Publications by authors named "Jianwei Liu"

201 Publications

Anti-inflammatory activity of the Tongmai Yangxin Pill in the treatment of Coronary Heart Disease is associated with Estrogen Receptor and NF-κB signaling pathway.

J Ethnopharmacol 2021 Apr 7:114106. Epub 2021 Apr 7.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address:

Ethnopharmacological Relevance: The Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear.

Aim Of The Study: This study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays.

Materials And Methods: Eight CHD patients' serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 μg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25-100 μg/mL).

Results: TMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/β, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions.

Conclusion: TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.
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http://dx.doi.org/10.1016/j.jep.2021.114106DOI Listing
April 2021

Bioactive small molecules in calcium phosphate scaffold enhanced osteogenic differentiation of human induced pluripotent stem cells.

Dent Mater J 2021 Apr 3. Epub 2021 Apr 3.

Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry.

Human induced pluripotent stem cells (hiPSCs) are exciting for regenerative medicine due to their multi-potent differentiation. SB431542 bioactive molecule can activate bone morphogenetic protein-signalling in osteoblasts. The objectives were to: (1) develop a novel injectable calcium phosphate cement (CPC)-SB431542 scaffold for dental/craniofacial bone engineering; and (2) investigate cell proliferation and osteo-differentiation of hiPSC-derived mesenchymal stem cells (hiPSC-MSCs) on CPC-SB431542 scaffold. Three groups were tested: CPC control; CPC with SB431542 inside CPC (CPCSM); CPC with SB431542 in osteogenic medium (CPC+SMM). SB431542 in CPC promoted stem cell proliferation and viability. hiPSC-MSCs differentiated into osteogenic lineage and synthesized bone minerals. CPC with SB431542 showed much greater osteo-expressions and more bone minerals than those without SB431542. In conclusion, hiPSC-MSCs on CPC scaffold containing SB431542 showed excellent osteo-differentiation and bone mineral synthesis for the first time. CPC was a suitable scaffold for delivering stem cells and SB431542 to promote bone regeneration in dental/craniofacial applications.
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http://dx.doi.org/10.4012/dmj.2019-263DOI Listing
April 2021

Maintenance of Cell Wall Integrity under High Salinity.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

Cell wall biosynthesis is a complex biological process in plants. In the rapidly growing cells or in the plants that encounter a variety of environmental stresses, the compositions and the structure of cell wall can be dynamically changed. To constantly monitor cell wall status, plants have evolved cell wall integrity (CWI) maintenance system, which allows rapid cell growth and improved adaptation of plants to adverse environmental conditions without the perturbation of cell wall organization. Salt stress is one of the abiotic stresses that can severely disrupt CWI, and studies have shown that the ability of plants to sense and maintain CWI is important for salt tolerance. In this review, we highlight the roles of CWI in salt tolerance and the mechanisms underlying the maintenance of CWI under salt stress. The unsolved questions regarding the association between the CWI and salt tolerance are discussed.
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http://dx.doi.org/10.3390/ijms22063260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004791PMC
March 2021

The Effect of Residential Environment on Respiratory Diseases and Pulmonary Function in Children from a Community in Jilin Province of China.

Risk Manag Healthc Policy 2021 25;14:1287-1297. Epub 2021 Mar 25.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin, 130021, People's Republic of China.

Purpose: Respiratory disease is a major and increasingly global epidemic that has a great impact on humans, especially children. The purpose of this study was to identify environmental risk factors for respiratory diseases and pulmonary function in children.

Patients And Methods: A population-based, cross-sectional survey of respiratory diseases and environmental risk factors was conducted in Jilin Province, China. Complete questionnaire information was available for 2419 children, while adequate pulmonary function data were available for a subgroup of 627 children.

Results: Our study found that environmental risk factors for respiratory health in children were mainly concentrated indoors. After adjusting for demographic factors, insecticide exposure and passive smoking were risk factors for respiratory disease and industrial pollutant sources, insecticide exposure and the use of a fume exhauster may be independent risk factors for recurrent respiratory infections. The main fuel for cooking in the winter and passive smoking were the main influencing factors of pulmonary function indicators.

Conclusion: The primary risk factors differ in different respiratory diseases. Passive smoking remains a critical adverse factor for respiratory illness and pulmonary function in children, and it is important to reduce children's exposure to passive smoking to increase pulmonary health. Insecticide exposure may be a neglected environmental risk factor, and further investigations are still needed to explore the relationship and mechanisms between insecticide exposure and children's respiratory health.
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http://dx.doi.org/10.2147/RMHP.S295553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007578PMC
March 2021

Differentially-expressed mRNAs, microRNAs and long noncoding RNAs in intervertebral disc degeneration identified by RNA-sequencing.

Bioengineered 2021 Dec;12(1):1026-1039

Department of Osteology, The Third Affiliated Hospital of Guangxi Medical University, Nanning Guangxi, P.R China.

