitudes is obtained. It is found that the fluidic thrust vectoring nozzle can effectively control the internal flow in the ground state and the high altitude/low density state. and the mainstream deflection angle can be continuously adjusted. The maximum deflection angle of the flow in the ground state is 21.86°, and the maximum deviation angle of the 20 km high altitude/low density state is 18.80°. The deflecting of the inner flow of the nozzle is beneficial to provide more lateral force and lateral torque for the aircraft. The high altitude/low density state is taken as an example. When the internal flow deflects 18.80°, the lateral force is 0.32 times the main thrust. For aircraft with high altitude and low density, sufficient lateral and lateral torque can make the flying aircraft more flexible, which can make up the shortcomings of the conventional rudder failure and even replace the conventional rudder surface.
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http://dx.doi.org/10.1177/0036850421998137DOI Listing
March 2021

Mesenchymal stem cell-based treatment in autoimmune liver diseases: underlying roles, advantages and challenges.

Ther Adv Chronic Dis 2021 12;12:2040622321993442. Epub 2021 Feb 12.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.

Autoimmune liver disease (AILD) is a series of chronic liver diseases with abnormal immune responses, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The treatment options for AILD remain limited, and the adverse side effects of the drugs that are typically used for treatment frequently lead to a low quality of life for AILD patients. Moreover, AILD patients may have a poor prognosis, especially those with an incomplete response to first-line treatment. Mesenchymal stem cells (MSCs) are pluripotent stem cells with low immunogenicity and can be conveniently harvested. MSC-based therapy is emerging as a promising approach for treating liver diseases based on their advantageous characteristics of immunomodulation, anti-fibrosis effects, and differentiation to hepatocytes, and accumulating evidence has revealed the positive effects of MSC therapy in AILD. In this review, we first summarize the mechanisms, safety, and efficacy of MSC treatment for AILD based on work in animal and clinical studies. We also discuss the challenges of MSC therapy in clinical applications. In summary, although promising data from preclinical studies are now available, MSC therapy is currently far for being applied in clinical practice, thus developing MSC therapy in AILD is still challenging and warrants further research.
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http://dx.doi.org/10.1177/2040622321993442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887681PMC
February 2021

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes.

Curr Med Sci 2021 Feb 13;41(1):87-93. Epub 2021 Feb 13.

Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

Insulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.
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http://dx.doi.org/10.1007/s11596-021-2323-4DOI Listing
February 2021

The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers.

Pharmgenomics Pers Med 2021 12;14:39-53. Epub 2021 Jan 12.

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People's Republic of China.

Background: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates.

Methods: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates.

Results: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients.

Conclusion: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.
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http://dx.doi.org/10.2147/PGPM.S293399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814251PMC
January 2021

Monitoring Astrocytic Ca Activity in Freely Behaving Mice.

Front Cell Neurosci 2020 3;14:603095. Epub 2020 Dec 3.

Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, China.

Monitoring astrocytic Ca activity is essential to understand the physiological and pathological roles of astrocytes in the brain. However, previous commonly used methods for studying astrocytic Ca activities can be applied in only anesthetized or head-fixed animals, which significantly affects astrocytic Ca dynamics. In the current study, we combined optic fiber recordings with genetically encoded Ca indicators (GECIs) to monitor astrocytic activity in freely behaving mice. This approach enabled selective and reliable measurement of astrocytic Ca activity, which was verified by the astrocyte-specific labeling of GECIs and few movement artifacts. Additionally, astrocytic Ca activities induced by locomotion or footshock were stably recorded in the cortices and hippocampi of freely behaving mice. Furthermore, this method allowed for the longitudinal study of astrocytic activities over several weeks. This work provides a powerful approach to record astrocytic activity selectively, stably, and chronically in freely behaving mice.
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http://dx.doi.org/10.3389/fncel.2020.603095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744696PMC
December 2020

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis.

Lancet Gastroenterol Hepatol 2021 02 14;6(2):106-119. Epub 2020 Nov 14.

Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland. Electronic address:

Background: In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines.

Methods: In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345.

Findings: Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8-10), ranging from 6% (4-8) in community settings to 10% (9-11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18-20), ranging from 12% (6-18) for studies in community settings to 25% (19-30) in clinic settings.

Interpretation: Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12-25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions.

Funding: WHO and US Centers for Disease Control and Prevention.
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http://dx.doi.org/10.1016/S2468-1253(20)30307-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801814PMC
February 2021

NAD Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion.

