Publications by authors named "Wen Zhang"

2,843 Publications

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Direct decoding of nonlinear OFDM-QAM signals using convolutional neural network.

Opt Express 2021 Apr;29(8):11591-11604

Nonlinear Fourier transform, as a technique that has a great potential to overcome the capacity limit in fibre optical communication system, faces speed and accuracy bottlenecks in practice. Machine learning using convolutional neural networks shows great potential in NFT-based applications. We have developed a convolutional neural network for decoding information in NFT-based communication and numerically demonstrated its performance in comparison to a fast NFT algorithm. The comparison indicates the potential of conventional neural network to replace NFT calculations for decoding of information.
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http://dx.doi.org/10.1364/OE.419609DOI Listing
April 2021

Surface Foliation Based Brain Morphometry Analysis.

Multimodal Brain Image Anal Math Found Comput Anat (2019) 2019 10;11846:186-195. Epub 2019 Oct 10.

Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.

Brain morphometry plays a fundamental role in neuroimaging research. In this work, we propose a novel method for brain surface morphometry analysis based on surface foliation theory. Given brain cortical surfaces with automatically extracted landmark curves, we first construct finite foliations on surfaces. A set of admissible curves and a height parameter for each loop are provided by users. The admissible curves cut the surface into a set of pairs of pants. A pants decomposition graph is then constructed. Strebel differential is obtained by computing a unique harmonic map from surface to pants decomposition graph. The critical trajectories of Strebel differential decompose the surface into topological cylinders. After conformally mapping those topological cylinders to standard cylinders, parameters of standard cylinders (height, circumference) are intrinsic geometric features of the original cortical surfaces and thus can be used for morphometry analysis purpose. In this work, we propose a set of novel surface features. To the best of our knowledge, this is the first work to make use of surface foliation theory for brain morphometry analysis. The features we computed are intrinsic and informative. The proposed method is rigorous, geometric, and automatic. Experimental results on classifying brain cortical surfaces between patients with Alzheimer's disease and healthy control subjects demonstrate the efficiency and efficacy of our method.
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http://dx.doi.org/10.1007/978-3-030-33226-6_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112249PMC
October 2019

Integrating Multimodal and Longitudinal Neuroimaging Data with Multi-Source Network Representation Learning.

Neuroinformatics 2021 May 12. Epub 2021 May 12.

School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, P.O. Box 878809, Tempe, AZ, 85287, USA.

Uncovering the complex network of the brain is of great interest to the field of neuroimaging. Mining from these rich datasets, scientists try to unveil the fundamental biological mechanisms in the human brain. However, neuroimaging data collected for constructing brain networks is generally costly, and thus extracting useful information from a limited sample size of brain networks is demanding. Currently, there are two common trends in neuroimaging data collection that could be exploited to gain more information: 1) multimodal data, and 2) longitudinal data. It has been shown that these two types of data provide complementary information. Nonetheless, it is challenging to learn brain network representations that can simultaneously capture network properties from multimodal as well as longitudinal datasets. Here we propose a general fusion framework for multi-source learning of brain networks - multimodal brain network fusion with longitudinal coupling (MMLC). In our framework, three layers of information are considered, including cross-sectional similarity, multimodal coupling, and longitudinal consistency. Specifically, we jointly factorize multimodal networks and construct a rotation-based constraint to couple network variance across time. We also adopt the consensus factorization as the group consistent pattern. Using two publicly available brain imaging datasets, we demonstrate that MMLC may better predict psychometric scores than some other state-of-the-art brain network representation learning algorithms. Additionally, the discovered significant brain regions are synergistic with previous literature. Our new approach may boost statistical power and sheds new light on neuroimaging network biomarkers for future psychometric prediction research by integrating longitudinal and multimodal neuroimaging data.
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http://dx.doi.org/10.1007/s12021-021-09523-wDOI Listing
May 2021

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene.

Sci Rep 2021 May 11;11(1):9971. Epub 2021 May 11.

Medical Laboratory, Shenzhen Prevention and Treatment Center for Occupational Diseases, 2019 Buxin Rd., Luohu district, Shenzhen, 518020, China.

Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P < 6.1 × 10). TRBV6-4 combination with TRBJ2-1, TRBJ2-2, TRBJ2-3, and TRBJ2-6, and TRBV7-9 combination with TRBJ2-1 were associated with the stage by OMDT severity (all P < 0.001). Ten CDR3-nt and 7 CDR3-aa sequences in TRBV7-9-TRBJ2-1 combination and 1 CDR3-nt and 1 CDR3-aa sequences in TRBV6-4-TRBJ2-1 combination were identified as associated with the severity of OMDT (all P < 0.001). We revealed further how TCR repertoires vary with the severity in the development of OMDT, and severity-related TCRs may provide important therapeutic targets for OMDT in clinical practice.
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http://dx.doi.org/10.1038/s41598-021-89431-wDOI Listing
May 2021

New insights into follicular helper T cell response and regulation in autoimmune pathogenesis.

