Publications by authors named "Chunfeng Li"

102 Publications

Nanostructured Lateral Boryl Substitution Conjugated Donor-Acceptor Oligomers for Visible-Light-Driven Hydrogen Production.

Small 2021 Apr 23:e2100132. Epub 2021 Apr 23.

State Key Laboratory of Applied Organic Chemistry (Lanzhou University), Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.

Poor charge separation is the main factor that limits the photocatalytic hydrogen generation efficiency of organic conjugated polymers. In this work, a series of linear donor-acceptor (D-A) type oligomers are synthesized by a palladium-catalyzed Sonogashira-Hagihara coupling of electron-deficient diborane unit and different dihalide substitution sulfur functionalized monomers. Such diborane-based A unit exerts great impact on the resulting oligomers, including distinct semiconductor characters with isolated lowest unoccupied molecular orbital (LUMO) orbits locating in diborane-containing fragment, and elevated LUMO level higher than water reduction potential. Relative to A-A type counterpart, the enhanced dipole polarization effect in D-A oligomers facilitates separation of photogenerated charge carriers, as evidenced by notably prolonged electron lifetime. Owing to π-π stacking of rigid backbone, the oligomers can aggregate into an interesting 2D semicrystalline nanosheet (≈2.74 nm), which is rarely reported in linear polymeric photocatalysts prepared by similar carbon-carbon coupling reaction. Despite low surface area (30.3 m g ), such ultrathin nanosheet D-A oligomer offers outstanding visible light (λ > 420 nm) hydrogen evolution rate of 833 µmol g h , 14 times greater than its A-A analogue (61 µmol g h ). The study highlights the great potential of using boron element to construct D-A type oligomers for efficient photocatalytic hydrogen generation.
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http://dx.doi.org/10.1002/smll.202100132DOI Listing
April 2021

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

Nature 2021 Apr 19. Epub 2021 Apr 19.

Tulane National Primate Research Center, Covington, LA, USA.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
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http://dx.doi.org/10.1038/s41586-021-03530-2DOI Listing
April 2021

mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition.

medRxiv 2021 Apr 7. Epub 2021 Apr 7.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.
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http://dx.doi.org/10.1101/2021.04.05.21254952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043478PMC
April 2021

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.

bioRxiv 2021 Feb 11. Epub 2021 Feb 11.

The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.
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http://dx.doi.org/10.1101/2021.02.10.430696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885918PMC
February 2021

Low-dose Diosbulbin-B (DB) activates tumor-intrinsic PD-L1/NLRP3 signaling pathway mediated pyroptotic cell death to increase cisplatin-sensitivity in gastric cancer (GC).

Cell Biosci 2021 Feb 12;11(1):38. Epub 2021 Feb 12.

Gastrointestinal Surgical Ward, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150081, Heilongjiang, China.

Background: Emerging evidences suggests that Diosbulbin-B (DB) is effective to improve cisplatin (DDP)-sensitivity in gastric cancer (GC), but its molecular mechanisms were not fully delineated, and this study managed to investigate this issue.

Methods: Genes expressions were determined by Real-Time qPCR and Western Blot at transcriptional and translational levels. Cell proliferation and viability were evaluated by cell counting kit-8 (CCK-8) and trypan blue staining assay. Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The Spheroid formation assay was used to evaluated cell stemness. The xenograft tumor-bearing mice models were established, and the tumors were monitored and the immunohistochemistry (IHC) was employed to examine the expressions and localization of Ki67 protein in mice tumor tissues.

Results: Low-dose DB (12.5 μM) downregulated PD-L1 to activate NLRP3-mediated pyroptosis, and inhibited cancer stem cells (CSCs) properties, to sensitize cisplatin-resistant GC (CR-GC) cells to cisplatin. Mechanistically, the CR-GC cells were obtained, and either low-dose DB or cisplatin alone had little effects on cell viability in CR-GC cells, while low-dose DB significantly induced apoptotic cell death in cisplatin treated CR-GC cells. In addition, low-dose DB triggered cell pyroptosis in CR-GC cells co-treated with cisplatin, which were abrogated by silencing NLRP3. Next, CSCs tended to be enriched in CR-GC cells, instead of their parental cisplatin-sensitive GC (CS-GC) cells, and low-dose DB inhibited spheroid formation and stemness biomarkers (SOX2, OCT4 and Nanog) expressions to eliminate CSCs in CR-GC cells, which were reversed by upregulating programmed death ligand-1 (PD-L1). Furthermore, we proved that PD-L1 negatively regulated NLRP3 in CR-GC cells, and low-dose DB activated NLRP3-mediated pyroptotic cell death in cisplatin treated CR-GC cells by downregulating PD-L1. Also, low-dose DB aggravated the inhibiting effects of cisplatin on tumorigenesis of CR-GC cells in vivo.

