Publications by authors named "Bingfeng Liu"

65 Publications

Significantly reduced abilities to cross-neutralize SARS-CoV-2 variants by sera from convalescent COVID-19 patients infected by Delta or early strains.

Cell Mol Immunol 2021 11 11;18(11):2560-2562. Epub 2021 Oct 11.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1038/s41423-021-00776-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503867PMC
November 2021

Response of the yellow mealworm (Tenebrio molitor) gut microbiome to diet shifts during polystyrene and polyethylene biodegradation.

J Hazard Mater 2021 08 26;416:126222. Epub 2021 May 26.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Plastic biodegradation by mealworm is regarded as an emerging strategy for plastic disposal. In this study, the polystyrene (PS) and low density polyethylene (LDPE) degradation efficiency by yellow mealworms (Tenebrio molitor larvae) supplemented with bran and the effects of plastics on the gut core microbiome were explored to construct a circular and continuous reactor for plastic biodegradation in the future. The gut microbiome was also investigated with dietary shift to explore the relationship between specific diets and gut microbes. The bran plus plastic (7:1 ratio, w/w) co-diet contributed to the mealworm survival and growth. The formation of -C˭O-/-C-O- groups in the plastic-fed mealworms frass represented the oxidation process of plastic biodegradation in the mealworm gut. The changes in molecular weights (M, M and M) of residual PS and LDPE in mealworms frass compared with that of PS and PE feedstock confirmed the plastic depolymerization and biodegradation. Lactobacillus and Mucispirillum were significantly associated with PE + bran diet compared to bran diet and PE diet, representing the response of mealworm gut microbiome to the bran and plastic mixture was distinguished from either bran or plastics alone. The gut microbiome changed substantially with the diet shift, indicating that microbial community assembly was a stochastic process and diverse plastic-degrading bacteria might occur in the mealworm gut.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126222DOI Listing
August 2021

Enhancing the decomposition of extracellular polymeric substances and the recovery of short-chain fatty acids from waste activated sludge: Analysis of the performance and mechanism of co-treatment by free nitrous acid and calcium peroxide.

J Hazard Mater 2022 02 24;423(Pt A):127022. Epub 2021 Aug 24.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

At present, the bioproduction of short-chain fatty acids (SCFAs) from waste activated sludge (WAS) has attracted worldwide attention due to the demand of carbon neutrality during waste treatment. Calcium peroxide (CaO) has been reported to be an effective method for the solubilization of WAS and the accumulation of SCFAs, but the high reagent cost limits its industrial application. Therefore, free nitrous acid (FNA) was introduced into the WAS pretreatment system to assist with CaO for enhancing the disruption of extracellular polymeric substances (EPS) and the subsequent acidogenesis process. The results showed that FNA and CaO synergistically enhanced EPS decomposition and the release of biodegradable organic compounds during pretreatment. The highest soluble chemical oxygen demand (3.1- and 2.6-fold higher compared to individual pretreatments at the same concentrations) after pretreatment and the highest SCFAs accumulation (2.0- and 6.4-fold compared to individual pretreatments at the same concentrations) after a 2-day fermentation period was observed in the FNA + CaO (0.15 g/g VSS) co-treated group. Therefore, the FNA + CaO (0.15 g/g VSS) co-treatment was determined to be the optimal strategy for ensuring the disintegration of the EPS matrix and enhancing the accumulation of SCFAs in pretreated sludge during anaerobic digestion.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127022DOI Listing
February 2022

Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1.

J Clin Invest 2021 10;131(19)

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

BACKGROUNDChimeric antigen receptor (CAR) T cells have emerged as an approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody-derived (bNAb-derived) CAR T cell therapy that can exert specific cytotoxic activity against HIV-1-infected cells.METHODSWe conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART).RESULTSA total of 14 participants completed only a single administration of bNAb-derived CAR T cells. CAR T cell therapy administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR T cell treatment. Analyses of HIV-1 variants before or after CAR T cell administration suggested that CAR T cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CAR T cell-mediated cytotoxicity.CONCLUSIONNo safety concerns were identified with adoptive transfer of bNAb-derived CAR T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03240328).FUNDINGMinistry of Science and Technology of China, National Natural Science Foundation of China, and Department of Science and Technology of Guangdong Province.
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http://dx.doi.org/10.1172/JCI150211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483761PMC
October 2021

The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.

Proc Natl Acad Sci U S A 2021 06;118(23)

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China;

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.
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http://dx.doi.org/10.1073/pnas.2024202118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201919PMC
June 2021

The synergistic effect of potassium ferrate and peroxymonosulfate application on biogas production and shaping microbial community during anaerobic co-digestion of a cow manure-cotton straw mixture.