Cell Mol Immunol 2021 May 10. Epub 2021 May 10.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong; Chongqing International Institute for Immunology, Hong Kong, China.

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http://dx.doi.org/10.1038/s41423-021-00688-7DOI Listing
May 2021

Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 May 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Some potent compounds were further evaluated to inhibit the proliferation of multiple myeloma (MM) cancer cell lines RPMI8226 and U266B. The results showed that some compounds were active against MM cancer cell lines with IC values of less than 50 nM. The microsomal metabolic stabilities in human, rat and mice species were carried out and the results showed that compounds 30 and 31 were stable enough to be in vivo investigated. The in vivo pharmacokinetic results showed that compounds 30 and 31 had acceptable biological parameters for both ig and iv administrations. In vivo antitumor activities of compounds 30 and 31 with the doses of 100 mg/kg and 50 mg/kg BIW were performed by using RPMI8226 xenograft nude mouse model. Toxicities of compounds 30 and 31 were not observed during the experiment and dose dependent effect was obvious and the tumor volume was greatly inhibited.
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http://dx.doi.org/10.1016/j.bmc.2021.116182DOI Listing
May 2021

Strain-Mediated Spin-Orbit Torque Enhancement in Pt/Co on Flexible Substrate.

ACS Nano 2021 May 10. Epub 2021 May 10.

School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.

Current-induced magnetization switching by spin-orbit torque generated in heavy metals offers an enticing realm for energy-efficient memory and logic devices. The spin Hall efficiency is a key parameter in describing the generation of spin current. Recent findings have reported enhancement of spin Hall efficiency by mechanical strain, but its origin remains elusive. Here, we demonstrate a 45% increase in spin Hall efficiency in the platinum/cobalt (Pt/Co) bilayer, of which 78% of the enhancement was preserved even after the strain was removed. Spin transparency and X-ray magnetic circular dichroism revealed that the enhancement was attributed to a bulk effect in the Pt layer. This was further confirmed by the linear relationship between the spin Hall efficiency and resistivity, which indicates an increase in skew-scattering. These findings shed light on the origin of enhancement and are promising in shaping future utilization of mechanical strain for energy-efficient devices.
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http://dx.doi.org/10.1021/acsnano.0c09404DOI Listing
May 2021

Immunosuppressive 9,10-Secosteroids from the Gorgonian Collected in the South China Sea.

J Nat Prod 2021 May 9. Epub 2021 May 9.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Gao-Ke Road, Hangzhou 311402, People's Republic of China.

Four new 9,10-secosteroids, verrucellols A-D (-), together with 12 known derivatives (-) were isolated from the gorgonian collected in the South China Sea. The structures of the new compounds were established by spectroscopic analysis and comparison with reported data. These compounds exhibited significant suppressive effects on CD4 T lymphocyte cell differentiation in an bioassay. This is the first report of 9,10-secosteroids exhibiting immunomodulation activity.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00200DOI Listing
May 2021

Multiple-heteroatom doped porous carbons from self-activation of lignosulfonate with melamine for high performance supercapacitors.

Int J Biol Macromol 2021 May 7;183:950-961. Epub 2021 May 7.

Key Laboratory of Bio-based Material Science and Technology, Ministry of Education, College of Materials Science and Engineering, Northeast Forestry University, Harbin, Heilongjiang 150040, China.

A facile synthesis strategy by combination self-activation of biomass materials with heteroatom dopant in one-step is developed to fabricate porous carbons (NO-PCMs) doping with N, O, and S elements from direct carbonization of sodium lignosulfonate and melamine mixture. Two different types of active defects are constructed simultaneously through the decomposition of sodium lignosulfonate in NO-PCMs, exhibiting hierarchical porosity and abundant heteroatoms contents. The typical NO-PCMs displayed high specific capacitance (300 F g at 0.1 A g) and outstanding cycling stability (99% capacitance retention after 10,000 charge/discharge cycles at 10 A g) in 6 M KOH electrolyte. Furthermore, the assembled symmetric supercapacitors exhibited high specific capacitance of 162 F g at 20 A g, 71% capacitance retention at current density up to 20 A g, and possessed high specific energy density of 21.6 Wh kg with an excellent power density of 92 W kg operated in the wide voltage range of 1.8 V in 1 M NaSO aqueous electrolyte, demonstrating the broad prospects of biomass/biowaste being used to prepare electrode materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.028DOI Listing
May 2021

Hepatic Arterioportal Fistula Is Associated with Decreased Future Liver Remnant Regeneration after Stage-I ALPPS for Hepatocellular Carcinoma.

