Publications by authors named "Mingyue Li"

150 Publications

Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Lung Adenocarcinoma.

J Immunol Res 2021 8;2021:6647122. Epub 2021 Apr 8.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.
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http://dx.doi.org/10.1155/2021/6647122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049788PMC
April 2021

Effects of Value Perception, Environmental Regulation and Their Interaction on the Improvement of Herdsmen's Grassland Ecological Policy Satisfaction.

Int J Environ Res Public Health 2021 03 17;18(6). Epub 2021 Mar 17.

School of Economics and Management, Beijing Forestry University, Beijing 100083, China.

Sustainable utilization of grassland resources was an important topic concerned by worldwide countries and regions, and ecological compensation had gradually become the main policy tool for grassland environmental management and ecological protection. This study adopted face-to-face interviews and questionnaires, and multiordered Logit model was then used to explore herdsmen's satisfaction with Grassland Ecological Conservation Subsidy and Reward Policy (GECSRP) focusing on identifying the key factors behind it. Results showed that herdsmen were not satisfied with GECSRP on the whole, while value perception, environmental regulation and their interaction played a positive role on improving the satisfaction. Specifically, economic benefits had the strongest promotion impacts, followed by social identity in the two-dimensional variables of value perception. The guiding regulation had stronger promoting impacts, followed by the incentive regulation in the two-dimensional variables of environmental regulation. Interestingly, incentive regulation played an enhanced interaction on the influence of economic benefits and environmental value on herdsmen's satisfaction, yet the interaction between guiding regulation and environmental value was not significant. These indicated that herdsmen paid more attention to substantial subsidies and rewards in the process of ecological livestock husbandry, and environmental regulation formulated by government had a phenomenon of "relative system failure". Thus, the grassland ecological environment policy should be further adjusted and improved to promote the economic development of pastoral areas.
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http://dx.doi.org/10.3390/ijerph18063078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002478PMC
March 2021

Isolation and Characterization of a Porcine Transmissible Gastroenteritis Coronavirus in Northeast China.

Front Vet Sci 2021 2;8:611721. Epub 2021 Mar 2.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Transmissible gastroenteritis virus (TGEV) is a coronavirus (CoV) that is a major pathogenity of viral enteritis and diarrhea in suckling piglets, causing high morbidity and mortality. In this study, a TGEV strain HQ2016 was isolated from northeast China and characterized its genome sequence and pathogenicity. The phylogenetic analysis indicated that the TGEV HQ2016 strain was more similar to the TGEV Purdue cluster than to the Miller cluster. Both recombination and phylogenetic analysis based on each structural and non-structural gene revealed no recombination event in the HQ2016 strain. Experimental infection study using colostrum-deprived newborn piglets successfully showed that the HQ2016 can cause clinical symptoms including anorexia and yellow-to-whitish watery diarrhea, which are characteristics of TGE, in the inoculated piglets 48 h post-inoculation. These results provide valuable information about the evolution of the porcine CoVs.
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http://dx.doi.org/10.3389/fvets.2021.611721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960647PMC
March 2021

LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1.

J Exp Clin Cancer Res 2021 Mar 16;40(1):101. Epub 2021 Mar 16.

Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China.

Background: Metastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis.

Methods: EVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesized and applied. Ovarian cancer orthotopic implantation mouse model was established in vivo.

Results: We found that ovarian cancer-secreted EVs could be taken into recipient mesothelial cells, induce the MMT phenotype and enhance cancer cell adhesion to mesothelial cells. Furthermore, SPOCD1-AS embedded in ovarian cancer-secreted EVs was transmitted to mesothelial cells to induce the MMT process and facilitate peritoneal colonization in vitro and in vivo. SPOCD1-AS induced the MMT process of mesothelial cells via interacting with G3BP1 protein. Additionally, G3BP1 interfering peptide based on the F380/F382 residues was able to block SPOCD1-AS/G3BP1 interaction, inhibit the MMT phenotype of mesothelial cells, and diminish peritoneal metastasis in vivo.