The underlying molecular mechanisms of intervertebral disc degeneration (IDD) remain unclear. This study aimed to identify the crucial molecules and explore the function of noncoding RNAs and related pathways in IDD. We randomly selected three samples each from an IDD and a spinal cord injury group (control) for RNA-sequencing. We identified 463 differentially-expressed long noncoding RNAs (lncRNAs), 47 differentially-expressed microRNAs (miRNAs), and 1,334 differentially-expressed mRNAs in IDD. Three hundred fifty-eight lncRNAs as cis-regulators could potentially target 865 genes. Protein-protein interaction (PPI) network analysis confirmed that and were hub genes. We built a competing endogenous RNA (ceRNA) network and identified lncRNA XIST-hsa-miR-4775-PLA2G7 and lncRNA XIST-hsa-miR-424-5p-AMOT/TGFBR3 ceRNA axes. Quantitative real-time PCR (qRT-PCR) was implemented in 15 IDD samples and 15 controls to validate differentially-expressed genes in ceRNA axes. From the ceRNA network, gene ontology (GO) enrichment analysis indicated that noncoding RNAs were associated with several biological processes, including extracellular matrix organization, extracellular structure organization, leukocyte migration, and mesenchyme development. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that noncoding RNAs were associated with several pathways including the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, axon guidance, and osteoclast differentiation. These results indicate that some specific noncoding RNAs and ceRNA axes may be vital during the development of IDD, and may have potential as alternative diagnostic biomarkers as well as novel therapeutic strategies for IDD.
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http://dx.doi.org/10.1080/21655979.2021.1899533DOI Listing
December 2021

Galectin-9 expression correlates with therapeutic effect in rheumatoid arthritis.

Sci Rep 2021 Mar 10;11(1):5562. Epub 2021 Mar 10.

Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Active RA patients were enrolled and treated with tacrolimus (TAC) alone or in combination therapy for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and week 12. We measured Gal-9 expression in different T cell subsets and in plasma. The disease activity of RA patients decreased after treatment. At baseline, the Gal-9 expression percentage was higher in the group with severe disease than in mild or moderate groups. After treatment, the Gal-9 expression in CD3, CD4, CD8 and CD4CD8 cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3, CD4 and CD8 T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3 and CD4 T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. Gal-9 can be regarded as a new biomarker for evaluating RA activity and therapeutic effect, including TAC.
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http://dx.doi.org/10.1038/s41598-021-85152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946964PMC
March 2021

Pollution Source Apportionment and Water Quality Risk Evaluation of a Drinking Water Reservoir during Flood Seasons.

Int J Environ Res Public Health 2021 Feb 15;18(4). Epub 2021 Feb 15.

Institution of Water and Environment Research, Dalian University of Technology, Dalian 116024, China.

Reservoirs play an important role in the urban water supply, yet reservoirs receive an influx of large amounts of pollutants from the upper watershed during flood seasons, causing a decline in water quality and threatening the water supply. Identifying major pollution sources and assessing water quality risks are important for the environmental protection of reservoirs. In this paper, the principal component/factor analysis-multiple linear regression (PCA/FA-MLR) model and Bayesian networks (BNs) are integrated to identify water pollution sources and assess the water quality risk in different precipitation conditions, which provides an effective framework for water quality management during flood seasons. The deterioration of the water quality of rivers in the flood season is found to be the main reason for the deterioration in the reservoir water quality. The nonpoint source pollution is the major pollution source of the reservoir, which contributes 53.20%, 48.41%, 72.69%, and 68.06% of the total nitrogen (TN), phosphorus (TP), fecal coliforms (F.coli), and turbidity (TUB), respectively. The risk of the water quality parameters exceeding the surface water standard under different hydrological conditions is assessed. The results show that the probability of the exceedance rate of TN, TP, and F.coli increases from 91.13%, 3.40%, and 3.34%, to 95.75%, 25.77%, and 12.76% as the monthly rainfall increases from ≤68.25 mm to >190.18 mm. The risk to the water quality of the Biliuhe River reservoir is found to increase with the rising rainfall intensity, the water quality risk at the inlet during the flood season is found to be much greater than that at the dam site, and the increasing trend of TP and turbidity is greater than that of TN and F.coli. The risk of five-day biochemical oxygen demand (BOD) does not increase with increasing precipitation, indicating that it is less affected by nonpoint source pollution. The results of this study can provide a research basis for water environment management during flood seasons.
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http://dx.doi.org/10.3390/ijerph18041873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918960PMC
February 2021

A comprehensive survey on smart contract construction and execution: paradigms, tools, and systems.

Patterns (N Y) 2021 Feb 12;2(2):100179. Epub 2021 Feb 12.

School of Computer Science, University of Guelph, Guelph, ON N1G 2W1, Canada.