Bioresour Technol 2021 Aug 16;333:125166. Epub 2021 Apr 16.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Anaerobic co-digestion of a cow manure-cotton straw mixture (CCM) has been shown to promote methanogenesis, but the recalcitrant crystal structure of organic polymers in CCM hinders its hydrolysis during anaerobic digestion (AD). Here, the efficacy of different pretreatment methods based on potassium ferrate (PF) and peroxymonosulfate (PMS) was evaluated to facilitate CCM decomposition and methanogenesis during AD. The maximum lignocellulosic removal rate (62.5%), the highest volatile fatty acids (VFAs) (7769.6 mg/L), and cumulative methane yield (109.4 mL CH/g VS) were both achieved in PF-pretreated samples after the digestion process. The dominant bacterial populations in PF-pretreated CCM were affiliated with Sideroxydans, Herbinix, Clostridium, and Smithella, which played an important role in the hydrolysis and acidification of CCM. The enrichment of Methanosarcina and Methanobacterium and highly-effective acidogenesis might account for the highest methane yield in the PF-pretreated group.
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http://dx.doi.org/10.1016/j.biortech.2021.125166DOI Listing
August 2021

The CD39 HBV surface protein-targeted CAR-T and personalized tumor-reactive CD8 T cells exhibit potent anti-HCC activity.

Mol Ther 2021 05 21;29(5):1794-1807. Epub 2021 Jan 21.

Department of Interventional Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. Electronic address:

CD39, expressed by tumor-infiltrating lymphocytes (TILs), is a marker to identify tumor-reactive T cells, which is frequently associated with stronger antitumor activity than bystander T cells in a variety of malignancies. Therefore, CD39 could be a promising marker for identifying the active antitumor immune cells used for cellular immunotherapy. To test this possibility, we constructed the hepatitis B virus (HBV) surface protein-specific chimeric antigen receptor T cells (HBVs-CAR-T cells) and generated the personalized tumor-reactive CD8 T cells. We subsequently assessed their antitumor efficiency mainly with a co-culture system for autologous HBVs HCC organoid and T cells. We found that both CD39 HBVs-CAR-T and CD39 personalized tumor-reactive CD8 T cells induced much more apoptosis in HCC organoids. Although the exhaustion status of CAR-T cells increased in CD39 CAR-T cells, triple knockdown of PD-1, Tim-3, and Lag-3 with shRNAs further enhanced antitumor activity in CD39 CAR-T cells. Furthermore, these CD39 CAR-T cells exerted an increased secretion of interferon-γ and stronger antitumor effect in a patient-derived xenograft mouse model. Our findings demonstrated that CD39 could be a promising biomarker to enrich active immune cells and become an indicator marker for evaluating the prognosis of immunotherapy for HCC patients.
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http://dx.doi.org/10.1016/j.ymthe.2021.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116602PMC
May 2021

Mini-metagenome analysis of psychrophilic electroactive biofilms based on single cell sorting.

Sci Total Environ 2021 Mar 17;762:144328. Epub 2020 Dec 17.

School of Environment, State Key Laboratory of Urban Water Resources and Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Understanding the metabolic function of psychrophilic electroactive bacteria is important for the investigation of extracellular electron transfer (EET) mechanisms under low temperatures (4-15 °C). In this study, Raman activated cell ejection coupled high throughput sequencing was used to accurately generate a mini-metagenome of psychrophilic bacterial community. Hierarchical cluster analysis of the Raman spectrum could accurately select the target Geobacter cluster. The high relative abundance of the membrane transport functional genes ftsEX in the biofilm community indicated an adaptation to reduced temperature, which aided survival of the electroactive bacteria under low temperature. The basal metabolism such as citrate cycle and glycolytic pathway maintained the electron pool for the EET process. The identification of iron (III) transport system genes in high abundance indicated their presence in an active metabolic reaction for potential electron transfer process. It showed the potential involvement c-type cytochromes (coxA and cox1) activity in EET. These results indicated that psychrophilic Geobacter had effective EET mediated by c-type cytochromes at low temperatures.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144328DOI Listing
March 2021

Nicotine Prevents Oxidative Stress-Induced Hippocampal Neuronal Injury Through α7-nAChR/Erk1/2 Signaling Pathway.

Front Mol Neurosci 2020 12;13:557647. Epub 2020 Nov 12.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

