Publications by authors named "Zheng Cao"

279 Publications

Two naturally occurring mutations of human GPR103 define distinct G protein selection bias.

Biochim Biophys Acta Mol Cell Res 2021 Jun 17;1868(7):119046. Epub 2021 Apr 17.

Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address:

The neuropeptide 26RFa plays important roles in the regulation of many physiological functions. 26RFa has been recognized as an endogenous ligand for receptor GPR103. In the present study, we demonstrate that GPR103 dually couples to Gαq and Gαi/o proteins. However, two naturally occurring missense mutations were identified from a young male patient. In the first, Y68H, induction of Ca mobilization was noted without detection of ERK1/2 activation. In the second, R371W, the potential to activate ERK1/2 signaling was retained but with failure to evoke Ca mobilization. Further analysis provides evidence that Gαq, L-type Ca channel and PKCβI and βII are involved in the Y68H-mediated signaling pathway, whereas Gαi/o, Gβγ, and PKCζ are implicated in the R371W-induced signaling. Our results demonstrate that two point mutations, Y68H and R371W, affect the equilibrium between the different receptor conformations, leading to alteration of G protein-coupling preferences. Importantly, these findings provide a foundation for future elucidation of GPCR-mediated biased signaling and the physiological implications of their bias.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119046DOI Listing
June 2021

Changes in Maxillary Sinus Mucosal Thickening following the Extraction of Teeth with Advanced Periodontal Disease: A Retrospective Study Using Cone-Beam Computed Tomography.

Authors:
Zheng Cao Jie Yuan

Biomed Res Int 2021 23;2021:6688634. Epub 2021 Mar 23.

Dental Clinic of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.

Objectives: To explore the alterations in maxillary sinus mucosal thickening after extracting teeth with severe periodontal disease using cone-beam computed tomography (CBCT).

Methods: 30 patients with severe periodontal disease of maxillary posterior teeth that needed to be extracted and who were radiographically diagnosed with mucosal thickening (MT) in the maxillary sinus participated in the study. CBCT scans were taken before tooth extraction and 2-29 months after tooth extraction. The postextraction follow-up time was divided into two groups: group 1 (<4 months) and group 2 (≥4 months). Dimensions of maxillary sinus MT, including the MT zone length (SL) and the maximum thickness of the MT zone (ST), were evaluated preextraction and postextraction; the residual ridge height (RRH) was evaluated at the sites of extracted and nonextracted teeth.

Result: Of the 24 patients with unilateral tooth extraction, there was a statistically significant difference in MT between the extraction and nonextraction sides ( < 0.05). The RRH at the site of the extracted teeth was significantly lower than that of the nonextracted teeth ( < 0.05). MT decreased significantly after tooth extraction on the extraction side but not on the nonextraction side. There was no significant difference between group 1 and group 2 regarding the reduction in mucosal thickness over time.

Conclusions: Severe periodontitis can cause MT in the maxillary sinus. The RRH was lower at the sites of extracted teeth. MT reduced quickly by a thorough debridement after tooth extraction in 4 months. MT will not decrease further over time.
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http://dx.doi.org/10.1155/2021/6688634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009702PMC
March 2021

Preparation and Laser Marking Properties of Poly(propylene)/Molybdenum Sulfide Composite Materials.

ACS Omega 2021 Apr 25;6(13):9129-9140. Epub 2021 Mar 25.

School of Materials Engineering, Changshu Institute of Technology, Changshu, Jiangsu 215500, P. R. China.

In this study, using molybdenum sulfide (MoS) as laser-sensitive particles and poly(propylene) (PP) as the matrix resin, laser-markable PP/MoS composite materials with different MoS contents ranging from 0.005 to 0.2% were prepared by melt-blending. A comprehensive analysis of the laser marking performance of PP/MoS composites was carried out by controlling the content of laser additives, laser current intensity, and the scanning speed of laser marking. The color difference test shows that the best laser marking performance of the composite can be obtained at the MoS content of 0.02 wt %. The surface morphology of the PP/MoS composite material was observed after laser marking using a metallographic microscope, an optical microscope, and a scanning electron microscope (SEM). During the laser marking process, the laser energy was absorbed and converted into heat energy to cause high-temperature melting, pyrolysis, and carbonization of PP on the surface of the PP/MoS composite material. The black marking from carbonized materials was formed in contrast to the white matrix. Using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and Raman spectroscopy, the composite materials before and after laser marking were tested and characterized. The PP/MoS composite material was pyrolyzed to form amorphous carbonized materials. The effect of the laser-sensitive MoS additive on the mechanical properties of composite materials was investigated. The results show that the PP/MoS composite has the best laser marking property when the MoS loading content is 0.02 wt %, the laser marking current intensity is 11 A, and the laser marking speed is 800 mm/s, leading to a clear and high-contrast marking pattern.
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http://dx.doi.org/10.1021/acsomega.1c00255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028170PMC
April 2021