Smart contracts are regarded as one of the most promising and appealing notions in blockchain technology. Their self-enforcing and event-driven features make some online activities possible without a trusted third party. Nevertheless, problems such as miscellaneous attacks, privacy leakage, and low processing rates prevent them from being widely applied. Various schemes and tools have been proposed to facilitate the construction and execution of secure smart contracts. However, a comprehensive survey for these proposals is absent, hindering new researchers and developers from a quick start. This paper surveys the literature and online resources on smart contract construction and execution over the period 2008-2020. We divide the studies into three categories: (1) design paradigms that give examples and patterns on contract construction, (2) design tools that facilitate the development of secure smart contracts, and (3) extensions and alternatives that improve the privacy or efficiency of the system. We start by grouping the relevant construction schemes into the first two categories. We then review the execution mechanisms in the last category and further divide the state-of-the-art solutions into three classes: private contracts with extra tools, off-chain channels, and extensions on core functionalities. Finally, we summarize several challenges and identify future research directions toward developing secure, privacy-preserving, and efficient smart contracts.
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http://dx.doi.org/10.1016/j.patter.2020.100179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892363PMC
February 2021

COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas.

Cell 2021 04 3;184(7):1895-1913.e19. Epub 2021 Feb 3.

Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing 100871, China; Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address:

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.
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http://dx.doi.org/10.1016/j.cell.2021.01.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857060PMC
April 2021

Investigating the survey instrument for the underground pipeline with inertial sensor and dead reckoning method.

Rev Sci Instrum 2021 Feb;92(2):025112

School of Instrument Science and Engineering, Southeast University, Nanjing 210096, China.

To survey deep-buried and non-metallic pipelines without excavation, a pipeline survey instrument composed of a data collection and data processing part is developed. The data collection part is composed of a walking machine, a nine-axis micro-electro-mechanical system inertial measurement unit (MEMS-IMU) installed on the walking machine, odometers based on Hall magnetic switches, and a control/data storage circuit, while data processing is executed on the personal computer, where the attitude and trajectory are acquired with the complementary filter and dead reckoning on the collected data. Key technologies include the following: (1) the gyro-bias is estimated with the parking mode when there is no angular motion excitation; (2) a magnetometer is introduced to assist MEMS-IMU tracking azimuth changes; (3) calibration based on ellipsoid fitting is designed for magnetometers and accelerometers without any references; (4) stretching and rotation on calculated trajectory are executed with position information of both pipeline ends. Test results on a pipeline of 104 m constructed on the ground show that the maximum error on the lateral direction is 0.13 m and the height is 0.06 m, while the mean errors are -0.04 m and -0.001 m, respectively.
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http://dx.doi.org/10.1063/5.0019095DOI Listing
February 2021

Removal characteristics of dissolved organic matter and membrane fouling in ultrafiltration and reverse osmosis membrane combined processes treating the secondary effluent of wastewater treatment plant.

Water Sci Technol 2021 Feb;83(3):689-700

Innovation Academy for Green Manufacture, CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

The widespread implementation of municipal wastewater treatment and reuse must first ensure the safety of reused wastewater. The effluent of the municipal wastewater treatment plant contains a large amount of dissolved organic matter (DOM), which adversely affects the reuse of wastewater. In this study, the ultrafiltration (UF) + reverse osmosis (RO) process was used to treat the secondary effluent from wastewater treatment plants. The relationship between the removal performance, membrane fouling of the UF + RO process, and DOM removal characteristics of influent were studied. The results show that DOM can be removed effectively by UF + RO process. The UF mainly removes DOM with a molecular weight greater than 10 kDa, while RO has a significant removal effect on low-molecular-weight DOM, which mainly causes UF and RO membrane fouling. The UF + RO process has a significant removal rate on fulvic acid, humic acid, tyrosine, and tryptophan, and the order is humic acid > fulvic acid > tyrosine > tryptophan. Fulvic acid contributed the most to the UF membrane fouling, while fulvic acid and protein-like proteins contributed mainly to the RO membrane fouling.
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http://dx.doi.org/10.2166/wst.2020.589DOI Listing
February 2021

Performance and substance transformation of low-pH and neutral-pH biofilters treating complex gases containing hydrogen sulfide, ammonia, acetic acid, and toluene.

Environ Sci Pollut Res Int 2021 Feb 13. Epub 2021 Feb 13.

Beijing Research Center of Sustainable Urban Drainage System and Risk Control, Beijing University of Civil Engineering and Architecture, Beijing, 100044, China.

Two biofilters with low pH and neutral pH were operated on pilot scale for the treatment of complex gases containing hydrogen sulfide, ammonia, acetic acid, and toluene during 205 days. Under the coexistence of complex gases, the low-pH biofilter (LPB) had higher removal efficiency (RE) for hydrogen sulfide and toluene, and the maximum efficiencies were 99.24% and 99.90% respectively, while the neutral-pH biofilter (NPB) had higher REs of ammonia and acetic acid, up to 99.90% and 99.92% respectively. Higher pressure drop up to 622 Pa was achieved in the LPB, most likely caused by the special structure of fungi different from bacteria. Determination of the concentration of carbon-based intermediates revealed the dominant microbial removal of acetic acid and clarified the relationship between the generation of intermediate and the performance of biofilters. Respective amount of CO in the inlet and outlet showed that the mineralization capacity of the NPB was higher than that of the LPB, and it was more influenced by empty bed residence time (EBRT). The proportion of different forms of nitrogen and sulfur in the filler indicated that the removal of ammonia in the LPB mainly depended on the adsorption by moisture, while that in the NPB was microbial degradation, which was also the main removal pathway of sulfur regardless of pH condition. The removal and transformation of different substances in coexisting complex gases showed different characteristics in the LPB and NPB respectively.
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http://dx.doi.org/10.1007/s11356-021-12602-9DOI Listing
February 2021

Quantitative Single-Particle Fluorescence Imaging Elucidates Semiconductor Shell Influence on Ag@TiO Photocatalysis.