Conclusions: Collectively, low-dose DB regulated intrinsic PD-L1/NLRP3 pathway to improve cisplatin-sensitivity in CR-GC cells, and this study provided alternative therapy treatments for GC.
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http://dx.doi.org/10.1186/s13578-021-00548-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881658PMC
February 2021

The role of NbTMP1, a surface protein of sporoplasm, in Nosema bombycis infection.

Parasit Vectors 2021 Jan 25;14(1):81. Epub 2021 Jan 25.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, China.

Background: Nosema bombycis is a unicellular eukaryotic pathogen of the silkworm, Bombyx mori, and is an economic and occupational hazard in the silkworm industry. Because of its long incubation period and horizontal and vertical transmission, it is subject to quarantine measures in sericulture production. The microsporidian life-cycle includes a dormant extracellular phase and intracellular proliferation phase, with the proliferation period being the most active period. This latter period lacks spore wall protection and may be the most susceptible stage for control.

Methods: In order to find suitable target for the selective breeding of N. bombycis-resistant silkworm strains, we screen highly expressed membrane proteins from the transcriptome data of N. bombycis. The subcellular localization of the candidate protein was verified by Indirect immunofluorescence analysis (IFA) and immunoelectron microscopy (IEM), and its role in N. bombycis proliferation was verified by RNAi.

Results: The N. bombycis protein (NBO_76g0014) was identified as a transmembrane protein and named NbTMP1. It is homologous with hypothetical proteins NGRA_1734 from Nosema granulosis. NbTMP1 has a transmembrane region of 23 amino acids at the N-terminus. Indirect immunofluorescence analysis (IFA) results suggest that NbTMP1 is secreted on the plasma membrane as the spores develop. Western blot and qRT-PCR analysis showed that NbTMP1 was expressed in all developmental stages of N. bombycis in infected cells and in the silkworm midgut. Downregulation of NbTMP1 expression resulted in significant inhibition of N. bombycis proliferation.

Conclusions: We confirmed that NbTMP1 is a membrane protein of N. bombycis. Reduction of the transcription level of NbTMP1 significantly inhibited N. bombycis proliferation, and this protein may be a target for the selective breeding of N. bombycis-resistant silkworm strains.
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http://dx.doi.org/10.1186/s13071-021-04595-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836179PMC
January 2021

Efficacy of Postoperative FOLFOX XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet-Lymphocyte Ratio in Patients Receiving XELOX.

Front Oncol 2020 23;10:584772. Epub 2020 Dec 23.

Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Background: Surgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet-lymphocyte ratio (PLR) in the XELOX group.

Methods: Patients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan-Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.

Results: Patients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX ( 0.001), especially for stage III GC ( = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.

Conclusion: XELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.
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http://dx.doi.org/10.3389/fonc.2020.584772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786002PMC
December 2020

Prognostic significance of serum inflammation indexes in different Lauren classification of gastric cancer.

Cancer Med 2021 02 6;10(3):1103-1119. Epub 2021 Jan 6.

Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Background: Inflammatory indexes are considered to be potential prognostic biomarkers for patients with gastric cancer (GC). However, little evidence has defined the prognostic significance of inflammatory indexes for GC with different Lauren classification.

Methods: A total of 852 patients with GC were randomly selected consecutively into intestinal type and diffuse/mixed type groups. Group bias was reduced by propensity score matching. The cutoff values of inflammatory indexes were analyzed by receiver operating characteristic curve. The Kaplan-Meier method and log-rank test were used to analyze the overall survival (OS). The chi-square test was used to analyze the association between inflammatory indexes and clinical characteristics. The independent risk factor for prognosis in each group was analyzed by univariate and multivariate analyses based on logistic regression. The nomogram models were constructed by R studio.

Results: Intestinal type GC patients (p < 0.05) had a lower percentage of neutrophils in stage I, higher percentage of neutrophils and higher platelet count in stage Ⅲ (p < 0.05). Systemic immune-inflammation index (SII) (p < 0.001), pTNM stage (p < 0.001), and postoperative chemotherapy (p = 0.002) were independent risk factors for prognosis in the intestinal type group. Platelet-lymphocyte ratio (PLR) (p < 0.001) and pTNM stage (p = 0.001) were independent risk factors for prognosis in the diffuse/mixed type group. The area under the curve of the nomogram model in predicting 5-year prognosis in the intestinal type group and diffuse/mixed type group were 0.807 and 0.788, respectively.