AFB-induced mice liver injury involves mitochondrial dysfunction mediated by mitochondrial biogenesis inhibition.

Ecotoxicol Environ Saf 2021 Apr 7;216:112213. Epub 2021 Apr 7.

Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

Aflatoxin B1 (AFB) pollutes foodstuffs and feeds, causing a food safety problem and seriously endangering human and animal health. Liver is the principal organ for AFB accumulation and biotransformation, during which AFB can cause acute and chronic liver damage, however, the specific mechanism is not completely clear. Mitochondria are the primary organelle of cellular bio-oxidation, providing 95% energy for liver to execute its multiple functions. Therefore, we speculated that mitochondrial dysfunction is involved in AFB-induced liver injury. To verify the hypothesis, a total of eighty healthy male mice were randomly divided into four groups on average, and exposed with 0, 0.375, 0.75 and 1.5 mg/kg body weight AFB by intragastric administration for 30 d. The results displayed that AFB triggered liver injury accompanied by oxidative stress. AFB exposure also damaged mitochondria structure, decreased mitochondrial membrane potential (MMP), as well as increased cytoplasmic cytochrome c (Cyt-c) protein expression, Bax, p53, Caspase-3/9 protein and/or mRNA expression levels and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling (TUNEL) staining positive cells in mice liver. Meanwhile, AFB exposure elevated pyruvate content, inhibited tricarboxylic acid (TCA) cycle rate-limiting enzymes and electron transport chain (ETC) complexes I-V activities, disturbed ETC complexes I-V subunits mRNA expression levels and reduced adenosine triphosphate (ATP) level in mice liver. These results indicated that AFB destroyed mitochondrial structure, activated mitochondrion-dependent apoptosis and induced mitochondrial dysfunction. In addition, AFB disrupted mitochondrial biogenesis, presented as the abnormalities of protein and/or gene expression levels of voltage dependent anion channel protein 1 (VDAC1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (Nrf1) and mitochondrial transcription factor A (Tfam). This may contribute to hepatic and mitochondrial lesions induced by AFB. These results provide a new perspective for elucidating the mechanisms of AFB hepatotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112213DOI Listing
April 2021

Gut Microbiota and Its Metabolite Deoxycholic Acid Contribute to Sucralose Consumption-Induced Nonalcoholic Fatty Liver Disease.

J Agric Food Chem 2021 Apr 23;69(13):3982-3991. Epub 2021 Mar 23.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan 430071, China.

As important signal metabolites within enterohepatic circulation, bile acids (BAs) play a pivotal role during the occurrence and development of diet-induced nonalcoholic fatty liver disease (NAFLD). Here, we evaluated the functional effects of BAs and gut microbiota contributing to sucralose consumption-induced NAFLD of mice. The results showed that sucralose consumption significantly upregulated the abundance of intestinal genera and , which produced deoxycholic acid (DCA) accumulating in multiple biological matrixes including feces, serum, and liver of mice. Subsequently, elevated hepatic DCA, one of the endogenous antagonists of the farnesol X receptor (), inhibited hepatic gene expression including a small heterodimer partner () and leading to sucralose-induced NAFLD in mice. Dietary supplements with fructo-oligosaccharide or metformin markedly restored genera and abundance and the DCA level of sucralose-consuming mice, which eventually ameliorated NAFLD. These findings highlighted the effects of gut microbiota and its metabolite DCA on sucralose-induced NAFLD of mice.
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http://dx.doi.org/10.1021/acs.jafc.0c07467DOI Listing
April 2021

Ultrasonic Osteotome Assisted Full-Endoscopic en Block Resection of Thoracic Ossified Ligamentum Flavum: Technical Note and 2 Years Follow-up.

Pain Physician 2021 Mar;24(2):E239-E248

Department of Orthopedic Surgery, the Fourth Medical Center of Chinese PLA General Hospital, Beijing, China.