ACS Appl Mater Interfaces 2021 Feb 4;13(6):7680-7687. Epub 2021 Feb 4.

Department of Chemistry, Shanghai Stomatological Hospital, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China.

The understanding of the structure-reactivity relationship is helpful for the nanocatalyst (NC) design. However, though precisely parse, this information is challenging due to the heterogeneity of NCs and the complex mechanism of energetic charge carrier (e/h pairs) generation and transfer within the catalysts upon light irradiation. Here, the effect of the semiconductor shell on the photocatalytic redox reaction is probed at the single-Ag@TiO NC level with single-molecule imaging. By engineering the TiO shell thickness, catalytic activities of the NCs are precisely controlled and quantitatively measured to show a parabolic-like distribution with increasing TiO thickness. Besides, the varied activity among different NCs and the dynamic activity fluctuation of single NCs during continuous redox conversion are observed. Mathematical analysis indicates that the TiO layer affects the activity of the core-shell NCs by simultaneously affecting the fate of photo-induced e/h pairs and hot electrons generated at the Ag core. This work sheds light on molecular-scale elucidation of the impact of metal-semiconductor NC structures on their reactivities.
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http://dx.doi.org/10.1021/acsami.0c18508DOI Listing
February 2021

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats.

Front Pharmacol 2020 14;11:600953. Epub 2021 Jan 14.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.
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http://dx.doi.org/10.3389/fphar.2020.600953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841406PMC
January 2021

Development and functional characterization of novel fully human anti-CD19 chimeric antigen receptors for T-cell therapy.

J Cell Physiol 2021 Jan 11. Epub 2021 Jan 11.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Impressive outcomes have been achieved by chimeric antigen receptor (CAR)-T cell therapy using murine-derived single-chain variable fragment (scFv) FMC63 specific for CD19 in patients with B cell malignancies. However, evidence suggests that human anti-mouse immune responses might be responsible for poor persistence and dysfunction of CAR-T cells, leading to poor outcomes or early tumor recurrence. Substituting a fully human scFv for murine-derived scFv may address this clinically relevant concern. In this study, we discovered two human anti-CD19 scFv candidates through an optimized protein/cell alternative panning strategy and evaluated their function in CAR-T cells and CD19/CD3 bispecific antibody formats. The two clones exhibited excellent cytotoxicity in CAR-T cells and bispecific antibodies in vitro compared with the benchmarks FMC63 CAR-T cells and blinatumomab. Furthermore, Clone 78-BBz CAR-T cells exhibited similar in vivo antitumor activity to FMC63-BBz CAR-T cells. Our results indicate that Clone 78-BBz CAR has excellent efficacy and safety profile and is a good candidate for clinical development.
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http://dx.doi.org/10.1002/jcp.30267DOI Listing
January 2021

Objective Methods for Quantifying Color Retention and Bleeding Potential of a Lipstick Through Large-Scale Panel Perception and Controlled Usability Studies.

J Cosmet Sci 2020 Nov-Dec;71(6):399-410

Amway Innovation and Science, Ada, MI (D.Q.), (A.J.), Amway Innovation and Science - East Hub, Shanghai, 201203 China (J.L.).

Color retention and bleeding are two properties of lipstick performance which impact consumer acceptability and preference. Before now, the claims of long-wear and non-bleeding had yet to be meaningfully substantiated quantitatively. Lack of objectively defined parameters and measurement methods inhibits one's ability of obtaining adequate claims support. In this study, we designed a 30-member, controlled-usability study to develop methods that quantify color retention and bleeding potential. Image analysis methods were used to measure lip color properties at the time points of baseline, immediate after application, and 8 hours of wear. Large-scale panel perception studies were conducted to obtain consumer acceptability criteria and establish consumer relevance of the objectively measured parameters. Our results show that the methods developed can quantitatively describe the color properties. Eight hours after application, the mean levels of color retention and bleeding potential for this specific lip color were 82.67% and 2.43, respectively. The results of panel perception studies helped establish threshold values for lip color performance acceptability, that is, if a color retention level was lower than 82.7%, or a bleeding potential level was higher than 2.37, the performance would not be deemed acceptable. The methods and results reported here serve as a useful tool for the evaluation of lip color performance in future development of quality lip color formulations.
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January 2021

Down-Regulation of Lnc-CYP7A1-1 Rejuvenates Aged Human Mesenchymal Stem Cells to Improve Their Efficacy for Heart Repair Through SYNE1.

Front Cell Dev Biol 2020 19;8:600304. Epub 2020 Nov 19.

Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Background: Several long non-coding RNAs (lncRNAs) have been associated with cell senescence, termed senescence-associated lncRNAs (SAL-RNAs). However, the mechanisms involved for SAL-RNAs in aging are not fully elucidated. In the present study, we investigated the effects of SAL-RNAs on aged human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and the possible means to counteract such effects to improve the regenerative capacity of aged hBM-MSCs.