Oxidative stress-induced neuronal damage has been implicated to play a dominant role in neurodegenerative disorders, such as Alzheimer's disease (AD). Nicotine, a principal additive compound for tobacco users, is thought as a candidate to attenuate amyloid-β-mediated neurotoxicity and NMDA-induced excitotoxicity. Previous studies demonstrated that nicotine exerted this neuroprotective action on oxidative stress. However, the mechanisms underlying how nicotine contributes on oxidative injury in immortalized hippocampal HT-22 cells remain largely unknown. Therefore, in this study we investigated that the potential effects of nicotine on hydrogen peroxide (HO)-induced oxidative injury and underlying mechanisms in HT-22 cells. We found that pretreatment with nicotine at low concentrations markedly recovered the cell cycle that was arrested at the G2/M phase in the presence of HO through reduced intracellular ROS generation. Moreover, nicotine attenuated HO-induced mitochondrial dysfunctions. Mechanistically, the application of nicotine significantly upregulated the levels of phosphorylated Erk1/2. The neuroprotective effects of nicotine, in turn, were abolished by PD0325901, a selective Erk1/2 inhibitor. Further obtained investigation showed that nicotine exerted its neuroprotective effects specifically activating α7 nicotinic acetylcholine receptors (α7-nAChRs). A selective inhibitor of α7-nAChRs, methyllycaconitine citrate (MLA), not only completely prevented nicotine-mediated antioxidation but also abolished expression of p-Erk1/2. Taken together, our findings suggest that nicotine suppresses HO-induced HT-22 cell injury through activating the α7-nAChR/Erk1/2 signaling pathway, which indicates that nicotine may be a novel strategy for the treatment of neurodegenerative disorders.
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http://dx.doi.org/10.3389/fnmol.2020.557647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717967PMC
November 2020

Effect of gas atmosphere on hydrogen production in microbial electrolysis cells.

Sci Total Environ 2021 Feb 28;756:144154. Epub 2020 Nov 28.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Inert gas is often used in the deoxygenation of microbial electrolysis cells (MECs) to maintain growth and viability of anaerobes. However, the effects of the gas atmosphere on hydrogen production and microbial community of MECs are often neglected. Here, the performances and biofilm microbiomes of MECs pre-sparged with different gases were compared. MECs pre-sparged with argon gas (Ar) yielded more hydrogen (3.73 ± 0.13 mol-H/mol-acetate) and a higher hydrogen production rate (2.99 ± 0.17 L-H/L-reactor-day) than MECs pre-sparged with N (3.41 ± 0.13 mol-H/mol-acetate and 2.27 ± 0.28 L-H/L-reactor-day, respectively). Microbiome analysis indicated that the relative abundance of Geobacter increased from 59.25% to 77.79% when the gas atmosphere in MECs shifted from N to Ar. Hydrogen production may have been catalyzed by nitrogenase from Geobacter and photosynthetic bacteria in MECs pre-sparged with Ar. These findings suggested that the gas atmosphere substantially influences the microbiome of anode biofilms and Ar sparging is most effective for enhancing hydrogen production in MECs.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144154DOI Listing
February 2021

Effect of waterproof breathable membrane based cathodes on performance and biofilm microbiomes in bioelectrochemical systems.

Sci Total Environ 2021 Jan 8;753:142281. Epub 2020 Sep 8.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China.. Electronic address:

A novel method for fabricating air-cathodes was developed by assembling an activated carbon (AC) catalyst together with a waterproof breathable membrane (WBM) and stainless steel mesh (SSM) to reduce manufacturing costs of bioelectrochemical systems (BESs). WBMs made of different materials were tested in the assembly, including a hybrid of polypropylene and polyolefin (PPPO), polyethylene (PE), and polyurethane (PU), and compared against poly tetrafluoroethylene (PTFE)-based cathodes. Results showed that the maximum power density of the activated carbon-stainless steel mesh-polyurethane ([email protected]/PU) assembly was 2.03 W/m while that of conventional carbon cloth cathode assembly ([email protected]/PTFE) was 1.51 W/m. Compared to conventional cathode fabrication, [email protected]/PU had a much lower cost and simpler manufacturing process. Illumina Miseq sequencing of 16S rRNA gene amplicons indicated that microbiomes were substantially different between anode and cathode biofilms. There was also a difference in the community composition between different cathode biofilms. The predominant population in the anode biofilms was Geobacter (38-75% relative abundance), while Thauera and Pseudomonas dominated the cathode biofilms. The results demonstrated that different types of air-cathodes influenced the microbial community assembly on the electrodes.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142281DOI Listing
January 2021

Self-regulating microbiome networks ensure functional resilience of biofilms in sand biofilters during manganese load fluctuations.

Water Res 2021 Jan 29;188:116473. Epub 2020 Sep 29.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China; School of Environment, Harbin Institute of Technology, P.O. Box 2614, 73 Huanghe Road, Nangang District, Harbin, Heilongjiang Province 150090, China. Electronic address:

Sand biofilters (SBFs) are commonly used to remove manganese (Mn(II)) from drinking water. Mn(II) load variation frequently occurs in SBFs due to fluctuating influent Mn(II) concentrations or flow rates. Therefore, it is important to understand the responses of microbial biofilms in SBFs to environmental disturbances and how they affect Mn(II) oxidation efficiency. Here, the responses of microbial ecological networks and Mn(II) removal in SBFs to increasing Mn(II) load were investigated. The Mn(II) removal efficiency in two SBFs remained at 99.8% despite an increase in influent Mn(II) from 2 mg/L to 4 mg/L, but significantly deteriorated (50.1-58.5%) upon increasing the filtration rate. A canonical correlation analysis of the microbial communities indicated that the local Mn(II) concentration and biofilter depth impacted community compositions of biofilms. The dominant species within the biofilms exhibited clear stratification, with simple associations in the upper layer of the SBFs and more complex interspecies interactions in the bottom layers. Putative manganese-oxidizing bacteria Hyphomicrobium and Pedomicrobium dominated the microbiomes in different layers of SBFs, and changed relatively little in abundance when Mn(II) and filtration rate increased. The community networks showed that biofilm microbiomes in SBFs were resilient to the disturbance of Mn(II) load, primarily via regulating microbial interactions. High manganese loads negatively affected the functional modules for Mn(II) removal. Furthermore, the relatively rare species Candidatus Entotheonella palauensis was identified as a module hub, implying taxa with low abundances can have important roles in ecosystem function. These results shed new light on the ecological rules guiding responses of microbiomes in sand biofilters to environmental stress.
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http://dx.doi.org/10.1016/j.watres.2020.116473DOI Listing
January 2021

Recovered COVID-19 patients with recurrent viral RNA exhibit lower levels of anti-RBD antibodies.

Cell Mol Immunol 2020 10 16;17(10):1098-1100. Epub 2020 Sep 16.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1038/s41423-020-00528-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493297PMC
October 2020

Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19.

Signal Transduct Target Ther 2020 09 2;5(1):180. Epub 2020 Sep 2.

Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild, and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.
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http://dx.doi.org/10.1038/s41392-020-00301-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464057PMC
September 2020

Rapid recruitment of hydrogen-producing biofilms for hydrogen production in a moving bed biofilm reactor by a sequential immobilization and deoxygenization approach.

Bioresour Technol 2020 Dec 8;317:123979. Epub 2020 Aug 8.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

To reduce start-up time and enhance hydrogen production efficiency, a sequential immobilization and deoxygenization (SIDO) strategy for hydrogen production was investigated in continuous-flow moving bed biofilm reactors (MBBRs). The pre-immobilization process accelerated the initial enrichment of hydrogen-producing bacteria (HPB) and promoted the biofilm formation, which contribute to higher hydrogen production efficiency in SIDO-MBBRs compared to a non-immobilized reactor. A similar deoxygenization effect was achieved by inoculation with Pseudomonas aeruginosa compared with N sparging, and the P. aeruginosa pre-immobilized MBBR (Pse-MBBR) showed a higher H yield in the initial stage of operation. Microbial community analysis found a higher abundance of putative HPB in the range of 82.82-96.56%, with the predominant populations in the SIDO-MBBR assigned to genera Clostridium and Enterobacter. The results suggest that the SIDO-MBBR is an effective approach for rapid recruitment of HPB and start-up of fermentative hydrogen production.
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http://dx.doi.org/10.1016/j.biortech.2020.123979DOI Listing
December 2020

Investigation and fate of microplastics in wastewater and sludge filter cake from a wastewater treatment plant in China.

Sci Total Environ 2020 Dec 30;746:141378. Epub 2020 Jul 30.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, P. O. Box 2614, 73 Huanghe Road, Harbin 150090, China. Electronic address:

Microplastics (MPs) have been widely detected in wastewater treatment plants (WWTPs) due to their small particle size, wide distribution, and difficulty in removal. Previous studies, however, mostly focused on MPs in wastewater, thereby neglecting sludge. To comprehensively understand the changes of MPs in WWTPs, we investigated the quantity and characteristics of MPs in wastewater and sludge of a WWTP in Harbin, a typical inland city in China, and calculated the MPs removal rate. The results showed that there were 126.0 ± 14.0 particles/L MPs in the influent and 30.6 ± 7.8 particles/L in the effluent, about 75.7% MPs were removed and transferred to the sludge during this WWTP. The abundance of MPs in dewatered sludge and sludge filter cake was 36.3 ± 5.7 and 46.3 ± 6.2 particles/g (dry sludge), the sludge disposal scale of this WWTP can reach 1300 tons/day, which was equivalent to about 7.74 × 10 microplastic particles accumulated in sludge per year. These sludges were used as fertilizers in the soil, which will cause secondary pollution of MPs. Raman spectroscopic analysis showed that about 89.5% of particles were plastic polymers, such as polyesters, polyamide (PA), polyethylene terephthalate (PET) and polyethylene (PE), which suggested that MPs may be derived from laundry and personal care products. Therefore, we recommend that more work should be devoted to how to control the release of MPs at the source and the reuse of sludge after treatment by WWTPs.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141378DOI Listing
December 2020

A novel integrated process to convert cellulose and hemicellulose in rice straw to biobutanol.

Environ Res 2020 07 28;186:109580. Epub 2020 Apr 28.