Conclusions: Our findings elucidate the mechanism associated with EVs and their cargos in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.
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http://dx.doi.org/10.1186/s13046-021-01899-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968157PMC
March 2021

Extracellular vesicles derived from EphB2-overexpressing bone marrow mesenchymal stem cells ameliorate DSS-induced colitis by modulating immune balance.

Stem Cell Res Ther 2021 Mar 15;12(1):181. Epub 2021 Mar 15.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: The bone marrow mesenchymal stem cell (BMSCs)-derived extracellular vesicles (EVs) open up a new avenue for ulcerative colitis (UC) treatment recently, but they are not selectively enriched in targeted tissues. EphB2, a cell-to-cell signaling receptor, is identified as a regulator for inflammatory response, immune homeostasis and cell migration. In this study, we investigated the therapeutic potential and underlying mechanism for EphB2 over-expressing BMSCs derived EVs (EphB2-EVs) in the treatment of UC.

Methods: BMSCs and EVs were obtained and characterized by a series of experiments. Lentivirus vector encoding EphB2 was transfected into BMSCs and verified by qRT-PCR. We analyzed the EphB2-EVs ability of colonic targeting in a DSS-induced colitis model by using confocal microscope and WB. The protective effect of EphB2-EVs in vivo was systematically evaluated by using a series of function experiments.

Results: We successfully constructed EphB2-overexpressing BMSCs derived EVs (EphB2-EVs). Overexpression of EphB2 significantly enhanced the homing of EVs to the damaged colon. In addition, EphB2-EVs were effective to attenuate inflammation in intestinal mucosa and restore the damaged colon tissue by inhibiting the release of proinflammatory cytokines and upregulating the anti-inflammatory mediators. EphB2-EVs effectively reduced the oxidative stress and repaired the intestinal mucosal barrier in the UC rats. Moreover, EphB2-EVs demonstrated a robust immunomodulatory effect to restore immune homeostasis via modulating Th17/Treg balance and restraining STAT3 activation.

Conclusions: Our results suggest that EphB2-EVs have high colonic targeting ability and could mitigate DSS-induced colitis via maintaining colonic immune homeostasis. These findings provide an effective therapeutic strategy for UC treatment in clinic.
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http://dx.doi.org/10.1186/s13287-021-02232-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962309PMC
March 2021

Hypoxia associated multi-omics molecular landscape of tumor tissue in patients with hepatocellular carcinoma.

Aging (Albany NY) 2021 03 10;13(5):6525-6553. Epub 2021 Mar 10.

Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.

The present study was designed to update the knowledge about hypoxia-related multi-omic molecular landscape in hepatocellular carcinoma (HCC) tissues. Large-size HCC datasets from multiple centers were collected. The hypoxia exposure of tumor tissue from patients in 10 HCC cohorts was estimated using a novel HCC-specific hypoxia score system constructed in our previous study. A comprehensive bioinformatical analysis was conducted to compare hypoxia-associated multi-omic molecular features in patients with a high hypoxia score to a low hypoxia score. We found that patients with different exposure to hypoxia differed significantly in transcriptomic, genomic, epigenomic, and proteomic alterations, including differences in mRNA, microRNA (miR), and long non-coding RNA (lncRNA) expression, differences in copy number alterations (CNAs), differences in DNA methylation levels, differences in RNA alternative splicing events, and differences in protein levels. HCC survival- associated molecular events were identified. The potential correlation between molecular features related to hypoxia has also been explored, and various networks have been constructed. We revealed a particularly comprehensive hypoxia-related molecular landscape in tumor tissues that provided novel evidence and perspectives to explain the role of hypoxia in HCC. Clinically, the data obtained from the present study may enable the development of individualized treatment or management strategies for HCC patients with different levels of hypoxia exposure.
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http://dx.doi.org/10.18632/aging.202723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993683PMC
March 2021

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

Neuropsychiatr Dis Treat 2021 1;17:695-702. Epub 2021 Mar 1.

Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Objective: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats.

Methods: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke.

Results: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (>0.05).

Conclusion: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.
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http://dx.doi.org/10.2147/NDT.S290148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935344PMC
March 2021

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways.

J Ethnopharmacol 2021 Jun 4;273:113989. Epub 2021 Mar 4.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China. Electronic address:

Ethnopharmacological Relevance: Glycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities.

Aim Of The Study: In this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo.

Materials And Methods: In vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells.

Results: In the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts.

Conclusion: In general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.
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http://dx.doi.org/10.1016/j.jep.2021.113989DOI Listing
June 2021

Gluing Techniques on Bond Performance and Mechanical Properties of Cross-Laminated Timber (CLT) Made from .

Polymers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Research Institute of Wood Industry, Chinese Academy of Forestry, Beijing 100091, China.

Previous studies have proved that is a good material for preparing cross-laminated timber (CLT), but under bending shear stress, CLT made by is prone to the phenomenon of bonding face cracking, which seriously affects the shear performance of CLT. To solve this problem, this paper took as raw material, conducted experiments on the surface sanding conditions, gluing pressure and adhesive types of sawing timber, and explored the influence of these three factors on the bonding quality of CLT. The microscopic characteristics of the bonding layer were further studied. The results showed that for with a density of 0.68 g/cm used in this experiment, a high bonding pressure is required. Among the three cold curing adhesives selected in the experiment, emulsion polymer isocyanate (EPI) adhesive needs 1.5 MPa bonding pressure to ensure the bonding quality, while for polyurethane (PUR) and phenol resorcinol formaldehyde (PRF), 1.2 MPa can meet the need of adhesive pressure. This is concerned with the permeability of different adhesives under different pressures. The microscopic results of the bonding layer show that EPI adhesives have poor permeability, so it requires high bonding pressure. The influence of sanding surface of different sand-belt on block shear strength (BSS) and wood failure percentage (WFP) is not obvious, while the durability of bonding layer is better when sanding mesh number is 100. Hence, a high pressure should be used for CLT industrial production when the laminate density is higher, especially when the adhesive has poor permeability. Reasonable sanding surface treatment can be used in laminate surface treatment to improve the durability of CLT.
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http://dx.doi.org/10.3390/polym13050733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956820PMC
February 2021

Responses of ammonia-oxidizing microorganisms to biochar and compost amendments of heavy metals-polluted soil.

J Environ Sci (China) 2021 Apr 10;102:263-272. Epub 2020 Oct 10.

Environmental Microbiomics Research Center, School of Environmental Science and Engineering, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

Heavy metal pollution affects soil ecological function. Biochar and compost can effectively remediate heavy metals and increase soil nutrients. The effects and mechanisms of biochar and compost amendments on soil nitrogen cycle function in heavy-metal contaminated soils are not fully understood. This study examined how biochar, compost, and their integrated use affected ammonia-oxidizing microorganisms in heavy metal polluted soil. Quantitative PCR was used to determine the abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB). Ammonia monooxygenase (AMO) activity was evaluated by the enzyme-linked immunosorbent assay. Results showed that compost rather than biochar improved nitrogen conversion in soil. Biochar, compost, or their integrated application significantly reduced the effective Zn and Cd speciation. Adding compost obviously increased As and Cu effective speciation, bacterial 16S rRNA abundance, and AMO activity. AOB, stimulated by compost addition, was significantly more abundant than AOA throughout remediation. Correlation analysis showed that AOB abundance positively correlated with NO-N (r = 0.830, P < 0.01), and that AMO activity had significant correlation with EC (r = -0.908, P < 0.01) and water-soluble carbon (r = -0.868, P < 0.01). Those seem to be the most vital factors affecting AOB community and their function in heavy metal-polluted soil remediated by biochar and compost.
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http://dx.doi.org/10.1016/j.jes.2020.09.029DOI Listing
April 2021

Evaluation of water conservation function of Danjiang River Basin in Qinling Mountains, China based on InVEST model.