Background: Conventional open laminectomy is considered to be the standard procedure for the treatment of thoracic ossified ligamentum flavum, but multi-segment thoracic laminectomy extensively removes the facet joints and ligamentous tissue, destroying the thoracic spine biomechanics and stability, may lead to delayed thoracic spine kyphosis deformities, which in turn can lead to potential neurological deterioration and local intractable pain.

Objective: To introduce the technical notes and clinical outcome of ultrasonic osteotome assisted full-endoscopic en block resection of thoracic ossified ligamentum flavum.

Study Design: A prospective cohort study.

Setting: Hospital and outpatient surgery center.

Methods: From January 2017 to March 2018, 15 patients with 1 - 2 segment thoracic ossified ligamentum flavum were treated with ultrasonic osteotome assisted full-endoscopic en block resection of thoracic ossified ligamentum flavum under local anesthesia. The magnetic resonance imaging and computed tomography of the thoracic spine was reexamined after the operation to evaluate the completeness of ossified ligamentum flavum resection and spinal cord decompression. The patients were followed up on the visual analog scale of back pain and radicular pain, Nurick score and mJOA score of neurological function, and Oswestry Disability Index at 1 week, 3 months, 6 months, one year, and 2 years after operation.

Results: All operations of 17 segments thoracic ossified ligamentum flavum in 15 patients were successfully completed without intraoperative conversion to open surgery. There were no intraoperative spinal cord injuries, dura tears, postoperative cerebrospinal fluid leakage, postoperative infections, and postoperative spinal cord injury aggravated symptoms. Postoperative thoracic spine magnetic resonance imaging and computed tomography examinations of all patients showed that the spinal cord was fully decompressed without any residual pressure. Back pain and radicular pain were relieved significantly, and spinal cord function (Nurick, mJOA, and Oswestry Disability Index scores) was obviously restored. The mJOA recovery rate at the 2-year follow-up was 78.3% in average.

Limitations: This is an observational cohort study with relative small sample and short-term follow-up.

Conclusions: Ultrasonic assisted full-endoscopic en block resection of ossified ligamentum flavum is a safe and effective minimally invasive spine surgery for thoracic myelography caused by thoracic ossified ligamentum flavum.
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March 2021

Ridership exceedance exposure risk: Novel indicators to assess PM health exposure of bike sharing riders.

Environ Res 2021 Mar 14;197:111020. Epub 2021 Mar 14.

School of Geographical Sciences and Remote Sensing, Guangzhou University, Guangzhou, 510006, China; Department of Urban Planning and Design, The University of Hong Kong, China.

Identifying the fine particulate matter (PM) exposure risk for bicycle riders is crucial for promoting the development of theory and technology in transportation-related air pollution assessment as well as urban health planning. Previous studies have employed daily mean PM concentrations and designed routes to evaluate air pollution exposure risk. However, because the daily mean PM concentrations cannot fully illustrate the intra-day variations in PM, which are typically higher than daily mean values, the adverse effects of PM concentrations remain underestimated. Moreover, the quantity and representativeness of monitoring samples make large spatial-scale and multi-temporal-scale analysis challenging. By defining hourly exceedance PM concentration and sharing bicycle rider data, two novel indicators were proposed in our study: exceedance exposure risk of PM for sharing bicycle riders (EPSR) and accumulative exceedance exposure risk of PM for sharing bicycle riders (AEPSR). Standard deviation ellipse analysis was conducted to investigate the multi-temporal variation of ESPR and AEPSR. A geographically weighted regression model was applied to quantify the relationship between city function zones and exceedance PM exposure risk for sharing bicycle riders. Results revealed that the mean values of EPSR and AEPSR during morning peak periods ranged between 0.109 min μg/m and 1.27 min μg/m and 6.83 min μg/m and 43.41 min μg/m, respectively, whereas the mean values of EPSR and AEPSR during evening peak periods ranged between 0.19 min μg/m and 4.28 min μg/m and 14.67 min μg/m and 357.66 min μg/m, respectively. This implied that sharing bicycle riders were exposed to higher PM-related risks during the evening than in the morning. When considering the accumulative effects, the average centers of the AEPSR moved to the north side as compared to the average centers of the EPSR. Expanding areas of EPSR shrunk by 20.25 km. This indicated that accumulative effects aggregated spatial clusters of exceedance PM exposure risk for sharing bicycle riders more tightly to the north of the study areas. Spatiotemporal variation of EPSR and AEPSR led us to investigate the mechanism behind this phenomenon. Spatial associations between city function zones and EPSR and AEPSR showed that sharing bicycle riders experienced more severe exceedance PM exposure risk around financial/corporations and leisure service areas, with R values of 0.33 and 0.35, respectively. This spatial association tended to be more significant during the evening peak periods. By developing two novel indicators, the increasing health threats for bicycle riders caused by exceedance PM were investigated in this study. The mechanism results should be included for developing mitigation strategies to alleviate the adverse effects of air pollution for public rider participators and achieving the goal of eco-health cities.
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http://dx.doi.org/10.1016/j.envres.2021.111020DOI Listing
March 2021