Cell Metab 2021 Jan 9;33(1):110-127.e5. Epub 2020 Nov 9.

International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Second Military Medical University, Shanghai 201805, China; Cancer Research Center, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China; Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address:

NAD metabolism is implicated in aging and cancer. However, its role in immune checkpoint regulation and immune evasion remains unclear. Here, we find nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD biogenesis, drives interferon γ (IFNγ)-induced PD-L1 expression in multiple types of tumors and governs tumor immune evasion in a CD8 T cell-dependent manner. Mechanistically, NAD metabolism maintains activity and expression of methylcytosine dioxygenase Tet1 via α-ketoglutarate (α-KG). IFNγ-activated Stat1 facilitates Tet1 binding to Irf1 to regulate Irf1 demethylation, leading to downstream PD-L1 expression on tumors. Importantly, high NAMPT-expressing tumors are more sensitive to anti-PD-L1 treatment and NAD augmentation enhances the efficacy of anti-PD-L1 antibody in immunotherapy-resistant tumors. Collectively, these data delineate an NAD metabolism-dependent epigenetic mechanism contributing to tumor immune evasion, and NAD replenishment combined with PD-(L)1 antibody provides a promising therapeutic strategy for immunotherapy-resistant tumors.
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http://dx.doi.org/10.1016/j.cmet.2020.10.021DOI Listing
January 2021

Effect of periostin silencing on Runx2, RANKL and OPG expression in osteoblasts.

J Orofac Orthop 2021 Mar 3;82(2):82-91. Epub 2020 Nov 3.

Department of Anesthesia, Maternal and Child Health Hospital of Lianyungang City, Lianyungang City, Jiangsu Province, China.

Objective: Normal tooth eruption is closely related to relevant genes and the dynamic balance between osteoblasts and osteoclasts. If secretion of RANKL and OPG by osteoblasts is disordered, relevant gene deficiencies or mutations will result in serious tooth eruption disturbances, e.g., cleidocranial dysplasia (CCD). Thus, we examined changes in Runx2, RANKL, and OPG protein expression in MC3T3-E1 cells after silencing the periostin gene, thus, providing an experimental basis to study tooth eruption mechanisms.

Methods: Based on previous research, cells were divided into two groups according to the virus number: the contrast group (NC group; pFU-GW-016 PSC53349-1) and the experimental group (KD group; LVpFU-GW-016PSC66473-1). Cells were infected with the lentiviral vector (multiplicity of infection = 100) and assessed by image cytometry 72 h after infection. After screening cells for the strongest gene silencing effect, Runx2, RANKL and OPG protein expression were detected by western blotting.

Results: Based on quantitative PCR, the periostin gene silencing efficiency in the KD group was over 90% (P < 0.01). After periostin gene silencing, compared with the control group, Runx2 and RANKL expression in the KD group was reduced (P < 0.01 and P < 0.05, respectively), but OPG protein expression showed no significant change (P > 0.05). The RANKL/OPG ratios in the KD group were lower than those in the NC group after periostin gene silencing (P < 0.05).

Conclusions: Silencing periostin may reduce the expression of Runx2, suggesting that there may be a synergistic relationship between periostin and Runx2 in their effects on osteoblast differentiation, while reducing RANKL expression obviously confirms that the NF-κB (nuclear factor κB) pathway plays an important role in this process and that periostin silencing changes the underlying tendency toward bone metabolism. This method could even provide an experimental basis for using exogenous periostin protein to treat some abnormal bone metabolism diseases, as it could be used as a supplement for the treatment of tooth eruption abnormalities caused by Runx2 gene deficiencies or mutations (CCD).
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http://dx.doi.org/10.1007/s00056-020-00253-3DOI Listing
March 2021

ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt/β-catenin signaling pathway.

Hepatobiliary Pancreat Dis Int 2020 Oct 14. Epub 2020 Oct 14.

International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer Research, Shanghai 200000, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200032, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells (LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase (ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown.

Methods: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/β-catenin signaling by ACLY. Rescue experiments were performed to investigate whether β-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells.

Results: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of β-catenin, and Lys49 acetylation of β-catenin might mediate ACLY-regulated β-catenin level in HCC cells.

Conclusions: ACLY is a potent regulator of Wnt/β-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.
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http://dx.doi.org/10.1016/j.hbpd.2020.05.010DOI Listing
October 2020

MSC-derived exosomes promote recovery from traumatic brain injury via microglia/macrophages in rat.