J Environ Manage 2021 May 23;286:112212. Epub 2021 Feb 23.

Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an, 710127, China; Institute of Qinling Mountains, Northwest University, Xi'an, 710127, China. Electronic address:

With the shortage of water resources becoming a global concern, the water conservation function has become one of the most important service functions and the key factor in the sustainable development of watershed ecosystem. The Danjiang River Basin as an important source of water for the middle route of China's South-to-North Water Diversion Project, its water conservation function has attracted extensive public attention under global climate change. In this study, InVEST water yield model based on Budyko hydrological method was employed to analyze the spatio-temporal dynamics of water conservation, and the response of water conservation to climate, land use and soil changes for the period from 2000 to 2019. The results show that the water conservation of Danjiang River Basin tends to decrease under the comprehensive influence of various factors. The spatial analysis of the importance of water conservation identified Shangnan County, the southern part of Danfeng County and the northern part of Shanyang County as important water conservation areas in the study area, which should be regarded as the key and priority protection areas in the regional water resource and ecological protection. The study provides insights for sustainable water management and ecological protection policies, and the InVEST model with localized parameters can also be applied to other areas lacking climate, hydrological and geological data.
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http://dx.doi.org/10.1016/j.jenvman.2021.112212DOI Listing
May 2021

Predictive Nomogram of Subsequent Liver Metastasis After Mastectomy or Breast-Conserving Surgery in Patients With Nonmetastatic Breast Cancer.

Cancer Control 2021 Jan-Dec;28:1073274821997418

Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Metastasis accounts for the majority of deaths in patients with breast cancer. Liver metastasis is reported common for breast cancer patients. The purpose of this study was to construct a nomogram to predict the likelihood of subsequent liver metastasis in patients with nonmetastatic breast cancer, thus high-risk patient populations can be prevented and monitored.

Methods: A total of 1840 patients with stage I-III breast cancer were retrospectively included and analyzed. A nomogram was constructed to predict liver metastasis based on multivariate logistic regression analysis. SEER database was used for external validation. C-index, calibration curve and decision curve analysis were used to evaluate the predictive performance of the model.

Results: The nomogram included 3 variables related to liver metastasis: HER2 status (odds ratio (OR) 1.86, 95%CI 1.02 to 3.41; = 0.045), tumor size (OR 3.62, 1.91 to 6.87; < 0.001) and lymph node metastasis (OR 2.26, 1.18 to 4.34; = 0.014). The C index of the training cohort, internal validation cohort and external validation cohort were 0.699, 0.814 and 0.791, respectively. The nomogram was well-calibrated, with no statistical difference between the predicted and the observed probabilities.

Conclusion: We have developed and validated a robust tool enabled to predict subsequent liver metastasis in patients with nonmetastatic breast cancer. Distinguishing a population of patients at high risk of liver metastasis will facilitate preventive treatment or monitoring of liver metastasis.
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http://dx.doi.org/10.1177/1073274821997418DOI Listing
February 2021

Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19).

Aging (Albany NY) 2021 02 13;13(4):4811-4830. Epub 2021 Feb 13.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.
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http://dx.doi.org/10.18632/aging.202622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950231PMC
February 2021

Turmeric Is Therapeutic on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence.

Front Oncol 2020 19;10:574827. Epub 2021 Jan 19.

Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China.

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.
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http://dx.doi.org/10.3389/fonc.2020.574827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856407PMC
January 2021

Spatial-temporal characteristics of mercury and methylmercury in marine sediment under the combined influences of river input and coastal currents.

Chemosphere 2021 Jan 25;274:129728. Epub 2021 Jan 25.