Construction of Self-Assembled Polyelectrolyte/Cationic Microgel Multilayers and Their Interaction with Anionic Dyes Using Quartz Crystal Microbalance and Atomic Force Microscopy.

ACS Omega 2021 Mar 15;6(8):5764-5774. Epub 2021 Feb 15.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, No. 53 Zhengzhou Road, Qingdao 266042, P. R. China.

This study aimed to reveal the interaction between self-assembled multilayers and dye molecules in the environment, which is closely related to the multilayers' stable performance and service life. In this work, the pH-responsive poly (-isopropylacrylamide--2-(dimethylamino) ethyl methacrylate) microgels were prepared by free-radical copolymerization and self-assembled with sodium alginate (SA) into multilayers by the layer-by-layer deposition method. Quartz crystal microbalance (QCM) and atomic force microscopy (AFM) results confirmed the construction of multilayers and the absorbed mass, resulting in a decrease in the frequency shift of the QCM sensor and the deposition of microgel particles on its surface. The interaction between the self-assembled SA/microgel multilayers and anionic dyes in the aqueous solution was further investigated by QCM, and it was found that the electrostatic attraction between dyes and microgels deposited on the QCM sensor surface was much larger than that of the microgels with SA in multilayers, leading to the release of the microgels from the self-assembled structure and a mass loss ratio of 27.6%. AFM observation of the multilayer morphology exposed to dyes showed that 29% of the microgels was peeled off, and the corresponding microgel imprints were generated on the surface. In contrast, the shape and size of the remaining self-assembled microgel particles did not change.
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http://dx.doi.org/10.1021/acsomega.0c06181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931438PMC
March 2021

Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice.

mSystems 2021 Feb 23;6(1). Epub 2021 Feb 23.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China

Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.
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http://dx.doi.org/10.1128/mSystems.00985-20DOI Listing
February 2021

Predictive values of various serum biomarkers in women with suspected preeclampsia: A prospective study.

J Clin Lab Anal 2021 Feb 22:e23740. Epub 2021 Feb 22.

Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Background: Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers.

Methods: The singleton pregnant women (20-36 gestational weeks) with PE-related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI-C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy-associated plasma protein-A2 (PAPP-A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc).

Results: Of the 196 recruited subjects, 25% (n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative (n = 147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc, and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%.

Conclusions: The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre-defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.
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http://dx.doi.org/10.1002/jcla.23740DOI Listing
February 2021

Bombyx neuropeptide G protein-coupled receptor A14 and A15 are two functional G protein-coupled receptors for CCHamide neuropeptides.

Insect Biochem Mol Biol 2021 Apr 11;131:103553. Epub 2021 Feb 11.

College of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, 212018, China. Electronic address:

