Publications by authors named "Minghua Li"

193 Publications

The remediation effects of microbial organic fertilizer on soil microorganisms after chloropicrin fumigation.

Ecotoxicol Environ Saf 2022 Jan 17;231:113188. Epub 2022 Jan 17.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, China; Yunnan Provincial Key Laboratory of Panax notoginseng, Kunming 650500, China; Key Laboratory of Panax notoginseng Resources Sustainable Development and Utilization of State Administration of Traditional Chinese Medicine, Kunming 650500, China; Kunming Key Laboratory of Sustainable Development and Utilization of Famous-Region Drug, Kunming 650500, China; Sanqi Research Institute of Yunnan Province, Kunming 650500, Yunnan, China. Electronic address:

Soil fumigation with chloropicrin (CP) is an effective means of overcoming continuous cropping obstacles (CCO) in Panax notoginseng and improving its yield and quality. CP fumigation can change the microbial community of soil. Therefore, a key step after CP fumigation is the rapid restoration of soil microorganisms and the promotion of beneficial microorganism proliferation as the dominant flora. In this study, continuously cropped soil of P. notoginseng was fumigated with CP, and general organic fertilizer (GOF) or microbial organic fertilizer (MOF) was used to restore soil microorganisms after fumigation. Soil physical and chemical properties, soil microorganisms, and quality of P. notoginseng were investigated. The application of MOF and GOF after CP fumigation promoted increases in soil nitrogen (9.88% and 8.21%, respectively), phosphorus (21.39% and 11.57%, respectively), potassium (7.99% and 2.75%, respectively), and the quality of P. notoginseng; it also promoted the accumulation of saponins in the main roots (23.62% and 9.12%, respectively). Application of MOF and GOF can restore the diversity of microorganisms in the soil. MOF increased the relative abundance of the beneficial soil microorganisms Glomeromycota, Mortierellomycota, Humicola and Bacillus, thereby lowering the relative abundance of the harmful Ascomycota and Fusarium relative to GOF. In summary, CP fumigation reduces the diversity of microorganisms in the soil. The addition of organic fertilizer can promote microbial diversity and increase the relative abundance of beneficial species. Moreover, the promotion effect of MOF is better than that of GOF, thereby improving soil fertility and ultimately promoting the quality and yield of P. notoginseng.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113188DOI Listing
January 2022

Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA.

Mol Biomed 2021 Sep 27;2(1):29. Epub 2021 Sep 27.

Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.
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http://dx.doi.org/10.1186/s43556-021-00054-zDOI Listing
September 2021

Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling.

Histol Histopathol 2021 Dec 15:18408. Epub 2021 Dec 15.

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.

Background: Lung cancer is one of the most common causes of cancer-associated mortality worldwide. Upregulation of kinesin family member 15 (KIF15) expression has been observed in non-small cell lung cancer (NSCLC), and high expression levels of KIF15 are associated with a poor prognosis in patients with NSCLC. However, to the best of our knowledge, the mechanisms by which KIF15 regulates apoptosis, migration and invasion in NSCLC remain unclear.

Methods: Cell Counting Kit-8, flow cytometry and Transwell assays were performed to determine the proliferation, apoptosis and invasion of NSCLC cells, respectively. In addition, western blotting was used to detect the levels of phosphorylated (p-)c-Raf, p-ERK and p-MEK in NSCLC cells.

Results: Downregulation of KIF15 expression markedly inhibited the proliferation, migration and invasion of NSCLC cells through mediation of MMP2 and MMP9. In addition, downregulation of KIF15 markedly induced apoptosis and cell cycle arrest in NSCLC cells through regulation of active caspase 3, p27 Kip1 and cyclin D1. Furthermore, KIF15 knockdown notably decreased the levels of activating transcription factor 2, p-c-Raf, p-ERK and p-MEK in A549 and NCI-H460 cells. Finally, KIF15 knockdown notably inhibited the tumor growth of NSCLC in vivo.

Conclusion: In conclusion, the present study indicated that downregulation of KIF15 expression was able to inhibit the tumorigenesis of NSCLC by inactivating Raf/MEK/ERK signaling. These findings may help improve the diagnosis and treatment of NSCLC.
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http://dx.doi.org/10.14670/HH-18-408DOI Listing
December 2021

Enriched clonal hematopoiesis in seniors with dietary vitamin C inadequacy.

Clin Nutr ESPEN 2021 Dec 30;46:179-184. Epub 2021 Oct 30.

Beijing Lu Daopei Institute of Hematology, Beijing, China; Division of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, China; Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital, Beijing, China. Electronic address:

Background: The anti-cancer effect of vitamin C (VC) has long been speculated, but studies yielded inconsistency. Recent studies reported that supraphysiological concentration of VC have therapeutic or prevention effects for myeloid malignancies with certain mutation signatures. There was a notable proportion of DAT (i.e., DNMT3A, ASXL1, and TET2) and dozens of other genes that mutate in age-related clonal hematopoiesis (ARCH).