Ministry of Education Laboratory of Earth Surface Process, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China. Electronic address:

Mercury, especially in the form of methylmercury (MeHg), is a global pollutant, and aquatic products are considered the main sources of Hg exposure to humans. The Bohai and Yellow seas are two important epicontinental seas for marine fisheries and aquaculture in China. A decreasing trend of the THg in the Yellow River Estuary toward the outer edge was reported according to 83 surface sediments (27.3 ± 15.0 ng g) and 3 sediment cores from the Bohai Sea and Yellow Sea. The relatively higher THg levels in the central Yellow Sea can be primarily attributed to higher organic carbon levels and finer-grained sediment sizes and partly to the particulates from the riverine input of the Yellow River driven by the currents. An increasing trend in THg levels since industrialization in north China around the Bohai and Yellow seas, and a decreasing trend of Yellow River THg input in recent years were recorded by sediment cores. The spatial distribution pattern of surface sediments MeHg (161 ± 130 pg g) was different from that of THg. A higher MeHg content and MeHg/THg ratio were found in the Bohai and Yellow seas compared to the East China Sea, and extremely high MeHg levels (714 pg g) were found in the Yellow Sea Cold Water Mass (YSCWM) area, which is considered an important region for fishery and marine breeding, suggesting that more attention should be paid to the potential ecological and human health risks in the region due to mercury exposure.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129728DOI Listing
January 2021

A Review on Recent Advances in Aloperine Research: Pharmacological Activities and Underlying Biological Mechanisms.

Front Pharmacol 2020 29;11:538137. Epub 2020 Oct 29.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aloperine, a quinolizidine-type alkaloid, was first isolated from the seeds and leaves of herbal plant, . Empirically, . is appreciated for its anti-dysentry effect, a property that is commonly observed in other phytomedicines. Following the rationale of reductionism, subsequent biochemical analyses attribute such anti-dysentry effect to the bactericidal activity of aloperine. From then on, the multiple roles of aloperine are gradually revealed. Accumulating evidence suggests that aloperine possesses multiple pharmacological activities and holds a promising potential in clinical conditions including skin hyper-sensitivity, tumor and inflammatory disorders etc.; however, the current knowledge on aloperine is interspersed and needs to be summarized. To facilitate further investigation, herein, we conclude the key pharmacological functions of aloperine, and most importantly, the underlying cellular and molecular mechanisms are clarified in detail to explain the functional mode of aloperine.
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http://dx.doi.org/10.3389/fphar.2020.538137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849205PMC
October 2020

Amygdala-hippocampal innervation modulates stress-induced depressive-like behaviors through AMPA receptors.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of People's Republic of China, IDG/McGovern Institute for Brain Research at Peking University, 100083 Beijing, People's Republic of China;

Chronic stress is one of the most critical factors in the onset of depressive disorders; hence, environmental factors such as psychosocial stress are commonly used to induce depressive-​like traits in animal models of depression. Ventral CA1 (vCA1) in hippocampus and basal lateral amygdala (BLA) are critical sites during chronic stress-induced alterations in depressive subjects; however, the underlying neural mechanisms remain unclear. Here we employed chronic unpredictable mild stress (CUMS) to model depression in mice and found that the activity of the posterior BLA to vCA1 (pBLA-vCA1) innervation was markedly reduced. Mice subjected to CUMS showed reduction in dendritic complexity, spine density, and synaptosomal AMPA receptors (AMPARs). Stimulation of pBLA-vCA1 innervation via chemogenetics or administration of cannabidiol (CBD) could reverse CUMS-induced synaptosomal AMPAR decrease and efficiently alleviate depressive-like behaviors in mice. These findings demonstrate a critical role for AMPARs and CBD modulation of pBLA-vCA1 innervation in CUMS-induced depressive-like behaviors.
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http://dx.doi.org/10.1073/pnas.2019409118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017726PMC
February 2021

c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy.

Nat Cancer 2020 May 18;1(5):507-517. Epub 2020 May 18.