Aging (Albany NY) 2020 Sep 23;12(18):18274-18296. Epub 2020 Sep 23.

Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy, Beijing 100005, China.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young individuals worldwide. There is currently no effective clinical treatment for TBI, but mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects. In this study, we performed intracerebroventricular microinjection of human adipose mesenchymal stem cell (hADSC)-derived exosomes (hADSC-ex) in a weight-drop-induced TBI rat model. We found that hADSC-ex promoted functional recovery, suppressed neuroinflammation, reduced neuronal apoptosis, and increased neurogenesis in TBI rats. The therapeutic effects of hADSC-ex were comparable to those of hADSC. Sequential imaging revealed increasing aggregation of DiR-labeled hADSC-ex in the lesion area. Immunofluorescent staining of coronal brain sections and primary mixed neural cell cultures revealed distinct overlap between CM-DiI-labeled hADSC-ex and microglia/macrophages, indicating that hADSC-ex were mainly taken up by microglia/macrophages. In a lipopolysaccharide-induced inflammatory model, hADSC-ex suppressed microglia/macrophage activation by inhibiting nuclear factor κB and P38 mitogen-activated protein kinase signaling. These data suggest that hADSC-ex specifically enter microglia/macrophages and suppress their activation during brain injury, thereby inhibiting inflammation and facilitating functional recovery. They also offer new insight into the cellular targeting, uptake and migration of hADSC-ex, and provide a theoretical basis for new therapeutic strategies for central nervous system diseases.
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http://dx.doi.org/10.18632/aging.103692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585083PMC
September 2020

Prediction of vaginal birth after cesarean delivery in Southeast China: a retrospective cohort study.

BMC Pregnancy Childbirth 2020 Sep 15;20(1):538. Epub 2020 Sep 15.

Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No.18, Daoshan Rd., Gulou Dist, Fuzhou City, Fujian province, China.

Background: We aimed to develop and validate a nomogram for effective prediction of vaginal birth after cesarean (VBAC) and guide future clinical application.

Methods: We retrospectively analyzed data from hospitalized pregnant women who underwent trial of labor after cesarean (TOLAC), at the Fujian Provincial Maternity and Children's Hospital, between October 2015 and October 2017. Briefly, we included singleton pregnant women, at a gestational age above 37 weeks who underwent a primary cesarean section, in the study. We then extracted their sociodemographic data and clinical characteristics, and randomly divided the samples into training and validation sets. We employed the least absolute shrinkage and selection operator (LASSO) regression to select variables and construct VBAC success rate in the training set. Thereafter, we validated the nomogram using the concordance index (C-index), decision curve analysis (DCA), and calibration curves. Finally, we adopted the Grobman's model to perform comparisons with published VBAC prediction models.

Results: Among the 708 pregnant women included according to inclusion criteria, 586 (82.77%) patients were successfully for VBAC. Multivariate logistic regression models revealed that maternal height (OR, 1.11; 95% CI, 1.04 to 1.19), maternal BMI at delivery (OR, 0.89; 95% CI, 0.79 to 1.00), fundal height (OR, 0.71; 95% CI, 0.58 to 0.88), cervix Bishop score (OR, 3.27; 95% CI, 2.49 to 4.45), maternal age at delivery (OR, 0.90; 95% CI, 0.82 to 0.98), gestational age (OR, 0.33; 95% CI, 0.17 to 0.62) and history of vaginal delivery (OR, 2.92; 95% CI, 1.42 to 6.48) were independently associated with successful VBAC. The constructed predictive model showed better discrimination than that from the Grobman's model in the validation series (c-index 0.906 VS 0.694, respectively). On the other hand, decision curve analysis revealed that the new model had better clinical net benefits than the Grobman's model.

Conclusions: VBAC will aid in reducing the rate of cesarean sections in China. In clinical practice, the TOLAC prediction model will help improve VBAC's success rate, owing to its contribution to reducing secondary cesarean section.
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http://dx.doi.org/10.1186/s12884-020-03233-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493317PMC
September 2020

Spatial Navigation.

Adv Exp Med Biol 2020 ;1284:63-90

Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, China.