J Gastrointest Surg 2021 May 7. Epub 2021 May 7.

Department of Hepatobiliary Surgery and Liver transplantation, the First Affiliated Hospital of Guangxi Medical University, Shuangrong Raod 6, Nanning, 530021, China.

Background: Hepatocellular carcinoma (HCC) patients often developed hepatic arterioportal fistula (APF). The aim of this study is to evaluate the impact of APF on future liver remnant (FLR) regeneration and surgical outcomes after the first stage of associating liver partition and portal vein ligation for staged hepatectomy (stage-I ALPPS).

Methods: Consecutive HCC patients who underwent ALPPS at our center between March 2017 and May 2019 were retrospectively studied. Data for the association between APF and clinicopathological details, liver volume, and surgical outcomes were analyzed.

Results: The enrolled 35 HCC patients were divided into three groups: 15 patients with preoperative APF were classified as the APF I group, 10 patients developed APF after stage-I ALPPS as the APF II group, whereas the other 10 patients without APF before and after stage-I ALPPS as the control group. After stage-I ALPPS, patients in the APF I and APF II groups had lower kinetic growth rate (KGR) of FLR volume (6.1±3.2%, 11.4±8.4%, 25.0±8.8% per week, respectively, P<0.001) and took longer median time to reach the sufficient FLR volume for stage-II ALPPS (17.5 days, 12 days, 6 days, respectively, P<0.001) than those in the control group. Meanwhile, the incidence of posthepatectomy liver failure (PHLF) in the APF I and APF II groups was significantly higher than that of the control group (P=0.007). There are 27 (77.1%) patients who completed stage-II ALPPS. The overall survival (OS) rates at 1 and 3 years were 59.3% and 35.1%, whereas the disease-free survival (DFS) rates at 1 and 3 years were 44.4% and 22.9%, respectively.

Conclusions: Hepatic APF is significantly associated with decreased FLR regeneration and a higher risk of PHLF after stage-I ALPPS. HCC patients who are to undergo ALPPS may benefit from the timely perioperative intervention of APF.
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http://dx.doi.org/10.1007/s11605-021-05022-0DOI Listing
May 2021

Direct Z-Scheme Heterojunction of Ligand-Free FAPbBr/α-FeO for Boosting Photocatalysis of CO Reduction Coupled with Water Oxidation.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

MOE International Joint Laboratory of Materials Microstructure, Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China.

Up to now, the majority of the developed photocatalytic CO reduction systems need to use expensive sacrificial reductants as electron source. It is still a huge challenge to drive the photocatalytic CO reduction using water as an electron source. Herein, we report a facile strategy for the construction of direct Z-scheme heterojunction of LF-FAPbBr/α-FeO, which is manufactured by the in situ and two-step controlled growth of ligand-free formamidinium lead bromide (LF-FAPbBr) nanocrystals on the surface of α-FeO nanorods. The matchable energy levels and direct contact between LF-FAPbBr and α-FeO significantly accelerate the interfacial charge transfer, with a charge separation efficiency (η) of 93%, much higher than that of 11% shown by the ligand-capped FAPbBr/α-FeO heterojunction. The resulting efficient separation and raised redox ability of photogenerated carriers endow the LF-FAPbBr/α-FeO heterojunction with an outstanding photocatalytic performance for CO reduction (to CO and CH) coupled with water oxidation (to O), achieving a highest electron consumption rate of 175.0 μmol g h among the reported metal halide perovskite-based photocatalysts, which are 5 and 11 times higher in comparison with those of sole LF-FAPbBr and ligand-capped FAPbBr/α-FeO, respectively.
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http://dx.doi.org/10.1021/acsami.1c01718DOI Listing
May 2021

Dose optimization based on pharmacokinetic/pharmacodynamic target of tigecycline.

J Glob Antimicrob Resist 2021 May 3. Epub 2021 May 3.

Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University; 324 Jingwu Road, Huaiyin District, Jinan, 250021, China; Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address:

Tigecycline, a new glycylcycline antibiotic, has a promising efficacy against a broad spectrum of microbials. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration, tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavorable outcomes correlate with inadequate drug exposure at the infective sites. A drug's pharmacokinetic/pharmacodynamic (PK/PD) profile plays an important role in predicting its antibiotic effect, which is determined as the ratio of area under the concentration curve (AUC) to minimum inhibitory concentration (MIC) for tigecycline. In this study, PK/PD targets based on infection sites, microbial isolates, and patient populations are discussed. Generally, a higher dosage of tigecycline for treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially decreasing the MIC values of multiple drug-resistant (MDR) bacteria.
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http://dx.doi.org/10.1016/j.jgar.2021.04.006DOI Listing
May 2021

Galectin-3 Mediated Inflammatory Response Contributes to Neurological Recovery by QiShenYiQi in Subacute Stroke Model.