Methods And Results: Through analyzing the plasma VC concentration and mutations of 21 genes in 215 senior volunteers, we revealed that ARCH is significantly associated with dietary plasma VC concentrations, especially TET2 mutations and non-DAT mutations.

Conclusion: This study firstly disclosed the significant association between VC inadequacy and ARCH in the senior population. It provides evidence that physiological VC concentration has ARCH prevention effect. It will illuminate future explorations on the oral VC supplement in maintaining sound hematopoiesis, reversal ARCH, adjuvant therapy for myeloid malignancies, and prevention of other ARCH related comorbidities.
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http://dx.doi.org/10.1016/j.clnesp.2021.10.014DOI Listing
December 2021

Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA.

Mol Biomed 2021 27;2(1):29. Epub 2021 Sep 27.

Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

Supplementary Information: The online version contains supplementary material available at 10.1186/s43556-021-00054-z.
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http://dx.doi.org/10.1186/s43556-021-00054-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475395PMC
September 2021

An intelligent responsive macrophage cell membrane-camouflaged mesoporous silicon nanorod drug delivery system for precise targeted therapy of tumors.

J Nanobiotechnology 2021 Oct 24;19(1):336. Epub 2021 Oct 24.

Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People's Republic of China.

Macrophage cell membrane-camouflaged nanocarriers can effectively reduce immune cell clearance and actively target tumors. In this study, a macrophage cell membrane-camouflaged mesoporous silica nanorod (MSNR)-based antitumor drug carrier equipped with a cationic polymer layer was developed. As drug carriers, these MSNRs were loaded with the thermosensitive phase change material L-menthol (LM), the chemotherapy drug doxorubicin (DOX) and the fluorescent molecule indocyanine green (ICG). The rod-like shape of the MSNRs was shown to enhance the penetration of the drug carriers to tumors. In the weakly acidic tumor microenvironment, the cationic polymer exhibited a proton sponge effect to trigger macrophage cell membrane coating detachment, promoting tumor cell uptake. Following nanocarrier uptake, ICG is heated by near-infrared (NIR) irradiation to make LM undergo a phase transition to release DOX and generate a synergistic effect of thermochemotherapy which kills tumor cells and inhibits tumor growth together with reactive oxygen species (ROS) produced by ICG. Overall, this nanohybrid drug delivery system demonstrates an intelligent cascade response, leads to tissue-cell specific targeting and improves drug release accuracy, thus proving to be an effective cancer therapy.
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http://dx.doi.org/10.1186/s12951-021-01082-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543955PMC
October 2021

Effects of Activation Conditions on the Properties of Sludge-Based Activated Coke.

ACS Omega 2021 Aug 18;6(34):22020-22032. Epub 2021 Aug 18.

Mechanical and Industrial Engineering Department, Northeastern University, Boston, Massachusetts 02115, United States.

Sewage sludge and waste biomass are unavoidable byproducts of municipal and industrial processes. Both materials have significant carbon contents. Activated coke with a developed pore structure can be obtained after its physical activation. In this study, sewage sludge and waste poplar bark were used as precursor materials to prepare activated coke by steam, carbon dioxide gas, and their mixtures. The effects of different concentrations of activation gas on the activated coke product were investigated. Through nitrogen adsorption analysis, it was found that activated coke has a higher specific surface area and better pore structure when activated in gas containing 20% steam. The activated coke prepared by carbon dioxide gas activation has higher microporosity than that prepared by steam activation. Infrared spectrum analysis shows that steam activation is beneficial to the formation of free hydroxyl functional groups. Through scanning electron microscopy analysis, the pores of activated coke prepared by steam activation appeared to extend deeper in the structure of the coke, while the pores of activated coke prepared by carbon dioxide activation appeared to have fine circular structures. The activated coke prepared by the activation of mixed gas appeared to have ablated particles on the surface due to the ablation of the pore structure. In order to prepare activated coke with excellent adsorption performance, the physical and chemical properties of activated coke under different activation conditions were studied in detail.
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http://dx.doi.org/10.1021/acsomega.1c02600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412919PMC
August 2021

Estimation of nitrate nitrogen content in cotton petioles under drip irrigation based on wavelet neural network approach using spectral indices.

Plant Methods 2021 Aug 18;17(1):90. Epub 2021 Aug 18.

School of Agriculture, Shihezi University, Shihezi, 832003, Xinjiang, People's Republic of China.

Background: Estimation of nitrate nitrogen (NO-N) content in petioles is one of the key approaches for monitoring nitrogen (N) nutrition in crops. Rapid, non-destructive, and accurate evaluation of NO-N contents in cotton petioles under drip irrigation is of great significance.

Methods: In this study, we discussed the use of hyperspectral data to estimate NO-N contents in cotton petioles under drip irrigation at different N treatments and growth stages. The correlations among trilateral parameters and six vegetation indices and petiole NO-N contents were first investigated, after which a traditional regression model for petioles NO-N content was established. A wavelet neural network (WNN) model for estimating petiole NO-N content was also established. In addition, the performance of WNN was compared to those of random forest (RF), radial basis function neural network (RBF) and back propagation neural network (BP).