State Key Laboratory of Urban Water Resources and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

A novel integrated process was established in this study to produce butanol from rice straw. In the first pretreatment, an alternative NaOH/Urea preatment operated at -12 C efficiently removed 10.9 g lignin and preserved 91.54% cellulose and hemicellulose in 100 g rice straw. Subsequently, crude cellulase produced from Trichoderma viride was used to convert pretreated rice straw to mono-sugars for fermentation. The yields of glucose, xylose and arabiose obtained from 100 g rice straw were 31 g, 13.4 g and 0.48 g, respectively, resulting in a 69.45% saccharification efficiency of crude enzyme. Finally, to alleviate the carbon catabolite repression (CCR) and enhance butanol production, the coculture system of Clostridium beijerinckii and Saccharomyces cerevisiae was applied. Compared to monoculture of C. beijerinckii F-6, more sugars were consumed, especially the reduction rate of xylose reached to 81.87%, 32.99% higher than that in monoculture system. With more substrate facilitied into metabolism, the butanol concentration reached to 10.62 g/L corresponding to 0.28 g/g substrate, 115.38% higher than that in monoculture system. Overall, this integrated process was a low-energy consumption and efficient method for butanol production from rice straw.
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http://dx.doi.org/10.1016/j.envres.2020.109580DOI Listing
July 2020

Accelerating nutrient release and pathogen inactivation from human waste by different pretreatment methods.

Sci Total Environ 2020 Sep 4;733:139105. Epub 2020 May 4.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

The limitation of hydrolysis and the health risks from pathogenic microorganisms are challenges in the treatment of human waste for volume reduction and nutrient recovery. In this study, potassium ferrate (PF), peroxymonosulfate (PMS), and PF combined with peroxymonosulfate (PMS+ PF) were used as pretreatment or co-treatment methods to enhance nutrient release and control pathogenic microorganisms in human waste. The PF pretreatment was the most effective regarding hydrolysis and organic matter release. The largest difference (D-value) in the soluble chemical oxygen demand (3117.0 mg/L) between the control and the treatment after 120 min was observed for the PF pretreatment, followed by the alkaline (ALK) pretreatment (1525.0 mg/L), the PF + PMS pretreatment (1169.3 mg/L), and the PMS pretreatment (1020.6 mg/L). The PF pre-treated waste exhibited the highest volatile solids reduction of 79.2% after 120 min compared with 15.0% reduction of the untreated waste, as well as the highest polysaccharide release, with a D-value of 198.5 mg/L. All pretreatments exhibited inactivation of pathogenic bacteria and helminths eggs; however, the PF pretreatment was the most efficient method to suppress pathogenic micrograms, with a 3.5 log (N/N) decrease in the number of total coliforms. The PF pretreatment and PMS + PF co-treatment both exhibited the good performance regarding nitrogen release, including soluble protein and ammonium. The maximum D-value of the total soluble nitrogen was 372.8 mg/L for the PF + PMS co-treatment. The maximum D-value of soluble protein was 156.2 mg/L for the ALK pretreatment. The results indicated that the PF pretreatment was the most effective method for disintegrating human waste, thus providing a new method for safe and rapid reduction of human waste, as well as nutrient release.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139105DOI Listing
September 2020

Co-treatment of potassium ferrate and peroxymonosulfate enhances the decomposition of the cotton straw and cow manure mixture.

Sci Total Environ 2020 Jul 30;724:138321. Epub 2020 Mar 30.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Since there is high lignocellulose content in the cotton straw and cow manure mixture (MCC), the appropriate MCC pretreatment is important to promote the anaerobic digestion (AD) hydrolysis. This study mainly explored the effect of potassium ferrate (PF) and peroxymonosulfate (PMS) pretreatments on MCC decomposition. PMS + PF co-treatment showed a higher reduction of total solid and volatile solid than PF pretreatment and PMS pretreatment. Hydrolysis of treated MCC indicated that the PF pretreatment was more effective to the release of organics than the PMS pretreatment and the PMS + PF co-treatment. However, the PMS + PF co-treatment resulted in a higher lignin removal rate (40.4%-50.5%) than the PMS pretreatment (30.8%) and the PF pretreatment (21.4%). The PMS + PF co-treatment (molar ratio of 1:2) acquired the optimal lignin removal rate and the release of organics among the PMS + PF co-treatment with different dosing ratio. Potential mechanism was that PF reduction products activated PMS to produce free radicals (SO, OH), which attacked lignocellulosic components and promoted MCC decomposition. The PMS + PF co-treatment was deduced to be the optimal pretreatment method when considering MCC decomposition, biodegradability, and mass transfer in the bioreactor.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138321DOI Listing
July 2020

Thermoanaerobacterium sp. Strain RBIITD as a dominant species in accelerating thermophilic dark fermentation start up through pH and substrate concentration regulation.