Methods: By comparing the lncRNAs expression of hBM-MSCs derived from young and old individuals, lnc-CYP7A1-1 was identified as being significantly increased with age. Using predictive software, the expression of Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1), was found to be decreased with age. Next, through lentiviral constructs, we downregulated the expression of lnc-CYP7A1-1 or SYNE1 in hBM-MSCs separately. Additionally, hBM-MSCs proliferation, survival, migration, and senescence were investigated , lnc-CYP7A1-1 downregulated aged hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI), and cardiac function was measured. Through lentivirus-mediated downregulation of lnc-CYP7A1-1 in aged hBM-MSCs, we revealed that cell senescence was decreased, whereas cell proliferation, migration, and survival were increased. On the other hand, downregulation of SYNE1, the target gene of lnc-CYP7A1-1, in young hBM-MSCs increased cell senescence, yet decreased cell proliferation, migration, and survival. Downregulation of lnc-CYP7A1-1 in aged hBM-MSCs induced cell rejuvenation, yet this effect was attenuated by repression of SYNE1. , transplantation of lnc-CYP7A1-1 downregulated old hBM-MSCs improved cardiac function after MI.

Conclusion: Down-regulation of lnc-CYP7A1-1 rejuvenated aged hBM-MSCs and improved cardiac function when implanted into the infarcted mouse hearts, possibly through its target gene SYNE1.
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http://dx.doi.org/10.3389/fcell.2020.600304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710953PMC
November 2020

sp. nov. (Hypocreales: Hypocreaceae) on sp. from Yunnan, PR China.

Biodivers Data J 2020 28;8:e53490. Epub 2020 Sep 28.

Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences Kunming China.

Background: is a large genus of fungicolous fungi, parasitising the fruiting bodies of Agaricales, Boletales, Helotiales, Pezizales and Polyporales. currently comprises of 147 species widely distributed in Australia, China, France, Germany, Italy, Japan, North America, Sri Lanka, Thailand and UK. Amongst them, 28 species have been recorded in China.

New Information: sp. nov., growing on the fruiting bodies of Russula sp. in subsect. Lactarioideae and collected from Yunnan, China, is described with illustrations and molecular phylogenetic data (combined ITS, LSU, - and RPB2 sequence dataset). The new species is characterised by semi-immersed to immersed perithecia and fusiform, apiculate and verrucose ascospores. We also review the species diversity of the genus in China.
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http://dx.doi.org/10.3897/BDJ.8.e53490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536245PMC
September 2020

Secure Deep Learning for Intelligent Terahertz Metamaterial Identification.

Sensors (Basel) 2020 Oct 5;20(19). Epub 2020 Oct 5.

School of Cyber Science and Technology, Beihang University, Beijing 100191, China.

Metamaterials, artificially engineered structures with extraordinary physical properties, offer multifaceted capabilities in interdisciplinary fields. To address the looming threat of stealthy monitoring, the detection and identification of metamaterials is the next research frontier but have not yet been explored. Here, we show that the crypto-oriented convolutional neural network (CNN) makes possible the secure intelligent detection of metamaterials in mixtures. Terahertz signals were encrypted by homomorphic encryption and the ciphertext was submitted to the CNN directly for results, which can only be decrypted by the data owner. The experimentally measured terahertz signals were augmented and further divided into training sets and test sets using 5-fold cross-validation. Experimental results illustrated that the model achieved an accuracy of 100% on the test sets, which highly outperformed humans and the traditional machine learning. The CNN took 9.6 s to inference on 92 encrypted test signals with homomorphic encryption backend. The proposed method with accuracy and security provides private preserving paradigm for artificial intelligence-based material identification.
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http://dx.doi.org/10.3390/s20195673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583053PMC
October 2020

The effect of microwave pretreatment on anaerobic co-digestion of sludge and food waste: Performance, kinetics and energy recovery.

Environ Res 2020 10 9;189:109856. Epub 2020 Jul 9.

Beijing Engineering Research Center of Sustainable Urban Sewage System Construction and Risk Control, Beijing University of Civil Engineering and Architecture, Beijing 100044, China; Key Laboratory of Urban Stormwater System and Water Environment, Ministry of Education, Beijing University of Civil Engineering and Architecture, Beijing 100044, China.

This paper studied the effect of microwave (MW) pretreatment on anaerobic co-digestion of sludge (SS) and food waste (FW). Using SS and FW as digestive substrates, the MW pretreatment method was used to determine the changes in the substrate matrix by means of batch anaerobic digestion at 37 °C. The kinetics of methane production were calculated, and the changes in organic matter during anaerobic co-digestion, the properties of the anaerobic-digested effluent, and the net energy output of the co-digestion system were determinated. The results showed that MW pretreatment was beneficial to the dissolution of organic matter, conversion of protein to NH-N, cumulative methane production, unit biomethane yield, and reaction rate of methane production in the SS and FW anaerobic co-digestion system. The highest cumulative methane production in the co-digestion system reached 3446.3 ± 172.3 mL (35 days), which was 19.93% higher than that of the control. Furthermore, MW pretreatment significantly increased the accumulation of VFAs and the content of butyric acid in the anaerobic-digested effluent, which was beneficial to the methanogenesis process. The MW pretreatment of all co-digested substrates produced a greater net energy output than the control, and the MW-SS + MW-FW group yielded the highest net energy output, which was 76.25 kJ/g Fed VS. The results indicated that MW pretreatment prior to SS and FW anaerobic co-digestion is an effective way to improve the anaerobic digestion efficiency and energy recovery rate.
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http://dx.doi.org/10.1016/j.envres.2020.109856DOI Listing
October 2020

Styrene removal with an acidic biofilter with four packing materials: Performance and fungal bioaerosol emissions.