Results: Between the blue edge amplitude (Db) and blue edge area (SDb) of the blue edge parameters was the optimal index for the estimation model of petiole NO-N content. We found that the prediction results of the blue edge parameters and WNN were 7.3% higher than the coefficient of determination (R) of the first derivative vegetation index and WNN. Root mean square error (RMSE) and mean absolute error (MAE) were 25.2% and 30.9% lower than first derivative vegetation, respectively, and the performance was better than that of RF, RBF and BP.

Conclusions: An inexpensive approach consisting of the WNN algorithm and blue edge parameters can be used to enhance the accuracy of NO-N content estimation in cotton petioles under drip irrigation.
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http://dx.doi.org/10.1186/s13007-021-00790-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371893PMC
August 2021

Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured of SCLC Patients.

Front Oncol 2021 25;11:683318. Epub 2021 Jun 25.

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Purpose: The prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.

Methods: Based on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured obtained from ClearCell FX System was tested and the therapy response was evaluated.

Results: All of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.

Conclusion: The results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured may not benefit the improvement of therapeutic regimen of SCLC patients.
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http://dx.doi.org/10.3389/fonc.2021.683318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267575PMC
June 2021

HIF-1α Affects the Neural Stem Cell Differentiation of Human Induced Pluripotent Stem Cells via MFN2-Mediated Wnt/β-Catenin Signaling.

Front Cell Dev Biol 2021 21;9:671704. Epub 2021 Jun 21.

Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential and . Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.
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http://dx.doi.org/10.3389/fcell.2021.671704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256873PMC
June 2021

Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection.

bioRxiv 2021 Jun 24. Epub 2021 Jun 24.

The ongoing COVID-19 pandemic has highlighted the dearth of approved drugs to treat viral infections, with only ∼90 FDA approved drugs against human viral pathogens. To identify drugs that can block SARS-CoV-2 replication, extensive drug screening to repurpose approved drugs is underway. Here, we screened ∼18,000 drugs for antiviral activity using live virus infection in human respiratory cells. Dose-response studies validate 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Amongst these drug candidates are 16 nucleoside analogs, the largest category of clinically used antivirals. This included the antiviral Remdesivir approved for use in COVID-19, and the nucleoside Molnupirivir, which is undergoing clinical trials. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral, and we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogs synergistically inhibits SARS-CoV-2 infection in vitro and in vivo suggesting a clinical path forward.
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http://dx.doi.org/10.1101/2021.06.24.449811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240684PMC
June 2021

Analysis of Risk Factors for Anterior Communicating Artery Aneurysm Rupture: A Single-Center Study.

World Neurosurg 2021 09 13;153:e59-e65. Epub 2021 Jun 13.

Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

Background: Congenital hypoplasia or aplasia of the A1 segment of the anterior cerebral artery is associated with an increased incidence of berry aneurysms at the anterior communicating artery (ACoA) complex. We analyzed the factors contributing to ACoA aneurysm rupture.

Methods: We retrospectively analyzed the data of patients with ACoA aneurysms who had undergone cerebral angiography from July 2008 to January 2020. The risk factors for rupture were identified using univariate and multivariate logistic regression models. We used the imaging data of patients without intracranial aneurysms as the control population.

Results: We confirmed 253 aneurysms in 253 patients, including 137 men (54.2%) and 116 women (45.8%), with a mean age of 54.6 ± 12.7 years. Of the 253 aneurysms, 218 (86.2%) were ruptured and 35 (13.8%) were unruptured, with a mean diameter of 4.56 ± 1.96 mm and 3.24 ± 1.79 mm, respectively. Of the 253 aneurysms, 176 (69.6%) were <5 mm in diameter, 146 (83%) of which were ruptured. Of the 253 patients, 141 (55.7%) exhibited A1 segment hypoplasia or aplasia: 106 (41.9%) on the right side of the circle of Willis and 35 (13.8%) on the left. Multivariate logistic regression analysis identified the aneurysm diameter (odds ratio, 4.11; 95% confidence interval, 1.601-16.07; P = 0.003) and age <65 years (odds ratio, 0.17; 95% confidence interval, 0.062-0.48; P < 0.001) as independent predictors of rupture.

Conclusions: ACoA aneurysms are small (<5 mm) and have a high risk of rupture. A1 segment hypoplasia or aplasia is a risk factor for ACoA aneurysm formation; however, it was uncorrelated with aneurysm diameter or rupture risk. The strongest independent risk factors for rupture were age <65 years and aneurysm diameter.
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http://dx.doi.org/10.1016/j.wneu.2021.06.007DOI Listing
September 2021

Glucose-oxidase like catalytic mechanism of noble metal nanozymes.

Nat Commun 2021 06 7;12(1):3375. Epub 2021 Jun 7.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin, PR China.