Bioresour Technol 2020 Aug 23;310:123426. Epub 2020 Apr 23.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, P. O. Box 2614, 73 Huanghe Road, Harbin 150090, China. Electronic address:

In this work, accelerated start-up of biological hydrogen production system fed with glucose and molasses at 55 °C by regulating pH and COD concentration was investigated in two groups. Then three reactors in each group were compared: controlling pH, controlling pH with COD, and controlling the COD. The reactors in group A presented best hydrogen yield of 1.84 mol H/mol glucose·day and worked stably at the 8th day. The highest hydrogen yield in group B was 2.13 mol H/mol molasses·day and steadily at the 11th day. It proved that controlling two key parameters of the inflow pH (8.0) and substrate concentration (4000 mg COD/L) could realize fast start-up of hydrogen production reactor. This study demonstrated that Thermoanaerobacterium sp. strain RBIITD could produce hydrogen and provide a new avenue for biological hydrogen production by dark fermentation using cheap substrate towards a more sustainable and feasible technology.
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http://dx.doi.org/10.1016/j.biortech.2020.123426DOI Listing
August 2020

PIWIL4 Maintains HIV-1 Latency by Enforcing Epigenetically Suppressive Modifications on the 5' Long Terminal Repeat.

J Virol 2020 05 4;94(10). Epub 2020 May 4.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China

Although substantial progress has been made in depicting the molecular pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection, the comprehensive mechanism of HIV-1 latency and the most promising therapeutic strategies to effectively reactivate the HIV-1 latent reservoir to achieve a functional cure for AIDS remain to be systematically illuminated. Here, we demonstrated that piwi (P element-induced Wimpy)-like RNA-mediated gene silencing 4 (PIWIL4) played an important role in suppressing HIV-1 transcription and contributed to the latency state in HIV-1-infected cells through its recruitment of various suppressive factors, including heterochromatin protein 1α/β/γ, SETDB1, and HDAC4. The knockdown of PIWIL4 enhanced HIV-1 transcription and reversed HIV-1 latency in both HIV-1 latently infected Jurkat T cells and primary CD4 T lymphocytes and resting CD4 T lymphocytes from HIV-1-infected individuals on suppressive combined antiretroviral therapy (cART). Furthermore, in the absence of PIWIL4, HIV-1 latently infected Jurkat T cells were more sensitive to reactivation with vorinostat (suberoylanilide hydroxamic acid, or SAHA), JQ1, or prostratin. These findings indicated that PIWIL4 promotes HIV-1 latency by imposing repressive marks at the HIV-1 5' long terminal repeat. Thus, the manipulation of PIWIL4 could be a novel strategy for developing promising latency-reversing agents (LRAs). HIV-1 latency is systematically modulated by host factors and viral proteins. During this process, the suppression of HIV-1 transcription plays an essential role in promoting HIV-1 latency. In this study, we found that PIWIL4 repressed HIV-1 promoter activity and maintained HIV-1 latency. In particular, we report that PIWIL4 can regulate gene expression through its association with the suppressive activity of HDAC4. Therefore, we have identified a new function for PIWIL4: it is not only a suppressor of endogenous retrotransposons but also plays an important role in inhibiting transcription and leading to latent infection of HIV-1, a well-known exogenous retrovirus. Our results also indicate a novel therapeutic target to reactivate the HIV-1 latent reservoir.
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http://dx.doi.org/10.1128/JVI.01923-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199406PMC
May 2020

Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis.

PLoS Pathog 2020 02 26;16(2):e1008334. Epub 2020 Feb 26.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of pro-inflammatory factors were released. A group of IAV-infected PD-L1+ neutrophils were the major contributor to the first wave at an earlier stage (day 1-3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4+)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1+ neutrophils and Pf4+-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of pro-inflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.
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http://dx.doi.org/10.1371/journal.ppat.1008334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062283PMC
February 2020

Biodegradation of Polyethylene and Polystyrene by Greater Wax Moth Larvae ( L.) and the Effect of Co-diet Supplementation on the Core Gut Microbiome.

Environ Sci Technol 2020 03 11;54(5):2821-2831. Epub 2020 Feb 11.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, P. R. China.

Plastics waste and microplastics including polyethylene (PE) and polystyrene (PS) have been an environmental concern for years. Recent research has revealed that larvae of are capable of biodegrading low density PE film. In this study, we tested the feasibility of enhancing larval survival and the effect of supplementing the co-diet on plastic degradation by feeding the larvae beeswax or wheat bran as a co-diet. Significant mass loss of plastic was observed over a 21-day period, i.e., with respective consumption of 0.88 and 1.95 g by 150 larvae fed only either PS or PE. The formation of C═O and C-O containing functional groups and long chain fatty acids as the metabolic intermediates of plastics in the residual polymers indicated depolymerization and biodegradation. Supplementing beeswax and bran increased the survival rates but decreased the consumption of plastic. The changes in the gut microbiome revealed that and were significantly associated with the PS and PE diets. Beeswax and bran showed different shaping effects on the core gut microbiome of larvae fed the PE and PS. These results suggest that supplementing the co-diet affected the physiological properties of the larvae and plastic biodegradation and shaped the core gut microbiome.
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http://dx.doi.org/10.1021/acs.est.9b07044DOI Listing
March 2020

Single molecule sequencing reveals response of manganese-oxidizing microbiome to different biofilter media in drinking water systems.