Conclusion: SII combined with postoperative chemotherapy and pTNM stage were used to construct a nomogram model to predict the prognosis of intestinal type GC. PLR combined with pTNM stage can be used to construct a nomogram model for diffuse/mixed type GC patients.
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http://dx.doi.org/10.1002/cam4.3706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897904PMC
February 2021

Type-IInterferon-Inducible SERTAD3 Inhibits Influenza A Virus Replication by Blocking the Assembly of Viral RNA Polymerase Complex.

Cell Rep 2020 11;33(5):108342

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Influenza A virus (IAV) infection stimulates a type I interferon (IFN-I) response in host cells that exerts antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). However, most ISGs are poorly studied for their roles in the infection of IAV. Herein, we demonstrate that SERTA domain containing 3 (SERTAD3) has a significant inhibitory effect on IAV replication in vitro. More importantly, Sertad3 mice develop more severe symptoms upon IAV infection. Mechanistically, we find SERTAD3 reduces IAV replication through interacting with viral polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acidic protein (PA) to disrupt the formation of the RNA-dependent RNA polymerase (RdRp) complex. We further identify an 8-amino-acid peptide of SERTAD3 as a minimum interacting motif that can disrupt RdRp complex formation and inhibit IAV replication. Thus, our studies not only identify SERTAD3 as an antiviral ISG, but also provide the mechanism of potential application of SERTAD3-derived peptide in suppressing influenza replication.
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http://dx.doi.org/10.1016/j.celrep.2020.108342DOI Listing
November 2020

GPC3-targeted and curcumin-loaded phospholipid microbubbles for sono-photodynamic therapy in liver cancer cells.

Colloids Surf B Biointerfaces 2021 Jan 22;197:111358. Epub 2020 Sep 22.

Harbin Medical University Cancer Hospital, Harbin, 150081 Heilongjiang Province, China. Electronic address:

More effective strategies are needed to improve the treatment of liver cancer. Sono-photodynamic therapy (SPDT) has a more obvious antitumor effect than sonodynamic therapy (SDT) or photodynamic therapy (PDT). We aimed to investigate Glypican-3-targeted, curcumin-loaded microbubbles (GPC3-CUR-MBs)-mediated SPDT in liver cancer cells in vitro and in vivo. GPC3-CUR-MBs were prepared by streptavidin-biotin interactions and the immune ligation method. The characterization and toxicity of GPC3-CUR-MBs and the anti-liver cancer effects of GPC3-CUR-MB-mediated SPDT in vitro and in vivo were studied. We synthetized GPC3-CUR-MBs and found that GPC3-CUR-MBs had no significant toxicity to HepG2 liver cancer cells. In terms of the anti-liver cancer effects in vitro and in vivo, when we used CUR, CUR-MBs or GPC3-CUR-MBs as the sono/photosensitizers, the outcome of SPDT was superior to that of SDT or PDT alone. The outcomes with GPC3-CUR-MBs were better than those with CUR or CUR-MBs in the SDT, PDT or SPDT groups. During the treatment period, the weight of the HepG2 tumor-bearing mice did not decrease significantly, and no significant evidence of lung, heart, liver, spleen and kidney damage was found with H&E staining. Our results indicated that the anti-liver tumor effect of SPDT was better than that of SDT and PDT and that GPC3-CUR-MBs were promising sono/photosensitizers.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111358DOI Listing
January 2021

Zika Virus Infection Leads to Variable Defects in Multiple Neurological Functions and Behaviors in Mice and Children.

Adv Sci (Weinh) 2020 Sep 2;7(18):1901996. Epub 2020 Aug 2.

State Key Laboratory of Molecular Developmental Biology CAS Center for Excellence in Brain Science and Intelligence Technology School of Future Technology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China.

Zika virus (ZIKV) has evolved into a global health threat because of its causal link to congenital Zika syndrome. ZIKV infection of pregnant women may cause a spectrum of abnormalities in children. In the studies in Brazil, a large cohort of children with perinatal exposure to ZIKV is followed, and a spectrum of neurodevelopmental abnormalities is identified. In parallel, it is demonstrated that infection of the mouse neonatal brain by a contemporary ZIKV strain instead of an Asian ancestral strain can cause microcephaly and various abnormal neurological functions. These include defects in social interaction and depression, impaired learning and memory, in addition to severe motor defects, which are present in adult mice as well as in the prospective cohort of children. Importantly, although mouse brains infected later after birth do not have apparent abnormal brain structure, those mice still show significant impairments of visual cortical functions, circuit organization, and experience-dependent plasticity. Thus, the study suggests that special attention should be paid to all children born to ZIKV infected mothers for screening of abnormal behaviors and sensory function during childhood.
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http://dx.doi.org/10.1002/advs.201901996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509663PMC
September 2020

A Toll-Spätzle Pathway in the Immune Response of .