Au nanoparticles (NPs) have been found to be excellent glucose oxidase mimics, while the catalytic processes have rarely been studied. Here, we reveal that the process of glucose oxidation catalyzed by Au NPs is as the same as that of natural glucose oxidase, namely, a two-step reaction including the dehydrogenation of glucose and the subsequent reduction of O to HO by two electrons. Pt, Pd, Ru, Rh, and Ir NPs can also catalyze the dehydrogenation of glucose, except that O is preferably reduced to HO. By the electron transfer feature of noble metal NPs, we overcame the limitation that HO must be produced in the traditional two-step glucose assay and realize the rapid colorimetric detections of glucose. Inspired by the electron transport pathway in the catalytic process of natural enzymes, noble metal NPs have also been found to mimic various enzymatic electron transfer reactions including cytochrome c, coenzymes as well as nitrobenzene reductions.
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http://dx.doi.org/10.1038/s41467-021-23737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184917PMC
June 2021

Pharmacological activation of STING blocks SARS-CoV-2 infection.

Sci Immunol 2021 05;6(59)

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia PA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection. To identify potent antiviral innate immune agonists, we screened a panel of 75 microbial ligands that activate diverse signaling pathways and identified cyclic dinucleotides (CDNs), canonical STING agonists, as antiviral. Since CDNs have poor bioavailability, we tested the small molecule STING agonist diABZI, and found that it potently inhibits SARS-CoV-2 infection of diverse strains including variants of concern (B.1.351) by transiently stimulating IFN signaling. Importantly, diABZI restricts viral replication in primary human bronchial epithelial cells and in mice in vivo. Our study provides evidence that activation of STING may represent a promising therapeutic strategy to control SARS-CoV-2.
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http://dx.doi.org/10.1126/sciimmunol.abi9007DOI Listing
May 2021

Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2.

Cell Rep 2021 04 23;35(1):108959. Epub 2021 Mar 23.

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.
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http://dx.doi.org/10.1016/j.celrep.2021.108959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985926PMC
April 2021

Monocarboxylate transporter 1 promotes proliferation and invasion of renal cancer cells by mediating acetate transport.

Cell Biol Int 2021 Jun 19;45(6):1278-1287. Epub 2021 Feb 19.

Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.

One hallmark of renal cell carcinoma (RCC) is metabolic reprogramming, which involves elevation of glycolysis and upregulation of lipid metabolism. However, the mechanism of metabolic reprogramming is incompletely understood. Monocarboxylate transporter 1 (MCT1) promotes transport for lactate and pyruvate, which are crucial for cell metabolism. The aim of present study was to investigate the function of MCT1 on RCC development and its mechanism on metabolic reprogramming. The results showed that MCT1 messenger RNA and protein levels significantly increased in cancer tissues of ccRCC compared to normal tissue. MCT1 was further found to mainly located in the cell membrane of RCC. The knockdown of MCT1 by RNAi significantly inhibited proliferation and migration of 786-O and ACHN cells. MCT1 also induced the expressions of proliferation marker Ki-67 and invasion marker SNAI1. Moreover, we also showed that acetate treatment could upregulate the expression of MCT1, but not other MCT isoforms. On the other hand, MCT1 was involved in acetate transport and intracellular histone acetylation. In summary, this study revealed that MCT1 is abnormally high in ccRCC and promotes cancer development. The regulatory effect of MCT1 on cell proliferation and invasion maybe mediated by acetate transport.
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http://dx.doi.org/10.1002/cbin.11571DOI Listing
June 2021

Multiple Intravenous Injections of Valproic Acid-Induced Mesenchymal Stem Cell from Human-Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model.

Biomed Res Int 2020 17;2020:2863501. Epub 2020 Dec 17.

Peking University Shenzhen Hospital, Ultrasound Department, China.

Mounting evidence indicates that the mesenchymal stem cell (MSC) injection is safe and efficacious for treating cardiomyopathy; however, there is limited information relating to multiple intravenous injections of human-induced pluripotent stem cell-derived mesenchymal stem cell (hiPSC-MSC) and long-term evaluation of the cardiac function. In the current study, MSC-like cells were derived from human-induced pluripotent stem cells through valproic acid (VPA) induction and continuous cell passages. The derived spindle-like cells expressed MSC-related markers, secreted angiogenic and immune-regulatory factors, and could be induced to experience chondrogenic and adipogenic differentiation. During the induction process, expression of epithelial-to-mesenchymal transition- (EMT-) related gene N-cadherin and vimentin was upregulated to a very high level, and the expression of pluripotency-related genes Sox2 and Oct4 was downregulated or remained unchanged, indicating that VPA initiated EMT by upregulating the expression of EMT promoting genes and downregulating that of pluripotency-related genes. Two and four intravenous hiPSC-MSC injections (10 cells/per injections) were provided, respectively, to model rats one week after acute myocardial infarction (AMI). Cardiac function parameters were dynamically monitored during a 12-week period. Two and four cell injections significantly the improved left ventricular ejection fraction and left ventricular fractional shortening; four-injection markedly stimulated angiogenesis reduced the scar size and cell apoptosis number in the scar area in comparison with that of the untreated control model rats. Although the difference was insignificant, the hiPSC-MSC administration delayed the increase of left ventricular end-diastolic dimension to different extents compared with that of the PBS-injection control. No perceptible immune reaction symptom or hiPSC-MSC-induced tumour formation was found over 12 weeks. Compared with the PBS-injection control, four injections produced better outcome than two injections; as a result, at least four rounds of MSC injections were suggested for AMI treatment.
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http://dx.doi.org/10.1155/2020/2863501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759411PMC
May 2021

Mono antiplatelet therapy for cardioembolic and undetermined etiological stroke after receiving successful mechanical thrombectomy.