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

Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, a majority of cancer patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be targeted to treat cancer is not well established. Here we show that c-Rel, a member of the nuclear factor (NF)-B family, specified the generation of myeloid-derived suppressor cells (MDSCs) by selectively turning on pro-tumoral genes while switching off anti-tumoral genes through a c-Rel enhanceosome. c-Rel deficiency in myeloid cells markedly inhibited cancer growth in mice, and pharmaceutical inhibition of c-Rel had the same effect. Combination therapy that blocked both c-Rel and the lymphoid checkpoint protein PD1 was more effective in treating cancer than blocking either alone. Thus, c-Rel is a myeloid checkpoint that can be targeted for treating cancer.
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http://dx.doi.org/10.1038/s43018-020-0061-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808269PMC
May 2020

Comparison of the expression levels of lysine-specific demethylase 1 and survival outcomes between triple-negative and non-triple-negative breast cancer.

Oncol Lett 2021 Feb 8;21(2):102. Epub 2020 Dec 8.

School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.

Lysine-specific demethylase 1 (LSD1) is a nuclear protein and the first histone demethylase to be identified. LSD1 is an evolutionarily conserved member of the FAD-dependent amine oxidase family and serves an important role in controlling gene expression. LSD1 has been implicated in the tumorigenesis and progression of several types of human cancer; however, to the best of our knowledge, the expression levels and clinical significance of LSD1 in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC) have not been investigated in detail. Therefore, the present study aimed to compare the expression levels of LSD1 in TNBC and NTNBC to determine the prognostic significance of LSD1 in breast cancer. Previous studies have suggested that LSD1 may be involved in the carcinogenesis and progression of breast cancer; however, the findings of the present study indicated that LSD1 may not be a suitable molecular treatment target and auxiliary diagnostic indicator for TNBC and NTNBC.
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http://dx.doi.org/10.3892/ol.2020.12363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751332PMC
February 2021

Retraction Note: Bronchial blocker versus double-lumen endobronchial tube in minimally invasive cardiac surgery.

BMC Pulm Med 2020 Dec 10;20(1):322. Epub 2020 Dec 10.

Department of Anesthesiology, The Second Hospital of Jilin University, No.218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China.

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http://dx.doi.org/10.1186/s12890-020-01365-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731478PMC
December 2020

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis.

Aging (Albany NY) 2020 12 11;13(2):2655-2667. Epub 2020 Dec 11.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.

Acute lung injury (ALI) is a critical clinical condition with a high mortality rate. It is believed that the inflammatory storm is a critical contributor to the occurrence of ALI. Fucoxanthin is a natural extract from marine seaweed with remarkable biological properties, including antioxidant, anti-tumor, and anti-obesity. However, the anti-inflammatory activity of Fucoxanthin has not been extensively studied. The current study aimed to elucidate the effects and the molecular mechanism of Fucoxanthin on lipopolysaccharide-induced acute lung injury. In this study, Fucoxanthin efficiently reduced the mRNA expression of pro-inflammatory factors, including IL-10, IL-6, iNOS, and Cox-2, and down-regulated the NF-κB signaling pathway in Raw264.7 macrophages. Furthermore, based on the network pharmacological analysis, our results showed that anti-inflammation signaling pathways were screened as fundamental action mechanisms of Fucoxanthin on ALI. Fucoxanthin also significantly ameliorated the inflammatory responses in LPS-induced ALI mice. Interestingly, our results revealed that Fucoxanthin prevented the expression of TLR4/MyD88 in Raw264.7 macrophages. We further validated Fucoxanthin binds to the TLR4 pocket using molecular docking simulations. Altogether, these results suggest that Fucoxanthin suppresses the TLR4/MyD88 signaling axis by targeting TLR4, which inhibits LPS-induced ALI, and fucoxanthin inhibition may provide a novel strategy for controlling the initiation and progression of ALI.
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http://dx.doi.org/10.18632/aging.202309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880391PMC
December 2020

PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery.

Autophagy 2020 Dec 15:1-18. Epub 2020 Dec 15.

Department of Pharmacology, School of Medicine, Southeast University , Nanjing, Jiangsu, China.