Water Res 2020 Mar 19;171:115424. Epub 2019 Dec 19.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

Rapid sand biofiltration (RSBF) is widely used for the removal of contaminants from drinking water treatment systems. Biofilm microbiomes in the biofilter media play essential roles in biotransformation of contaminants, but is not comprehensively understood. This study reports on Mn(II) oxidation and the core microbiomes in magnetite sand RSBF (MagS-RSBF) and manganese sand RSBF (MnS-RSBF). MnS-RSBF showed a relatively higher Mn(II) removal rate (40-91.2%) than MagS-RSBF during the start-up. MagS-RSBF and MnS-RSBF had similar Mn(II) removal rates (94.13% and 99.16%) over stable operation for 80 days. Mn(II) removal rates at different depths in the MnS-RSBF reactor significantly changed with operation time, and the filter in the upper layer of MnS-RSBF made the largest contribution to Mn(II) oxidation once operation had stabilized. PacBio single molecule sequencing of full-length 16S rRNA gene indicated that biofilter medium had a significant impact on the core microbiomes of the biofilms from the two biofilters. The magnetite sand biofilter facilitated the enrichment of Mn(II)-oxidizing biofilms. The dominant populations consisted of Pedomicrobium, Pseudomonas, and Hyphomicrobium in the RSBF, which have been affiliated with putative manganese-oxidizing bacteria (MnOB). The relative abundance of Pedomicrobium manganicum increased with operation time in both RSBF reactors. In addition, Nordella oligomobilis and Derxia gummosa were statistically correlated with Mn(II) oxidation. Species-species co-occurrence networks indicated that the microbiome of MnS-RSBF had more complex correlations than that of MagS-RSBF, implying that biofilter medium substantially shaped the microbial community in the RSBF. Hyphomicrobium and nitrite-oxidizing Nitrospira moscoviensis were positively correlated. The core microbiomes' composition of both RSBF reactors converged over operation time. A hybrid biofilter medium with magnetite sand and manganese sand may therefore be best in rapid sand filtration for Mn(II) oxidation.
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http://dx.doi.org/10.1016/j.watres.2019.115424DOI Listing
March 2020

X4-Tropic Latent HIV-1 Is Enriched in Peripheral Follicular Helper T Cells and Is Correlated with Disease Progression.

J Virol 2020 01 6;94(2). Epub 2020 Jan 6.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus type 1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory, and naive CD4 T cells from individuals with HIV-1 infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to levels in the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells not only was robustly and inversely correlated with blood CD4 T cell counts across patients but also was prognostic of CD4 T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy. TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4 T cell subsets is inversely and closely correlated with blood CD4 T cell counts and CD4 T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.
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http://dx.doi.org/10.1128/JVI.01219-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955254PMC
January 2020

Lovastatin Inhibits HIV-1-Induced MHC-I Downregulation by Targeting Nef-AP-1 Complex Formation: A New Strategy to Boost Immune Eradication of HIV-1 Infected Cells.

Front Immunol 2019 10;10:2151. Epub 2019 Sep 10.

Department of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.

Current combined antiretroviral therapy (cART) mainly targets 3 of the 15 HIV proteins leaving many potential viral vulnerabilities unexploited. To purge the HIV-1 latent reservoir, various strategies including "shock and kill" have been developed. A key question is how to restore impaired immune surveillance. HIV-1 protein Nef has long been known to mediate the downregulation of cell-surface MHC-I and assist HIV-1 to evade the immune system. Through high throughput screening of Food and Drug Administration (FDA) approved drugs, we identified lovastatin, a statin drug, to significantly antagonize Nef to downregulate MHC-I, CD4, and SERINC5, and inhibit the intrinsic infectivity of virions. In addition, lovastatin boosted autologous CTLs to eradicate the infected cells and effectively inhibit the subsequent viral rebound in CD4 T-lymphocytes isolated from HIV-1-infected individuals receiving suppressive cART. Furthermore, we found that lovastatin inhibits Nef-induced MHC-I downregulation by directly binding with Nef and disrupting the Nef-AP-1 complex. These results demonstrate that lovastatin is a promising agent for counteracting Nef-mediated downregulation of MHC-I, CD4, and SERINC5. Lovastatin could potentially be used in the clinic to enhance anti-HIV-1 immune surveillance.
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http://dx.doi.org/10.3389/fimmu.2019.02151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749138PMC
November 2020

Enhanced butanol-hydrogen coproduction by Clostridium beijerinckii with biochar as cell's carrier.

Bioresour Technol 2019 Dec 10;294:122141. Epub 2019 Sep 10.