Clin Neurol Neurosurg 2021 02 4;201:106412. Epub 2020 Dec 4.

Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yi Shan Road, Shanghai, 200233, China. Electronic address:

Background: Recent studies indicated that majority of stroke with undetermined etiology (SUE) showed strong overlap with cardioembolic stroke (CE). We intended to determine the efficacy of the mono antiplatelet (MA) therapy in both stroke types after receiving successful mechanical thrombectomy (MT) recanalization in the acute stage.

Methods: 178 consecutive stroke patients who received MT treatment were retrospectively analyzed. For CE and SUE type stroke patients, aspirin 100 mg or clopidogrel 75 mg was added immediate for those didn`t received IV-rtPA and after 24 h for those received IV-rtPA if symptomatic intracranial hemorrhage (sICH) was not found. MA treatment outcomes included recanalized artery patency, subsequent sICH and functional independence (mRS score 0-2) were compared between two stroke types.

Results: 75 CE and 50 SUE patients were included into final analysis. Target artery was confirmed 100 % patency in the CE group and 97.5 % in the SUE group at 7 days after recanalization. Hemorrhagic transformation after 24 h was found in 10 % patients in the SUE group and in 12 % patients in the CE group (P > 0.05). sICH was confirmed in 1 patient in the SUE group and in 2 patients in the CE group. At 90 days, 45.8 % in the SUE group and 46.5 % in the CE group of patients had achieved good outcomes (P = 1.00). However, accumulative death was higher in the CE group than in the SUE group (21 % vs. 15 %; P = 0.47).

Conclusion: For patients considered CE or SUE stroke types, mono antiplatelet therapy after good flow restoration by thrombectomy is safe and effective.
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http://dx.doi.org/10.1016/j.clineuro.2020.106412DOI Listing
February 2021

Visualization of Thrombus Enhancement on Thin-Slab Maximum Intensity Projection of CT Angiography: An Imaging Sign for Predicting Stroke Source and Thrombus Compositions.

Radiology 2021 02 15;298(2):374-381. Epub 2020 Dec 15.

From the Departments of Radiology (L.W., Y. Zhu, Y.L., M.L., H.L.) and Neurology (J.D., Y. Zhao), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.

Background Thrombus enhancement (TE) in large vessel occlusion in patients with acute ischemic stroke can be visualized with thin-slab maximum intensity projection (TS-MIP) image reconstruction of CT angiograms. Purpose To evaluate whether TE on TS-MIP reconstructed CT angiograms can be used to predict thrombus composition and stroke source. Materials and Methods This retrospective study included consecutive patients with acute ischemic stroke who underwent thrombectomy in the anterior circulation between August 2016 and July 2019. Stroke types were classified according to the Trial of ORG 10172 in Acute Stroke Treatment. TE on TS-MIP reconstructed CT angiograms was evaluated by two readers. Various clinical and interventional parameters and histopathologic thrombi examination results were compared between the TE-positive and TE-negative groups. The associations between TE and thrombus compositions and stroke sources were analyzed by using multivariable linear and logistic regression models. Results A total of 148 patients (mean age, 71 years ± 11 [standard deviation]; 94 men) were included. TE was confirmed in 80% (119 of 148) of the patients. TE-positive thrombi contained a higher fibrin and platelet proportion (mean, 46% ± 16 vs 34% ± 13; = .02) and fewer erythrocytes (mean, 33% ± 14 vs 48% ± 20, = .002) than the TE-negative thrombi. The proportion of cardioembolic and cryptogenic strokes in the TE-positive and TE-negative groups was 92% (110 of 119) and 24% (seven of 29), respectively ( < .001). In adjusted analysis, the presence of TE (odds ratio, 155; 95% CI: 17, 1438; < .001) was associated with a combination of cardioembolic and cryptogenic strokes. A multiple logistic regression model showed that TE (odds ratio, 23; 95% CI: 1.8, 288; = .02) was significantly associated with cardioembolic stroke. Conclusion Thrombus enhancement on thin-slab maximum intensity projection of CT angiography can be used to predict cardioembolic and cryptogenic strokes and identify thrombi with a higher fibrin-to-platelet fraction and a lower erythrocyte proportion. © RSNA, 2020 See also the editorial by Kansagra and Goyal in this issue.
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http://dx.doi.org/10.1148/radiol.2020201548DOI Listing
February 2021

Coenzyme-dependent nanozymes playing dual roles in oxidase and reductase mimics with enhanced electron transport.

Nanoscale 2020 Dec;12(46):23578-23585

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, PR China.