Front Pharmacol 2021 19;12:588587. Epub 2021 Apr 19.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly regulating galectin-3 mediated inflammatory reaction.
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http://dx.doi.org/10.3389/fphar.2021.588587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089377PMC
April 2021

T cell membrane cloaking tumor microenvironment-responsive nanoparticles with a smart "membrane escape mechanism" for enhanced immune-chemotherapy of melanoma.

Biomater Sci 2021 May;9(9):3453-3464

College Pharmacy, Jiamusi University, 258 Xuefu Street, Jiamusi, Heilongjiang 154007, China.

The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment-responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)-disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) "antibody" to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a "membrane escape effect" and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.
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http://dx.doi.org/10.1039/d1bm00331cDOI Listing
May 2021

Discovery of Pyrrole-imidazole Polyamides as PD-L1 Expression Inhibitors and Their Anticancer Activity via Immune and Nonimmune Pathways.

J Med Chem 2021 May 5;64(9):6021-6036. Epub 2021 May 5.

Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.

In recent years, PD-1 immune checkpoint inhibitors based on monoclonal antibodies have revolutionized cancer therapy, but there still exist unresolved issues, such as the high cost, the relatively low response rates, and so on, compared with small-molecule drugs. Herein a type of pyrrole-imidazole (Py-Im) polyamide as a small-molecule DNA binder was designed and synthesized, which could competitively bind to the same double-stranded DNA stretch in the PD-L1 promoter region as the STAT3 binding site and thus downregulate PD-L1 expression. It was demonstrated that the Py-Im polyamides directly caused apoptosis in tumor cells and retarded cell migration in the absence of T cells through inhibiting the Akt/caspase-3 pathway. Also, in a coculture system, they enhanced the T-cell-mediated killing of tumor cells by the reversal of immune escape. Because such polyamides induced antitumor effects via both immune and nonimmune pathways, they could be further developed as promising PD-L1 gene-targeting antitumor drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00120DOI Listing
May 2021

Complications of thoracoscopic talc insufflation for the treatment of malignant pleural effusions: a meta-analysis.

J Cardiothorac Surg 2021 May 4;16(1):125. Epub 2021 May 4.

Department of Chest Surgery, The Fourth Medical Center of PLA General Hospital, No.51, Fucheng Road, Haidian District, Beijing, 100048, China.

Background: Talc pleurodesis is an effective treatment for malignant pleural effusions (MPEs). This study was designed to estimate complication rates of thoracoscopic talc insufflation.

Methods: Literature search was conducted in electronic databases and studies were selected if they reported complication rates of thoracoscopic talc insufflation in cancer patients with MPEs. Meta-analyses of proportions were performed to obtain incidence rates of complications.

Results: Twenty-six studies (4482 patients; age 62.9 years [95% confidence interval (CI): 61.5, 64.4]; 50% [95% CI: 43, 58] females) were included. Intraoperative, perioperative, 30-day, and 90-day mortality rates were 0% [95% CI: 0, 1], 2% [95% CI: 0, 4], 7% [95% CI: 3, 13] and 21% [95% CI: 5, 43] respectively. Incidence rates [95% CI] of various complications were: pain (20% [1, 2]), fever (14% [3, 4]), dyspnea (13% [5, 6]), pneumothorax (6% [7, 8]) pneumonia (4% [0, 12]), emphysema (3% [3, 7]), prolonged air leakage (3% [0, 7]), prolonged drainage (3% [9, 10]), thromboembolism (3% [9, 11]), lung injury (2% [7, 12]), respiratory insufficiency (2% [0, 5]), re-expansion pulmonary edema (1% [0, 3]), empyema (1% [0, 2]), respiratory failure (0% [0, 1]), and acute respiratory distress syndrome (ARDS; 0% [0, 1].

Conclusions: Whereas pain and fever were the most frequent complications of thoracoscopic talc insufflation, the incidence of ARDS was low. Pneumothorax, pneumonia, emphysema, prolonged air leakage, pulmonary embolism, arrythmia, re-expansion pulmonary edema, and empyema are important complications of thoracoscopic talc insufflation.
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http://dx.doi.org/10.1186/s13019-021-01475-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097876PMC
May 2021

The pleiotropic of GLP-1/GLP-1R axis in central nervous system diseases.

Int J Neurosci 2021 May 3:1-38. Epub 2021 May 3.