State Key Laboratory of Urban Water Resources and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

In this study, the effects of biochar on the fermentation performance of butanol-hydrogen coproduction by Clostridium beijerinckii F-6 were investigated. Results showed that the biochar with rich porous and graphitized structure can significantly promote the coproduction of butanol and hydrogen. The productivity of butanol and hydrogen reached 0.148 g/L/h and 0.299 mmol/L/h with biochar addition which were 20.23% and 48.76% higher than that in control without biochar addition, respectively. Moreover, the whole energy conversion efficiency calculated based on the heat value showed increment from 43.69% to 51.75% with biochar addition. Combined analysis of organic acids accumulation and oxidation-reduction potential fluctuation proved that biochar can regulate reducing power during fermentation and accelerate the conversion of acid phase to solvent phase. Scanning electron microscope images showed that biochar acted as carriers for cells absorption. Confirmation experiment further proved that biochar enhanced the butanol tolerant ability of Clostridium beijerinckii F-6.
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http://dx.doi.org/10.1016/j.biortech.2019.122141DOI Listing
December 2019

Simultaneous nutrition removal and high-efficiency biomass and lipid accumulation by microalgae using anaerobic digested effluent from cattle manure combined with municipal wastewater.

Biotechnol Biofuels 2019 12;12:218. Epub 2019 Sep 12.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090 China.

Background: Microalgae as a viable biodiesel feedstock show great potential to approach the challenges of energy shortage and environment pollution, but their economic feasibility was seriously hampered by high production cost. Thus, it is in urgent need to reduce the cost of cultivation and improve the biomass and lipid production of microalgae. In this work, anaerobic digestion effluent from cattle manure combined with municipal wastewater was used as a cost-effective medium for cultivating microalgae and expected to obtain high biomass. The pretreatment of anaerobic digested effluent containing dilution rate, sterilization and nutrient optimization was investigated. Then, initial pH and light intensity for algal growth, lipid production and wastewater purification were optimized in this study.

Results: sp. could grow rapidly in 10% anaerobic digestion effluent from cattle manure combined with secondary sedimentation tank effluent without sterilization. Optimum nutrient additives for higher biomass were as follows: glucose 10 g/L, NaNO 0.3 g/L, KHPO·3HO 0.01 g/L, MgSO·7HO 0.075 g/L and trace element A5 solution 1 mL/L. Biomass of 4.65 g/L and lipid productivity of 81.90 mg/L/day were achieved during 7-day cultivation accompanying over 90% of COD, NO -N, NH -N, and 79-88% of PO -P removal with optimized initial pH of 7.0 and light intensity of 5000 l×. The FAME profile in ADEC growth medium consisted in saturated (39.48%) and monounsaturated (60.52%) fatty acids with the 16- to 18-chain-length fatty acids constituting over 98% of total FAME.

Conclusions: This study proves the potential of anaerobic digested effluent combined with municipal wastewater for microalgae culture, and provides an effective avenue for simultaneous microalgal lipid production and treatment of two kinds of wastewater.
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http://dx.doi.org/10.1186/s13068-019-1553-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739908PMC
September 2019

Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56.

Nat Commun 2019 09 11;10(1):4109. Epub 2019 Sep 11.

Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

The inhibitory receptors PD-1, Tim-3, and Lag-3 are highly expressed on tumor-infiltrating lymphocytes and compromise their antitumor activity. For efficient cancer immunotherapy, it is important to prevent chimeric antigen receptor T (CAR-T)-cell exhaustion. Here we downregulate these three checkpoint receptors simultaneously on CAR-T cells and that show the resulting PTL-CAR-T cells undergo epigenetic modifications and better control tumor growth. Furthermore, we unexpectedly find increased tumor infiltration by PTL-CAR-T cells and their clustering between the living and necrotic tumor tissue. Mechanistically, PTL-CAR-T cells upregulate CD56 (NCAM), which is essential for their effector function. The homophilic interaction between intercellular CD56 molecules correlates with enhanced infiltration of CAR-T cells, increased secretion of interferon-γ, and the prolonged survival of CAR-T cells. Ectopically expressed CD56 promotes CAR-T cell survival and antitumor response. Our findings demonstrate that genetic blockade of three checkpoint inhibitory receptors and the resulting high expression of CD56 on CAR-T cells enhances the inhibition of tumor growth.
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http://dx.doi.org/10.1038/s41467-019-11893-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739330PMC
September 2019

USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication.

Elife 2019 08 9;8. Epub 2019 Aug 9.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

The antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquitination enzymes (DUBs) in innate immunity, it is unknown if they participate in A3G stability. Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity. Unexpectedly, A3G degradation was also mediated by a Vif- and cullin-ring-independent pathway, which was effectively counteracted by USP49. Furthermore, clinical data suggested that USP49 is correlated with A3G protein expression and hypermutations in Vif-positive proviruses, and inversely with the intact provirus ratio in the HIV-1 latent reservoir. Our studies demonstrated a mechanism to effectively stabilize A3G expression, which could comprise a target to control HIV-1 infection and eradicate the latent reservoir.
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http://dx.doi.org/10.7554/eLife.48318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701944PMC
August 2019
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