Although nanozymes overcome a series of shortcomings of natural enzymes, their wide applications are hampered due to their limited varieties. In this work, we propose a coenzyme-dependent nanozyme, a synergistic composite comprising zeolitic imidazolate frameworks encapsulated with polyethylenimine (PEI) and functionalized with a flavin mononucleotide (PEI/ZIF-FMN). The flavin mononucleotide (FMN) plays the role of a prosthetic group, and the positively charged NH2 groups in PEI readily provide the binding affinity to nicotinamide adenine dinucleotide (NADH), which facilitates the electron transfer from NADH to FMN and terminal electron acceptors (such as O2) with a greatly enhanced (80 times) catalytic performance. The integrated nanoparticle-coenzyme composite works as an NADH oxidase mimic and couples with dehydrogenases for the tandem enzymatic reaction. PEI/ZIF-FMN also mediated the electron transfer from NADH to cytochrome c (Cyt c), thereby exhibiting Cyt c reductase-like activity.
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http://dx.doi.org/10.1039/d0nr06605bDOI Listing
December 2020

Crystallization Kinetics Modulation of FASnI Films with Pre-nucleation Clusters for Efficient Lead-Free Perovskite Solar Cells.

Angew Chem Int Ed Engl 2021 Feb 15;60(7):3693-3698. Epub 2020 Dec 15.

Guangdong Key Lab of Nano-Micro Material Research, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China.

Tin halide perovskites are rising as promising materials for lead-free perovskite solar cells (PSCs). However, the crystallization rate of tin halide perovskites is much faster than the lead-based analogs, leading to more rampant trap states and lower efficiency. Here, we disclose a key finding to modulate the crystallization kinetics of FASnI through a non-classical nucleation mechanism based on pre-nucleation clusters (PNCs). By introducing piperazine dihydriodide to tune the colloidal chemistry of the FASnI perovskite precursor solution, stable clusters could be readily formed in the solution before nucleation. These pre-nucleation clusters act as intermediate phase and thus can reduce the energy barrier for the perovskite nucleation, resulting in a high-quality perovskite film with lower defect density. This PNCs-based method has led to a conspicuous photovoltaic performance improvement for FASnI -based PSCs, delivering an impressive efficiency of 11.39 % plus improved stability.
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http://dx.doi.org/10.1002/anie.202012280DOI Listing
February 2021

Biomimetic Human Disease Model of SARS-CoV-2 Induced Lung Injury and Immune Responses on Organ Chip System.

Adv Sci (Weinh) 2020 Oct 24:2002928. Epub 2020 Oct 24.

Division of Biotechnology CAS Key Laboratory of SSAC Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian China.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The models that can accurately resemble human-relevant responses to viral infection are lacking. Here, we create a biomimetic human disease model on chip that allows to recapitulate lung injury and immune responses induced by SARS-CoV-2 in vitro at organ level. This human alveolar chip reproduced the key features of alveolar-capillary barrier by co-culture of human alveolar epithelium, microvascular endothelium and circulating immune cells under fluidic flow in normal and disease. Upon SARS-CoV-2 infection, the epithelium exhibited higher susceptibility to virus than endothelium. Transcriptional analyses showed activated innate immune responses in epithelium and cytokine-dependent pathways in endothelium at 3 days post-infection, revealing the distinctive responses in different cell types. Notably, viral infection caused the immune cell recruitment, endothelium detachment, and increased inflammatory cytokines release, suggesting the crucial role of immune cells involving in alveolar barrier injury and exacerbated inflammation. Treatment with remdesivir could inhibit viral replication and alleviate barrier disruption on chip. This organ chip model can closely mirror human-relevant responses to SARS-CoV-2 infection, which is difficult to be achieved by in vitro models, providing a unique platform for COVID-19 research and drug development. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/advs.202002928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646023PMC
October 2020

Mechanism of intrinsic resistance of lung squamous cell carcinoma to epithelial growth factor receptor-tyrosine kinase inhibitors revealed by high-throughput RNA interference screening.

Oncol Lett 2020 Dec 15;20(6):363. Epub 2020 Oct 15.

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shang University of Traditional Chinese Medicine, Shanghai 200071, P.R. China.

Although targeted therapy has achieved a great breakthrough in the treatment of lung adenocarcinoma, there are still no effective targeted drugs for lung squamous cell carcinoma (SqCC). In addition, as immunotherapy can only prolong the overall survival (OS) of lung SqCC by ≤5 months, chemotherapy and radiotherapy are still the main types of therapy for advanced SqCC. The expression level of epithelial growth factor receptor (EGFR) in patients with lung SqCC is higher compared with those with adenocarcinoma, but the former group is intrinsically resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Therefore, if the drug resistance in patients with lung SqCC could be reversed, the majority of patients may benefit from EGFR-TKIs. In the present study, the high-throughput RNA interference technology was used to screen the genes involved in the EGFR-TKI erlotinib resistance of lung SqCCs, and integrin-linked kinase (ILK) was identified to be the most effective. The role of ILK in erlotinib resistance was further studied in cell lines, and the expression of ILK was analyzed in patients with SqCC and adenocarcinoma. Finally, the mechanism of ILK in EGFR-TKIs resistance was analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and ingenuity pathway analysis (IPA). The results demonstrated that the ILK gene knockdown could overcome erlotinib resistance by inhibiting cell proliferation, inducing apoptosis and blocking the cell cycle at the G2/M phase. The expression of ILK in patients with SqCC was significantly higher compared with those with adenocarcinoma with sensitizing EGFR mutations. In addition, the cell cycle pathway 'G2/M DNA damage and checkpoint regulation' was identified to be significantly inhibited by ILK knockdown in IPA, KEGG and GO analysis. The results of the present study may improve the understanding of EGFR-TKI resistance in lung SqCCs, thus promoting the development of potential targeted therapies for lung SqCCs.
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http://dx.doi.org/10.3892/ol.2020.12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590427PMC
December 2020