Insects 2020 Sep 1;11(9). Epub 2020 Sep 1.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.

The Toll-Spätzle pathway is a crucial defense mechanism in insect innate immunity, it plays an important role in fighting against pathogens through the regulation of antimicrobial peptide gene expression. Although and () genes have been identified in , little is known regarding the specific and genes members involved in innate immunity. There is also limited direct evidence of the interaction between Spz and Toll. In this study, the dual-luciferase reporter assay results showed that BmToll11 and BmToll9-1 could activate both and promoters in S2 cells. Furthermore, , , and five genes were found to be significantly upregulated in infected by and . Additionally, the yeast two-hybrid assay results confirmed that BmSpz2, but not other BmSpzs, could interact with both BmToll11 and BmToll9-1. These findings suggest that the activated BmSpz2 can bind with BmToll11 and BmToll9-1 to induce the expression of AMPs after the silkworm is infected by pathogens.
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http://dx.doi.org/10.3390/insects11090586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564906PMC
September 2020

Impact of CD144 gene expression on outcomes in stage III gastric cancer patients.

Pathology 2020 Oct 25;52(6):657-669. Epub 2020 Aug 25.

Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, P.R. China. Electronic address:

CD144 has been shown to promote tumour angiogenesis, invasion and metastasis in malignant tumours. The purpose of the present study was to investigate the clinical prognostic significance of CD144 in advanced gastric cancer (GC) to complement the American Joint Committee on Cancer (AJCC) 8th Edition convention. We established that CD144 was highly related to angiogenesis using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public databases. We randomly selected 173 stage III GC patients who received curative gastrectomy. The expression level of CD144 was assessed by immunohistochemistry and Image-Pro Plus software. After survival analysis, nomograms were created to predict the risk of stage III gastric cancer patients' 5-years survival. In this study, the median value of the CD144 positive area/total area under the microscope was 5.6%, and this was defined as the cut-off value. The expression of CD144 assisted further subgrouping of stage Ⅲa, Ⅲb, and Ⅲc GC patients. To evaluate the disease-free survival (DFS) and overall survival (OS) of patients, univariate and multivariate analysis was performed, which showed that the expression of CD144 was an independent predictor for DFS, and Borrmann type and expression of CD144 were independent predictors for OS (p<0.05). Nomograms were used to evaluate the risk of stage III GC by combining Borrmann type and the expression level of CD144. In advanced GC patients, the expression level of CD144 is a useful prognostic indicator in evaluating the risk of disease prognosis.
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http://dx.doi.org/10.1016/j.pathol.2020.05.008DOI Listing
October 2020

Puerarin alleviates cisplatin-induced acute renal damage and upregulates microRNA-31-related signaling.

Exp Ther Med 2020 Oct 29;20(4):3122-3129. Epub 2020 Jul 29.

Department of Blood Transfusion, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.

Cisplatin (DDP) is a commonly used chemotherapy drug; however, the side effects associated with its use, particularly acute kidney injury (AKI), limit its clinical application. Puerarin is a natural flavonoid extracted from the Chinese medical herb , which has been reported to alleviate DDP-induced nephrotoxicity. However, the mechanisms underlying puerarin regulation on microRNA (miR)-31-mediated signaling pathways in AKI remain unknown. Thus, the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that DDP upregulated the levels of miR-31 in a concentration-dependent manner, both and . Furthermore, DDP significantly increased blood urea nitrogen and malondialdehyde content, serum creatinine and histopathological changes, while significantly decreasing the expression levels of superoxide dismutase, catalase and glutathione S-transferase in kidney tissues. TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway, which is downstream of miR-31. The effects induced by DDP were counteracted following treatment with puerarin. Taken together, the results of the present study suggest that puerarin exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway.
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http://dx.doi.org/10.3892/etm.2020.9081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444337PMC
October 2020

Will Hydroxychloroquine Still Be a Game-Changer for COVID-19 by Combining Azithromycin?

Front Immunol 2020 7;11:1969. Epub 2020 Aug 7.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, United States.