The hippocampus is critical for spatial navigation. In this review, we focus on the role of the hippocampus in three basic strategies used for spatial navigation: path integration, stimulus-response association, and map-based navigation. First, the hippocampus is not required for path integration unless the path of path integration is too long and complex. The hippocampus provides mnemonic support when involved in the process of path integration. Second, the hippocampus's involvement in stimulus-response association is dependent on how the strategy is conducted. The hippocampus is not required for the habit form of stimulus-response association. Third, while the hippocampus is fully engaged in map-based navigation, the shared characteristics of place cells, grid cells, head direction cells, and other spatial encoding cells, which are detected in the hippocampus and associated areas, offer a possibility that there is a stand-alone allocentric space perception (or mental representation) of the environment outside and independent of the hippocampus, and the spatially specific firing patterns of these spatial encoding cells are the unfolding of the intermediate stages of the processing of this allocentric spatial information when conveyed into the hippocampus for information storage or retrieval. Furthermore, the presence of all the spatially specific firing patterns in the hippocampus and the related neural circuits during the path integration and map-based navigation support such a notion that in essence, path integration is the same allocentric space perception provided with only idiothetic inputs. Taken together, the hippocampus plays a general mnemonic role in spatial navigation.
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http://dx.doi.org/10.1007/978-981-15-7086-5_7DOI Listing
October 2020

Internal Control Quality, Enterprise Environmental Protection Investment and Finance Performance: An Empirical Study of China's A-Share Heavy Pollution Industry.

Int J Environ Res Public Health 2020 08 21;17(17). Epub 2020 Aug 21.

National Research Base of Intelligent Manufacturing Service, Chongqing Technology and Business University, Chongqing 400067, China.

As an important measure of enterprise governance, internal control can enhance the organizational rationality of the enterprise, ensure that the enterprise consciously assumes social responsibility for the protection of the natural environment and resources, and promote the sustainable development of the national economy. Using data from China's A-share heavy pollution industry listed companies from 2009 to 2018, this study explored the relationships among internal control quality, enterprise environmental protection investment, and financial performance. The results show that the quality of internal control has a significant positive impact on enterprise environmental protection investment and financial performance. Enterprise environmental protection investment has a significant positive impact on financial performance and plays a partial intermediary role in the positive impact of internal control quality on financial performance. While expanding the theory of resource-based concepts, this study clarified the positive impact of corporate environmental management and practical behavior on corporate value and provides a theoretical basis for companies to actively implement environmental protection responsibilities, strengthen internal environmental management capabilities, and enhance corporate value. At the same time, it also provides a basis for the government to issue relevant environmental protection policies, strengthen enterprise internal control construction guidelines, and encourage third-party organizations to evaluate the effectiveness of enterprise internal control.
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http://dx.doi.org/10.3390/ijerph17176082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503461PMC
August 2020

Resveratrol inhibits proliferation and promotes apoptosis of keloid fibroblasts by targeting HIF-1α.

J Plast Surg Hand Surg 2020 Oct 4;54(5):290-296. Epub 2020 Jun 4.

Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China.

A keloid is characterized by red, tickling, hard, and irregular raised tissues, and it tends to outgrow its origin. It frequently occurs in young adults and appears to be refractory to prevailing therapies. Resveratrol is a new drug that has anti-proliferative effect. In this study, keloid-derived fibroblasts were cultured under hypoxia environment and was treated by resveratrol. CCK-8 assay and Annexin V-FITC were used to evaluate cell activity and apoptosis level. Western blot and RT-qPCR were also used to assess the expression of HIF-α, Collagen I and Collagen III. Besides, siRNA was also used to explore the mechanisms of resveratrol's effect. In this study, hypoxia promotes proliferation and inhibits apoptosis of keloid fibroblasts. These findings highlight the potential obstacle in treating keloids. Furthermore, we demonstrated that resveratrol could reverse the effect of hypoxia on keloids through down-regulation of HIF-1α. Moreover, collagen synthesis in keloid fibroblasts was also inhibited by resveratrol, which corresponded with HIF-1α suppression. These results provide evidence for resveratrol's treatment effect against keloids through inhibiting cell proliferation and promoting cell apoptosis, while, HIF-1α may play the key role in this process.
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http://dx.doi.org/10.1080/2000656X.2020.1771719DOI Listing
October 2020

RpoS is a pleiotropic regulator of motility, biofilm formation, exoenzymes, siderophore and prodigiosin production, and trade-off during prolonged stationary phase in Serratia marcescens.

PLoS One 2020 2;15(6):e0232549. Epub 2020 Jun 2.

Microbiology and Metabolic Engineering of Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu, P.R. China.