Erratum: An erratum on "Application of three-dimensional printing in interventional medicine" [J Interv Med (February 2020) 1-16].

J Interv Med 2020 Sep 19;3(3):156. Epub 2020 Sep 19.

Department of Radiology, No. 85, Hospital of PLA, Shanghai, 200052, China.

[This corrects the article DOI: 10.1016/j.jimed.2020.01.001.].
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http://dx.doi.org/10.1016/j.jimed.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562184PMC
September 2020

Oxidase-like MOF-818 Nanozyme with High Specificity for Catalysis of Catechol Oxidation.

J Am Chem Soc 2020 09 27;142(36):15569-15574. Epub 2020 Aug 27.

College of Chemistry, Jilin University, Changchun 130012, P. R. China.

Despite the extensive studies of the nanozymes showing their superior properties compared to natural enzymes and traditional artificial enzymes, the development of highly specific nanozymes is still a challenge. The catechol oxidase specifically catalyzing the oxidations of -diphenol to the corresponding -quinone is important to the biosynthesis of melanin and other polyphenolic natural products. In this study, we first propose that MOF-818, containing trinuclear copper centers mimicking the active sites of natural catechol oxidase, shows efficient catechol oxidase activity with good specificity and no peroxidase-like characteristics. MOF-818 has good specificity and high catalytic activity as a novel catechol oxidase nanozyme.
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http://dx.doi.org/10.1021/jacs.0c07273DOI Listing
September 2020

Deciphering flavivirus-host interactions using quantitative proteomics.

Curr Opin Immunol 2020 10 15;66:90-97. Epub 2020 Jul 15.

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Flaviviruses are a group of important emerging and re-emerging human pathogens that cause worldwide epidemics with thousands of deaths annually. Flaviviruses are small, enveloped, positive-sense, single-stranded RNA viruses that are obligate intracellular pathogens, relying heavily on host cell machinery for productive replication. Proteomic approaches have become an increasingly powerful tool to investigate the mechanisms by which viruses interact with host proteins and manipulate cellular processes to promote infection. Here, we review recent advances in employing quantitative proteomics techniques to improve our understanding of the complex interplay between flaviviruses and host cells. We describe new findings on our understanding of how flaviviruses impact protein-protein interactions, protein-RNA interactions, protein abundance, and post-translational modifications to modulate viral infection.
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http://dx.doi.org/10.1016/j.coi.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749055PMC
October 2020

Absence of HTATIP2 Expression in A549 Lung Adenocarcinoma Cells Promotes Tumor Plasticity in Response to Hypoxic Stress.

Cancers (Basel) 2020 Jun 11;12(6). Epub 2020 Jun 11.

Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.

HIV-1 Tat Interactive Protein 2 (HTATIP2) is a tumor suppressor, of which reduced or absent expression is associated with increased susceptibility to tumorigenesis and enhanced tumor invasion and metastasis. However, whether the absent expression of HTATIP2 is a tumor-promoting factor that acts through improving tumor adaptation to hypoxia is unclear. Here, we established a stable HTATIP2-knockdown A549 human lung adenocarcinoma cell line (A549shHTATIP2) using lentiviral-delivered HTATIP2-targeting short hairpin RNA (shRNA), employed a double subcutaneous xenograft model and incorporated photoacoustic imaging and metabolomics approaches to elucidate the impact of the absent HTATIP2 expression on tumor response to hypoxic stress. Results from the study showed that A549shHTATIP2 tumors exhibited accelerated growth but decreased intratumoral oxygenation and angiogenesis and reduced sensitivity to sorafenib treatment as compared with their parental counterparts. Moreover, results of the immunoblot and real-time PCR analyses revealed that the HIF2α protein and mRNA levels in vehicle-treated A549shHTATIP2 tumors were significantly increased ( < 0.01 compared with the parental control tumors). Despite the strong HIF2α-c-Myc protein interaction indicated by our co-immunoprecipitation data, the increase in the c-Myc protein and mRNA levels was not significant in the A549shHTATIP2 tumors. Nonetheless, MCL-1 and β-catenin protein levels in A549shHTATIP2 tumors were significantly increased ( < 0.05 compared with the parental control tumors), suggesting an enhanced β-catenin/c-Myc/MCL-1 pathway in the absence of HTATIP2 expression. The finding of significantly decreased E-cadherin ( < 0.01 compared with vehicle-treated A549shHTATIP2 tumors) and increased vimentin ( < 0.05 compared with sorafenib-treated A549 tumors) protein levels in A549shHTATIP2 tumors implicates that the absence of HTATIP2 expression increases the susceptibility of A549 tumors to sorafenib-activated epithelial-mesenchymal transition (EMT) process. Comparison of the metabolomic profiles between A549 and A549shHTATIP2 tumors demonstrated that the absence of HTATIP2 expression resulted in increased tumor metabolic plasticity that enabled tumor cells to exploit alternative metabolic pathways for survival and proliferation rather than relying on glutamine and fatty acids as a carbon source to replenish TCA cycle intermediates. Our data suggest a mechanism by which the absent HTATIP2 expression modulates tumor adaptation to hypoxia and promotes an aggressive tumor phenotype by enhancing the HIF2α-regulated β-catenin/c-Myc/MCL-1 signaling, increasing the susceptibility of tumors to sorafenib treatment-activated EMT process, and improving tumor metabolic plasticity.
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http://dx.doi.org/10.3390/cancers12061538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352940PMC
June 2020