Environ Res 2020 12 30;191:110154. Epub 2020 Aug 30.

Beijing Engineering Research Center of Sustainable Urban Sewage System Construction and Risk Control, Beijing University of Civil Engineering and Architecture, Beijing, 100044, China; Key Laboratory of Urban Stormwater System and Water Environment, Ministry of Education, Beijing University of Civil Engineering and Architecture, Beijing, 100044, China.

The packing material used in acidic biofilters (ABFs) has a significant impact on styrene removal. The bioaerosol emission was rarely considered when evaluating the packing materials in the ABFs. Four ABFs packed with ceramsite, compost, lava and polyurethane (PU) were developed and compared for their styrene removal and fungal bioaerosol emissions characteristics over 529 days. The removal efficiencies of styrene in the ABFs were higher under the condition of longer empty bed residence time (EBRT) and lower inlet concentration. The maximum styrene elimination capacities of the ABFs with ceramsite, compost, lava and PU were 74.57, 87.81, 67.13 and 101.88 g/m h, respectively. A lower pressure drop and the highest fungi count were observed in the ABF packed with PU. The emissions concentrations of fungal bioaerosols at the humidity of 63.5% were lower than those at a humidity of 42.7% and it increased with the air velocity. Additionally, the concentrations of fungal bioaerosols emitted from the ABFs packed with PU were 2168 ± 145-3661 ± 257 CFU/m, which was 33%-90% lower than those of the other three ABFs. The particle size distributions of the fungal bioaerosols emitted from the ABFs packed with PU and compost were mainly centered around large particles. Considering the removal of styrene and the fungal bioaerosols emissions, PU was the optimal packing material for ABF.
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http://dx.doi.org/10.1016/j.envres.2020.110154DOI Listing
December 2020

Artificial Aquaporin That Restores Wound Healing of Impaired Cells.

J Am Chem Soc 2020 09 3;142(37):15638-15643. Epub 2020 Sep 3.

Department of Chemistry, Fudan University, Shanghai, China.

Artificial aquaporins are synthetic molecules that mimic the structure and function of natural aquaporins (AQPs) in cell membranes. The development of artificial aquaporins would provide an alternative strategy for treatment of AQP-related diseases. In this report, an artificial aquaporin has been constructed from an amino-terminated tubular molecule, which operates in a unimolecular mechanism. The artificial channel can work in cell membranes with high water permeability and selectivity rivaling those of AQPs. Importantly, the channel can restore wound healing of the cells that contain function-lost AQPs.
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http://dx.doi.org/10.1021/jacs.0c00601DOI Listing
September 2020

Roles of estrogen receptor α and β in the regulation of proliferation in endometrial carcinoma.

Pathol Res Pract 2020 Oct 30;216(10):153149. Epub 2020 Jul 30.

Department of Obstetrics and Gynecology, Xuzhou Central Hospital, 199 Jiefang South Street, Xuzhou, Jiangsu 221004, P.R. China. Electronic address:

Endometrial carcinoma (EC), an estrogen-dependent gynecological malignancy, is prevalent worldwide. Estrogen receptor α (ERα) and estrogen receptor β (ERβ) are two main estrogen receptor isoforms, which mediate estrogen-induced proliferation in EC. However, the dynamic changes of ERα and ERβ subtype expression and their functions on proliferation in EC remain elusive. In this study, we aimed to investigate the expression of ERα and ERβ in para-tumor eutopic endometrium, endometrial atypical hyperplasia and EC by immunohistochemistry and then analyse their clinical significance. Subsequently, Ishikawa cells with ERα or ERβ knockdown by lentivirus transfection were used to explore the relationship between ERα/ERβ and cell proliferation, and preliminarily evaluate whether metformin's inhibitory effect on estrogen-induced cell proliferation was mediated by ERα and ERβ. We found that the expression of ERα and ERβ were markedly changed in endometrial hyperplasia and EC compared with that in para-tumor eutopic endometrium and exhibited different expression trends. Through further analysis, we discovered that ERα presented higher expression in endometrial atypical hyperplasia and early stage of EC than that in para-tumor eutopic endometrium, while the expression of ERβ gradually decreased from para-tumor eutopic endometrium to EC. Additionally, the cell cycle-related protein, CyclinD1 was gradually increased but p21 decreased. Furthermore, knockdown of ERα and ERβ severally in Ishikawa cells either inhibited or promoted estrogen-induced cell proliferation through regulating CyclinD1 and p21 expression. Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERα or ERβ. Altogether, ERα and ERβ have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation.
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http://dx.doi.org/10.1016/j.prp.2020.153149DOI Listing
October 2020

Simultaneous removal of bioaerosols, odors and volatile organic compounds from a wastewater treatment plant by a full-scale integrated reactor.