Recent small-scale clinical trials have shown promising results in the use of hydroxychloroquine, an FDA approved anti-malaria drug, for the treatment of COVID-19. However, large scale, randomized and double-blind clinical trials are needed to confirm the safety and efficacy of hydroxychloroquine in COVID-19 patients. Here, we review the progress of using hydroxychloroquine or chloroquine as anti-viral agents, failed clinical trials of chloroquine in treatment of dengue virus and influenza infection, and especially the mechanism of azithromycin in inhibiting viral replication, so as to shed light on the ongoing clinical trials and further researches of hydroxychloroquine on SARS-CoV-2 infected patients.
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http://dx.doi.org/10.3389/fimmu.2020.01969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426511PMC
September 2020

Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.

Nat Genet 2020 09 17;52(9):908-918. Epub 2020 Aug 17.

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.
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http://dx.doi.org/10.1038/s41588-020-0642-1DOI Listing
September 2020

The Predictive and Prognostic Factors in Patients with Gastric Cancer Accompanied by Gastric Outlet Obstruction.

Gastroenterol Res Pract 2020 25;2020:6529563. Epub 2020 Jul 25.

Department of Gastroenterologic Surgery, Affiliated Tumor Hospital of Harbin Medical University, China.

Purpose: This study is aimed at evaluating the clinicopathological features and prognostic significance of gastric outlet obstruction (GOO) in patients with distal gastric cancer.

Methods: A retrospective review of 1564 individuals with distal gastric cancer from 2002 to 2010 was performed. In total, 157 patients had GOO. The clinicopathological features of the patients with GOO were compared with those of the patients without GOO. A Kaplan-Meier survival analysis and Cox proportional hazard model were used to assess the overall survival.

Results: The patients with distal gastric cancer with GOO generally presented more aggressive pathologic features, a poorer nutritional status, more duodenal infiltration, and peritoneal dissemination than those with cancer without GOO. In the univariate analysis, curability, GOO, age, prealbumin, albumin, hemoglobin (Hb), the tumor size, the macroscopic type, lymph node metastasis, and the depth of invasion had a statistically significant influence on prognosis. The multivariate analysis showed that curability, GOO, the tumor size, lymph node metastasis, and the depth of invasion were independent prognostic factors.

Conclusions: Gastric cancer with GOO exhibits aggressive biological features and has poor outcomes. The multivariate analysis showed that curability, GOO, the tumor size, lymph node metastasis, and the depth of invasion were independent prognostic factors. The gastric outlet status should be considered in the selection of surgical treatment methods for patients with gastric cancer.
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http://dx.doi.org/10.1155/2020/6529563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397385PMC
July 2020

ERG orchestrates chromatin interactions to drive prostate cell fate reprogramming.

J Clin Invest 2020 11;130(11):5924-5941

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

Although cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early-stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer proluminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we found that ERG was highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibited those cells' normal plasticity to transdifferentiate into a basal lineage, and ERG superseded PTEN loss, which favored basal differentiation. ERG KO disrupted prostate cell luminal differentiation, whereas AR KO had no such effects. Trp63 is a known master regulator of the prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG bound and inhibited the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG, in its fundamental role in lineage differentiation in prostate cancer initiation, orchestrated chromatin interactions and regulated prostate cell lineage toward a proluminal program.
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http://dx.doi.org/10.1172/JCI137967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598085PMC
November 2020

The roles of microRNA in human cervical cancer.

Arch Biochem Biophys 2020 09 16;690:108480. Epub 2020 Jul 16.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Haikou, Hainan, 570100, China; School of Pharmacy, Hainan Medical University, Haikou, Hainan, 570100, China; Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou, Hainan, 570100, China.

Although a potentially preventable disease, cervical cancer (CC) is the second most commonly diagnosed gynaecological cancer with at least 530,000 new cases annually, and the prognosis with CC is still poor. Studies suggest that aberrant expression of microRNA (miRNA) contributes to the progression of CC. As a group of small non-coding RNA with 18-25 nucleotides, miRNA regulate about one-third of all human genes. They function by repressing translation or inducing mRNA cleavage or degradation, including genes involved in diverse and important cellular processes, including cell cycling, proliferation, differentiation, and apoptosis. Results showed that misexpression of miRNA is closely related to the onset and progression of CC. This review will provide an overview of the function of miRNA in CC and the mechanisms involved in cervical carcinogenesis.
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http://dx.doi.org/10.1016/j.abb.2020.108480DOI Listing
September 2020

Preoperative Systemic Immune-Inflammation Index (SII) for Predicting the Survival of Patients with Stage I-III Gastric Cancer with a Signet-Ring Cell (SRC) Component.

Biomed Res Int 2020 22;2020:5038217. Epub 2020 May 22.

Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

Background: Recently, a novel systemic immune-inflammation index (SII) based on peripheral lymphocytes, neutrophils, and platelets has been reported to be correlated with patient prognosis in several malignancies, including gastric cancer. However, the prognostic value of the SII for gastric cancer patients with a signet-ring cell (SRC) component has not yet been reported. In this study, we aimed to assess the prognostic value of the SII in gastric cancer patients with an SRC component after curative resection.

Methods: This study was a retrospective analysis of 512 GC patients with an SRC component who underwent curative resection. The prognostic value of the SII was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.

Results: In our study cohort, an optimal cut-off value for the SII of 527 was used to stratify patients with gastric cancer (GC) into low (<527) and high SII (≥527) groups. Our study indicated that a high SII (≥527) was significantly correlated with a large tumor size ( < 0.001), infiltration of serosa ( < 0.001), lymph node metastasis ( < 0.001), and advanced TNM stage ( < 0.001). Univariate and multivariate analyses further demonstrated that a low SII was correlated with better clinical outcome and was an independent prognostic predictor in GC patients with an SRC component. Furthermore, the SII retained prognostic value in the subgroup analysis, including subgroup of different TNM stages and pure or mixed signet-ring cell carcinomas (SRCCs).

Conclusion: The SII is a simple, promising, and practical prognostic biomarker for patients with surgically resected mixed SRCC and pure SRCC. The SII could complement current prognostic tools for better treatment planning and stratification of patients.
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http://dx.doi.org/10.1155/2020/5038217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273421PMC
March 2021

Organoid technology for tissue engineering.

J Mol Cell Biol 2020 08;12(8):569-579

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.
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http://dx.doi.org/10.1093/jmcb/mjaa012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683016PMC
August 2020

Diagnostic Sensitivity of NLR and PLR in Early Diagnosis of Gastric Cancer.

J Immunol Res 2020 7;2020:9146042. Epub 2020 Mar 7.

Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China.

The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are markers of systemic inflammation. However, there is little evidence of the value of inflammation in the early diagnosis of gastric cancer (GC). A total of 2,606 patients diagnosed with GC in the past three years and 3,219 healthy controls over the same period were included in this study. Peripheral blood samples were obtained to analyze the NLR, PLR, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). The optimal cutoff levels for the NLR and PLR were defined by receiver operating characteristic (ROC) curve analysis (NLR = 2.258, PLR = 147.368). The value of different biomarkers for diagnosing GC was compared by the area under the curve (AUC). The NLR and PLR showed diagnostic sensitivity in GC (AUC = 0.715, AUC = 0.707). Using the Bonferroni correction, the NLR and PLR were superior to CEA and CA19-9 in the diagnosis of GC ( < 0.0001). The systemic inflammatory markers were significantly higher in the early stage of GC than tumor markers. After grouping patients and healthy controls by gender, we found that the diagnostic significance of combined NLR and PLR for GC was greater in male patients than in female patients ( < 0.0001). The diagnostic value of the NLR and PLR in GC is higher than that of the traditional tumor markers CEA and CA19-9. Systemic markers of inflammation are more valuable in male than female patients.
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http://dx.doi.org/10.1155/2020/9146042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081040PMC
September 2020

Preoperative prealbumin levels on admission as an independent predictive factor in patients with gastric cancer.

Medicine (Baltimore) 2020 Mar;99(11):e19196

Department of Gastroenterologic Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Background: To explore the role of preoperative prealbumin levels in predicting the prognosis of patients with gastric cancer.

Methods: A total of 989 gastric cancer patients in the Affiliated Tumour Hospital of Harbin Medical University who underwent gastrectomy were included in this retrospective study. The preoperative prealbumin level, clinicopathological data, and follow-up data were recorded. According to the maximum chi-square survival correlation value, the survival of patients with low preoperative prealbumin (<140 mg/L) and high preoperative prealbumin (≥140 mg/L) were compared using the log-rank test and the Cox proportional hazard regression model.

Results: Based on the best cut-off value of 140 mg/L, we divided the patients into the lower prealbumin group (<140 mg/L) and the higher prealbumin group (≥140 mg/L). Compared with the higher prealbumin group, the lower prealbumin group were older and had larger tumor volumes, lower hemoglobin (Hb) levels, and more upper gastric cancer tumors. The univariate analysis showed that prealbumin and other clinicopathological factors, including age, hemoglobin, tumor size, macroscopic type, cell differentiation, liver metastasis, operation type, N stage, and T stage, were significant prognostic factors. The multivariable analysis showed that age, prealbumin, macroscopic type, location, T stage, and N stage were independent prognostic factors.