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

Glucagon-like peptide-1(GLP-1) is a multifunctional polypeptide throughout the lifespan via activating Glucagon-like peptide-1 receptor (GLP-1R).GLP-1 can affect food ingestion, enhance the secretion of insulin from pancreatic islets induced by glucose and be utilized to treat type 2 diabetes mellitus(T2DM).But, accumulating evidences from the decades suggest that activation GLP-1R can not only regulate the blood glucose, but also sustain the homeostasis of intracellular environment and protect neuron from various damaged responses such as oxidative stress, inflammation, excitotoxicity, ischemia and so on. And more and more pre-clinical and clinical studies identified that GLP-1 and its analogues may play a significant role in improving multiple central nervous system (CNS) diseases including neurodegenerative diseases, epilepsy, mental disorders, ischemic stroke, hemorrhagic stroke, traumatic brain injury, spinal cord injury, chronic pain, addictive disorders, other diseases neurological complications and so on. In order to better reveal the relationship between GLP-1/GLP-1R axis and the growth, development and survival of neurons, herein, this review is aimed to summarize the multi-function of GLP-1/GLP-1R axis in CNS diseases.
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http://dx.doi.org/10.1080/00207454.2021.1924707DOI Listing
May 2021

Blood lead, nutrient intake, and renal function among type 2 diabetic patients.

Environ Sci Pollut Res Int 2021 Apr 30. Epub 2021 Apr 30.

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Lead (Pb) exposure has been reported to have nephrotoxicity. However, such an effect has not been well investigated in type 2 diabetes (T2D) patients, especially when taking into account the nutrition status of the patients. Therefore, we explore the association between blood lead levels (BLLs), dietary intake of nutrients, and impaired renal function among patients with T2D. We measured BLLs and biochemical parameters of renal injury in 780 patients. Dietary nutrients intake was assessed by a food frequency questionnaire in 420 of 780 participants. We found high BLLs were significantly associated with certain parameters of renal injury, and dietary intake of specific nutrients (mainly micronutrients) was associated with reduced BLLs at high percentile distribution of concentration. BLLs were also found to have moderation effects on the association between specific dietary nutrients and specific renal function parameters.
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http://dx.doi.org/10.1007/s11356-021-13623-0DOI Listing
April 2021

Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases.

Sci Immunol 2021 Apr;6(58)

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.

Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate-induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)-mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.
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http://dx.doi.org/10.1126/sciimmunol.abe2933DOI Listing
April 2021

The Role of PD-1/PD-Ls in the Pathogenesis of IgG4-RD.

Rheumatology (Oxford) 2021 Apr 30. Epub 2021 Apr 30.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, China.

Objective: To investigate the role of Programmed cell death protein 1 (PD-1) and its two ligands PD-L1 and PD-L2 in the pathogenesis of IgG4-RD.

Methods: Patients with IgG4-RD (n = 43) as well as healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naive T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+Treg cells was detected by flow cytometry.

Results: The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells were increased in IgG4-RD patients. Plasma sPD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD RI and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naive T cells from IgG4-RD patients into CD4+CD25+Treg cells.

Conclusion: Plasma concentration of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells were upregulated. PD-1/PD-L1 can promote the differentiation of naive T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.
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http://dx.doi.org/10.1093/rheumatology/keab360DOI Listing
April 2021

Clinical features and risk factors of Raynaud's phenomenon in primary Sjögren's syndrome.

Clin Rheumatol 2021 Apr 29. Epub 2021 Apr 29.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China.

Objective: The aim at the current study was to investigate the clinical characteristics and risk factors of Raynaud's phenomenon (RP) in patients with primary Sjögren's syndrome (pSS).

Methods: Retrospective analysis of the medical records of 333 new-onset pSS patients was performed. Demographic, clinical, and serological data were compared between individuals with and without RP. Logistic regression analysis was used to identify risk factors.

Results: RP was present in 11.41% of the pSS patients. pSS-RP patients were younger (49.74±14.56 years vs. 54.46±13.20 years, p=0.04) and exhibited higher disease activity (11 [5.75-15] vs. 7 [4-12], p=0.03) than those without. The prevalence of lung involvement was significantly higher in pSS patients with RP (60.53% vs. 17.29%; p<0.001). A significantly higher proportion of patients with pSS-RP tested positive about antinuclear (ANA), anti-RNP, and anti-centromere antibodies (ACA) compared to those without (p=0.003, <0.001, and 0.01, respectively). Multivariate analysis identified lung involvement (odds ratio [OR]=8.81, 95% confidence interval [CI] 2.02-38.47; p=0.04), anti-RNP positive status (OR=79.41, 95% CI 12.57-501.78; p<0.0001), as well as ACA (OR=13.17, 95% CI 2.60-66.72; p=0.002) as prognostic factors for pSS-RP.