Process Saf Environ Prot 2020 Dec 4;144:2-14. Epub 2020 Jul 4.

Beijing Engineering Research Center of Sustainable Urban Sewage System Construction and Risk Control, Beijing University of Civil Engineering and Architecture, Beijing 100044, China.

Biological control of odors and bioaerosols in wastewater treatment plants (WWTPs) have gained more attention in recent years. The simultaneous removal of odors, volatile organic compounds (VOCs) and bioaerosols in each unit of a full-scale integrated-reactor (FIR) in a sludge dewatering room was investigated. The average removal efficiencies (REs) of odors, VOCs and bioaerosols were recorded as 98.5 %, 94.7 % and 86.4 %, respectively, at an inlet flow rate of 5760 m/h. The RE of each unit decreased, and the activated carbon adsorption zone (AZ) played a more important role as the inlet flow rate increased. The REs of hydrophilic compounds were higher than those of hydrophobic compounds. For bioaerosols, roughly 35 % of airborne heterotrophic bacteria (HB) was removed in the low-pH zone (LPZ) while over 30 % of total fungi (TF) was removed in the neutral-pH zone (NPZ). Most bioaerosols removed by the biofilter (BF) had a particle size larger than 4.7 μm while bioaerosols with small particle size were apt to be adsorbed by AZ. The microbial community in the BF changed significantly at different units. Health risks were found to be associated with HS rather than with bioaerosols at the FIR outlet.
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http://dx.doi.org/10.1016/j.psep.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341965PMC
December 2020

Identification of potential prognostic small nucleolar RNA biomarkers for predicting overall survival in patients with sarcoma.

Cancer Med 2020 10 11;9(19):7018-7033. Epub 2020 Aug 11.

Department of Reproductive Center, The Third Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Objective: The main purpose of the present study is to screen prognostic small nucleolar RNA (snoRNA) markers using the RNA-sequencing (RNA-seq) dataset of The Cancer Genome Atlas (TCGA) sarcoma cohort.

Methods: The sarcoma RNA-seq dataset comes from the TCGA cohort. A total of 257 sarcoma patients were included into the prognostic analysis. Multiple bioinformatics analysis methods for functional annotation of snoRNAs and screening of targeted drugs, including biological network gene ontology tool, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and connectivity map (CMap) are used.

Results: We had identified 15 snoRNAs that were significantly related to the prognosis of sarcoma and constructed a prognostic signature based on four prognostic snoRNA (U3, SNORA73B, SNORD46, and SNORA26) expression values. Functional annotation of these four snoRNAs by their co-expression genes suggests that some of them were closely related to cell cycle-related biological processes and tumor-related signaling pathways, such as Wnt, mitogen-activated protein kinase, target of rapamycin, and nuclear factor-kappa B signaling pathway. GSEA of the risk score suggests that high risk score phenotype was significantly enriched in cell cycle-related biological processes, protein SUMOylation, DNA replication, p53 binding, regulation of DNA repair, and DNA methylation, as well as Myc, Wnt, RB1, E2F, and TEL pathways. Then we also used the CMap online tool to screen five targeted drugs (rilmenidine, pizotifen, amiprilose, quipazine, and cinchonidine) for this risk score model in sarcoma.

Conclusion: Our study have identified 15 snoRNAs that may be serve as novel prognostic biomarkers for sarcoma, and constructed a prognostic signature based on four prognostic snoRNA expression values.
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http://dx.doi.org/10.1002/cam4.3361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541128PMC
October 2020

A novel Rauch-Tung-Streibel smoothing scheme based on the factor graph for autonomous underwater vehicles.

Rev Sci Instrum 2020 Jul;91(7):075109

School of Instrument Science and Engineering, Southeast University, Nanjing 210096, China.

In submarine surveying and mapping applications, a novel Rauch-Tung-Streibel smoothing (RTSS) scheme based on the factor graph for autonomous underwater vehicles is presented to gain a better offline navigation solution in this paper. The factor graph method is applied to optimally use observation information of multi-sensors with the asynchronous and short-term failure problems to overcome deficiencies of the federal Kalman filter in information fusion processing. Furthermore, the revised RTSS as a post-mission smoothing algorithm is performed by combining the results of the factor graph and one backward data processing through recursively updating the smoothed state and its covariance. From the simulation analysis, it is found that the factor graph mainly owns plug and play capability and contributes to the real-time navigation accuracy over the federal Kalman filtering. The RTSS provides better accuracy and smoothness for the position, velocity, and attitude at the same time compared to the corresponding real-time navigation solution, especially when signals are lost or sensors fail for a short time. With the best of both methods, a novel smoothing scheme combining the factor graph with the RTSS is built. Semi-physical experiment results verify the reliability and effectiveness of the proposed method.
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http://dx.doi.org/10.1063/5.0007538DOI Listing
July 2020

Ligand-bound glutamine binding protein assumes multiple metastable binding sites with different binding affinities.