Conclusions: The preoperative prealbumin level was an independent prognostic factor for patients with gastric cancer. The preoperative prealbumin level can be used to predict the prognosis of patients with gastric cancer and guide clinical practice.
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http://dx.doi.org/10.1097/MD.0000000000019196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440214PMC
March 2020

Selectivity of Benzyl Hydroxamic Acid in the Flotation of Ilmenite.

Front Chem 2019 24;7:886. Epub 2019 Dec 24.

Beijing Research Institute of Chemical Engineering and Metallurgy, CNNC, Beijing, China.

The decreased ground size of ilmenite-bearing ores challenges the selectivity of collectors of ilmenite. Taking advantage of flotation tests and density functional theory (DFT), the selectivity of benzyl hydroxamic acid (BHA) and the adsorption mechanism of oleate and BHA on ilmenite were systematically investigated. The flotation tests showed that BHA had good selectivity to ilmenite. In the DFT study, the favorable adsorption of BHA and oleate on the ilmenite surface were verified by the Mulliken population and the calculated interaction energies. Results indicated that the covalent bonds caused the adsorption of oleate on the ilmenite surface. The strong selectivity of BHA was due to abundant adsorption sites and solid adsorption of five-membered rings. The present investigation has important implications for further studies of BHA and will be helpful for screening and designing collectors for ilmenite flotation.
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http://dx.doi.org/10.3389/fchem.2019.00886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937432PMC
December 2019

A specific molecular label for identifying mature Nosema bombycis spores.

J Invertebr Pathol 2020 02 31;170:107322. Epub 2019 Dec 31.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China; Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, China; Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest University, Chongqing 400715, China; College of Life Sciences, Chongqing Normal University, Chongqing 401331, China.

Microsporidia are a fascinating phylum of obligate intracellular pathogens with unique infection processes and complicated life cycles. Microsporidian life cycles can be divided roughly into intracellular and extracellular stages. Currently, research on their life cycles were mainly explored by morphology because there are few molecular markers available with which to distinguish the different life stages. In this study, we generated H20, a monoclonal antibody (MAb) to label mature spores of Nosema bombycis. Immunofluorescence assays showed that the target protein of H20, which is highly stable and was barely affected by alkali and sodium dodecyl sulfate (SDS) treatments, was located on the mature spore surface. Western blot analysis showed that spore wall protein 26 (SWP26) was the likely target of H20. This MAb can specifically identify mature spores in a complex biological sample based on immunological detection of the parasite.
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http://dx.doi.org/10.1016/j.jip.2019.107322DOI Listing
February 2020

Baculovirus Utilizes Cholesterol Transporter NIEMANN-Pick C1 for Host Cell Entry.

Front Microbiol 2019 5;10:2825. Epub 2019 Dec 5.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

The dual roles of baculovirus for the control of natural insect populations as an insecticide, and as a tool for foreign gene expression and delivery, have called for a comprehensive understanding of the molecular mechanisms governing viral infection. Here, we demonstrate that the Niemann-Pick C1 (BmNPC1) is essential for baculovirus infection in insect cells. Both pretreatment of embryonic cells (BmE) with NPC1 antagonists (imipramine or U18666A) and down-regulation of NPC1 expression resulted in a significant reduction in baculovirus BmNPV ( nuclear polyhedrosis virus) infectivity. Disruption of BmNPC1 could decrease viral entry (2 hpi) rather than reduce the viral binding to the BmE cells. Furthermore, our results showed that NPC1 domain C binds directly and specifically to the viral glycoprotein GP64, which is responsible for both receptor binding and fusion. Antibody blocking assay also revealed that the domain C specific polyclonal antibody inhibited BmNPV infection, indicating that NPC1 domain C most likely plays a role during viral fusion in endosomal compartments. Our results, combined with previous studies identifying an essential role of human NPC1 (hNPC1) in filovirus infection, suggest that the glycoprotein of several enveloped viruses possess a shared strategy of exploiting host NPC1 proteins during virus intracellular entry events.
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http://dx.doi.org/10.3389/fmicb.2019.02825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906155PMC
December 2019

Proliferation characteristics of the intracellular microsporidian pathogen Nosema bombycis in congenitally infected embryos.