Stroke is a major public health problem leading to high rates of death and disability worldwide, but no effective pharmacological therapy is currently available except for the use of PLAT (plasminogen activator, tissue). Here we show that PARP14 (poly (ADP-ribose) polymerase family, member 14) level was significantly increased in the peri-infarct zone of photothrombotic stroke (PT) mice. Genetic knockdown and pharmacological inhibition of PARP14 aggravated functional impairment and increased infarct volume in PT mice, while overexpression of PARP14 displayed the opposite effects. Furthermore, PARP14 was abundant in microglia, and downregulation of PARP14 increased post-stroke microglial activation, whereas overexpression of PARP14 alleviated microglial activation, possibly through microglial macroautophagy/autophagy modulation. Mechanistically, overexpression of PARP14 suppressed (lysophosphatidic acid receptor 5) gene transcription to inhibit microglial activation post stroke. Taken together, PARP14 is a stroke-induced signal that restricts microglial activation and promotes functional recovery, and can serve as a novel target to develop new therapeutic agents for stroke. Moreover, these findings may be conducive to proper use of various PARP inhibitors. : 3-MA: 3-methyladenine; AIF1/Iba-1: allograft inflammatory factor 1; CNS: central nervous system; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; ELISA: enzyme-linked immunosorbent assay; FBS: fetal bovine serum; GFAP: glial fibrillary acidic protein; IL1B/IL-1β: interleukin 1 beta; IL6/IL-6: interleukin 6; LPAR5: lysophosphatidic acid receptor 5; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; NOS2/iNOS: nitric oxide synthase 2, inducible; OGD: oxygen glucose deprivation; PAR: polymer of poly (ADP ribose); PARP: poly (ADP-ribose) polymerase family; PBS: phosphate-buffered saline; PLAT/tPA: plasminogen activator, tissue; PT: photothrombotic stroke; qPCR: quantitative polymerase chain reaction; Rap: rapamycin; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; SQSTM1: sequestosome 1; TNF/TNF-α: tumor necrosis factor.
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http://dx.doi.org/10.1080/15548627.2020.1847799DOI Listing
December 2020

Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor.

Cancer Cell Int 2020 Nov 23;20(1):561. Epub 2020 Nov 23.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China.

Background: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known.

Methods: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model.

Results: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway.

Conclusions: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.
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http://dx.doi.org/10.1186/s12935-020-01658-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686780PMC
November 2020

Development of small molecule inhibitors/agonists targeting STING for disease.

Biomed Pharmacother 2020 Dec 1;132:110945. Epub 2020 Nov 1.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, 524023, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, Guangdong, 524023, China. Electronic address:

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) -stimulator of interferon genes (STING) signaling pathway is the primary immune response pathway in the cytoplasm. Pharmacological regulation of the STING pathway has good characteristics in both structure and function, which plays a significant role in the immunotherapy of autoimmune diseases, autoinflammatory diseases, and cancer. In this review, we summarized the activation of STING signaling pathway, the STING-related diseases, the development principle and the latest progress of inhibitors and agonists targeting STING. Our review demonstrates that STING signal pathway is a promising drug target, providing effective clues and correct guidance for the discovery of novel small molecule inhibitors/agonists that targeted STING for cancer, autoimmune, and inflammatory diseases.
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http://dx.doi.org/10.1016/j.biopha.2020.110945DOI Listing
December 2020

Probing Microenvironmental Acidity in Lyophilized Protein and Vaccine Formulations Using Solid-state NMR Spectroscopy.

J Pharm Sci 2021 03 26;110(3):1292-1301. Epub 2020 Nov 26.