Prodigiosin is an important secondary metabolite produced by Serratia marcescens. It can help strains resist stresses from other microorganisms and environmental factors to achieve self-preservation. Prodigiosin is also a promising secondary metabolite due to its pharmacological characteristics. However, pigmentless S. marcescens mutants always emerge after prolonged starvation, which might be a way for the bacteria to adapt to starvation conditions, but it could be a major problem in the industrial application of S. marcescens. To identify the molecular mechanisms of loss of prodigiosin production, two mutants were isolated after 16 days of prolonged incubation of wild-type (WT) S. marcescens 1912768R; one mutant (named 1912768WR) exhibited reduced production of prodigiosin, and a second mutant (named 1912768W) was totally defective. Comparative genomic analysis revealed that the two mutants had either mutations or deletions in rpoS. Knockout of rpoS in S. marcescens 1912768R had pleiotropic effects. Complementation of rpoS in the ΔrpoS mutant further confirmed that RpoS was a positive regulator of prodigiosin production and that its regulatory role in prodigiosin biosynthesis was opposite that in Serratia sp. ATCC 39006, which had a different type of pig cluster; further, rpoS from Serratia sp. ATCC 39006 and other strains complemented the prodigiosin defect of the ΔrpoS mutant, suggesting that the pig promoters are more important than the genes in the regulation of prodigiosin production. Deletion of rpoS strongly impaired the resistance of S. marcescens to stresses but increased membrane permeability for nutritional competence; competition assays in rich and minimum media showed that the ΔrpoS mutant outcompeted its isogenic WT strain. All these data support the idea that RpoS is pleiotropic and that the loss of prodigiosin biosynthesis in S. marcescens 1912768R during prolonged incubation is due to a mutation in rpoS, which appears to be a self-preservation and nutritional competence (SPANC) trade-off.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232549PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266296PMC
August 2020

p16/Ki-67 dual-stained cytology used for triage in cervical cancer opportunistic screening.

Chin J Cancer Res 2020 Apr;32(2):208-217

Department of Gynecology and Obstetrics, The Third Hospital of Peking University, Beijing 100191, China.

Objective: To evaluate the efficiency of p16/Ki-67 dual stain used as a triage in cervical cancer screening.

Methods: In this study, we did 468 p16/Ki-67 dual stain in human papillomavirus (HPV) 16/18-positive or 12 other high-risk HPV (OHR-HPV) positive Thinprep cytologic test (TCT) atypical squamous cells of undetermined significance (ASCUS)/ lower-grade squamous intraepithelial lesion (LSIL) women. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the triage test.

Results: The sensitivity, specificity, PPV and NPV of p16/Ki-67 dual stain in HPV 16/18-positive women were 91.5%/68.4%, 77.0%/75.0%, 73.9%/59.1% and 92.8%/81.8%. In 12 OHR-HPV positive TCT ASCUS/LSIL women, the results were 79.1%/95.0%, 88.5%/66.7%, 88.5%/70.4% and 89.2%/94.1%. The risk of precancerous lesions in p16/Ki-67 dual stain positive cases was much higher than before, and the negative cases had lower risk. Besides, there was no cervical intraepithelial neoplasia (CIN) III case missed after triaged by p16/Ki-67 dual-stained cytology. In p16/Ki-67 dual-stained cytology positive women with benign pathology or CIN I, the 1-year progression rate is 20.5% and in p16/Ki-67 dual-stained cytology negative women, the 1-year progression rate is 5.6%.

Conclusions: hr-HPV genotyping test plays an important role in cervical cancer screening. p16/Ki-67 dual stain may be a promising triage test. As for chronic cervicitis or CIN I patients, a positive p16/Ki-67 dual-stained cytology suggests a high risk in progression and need to be followed up closely.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2020.02.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219095PMC
April 2020

Cigarette smoke exposure impairs lipid metabolism by decreasing low-density lipoprotein receptor expression in hepatocytes.

Lipids Health Dis 2020 May 8;19(1):88. Epub 2020 May 8.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Background: Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear.

Methods: In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%.

Results: The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 μM melatonin.

Conclusions: In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers.
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http://dx.doi.org/10.1186/s12944-020-01276-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210682PMC
May 2020

Variation in rhizosphere microbial communities and its association with the symbiotic efficiency of rhizobia in soybean.

ISME J 2020 08 27;14(8):1915-1928. Epub 2020 Apr 27.