Conclusion: The presence of RP defined a subset of pSS with a unique phenotype, manifesting as increased lung involvement and a higher frequency of anti-RNP antibodies and ACA, as well as greater disease activity. These results suggest that RP has clinical and prognostic value of pSS patients. Further prospective studies with a larger number of subjects are warranted to confirm our findings and assess the prognostic and treatment implications of RP in pSS patients. Key Points • Raynaud's phenomenon (RP) was present in 38 (11.41%) of 333 patients with primary Sjögren's syndrome (pSS), with patients with RP exhibiting a younger age and higher disease activity. • The presence of RP indicates a subset of pSS with a unique phenotype, with manifestations including increased lung involvement and a higher frequency of anti-RNP antibodies and anti-centromere antibodies. • Patients with pSS and RP need close follow-up and long-term observation (including assessment of microangiopathy), with specific attention paid to the possible development of clinical features of systemic sclerosis.
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http://dx.doi.org/10.1007/s10067-021-05749-wDOI Listing
April 2021

Quantitative evaluation of mechanical stimulation for tissue-engineered blood vessels.

Tissue Eng Part C Methods 2021 Apr 29. Epub 2021 Apr 29.

Guangdong Provincial People's Hospital, 89346, Department of Cardiology, Guangzhou, Guangdong, China;

Functional small-diameter tissue engineered blood vessels (TEBVs) have been developed in-silico using biodegradable polymeric scaffolds under pulsatile perfusion. Accurate simulation of the physiological mechanical stimulation in vitro is a crucial factor in vascular engineering. However, little is known regarding the patterns of mechanical stimulation on silicone tubes. The aim of this study was to determine the optimal mechanical conditions required for inducing circumferential deformations in the silicone tubes during in vitro vascular development under pulsatile perfusion. To this end, we established a data acquisition (DAQ) system with laser micrometer and pressure transducers to evaluate the changes in the diameter of silicone tubing in response to pulsatile flow, and validated the results on cultured TEBVs. The DAQ system showed satisfactory reproducibility for measuring diameter variation in the in silico model. Furthermore, the hardness and thickness of the silicone tubes affected the mechanical conditioning on three-dimensional culture system under different working pressures, frequencies and circumferential deformations. We demonstrated a simple and reliable approach to quantify circumferential strain and deformations in order to ensure optimal mechanical stimulation of cultured TEBVs under pulsatile perfusion. Based on the results, we were able to dynamically culture dense, cellularized small-diameter TEBVs. This study highlights the importance of mechanical stimulation for vascular tissue engineering.
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http://dx.doi.org/10.1089/ten.TEC.2021.0007DOI Listing
April 2021

Isolating α-Pinene Ozonolysis Pathways Reveals New Insights into Peroxy Radical Chemistry and Secondary Organic Aerosol Formation.

Environ Sci Technol 2021 Apr 29. Epub 2021 Apr 29.

Department of Chemistry, University of California, Riverside, California 92521, United States.

α-Pinene ozonolysis is a key process that impacts the formation of new particles and secondary organic aerosol (SOA) in the atmosphere. The mechanistic understanding of this chemistry has been inconclusive despite extensive research, hindering accurate simulations of atmospheric processes. In this work, we examine the ozonolysis of two synthesized unsaturated carbonyl isomers (CHO) which separately produce the two Criegee intermediates (CIs) that would form simultaneously in α-pinene ozonolysis. Direct gas-phase measurements of peroxy radicals (RO) from flowtube ozonolysis experiments by an iodide-adduct chemical ionization mass spectrometer suggest that the initial CHO RO from the CI with a terminal methyl ketone undergo autoxidation 20-fold faster than the CI with a terminal aldehyde and always outcompete the bimolecular reactions under typical laboratory and atmospheric conditions. These results provide experimental constraints on the detailed RO autoxidation mechanisms for understanding new particle formation in the atmosphere. Further, isomer-resolved characterization of the SOA formed from a continuous-flow stirred tank reactor using ion mobility spectrometry mass spectrometry suggests that the two structurally different CIs predominantly and unexpectedly form constituents with identical structures. These results open up possibilities of diverse isomerization pathways that the two CIs may undergo that form mutual products to a large extent toward their way forming the SOA. This work highlights new insights into α-pinene ozonolysis pathways and call for future studies to uncover the detailed mechanisms.
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http://dx.doi.org/10.1021/acs.est.1c02107DOI Listing
April 2021

Combination of CT and telomerase-positive circulating tumor cells improves diagnosis of small pulmonary nodules.