Pharmaceutical Sciences, Merck & Co., Inc, Kenilworth, NJ 07033, USA; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, IN 47907, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address:

Biophysical and biochemical instability of therapeutic proteins in the solution state may necessitate the development of products in the solid form, due to their enhanced stability. Lyophilization is a widely used method to ensure dry state stabilization of biological products. A commonly encountered issue is the pH shifts that can occur due to undesired crystallization of a buffer component, resulting in loss of protein activities. However, it is technically challenging to noninvasively investigate the physicochemical environment in the lyophile matrix. In this work, we demonstrate an approach based on solid-state NMR to investigate the microenvironmental acidity in lyophilized protein formulations, using histidine, a commonly used buffer agent, as a molecular probe. The solid-state acidity in the lyophilized matrix can be assessed by monitoring the chemical shift changes of histidine. The protonation and tautomeric states of histidine lyophilized at a range of pH values from 4.5 to 11.0 were identified from full C and N resonance assignments in one-dimensional and two-dimensional NMR experiments. The results demonstrated a pH-dependence of histidine chemical shift in the amorphous state. Moreover, we successfully applied this protocol to investigate the microenvironmental pH in lyophilized formulations of the HPV vaccine and lactate dehydrogenase protein.
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http://dx.doi.org/10.1016/j.xphs.2020.11.017DOI Listing
March 2021

TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019.

Front Genet 2020 30;11:575770. Epub 2020 Sep 30.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China.

Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely related to the occurrence of the coronavirus disease 2019 (COVID-19). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression and after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection . The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse.
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http://dx.doi.org/10.3389/fgene.2020.575770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556306PMC
September 2020

Active bacterial and archaeal communities in coastal sediments: Biogeography pattern, assembly process and co-occurrence relationship.

Sci Total Environ 2021 Jan 12;750:142252. Epub 2020 Sep 12.

Laboratory for Marine Ecology and Environmental Science, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China; Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education/Institute for Advanced Ocean Study, Ocean University of China, Qingdao 266100, China.

The biogeography of active microbial communities and the underlying mechanisms in marine sediments are important in microbial ecology but remain unclear. Here, using qPCR and high-throughput sequencing, we investigated bacterial and archaeal community abundances and activities by quantifying the abundance and expression of the 16S rRNA gene respectively, RNA-derived bacterial and archaeal community biogeography, assembly mechanisms and co-occurrence relationships in surface sediment samples from the Bohai Sea (BS), South Yellow Sea (SYS) and the north East China Sea (NECS) of the eastern Chinese marginal seas. The results revealed a higher heterogeneity of bacterial and archaeal community activities than of abundances and heterogeneous ecological functions among areas reflected by community compositions. Furthermore, clear geographic groups (i.e., the BS, SYS and NECS groups) were observed for all, abundant and rare active bacterial and archaeal communities, accompanied by significant distance-decay patterns. However, the abundant and rare taxa showed inconsistent geographic patterns. More importantly, deterministic processes played a greater role than stochastic processes in active bacterial and archaeal community assembly. The rare taxa had weaker abilities to disperse and/or adapt and more complex ecological processes than the abundant taxa. In addition, this study also showed that intertaxa competition was the dominant interaction between active bacterial and archaeal members, which could greatly contribute to dispersal limitation. Moreover, active bacterial and archaeal co-occurrence patterns showed significant distance-decay patterns, which were consistent with the community compositions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142252DOI Listing
January 2021

Elevated Exhaustion Levels of NK and CD8 T Cells as Indicators for Progression and Prognosis of COVID-19 Disease.

Front Immunol 2020 14;11:580237. Epub 2020 Oct 14.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity.

Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19.

Results: The counts and percentages of NK cells, CD4 T cells, CD8 T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3CD56CD16 cell population significantly decreased, while the CD3CD56CD16 part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3CD56CD16 cells were screened out as an influential factor in severe cases by LASSO logistic regression.

Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.
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http://dx.doi.org/10.3389/fimmu.2020.580237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591707PMC
December 2020

Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers.

Dis Markers 2020 26;2020:8884450. Epub 2020 Sep 26.

Department of Thyroid and Breast Surgery, Zibo Central Hospital, Zibo 255036, China.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.
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http://dx.doi.org/10.1155/2020/8884450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557915PMC
September 2020