State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, Huazhong Agricultural University, No. 1 Shizishan Road, Hongshan District, Wuhan, 430070, Hubei, China.

Rhizobia-legume symbiosis is an important type of plant-microbe mutualism; however, the establishment of this association is complicated and can be affected by many factors. The soybean rhizosphere has a specific microbial community, yet whether these organisms affect rhizobial nodulation has not been well investigated. Here, we analyzed the compositions and relationships of soybean rhizocompartment microbiota in three types of soil. First, we found that the rhizosphere community composition of soybean varied significantly in different soils, and the association network between rhizobia and other rhizosphere bacteria was examined. Second, we found that some rhizosphere microbes were correlated with the composition of bradyrhizobia and sinorhizobia in nodules. We cultivated 278 candidate Bacillus isolates from alkaline soil. Finally, interaction and nodulation assays showed that the Bacillus cereus group specifically promotes and suppresses the growth of sinorhizobia and bradyrhizobia, respectively, and alleviates the effects of saline-alkali conditions on the nodulation of sinorhizobia as well as affecting its colonization in nodules. Our findings demonstrate a crucial role of the bacterial microbiota in shaping rhizobia-host interactions in soybean, and provide a framework for improving the symbiotic efficiency of this system of mutualism through the use of synthetic bacterial communities.
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http://dx.doi.org/10.1038/s41396-020-0648-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367843PMC
August 2020

Transplantation of ACE2 Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

Aging Dis 2020 Apr 9;11(2):216-228. Epub 2020 Mar 9.

1School of Life Sciences, Shanghai University, Shanghai, China.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2 and TMPRSS2 which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
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http://dx.doi.org/10.14336/AD.2020.0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069465PMC
April 2020

The Raman and IR vibration modes of metal pentazolate hydrates [Na(HO)(N)]·2HO and [Mg(HO)(N)]·4HO.

J Mol Model 2020 Mar 24;26(4):84. Epub 2020 Mar 24.

School of Physical Science and Technology, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.

The detailed illustrations of the structures, elastic properties, and Raman and IR vibration modes for [Na(HO)(N)]·2HO (a) and [Mg(HO)(N)]·4HO (b) have been presented in this investigation by using the first-principles method based on the density functional theory. Our results indicate that the active centers of both two types of the energetic metal pentazolate hydrates appear on the cyclo-N. The bonding character of N atoms in the cyclo-N is shown to be covalent, and the cyclo-N ring can be considered as an anion. Based on the analysis of elastic properties, we conclude that complex a is easier to deform than b, and both complexes are mechanically stable. From the calculated Raman and IR vibration modes, the vibration in the region of 960-1206 cm (for a) and 985-1208 cm (for b) is determined by basically mixing the cyclo-N stretching and deformation modes. The vibrational modes of a and b in their highest frequency zones are both related to the stretching of the O-H bonds.
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http://dx.doi.org/10.1007/s00894-020-4345-4DOI Listing
March 2020

Chlorzoxazone, a small molecule drug, augments immunosuppressive capacity of mesenchymal stem cells via modulation of FOXO3 phosphorylation.

Cell Death Dis 2020 03 2;11(3):158. Epub 2020 Mar 2.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381); Qingdao University, Qingdao, PR China.

Nowadays, immune diseases are a large burden in healthcare. Mesenchymal stem cells (MSCs) have prominent ability in immunomodulation and have been applicated on treating many immune-related diseases. However, the clinical outcomes can be disparate and sometimes completely counterproductive beyond explanation of cell heterogeneity. The theory of immunomodulation plasticity in MSCs has then emerged to explain that MSCs can be induced into proinflammatory MSC1 or anti-inflammatory MSC2 responding to different immune environment. It would be safer and more efficient if we could induce MSCs into a certain immune phenotype, in most cases MSC2, prior to medical treatment. In this study, we screened and identified a classical FDA-approved drug, chlorzoxazone (CZ). Unlike traditional method induced by IFN-γ, CZ can induce MSC into MSC2 phenotype and enhance the immunosuppressive capacity without elevation of immunogenicity of MSCs. CZ-treated MSCs can better inhibit T cells activation and proliferation, promote expression of IDO and other immune mediators in vitro, and alleviate inflammatory infiltration and tissue damage in acute kidney injury rat model more effectively. Moreover, we discovered that CZ modulates phosphorylation of transcriptional factor forkhead box O3 (FOXO3) independent of classical AKT or ERK signaling pathways, to promote expression of downstream immune-related genes, therefore contributing to augmentation of MSCs immunosuppressive capacity. Our study established a novel and effective approach to induce MSC2, which is ready for clinical application.
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http://dx.doi.org/10.1038/s41419-020-2357-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052156PMC
March 2020

Vibrational, thermodynamic, and dielectric properties of ε-CL-20: first-principles calculations.