J Invertebr Pathol 2020 01 17;169:107310. Epub 2019 Dec 17.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China; Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, China; College of Life Sciences, Chongqing Normal University, Chongqing, China; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture, College of Biotechnology, Southwest University, Chongqing, China. Electronic address:

Nosema bombycis is an obligate intracellular pathogen that can be transmitted vertically from infected females to eggs, resulting in congenital infections in embryos. Here we investigated the proliferation characteristics of N. bombycis in silkworm embryos using a histopathological approach and deep RNA sequencing. We found that N. bombycis proliferated mainly around yolk granules at the early stage of the embryonic development, 1-2 days post oviposition (dpo). At 4-6 dpo, a portion of N. bombycis in different stages adjacent to the embryo were packaged into the newly formed intestinal lumen, while the remaining parasites continued to proliferate around yolk granules. In the newly hatched larvae (9 dpo), the newly formed spores accumulated in the gut lumen and immediately were released into the environment via the faeces. Transcriptional profiling of N. bombycis further confirmed multiplication of N. bombycis throughout every stage of embryonic development. Additionally, the increased transcriptional level of spore wall proteins and polar tube proteins from 4 dpo indicated an active formation of mature spores. Taken together, our results have provided a characterization of the proliferation of this intracellular microsporidian pathogen in congenitally infected embryos leading to vertical transmission.
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http://dx.doi.org/10.1016/j.jip.2019.107310DOI Listing
January 2020

Combinatorial screening of a panel of FDA-approved drugs identifies several candidates with anti-Ebola activities.

Biochem Biophys Res Commun 2020 02 2;522(4):862-868. Epub 2019 Dec 2.

Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China. Electronic address:

Ebola virus (EBOV), pathogen of Ebola hemorrhagic fever (EHF), is an enveloped filamental RNA virus. Recently, the EHF crisis occurred in the Democratic Republic of the Congo again highlights the urgency for its clinical treatments. However, no Food and Drug Administration (FDA)-approved therapeutics are currently available. Drug repurposing screening is a time- and cost-effective approach for identifying anti-EBOV therapeutics. Here, by combinatorial screening using pseudovirion and minigenome replicon systems we have identified several FDA-approved drugs with significant anti-EBOV activities. These potential candidates include azithromycin, clomiphene, chloroquine, digitoxin, epigallocatechin-gallate, fluvastatin, tetrandrine and tamoxifen. Mechanistic studies revealed that fluvastatin inhibited EBOV pseudovirion entry by blocking the pathway of mevalonate biosynthesis, while the inhibitory effect of azithromycin on EBOV maybe due to its intrinsic cationic amphiphilic structure altering the homeostasis of later endosomal vesicle similar as tamoxifen. Moreover, based on structure and pathway analyses, the anti-EBOV activity has been extended to other family members of statins, such as simvastatin, and multiple other cardiac glycoside drugs, some of which exhibited even stronger activities. More importantly, in searching for drug interaction, we found various synergy between several anti-EBOV drug combinations, showing substantial and powerful synergistic against EBOV infection. In conclusion, our work illustrates a successful and productive approach to identify new mechanisms and targets for treating EBOV infection by combinatorial screening of FDA-approved drugs.
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http://dx.doi.org/10.1016/j.bbrc.2019.11.065DOI Listing
February 2020

Detrimental effects of SO on gaseous mercury(II) adsorption and retention by CaO-based sorbent traps: Competition and heterogeneous reduction.

J Hazard Mater 2020 04 12;387:121679. Epub 2019 Nov 12.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing, Jiangsu, 210096, China. Electronic address:

Reliable gaseous Hg(II) measurement is crucial to mercury emissions control from coal-fired flue gas, but Hg(II) sampling under SO condition could probably increase the uncertainty of sorbent traps. CaO-AcS synthesized from calcium acetate and porous support were previously demonstrated to be effective for Hg(II) trapping under SO-free condition. This work further evaluated SO influence on its Hg(II) retention ability via integrating experimental and DFT computational studies. Increased breakthrough rate of HgCl was found in a two-section CaO-AcS trap under SO conditions. Significant basicity and porosity loss of CaO-AcS were attributed to the formation of agglomerate CaSO. Hg release from CaO-AcS samples suggested potential reactions between Hg(II) and SO. The detected HgO and HgSO species by Hg-TPD in CaO-AcS further confirmed this speculation. Moreover, both competition and reduction effects of SO on surface-bound Hg(II) species were substantiated by DFT calculations. SO showed a stronger interaction with CaO than HgCl because SO has a lower LUMO level and can accept electrons easier. Reaction pathways indicated Hg(II) was partially reduced to HgSO under SO-deficient condition, or directly reduced to Hg under SO-rich condition. This work fully proposed the SO influence mechanisms and improvement countermeasures for practical gaseous Hg(II) sampling.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121679DOI Listing
April 2020