JCI Insight 2021 Apr 27. Epub 2021 Apr 27.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Early diagnosis and treatment are key to the long-term survival of lung cancer patients. Although CT has significantly contributed to the early diagnosis of lung cancer, there are still consequences of excessive or delayed treatment. By improving the sensitivity and specificity of circulating tumour cell (CTC) detection, a new solution was proposed for differentiating benign from malignant pulmonary nodules.

Methods: In this study, we used telomerase reverse transcriptase-based CTC detection (TBCD) to distinguish benign from malignant pulmonary nodules <2 cm and compared this method with the pathological diagnosis as the gold standard. FlowSight and FISH were used to confirm the CTCs detected by TBCD.

Results: Our results suggest that CTCs based on TBCD can be used as an independent biomarker to distinguish benign from malignant nodules and are significantly superior to serum tumour markers. When the detection threshold was 1, the detection sensitivity and specificity of CTC diagnosis were 0.854 and 0.839, respectively. For pulmonary nodules ≦1 cm and 1-2 cm, the sensitivity and specificity of CTCs were both higher than 77%. Additionally, the diagnostic ability of CTC-assisted CT was compared by CT detection. The results showed that CT combined with CTCs could significantly improve the differentiation ability of benign and malignant nodules in lung nodules <2 cm, and the sensitivity and specificity could reach 0.899 and 0.839, respectively.

Conclusions: In conclusion, TBCD can effectively diagnose pulmonary nodules and be used as an effective auxiliary diagnostic scheme for CT diagnosis.

Funding: National Key Research and Development Project grants No. 2019YFC1315700 and No. 2017YFC1308702, CAMS Initiative for Innovative Medicine grants No. 2017-I2M-1-005, and National Natural Science Foundation of China grants No. 81472013.
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http://dx.doi.org/10.1172/jci.insight.148182DOI Listing
April 2021

Retrospective analysis of clinicopathological characteristics of 19 ovarian juvenile granulosa cell tumor cases.

J Obstet Gynaecol Res 2021 Apr 27. Epub 2021 Apr 27.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aim: To describe the clinical and pathological characteristics, diagnosis, treatment, and outcomes of juvenile granulosa cell tumor (JGCT).

Methods: We retrospectively analyzed the data of 19 patients with histopathologically confirmed juvenile granulosa cell tumors treated in two medical centers in Wuhan city of China between 1999 and 2019.

Results: Totally, 19 patients were included during the period. The median age at diagnosis was 8.25 years (range, 0.25-28 years). The most common clinical presentation was abdominal pain, five out of 10 prepubertal children presented with precocious puberty. Three patients underwent radical surgery (including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy), the other 16 patients had fertility-sparing surgery (cystectomy or ipsilateral salpingo-oophorectomy with or without omentectomy and lymphadenectomy). Eighteen patients had the international federation of gynecology and obstetrics (FIGO) stage I tumors, one patient had FIGO stage II disease. Twelve patients received postoperative adjuvant chemotherapy. The median follow-up time from the time of diagnosis was 35 months (range, 13-250 months). One patient experienced relapse and died of the disease 32 months after the initial diagnosis. Eighteen patients were alive and had not experienced recurrence during the follow-up period. The reproductive age patients that received fertility-sparing surgery had regular menstruation.

Conclusions: A majority of JGCTs are diagnosed as FIGO stage I tumors and have favorable clinical outcomes. Adjuvant chemotherapy seems to improve outcomes for patients with advanced-stage JGCTs; however, the value of chemotherapy in stage Ic patients is still unknown. Fertility sparing surgery should be considered in young patients who wish to bear children.
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http://dx.doi.org/10.1111/jog.14805DOI Listing
April 2021

Severe Case of Rickettsiosis Identified by Metagenomic Sequencing, China.

Emerg Infect Dis 2021 May;27(5):1530-1532

A case of Rickettsia sibirica subspecies sibirica BJ-90 infection in China was identified by metagenomic analysis of an eschar biopsy specimen and confirmed by nested PCR. Seroprevalence of spotted fever group Rickettsia was ≈17.4% among the local population. This report highlights the threat of rickettsioses to public health in the Qinghai-Tibet Plateau.
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http://dx.doi.org/10.3201/eid2705.203265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084477PMC
May 2021

Environmental implications of reduced electricity consumption in Wuhan during COVID-19 outbreak: A brief study.

Environ Technol Innov 2021 Aug 20;23:101578. Epub 2021 Apr 20.

Heze Branch, Qilu University of Technology (Shandong Academy of Sciences), Biological Engineering Technology Innovation Center of Shandong Province, Heze, 274000, China.