Acetate promotes SNAI1 expression by ACSS2-mediated histone acetylation under glucose limitation in renal cell carcinoma cell.

Biosci Rep 2020 06;40(6)

Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China.

Metastasis is the main cause of cancer-associated deaths, yet this complex process is still not well understood. Many studies have shown that acetate is involved in cancer metastasis, but the molecular mechanisms remain to be elucidated. In the present study, we first measured the effect of acetate on zinc finger transcriptional repressor SNAI1 and acetyl-CoA synthetase 2 (ACSS2) under glucose limitation in renal cell carcinoma cell lines, 786-O and ACHN. Then, RNA interference and overexpression of ACSS2 were used to detect the role of acetate on SNAI1 expression and cell migration. Finally, chromatin immunoprecipitation assay (ChIP) was used to investigate the regulatory mechanism of acetate on SNAI1 expression. The results showed that acetate increased the expressions of SNAI1 and ACSS2 under glucose limitation. ACSS2 knockdown significantly decreased acetate-induced SNAI1 expression and cell migration, whereas overexpression of ACSS2 increased SNAI1 level and histone H3K27 acetylation (H3K27ac). ChIP results revealed that acetate increased H3K27ac levels in regulatory region of SNAI1, but did not increase ACSS2-binding ability. Our study identified a novel inducer, acetate, which can promote SNAI1 expression by ACSS2-mediated histone acetylation in partly. This finding has important implication in treatment of metastatic cancers.
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http://dx.doi.org/10.1042/BSR20200382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295626PMC
June 2020

Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.

Clin Nutr 2021 01 29;40(1):94-102. Epub 2020 Apr 29.

Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Beijing, China. Electronic address:

Background: Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients.

Objective: We aimed to explore potential factors that influence muscle outcomes after nutritional intervention.

Methods: In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765).

Results: SWP significantly improved muscle status (muscle area: from 330.4 mm to 384.8 mm, p = 0.02; muscle strength: from 19.2 kg to 21.3 kg, p = 0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p = 0.01; Simpson: from 0.6 to 0.8, p = 0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p = 0.048) and amino acid biosynthesis (p = 0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction.

Conclusions: Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.
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http://dx.doi.org/10.1016/j.clnu.2020.04.030DOI Listing
January 2021

FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling.

Cell Death Dis 2020 04 24;11(4):272. Epub 2020 Apr 24.

Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Metabolic abnormality is the major feature of laryngeal squamous cell carcinoma (LSCC), however, the underlying mechanism remain largely elusive. Fatty acid desaturase 1 (FADS1), as the key rate-limiting enzyme of polyunsaturated fatty acids (PUFAs), catalyzes dihomo-gamma-linolenic acid (DGLA) to arachidonic acid (AA). In this study, we reported that the expression of FADS1 was upregulated in LSCC, high FADS1 expression was closely associated with the advanced clinical features and poor prognosis of the recurrent LSCC patients after chemotherapy. Liquid chromatograph-mass spectrometry (LC-MS) analysis revealed that FADS1 overexpression induced greater conversion of DGLA to AA, suggesting an increased activity of FADS1. Similarly, the level of prostaglandin E2 (PGE), a downstream metabolite of AA, was also elevated in cancerous laryngeal tissues. Functional assays showed that FADS1 knockdown suppressed the proliferation, migration and invasion of LSCC cells, while FADS1 overexpression had the opposite effects. Bioinformatic analysis based on microarray data found that FADS1 could activate AKT/mTOR signaling. This hypothesis was further validated by both in vivo and in vitro assays. Hence, our data has supported the viewpoint that FADS1 is a potential promoter in LSCC progression, and has laid the foundation for further functional research on the PUFA dietary supplementation interventions targeting FADS1/AKT/mTOR pathway for LSCC prevention and treatment.
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http://dx.doi.org/10.1038/s41419-020-2457-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181692PMC
April 2020
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