Commun Biol 2020 Aug 3;3(1):419. Epub 2020 Aug 3.

Department of Chemistry, Institutes of Biomedical Sciences, Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, China.

Protein dynamics plays key roles in ligand binding. However, the microscopic description of conformational dynamics-coupled ligand binding remains a challenge. In this study, we integrate molecular dynamics simulations, Markov state model (MSM) analysis and experimental methods to characterize the conformational dynamics of ligand-bound glutamine binding protein (GlnBP). We show that ligand-bound GlnBP has high conformational flexibility and additional metastable binding sites, presenting a more complex energy landscape than the scenario in the absence of ligand. The diverse conformations of GlnBP demonstrate different binding affinities and entail complex transition kinetics, implicating a concerted ligand binding mechanism. Single molecule fluorescence resonance energy transfer measurements and mutagenesis experiments are performed to validate our MSM-derived structure ensemble as well as the binding mechanism. Collectively, our study provides deeper insights into the protein dynamics-coupled ligand binding, revealing an intricate regulatory network underlying the apparent binding affinity.
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http://dx.doi.org/10.1038/s42003-020-01149-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400645PMC
August 2020

Interspecies Interactions Between Streptococcus Mutans and Streptococcus Agalactiae .

Front Cell Infect Microbiol 2020 7;10:344. Epub 2020 Jul 7.

Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.

is an oral species closely associated with dental caries. As an early oral colonizer, utilizes interspecies coaggregation to promote the colonization of subsequent species and affect polymicrobial pathogenesis. Previous studies have confirmed several adhering partner species of , including and . In this study, we discovered new intergeneric co-adherence between and the saliva isolate (GBS-SI101). Research shows that GBS typically colonizes the human gastrointestinal and vaginal tracts. It is responsible for adverse pregnancy outcomes and life-threatening infections in neonates and immunocompromised people. Our results revealed that GtfB and GtfC of , which contributed to extracellular polysaccharide synthesis, promoted coaggregation of with GBS-SI101. In addition, oral streptococci, including and , barely inhibited the growth of GBS-SI101. This study indicated that could help GBS integrate into the associated oral polymicrobial community and become a resident species in the oral cavity, increasing the risk of oral infections.
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http://dx.doi.org/10.3389/fcimb.2020.00344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358462PMC
July 2020

Case report: one case of coronavirus disease 2019 (COVID-19) in a patient co-infected by HIV with a normal CD4 T cell count.

AIDS Res Ther 2020 07 23;17(1):46. Epub 2020 Jul 23.

Department of Critical care medicine of liver disease, Beijing You'an Hospital, Capital Medical University, Beijing, China.

Background: The COVID-19 has been a severe pandemic all around the world. Nowadays the patient with co-infection of HIV and SARS-CoV-2 was rarely reported. Here we reported a special case with HIV and SARS-CoV-2 co-infection, which showed a prolonged viral shedding duration.

Case Presentation: The patient was infected with HIV 8 years ago through sexual transmission and had the normal CD4T cell count. She was found SARS-CoV-2 positive using real-time Polymerase Chain Reaction (RT-PCR) during the epidemic. Most importantly, the patient had a prolonged viral shedding duration of SARS-CoV-2 about 28 days.

Conclusion: The viral shedding duration may be prolonged in people living with HIV. The 14 days isolation strategy might not be long enough for them. The isolation or discharge of these patients needs further confirmation for preventing epidemics.
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http://dx.doi.org/10.1186/s12981-020-00301-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376323PMC
July 2020

Synchronous primary pulmonary adenocarcinoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: A case report and literature review.

Medicine (Baltimore) 2020 Jul;99(29):e20865

Department of Pathology.

Rationale: Synchronous pulmonary lymphoma and carcinoma is relatively rare. And synchronous pulmonary lymphoma and adenocarcinoma in the same site is extremely rare.

Patient Concerns: We presented a 69-year-old female with a tumor mass in right upper lung.

Diagnosis: Pathological and immunohistochemical findings revealed lung adenocarcinoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Interventions: The patient received thoracoscopic guided right upper lobectomy and focal lymph node dissection after systemic anesthesia. Besides, 6 cycles of chemotherapy were given based on meprednisone, gemcitabine and cisplatin in local hospital.

Outcomes: In the 12-month follow-up, the patient was still alive with no local recurrence, metastasis and lymph node involvement.

Lesson: A comprehensive literature research was performed, and 6 cases of synchronous pulmonary lymphoma and adenocarcinoma in the same site and 10 cases in different sites were identified since 2000. Most patients with synchronous pulmonary lymphoma and carcinoma were middle-aged and elderly with the median age was 64 years presenting a male predisposition. The most frequent type of primary pulmonary lymphoma was B-cell non Hodgkin lymphoma, especially mucosa-associated lymphoid tissue lymphoma, and the lung cancer is predominantly adenocarcinoma.
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http://dx.doi.org/10.1097/MD.0000000000020865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373577PMC
July 2020