Due to the COVID-19 outbreak, Wuhan was locked down from 23 January 2020 to 8 April 2020, a total of 76 days. It is well known that the electricity consumption is a direct reflection of human activity. During the lockdown of Wuhan, most of human activities were forbidden. The reduction in human activity would inevitably lead to a reduction in electricity consumption. At the same time, anthropogenic emissions of air pollutants would also be reduced with the reduction of human activity. In this study, the correlation between electricity consumption and air pollutants during lockdown was discussed in detail. The result showed that the drop in pollutants concentrations in January should be attributed to the washout effect of rainfall rather than the lockdown. The decrease of electricity consumption in the secondary industry might play a significant role on the decrease of PM and NO concentrations in Wuhan in February 2020. The decrease in NO concentration in March should be attributed to the reduction of pollutants emissions from the tertiary industry, which means that more attention should be paid to the control of NO emission in the tertiary industry. Due to reduced emissions from local sources, the role of long-range transport sources might be more significant during the lockdown of Wuhan. By PSCF analysis, southeast of Wuhan could be the major potential emission sources of PM , especially in the northern part of Jiangxi province. It was suggested that stricter regulation of pollutants emissions should be implemented in this area.
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http://dx.doi.org/10.1016/j.eti.2021.101578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056989PMC
August 2021

Point-of-care ultrasound for the early diagnosis of emphysematous pyelonephritis: A case report and literature review.

World J Clin Cases 2021 Apr;9(11):2584-2594

Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China.

Background: Emphysematous pyelonephritis (EPN) is a rare but fatal necrotic infection of the kidney, which usually leads to septic shock. Therefore, early diagnosis and optimized therapy are of paramount importance. In the past two decades, point-of-care ultrasound (POCUS) has been widely used in clinical practice, especially in emergency and critical care settings, and helps to rapidly identify the source of infection in sepsis. We report a rare case in which a "falls" sign on POCUS played a pivotal role in the early diagnosis of EPN.

Case Summary: A 57-year-old man presented with fever and lumbago for 3 d prior to admission. He went to the emergency room, and the initial POCUS detected gas bubbles in the hepatorenal space showing a hyperechoic focus with dirty shadowing and comet-tail artifacts. This imaging feature was like a mini waterfall. His blood and urine culture demonstrated bacteremia, and EPN associated with septic shock was diagnosed. The patient did not respond to broad-spectrum antibiotic treatment and a perirenal abscess developed. He subsequently underwent computed tomography-guided percutaneous catheter drainage, and fully recovered. We also review the literature on the sonographic features of POCUS in EPN.

Conclusion: This case indicates that a "falls" sign on POCUS facilitates the rapid diagnosis of severe EPN at the bedside.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040185PMC
April 2021

Metabolites in the association between early-life famine exposure and type 2 diabetes in adulthood over a 5-year follow-up period.

BMJ Open Diabetes Res Care 2021 Apr;9(1)

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Introduction: Exposure to malnutrition in early life has been found to significantly elevate type 2 diabetes risk in adulthood. However, the changes in metabolites resulting from malnutrition in early life have not been studied. The aim of this study was to identify metabolites with levels associated with type 2 diabetes resulting from exposure to China's Great Famine (1959-1962).

Research Design And Methods: Participants were from SPECT-China 2014 and SPECT-China2 2019, two cross-sectional studies performed at the same site. In total, 2171 subjects participated in SPECT-China and SPECT-China2 simultaneously. The sample size of fetal-exposed (1959-1962) versus non-exposed (1963-1974) individuals was 82 vs 79 in 2014 and 97 vs 94 in 2019. Metabolomic profiling was performed between famine-exposed and non-exposed groups.

Results: Among the different famine exposure groups, the fetal-exposed group (1959-1962) had the greatest incidence rate (12.5%), with an OR of 2.11 (95% CI 1.01 to 4.44), compared with the non-exposed group (1963-1974). Moreover, compared with those in the non-exposed group (1963-1974), four metabolites (indole-3-carbinol (I3C), phosphatidylcholine (PC) (22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:1(9Z)), pyrimidine, and PC(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z))) showed significantly lower relative intensities in the famine and diabetes groups both in 2014 and 2019. Pyrimidine significantly mediated the association of famine exposure with diabetes, and I3C marginally mediated this association.

Conclusions: Famine exposure in the fetal period could increase type 2 diabetes risk in adults, even those in their 60s. I3C and pyrimidine are potential mediators of the effects of famine exposure on diabetes development.
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http://dx.doi.org/10.1136/bmjdrc-2020-001935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070877PMC
April 2021

Alisol A 24-acetate stimulates lipolysis in 3 T3-L1 adipocytes.

BMC Complement Med Ther 2021 Apr 22;21(1):128. Epub 2021 Apr 22.

School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Background: Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells.

Methods: We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis.

Results: AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A.

Conclusions: Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.
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http://dx.doi.org/10.1186/s12906-021-03296-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063434PMC
April 2021