J Mol Model 2020 Feb 4;26(3):47. Epub 2020 Feb 4.

School of Physical Science and Technology, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.

The DFT theory is used to investigate the vibration forms of ε-CL-20 by discussing the phonon DOS and infrared and Raman spectra. By observing them, the detailed vibration forms can be obtained, and the vibrations are different in the different regions. Our calculated vibrational results are consistent with previous data. In order to deeply comprehend CL-20, we also investigate the thermodynamic properties, finding that entropy, enthalpy, Debye temperature, and heat capacity are increased with the rising temperature and the vibrational free energy decreases with the increasing temperature. The ε, ε, and ε are similar, which reflects the small anisotropy among [100], [010], and [001]. Moreover, it can be noticed that the major contribution for static dielectric constants originates from the electronic contribution.
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http://dx.doi.org/10.1007/s00894-020-4311-1DOI Listing
February 2020

Daphnetin Ameliorates Experimental Autoimmune Encephalomyelitis Through Regulating Heme Oxygenase-1.

Neurochem Res 2020 Apr 16;45(4):872-881. Epub 2020 Jan 16.

Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

To assess the potential role of daphnetin, a clinically used anti-inflammatory agent, on the development of the inflammatory and neurodegenerative disease, we investigated its immune regulatory function in a murine model of experimental autoimmune encephalomyelitis (EAE). Significantly, lower levels of pro-inflammatory cytokines including interleukin (IL)-17, interferon-γ, Il6, Il12a, and Il23a were observed in brains of daphnetin-treated EAE mice, compared with those in control littermates. We also confirmed that daphnetin suppressed the production of IL-1β, IL-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated mouse BV2 microglial cells. Mechanistically, heme oxygenase-1 (HO-1), a canonical anti-oxidant and anti-inflammatory factor, was found to be substantially induced by daphnetin treatment in BV2 cells. Also, a significantly higher level of HO-1, accompanied by a decreased level of malondialdehyde, was observed in daphnetin-treated EAE mice. More importantly, the deletion of HO-1 in BV2 microglia largely abrogated daphnetin-mediated inhibition of the inflammatory response. Together, our data demonstrate that daphnetin has an anti-inflammatory and neuroprotective role during the pathogenesis of EAE, which is partially at least, dependent on its regulation of HO-1.
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http://dx.doi.org/10.1007/s11064-020-02960-0DOI Listing
April 2020

Efficient Expression of Human Lysozyme Through the Increased Gene Dosage and Co-expression of Transcription Factor Hac1p in Pichia pastoris.

Curr Microbiol 2020 May 13;77(5):846-854. Epub 2020 Jan 13.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China.

In this work, the high-level expression of the human lysozyme (HLY) was achieved by both optimization of the gene copy number and co-expression of the transcription factor Hac1p for the unfolded protein response (UPR) in the host strain Pichia pastoris KM71H. A series of recombinant constructs with various numbers of HLY expression cassettes was generated for the production of recombinant strains integrated with different copies of the HLY gene. The copy number of the HLY gene was determined by real-time quantitative polymerase chain reaction, and the recombinant strains of P. pastoris carrying one, two, three, four, or six copies of the HLY gene were obtained. Maximum extracellular protein and lysozyme enzyme activity reached 436.99 ± 26.08 μg/mL and 61,900 ± 2036.47 U/mL, respectively, in the recombinant strain HLYH4-3 with the four copies of the HLY gene after shaking flask fermentation. Moreover, the co-expression of the transcription factor Hac1p in the recombinant strains further enhanced the HLY yields. Extracellular protein and lysozyme enzyme activity, respectively, reached 517.82 ± 4.19 μg/mL and 78,600 ± 1134.95 U/mL by using the Hac1p co-expression strain HLYH4-3/Hac1p. These values are the highest recorded level of human lysozyme expressed by P. pastoris in shaking flask fermentation so far.
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http://dx.doi.org/10.1007/s00284-019-01872-9DOI Listing
May 2020

Genome shuffling enhances stress tolerance of to two inhibitors.

Biotechnol Biofuels 2019 16;12:288. Epub 2019 Dec 16.

1Biomass Energy Technology Research Centre, Key Laboratory of Development and Application of Rural Renewable Energy (Ministry of Agriculture and Rural Affairs), Biogas Institute of Ministry of Agriculture and Rural Affairs, Section 4-13, Renmin Rd. South, Chengdu, 610041 People's Republic of China.

Background: Furfural and acetic acid are the two major inhibitors generated during lignocellulose pretreatment and hydrolysis, would severely inhibit the cell growth, metabolism, and ethanol fermentation efficiency of . Effective genome shuffling mediated by protoplast electrofusion was developed and then applied to .

Results: After two rounds of genome shuffling, 10 different mutants with improved cell growth and ethanol yield in the presence of 5.0 g/L acetic acid and 3.0 g/L furfural were obtained. The two most prominent genome-shuffled strains, 532 and 533, were further investigated along with parental strains in the presence of 7.0 g/L acetic acid and 3.0 g/L furfural. The results showed that mutants 532 and 533 were superior to the parental strain AQ8-1 in the presence of 7.0 g/L acetic acid, with a shorter fermentation time (30 h) and higher productivity than AQ8-1. Mutant 533 exhibited subtle differences from parental strain F34 in the presence of 3.0 g/L furfural. Mutations present in 10 genome-shuffled strains were identified via whole-genome resequencing, and the source of each mutation was identified as either de novo mutation or recombination of the parent genes.

Conclusions: These results indicate that genome shuffling is an efficient method for enhancing stress tolerance in . The engineered strains generated in this study could be potential cellulosic ethanol producers in the future.
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http://dx.doi.org/10.1186/s13068-019-1631-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913010PMC
December 2019

Judging the phase transition pressure of the unknown parent phase if the resulting state is known.

Phys Chem Chem Phys 2020 Jan;22(2):624-627

School of Physical Science and Technology, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, Chengdu 610031, China.

In high-pressure phase transition experiments, the crystal structure of the intermediate phase in some phase transitions is difficult to successfully measure due to the limitations of the experimental conditions. The absence of crystal structure data for the intermediate phase also makes it difficult to calculate the pressure point from the intermediate phase to the new phase by the traditional thermodynamic criterion in theoretical simulations. The Conch Criterion is employed by us to successfully verify the phase transition points by observing the reverse shifts of the DOS (electron density of states) curves for the new phase of Cu2S, PbS, PbSe and PbTe, which breaks through the constraints of the traditional criterion and realizes tracing the source of the phase transition in theoretical calculations.
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http://dx.doi.org/10.1039/c9cp05985gDOI Listing
January 2020

Ortho and para oxydehalogenation of dihalophenols catalyzed by the monooxygenase TcpA and NAD(P)H:FAD reductase Fre.

J Hazard Mater 2020 04 29;388:121787. Epub 2019 Nov 29.

Key Laboratory for Agri-Food Safety, School of Resource & Environment, Anhui Agricultural University, Hefei, Anhui 230036, China. Electronic address:

Dihalophenols such as dichlorophenols (DCPs) are important industrial chemical intermediates, but also persistent pollutants in the environment. Oxidative dehalogenation by microbes is an efficient biological method to degrade halophenols, but the mechanism is unclear yet. Cupriavidus nantongensis X1 was a type strain of genus Cupriavidus, and could degrade 2,4-dichlorophenol of 50 mg/L within 12 h. The degradation rate constant was approximately 84 fold greater than that by Bacillus endophyticus CP1R43, a well-studied 2,4-DCP-degrading bacterial strain. The genes encoding 2,4,6-trichlorophenol monooxygenase (TcpA) and NAD(P)H:FAD reductase (Fre) from strain X1 were cloned and expressed. The expressed TcpA Fre were purified. The molecular docking of TcpA with DCPs and point mutation experiments showed that the degradation activity of TcpA was associated with the length of the hydrogen bond between the substrates and the amino acids in the active pocket. DCPs were degraded via a stepwise oxidative dechlorination in a positive relationship between the oxidation ability and the electron-withdrawing potential of the p-position group. In addition, TcpA has dual dehalogenation and denitration functions. The results demonstrate that either strain X1 or TcpA and Fre can effectively dehalogenate dihalophenols, which can be useful for the treatment of dihalophenols in wastewaters and remediation of DCP-contaminated environments.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121787DOI Listing
April 2020