CCHamides are newly identified insect neuropeptides, which are widely occurring in most insects. However, our knowledge about their signaling characteristics and physiological roles is still limited. Here, we cloned two full-length cDNAs encoding putative CCHamide receptors, Bombyx neuropeptide GPCR A14 (BNGR-A14) and -A15 (BNGR-A15), from the brain of B. mori larvae. Characterization of signaling indicated that Bombyx CCHamide-1 and CCHamide-2 are specific endogenous ligands for BNGR-A15 and BNGR-A14, respectively. Further functional assays combined with specific inhibitors demonstrated that upon activation by CCHamide-2, BNGR-A14 elicited significant increases in CRE-driven luciferase activity, intracellular Ca mobilization and ERK1/2 phosphorylation in a G inhibitor-sensitive manner, while BNGR-A15 was activated by CCHamide-1, thus leading to intracellular accumulation of cAMP, Ca mobilization, and ERK1/2 phosphorylation in a G and G inhibitor-sensitive manner. Based on these findings, we designated the receptors BNGR-A15 and -A14 as Bommo-CCHaR-1 and -2, respectively. In addition, our results showed that CCHamides are considered to require intrachain disulfide bonds to activate their respective receptor in the physiological concentration range. Moreover, quantitative RT-PCR analysis revealed that CCHamide-1 is more likely to serve as a brain-gut peptide to regulate feeding behavior and growth through BNGR-A15, whereas the CCHamide-2 signaling system might play an important role in the control of multiple physiological processes. Our findings provide in-depth information on CCHamide-1 and -2-mediated signaling, facilitating further elucidation of their endocrinological roles in the regulation of fundamental physiological processes.
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http://dx.doi.org/10.1016/j.ibmb.2021.103553DOI Listing
April 2021

Metabolomics safety assessments of microcystin exposure via drinking water in rats.

Ecotoxicol Environ Saf 2021 Apr 30;212:111989. Epub 2021 Jan 30.

CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China; Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China. Electronic address:

Drinking water exposure to microcystin-leucine-arginine (MC-LR), the most widely occurring cyanotoxins, poses a highly potential risk for human health. However, the health risk of MC-LR exposure at current guideline value in drinking water has not yet entirely evaluated. In the current study, we used H NMR-based metabolomics combined with targeted metabolic profiling by GC/LC-MS to explore the toxic effects of MC-LR exposure at environmentally relevant concentrations via drinking water in rats. The results revealed that multiple biological consequences of MC-LR exposure on host metabolism in rats. Both relatively low and high doses of MC-LR used here induced hepatic lipogenesis and inflammation. While only relatively high dose MC-LR (10 μg/L) in drinking water caused more metabolic disorders including inhibition of gluconeogenesis and promotion of β-oxidation of fatty acid. Although the dose of 1.0 μg/L MC-LR is extremely low for rats, alterations of metabolic profiles were unexpectedly found in rat liver and serum, alarming potential health risk of MC-LR at the WHO guideline level.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111989DOI Listing
April 2021

Mesenchymal Stem Cell-Laden Hydrogel Microfibers for Promoting Nerve Fiber Regeneration in Long-Distance Spinal Cord Transection Injury.

ACS Biomater Sci Eng 2020 02 30;6(2):1165-1175. Epub 2020 Jan 30.

Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration, and differentiation of stem cells after implantation represent major challenges toward the clinical deployment of this approach. In this study, we fabricated three-dimensional MSC-laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior, and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSC carrier though a rotating method and the aligned fiber structure induced the MSC-aligned adhesion on the surface of the hydrogel to form microscale cell fibers. The MSC-laden microfiber implantation enhanced the donor MSC neural differentiation, encouraged the migration of host neurons into the injury gap and significantly promoted nerve fiber regeneration across the injury site. Abundant GAP-43- and NF-positive nerve fibers were observed to regenerate in the caudal, rostral, and middle sites of the injury position 8 weeks after the surgery. The NF fiber density reached to 29 ± 6 per 0.25 mm at the middle site, 82 ± 13 per 0.25 mm at the adjacent caudal site, and 70 ± 23 at the adjacent rostral site. Similarly, motor axons labeled with 5-hydroxytryptamine were significantly regenerated in the injury gap, which was 122 ± 22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSC-laden microfibers significantly improved electrophysiological expression and re-established limb motor function. These findings highlight the combination of MSCs with microhydrogel fibers, the use of which may become a promising method for MSC implantation and SCI repair.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01557DOI Listing
February 2020

Aflatoxin B disrupts blood-testis barrier integrity by reducing junction protein and promoting apoptosis in mice testes.

Food Chem Toxicol 2021 Feb 6;148:111972. Epub 2021 Jan 6.

Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address:

Aflatoxin B (AFB) is an unavoidable food and environmental contaminant, which can lead to disorders in spermatogenesis and its mechanism remains unclear. The blood-testis barrier (BTB) is responsible for ensuring normal spermatogenesis in testes. Therefore, we hypothesized that disruption of the BTB was involved in AFB-induced spermatogenesis disorders. To confirm our hypothesis, male Kunming mice were orally gavaged AFB (0, 0.375, 0.75, or 1.5 mg/kg) for 30 days. Primarily, we first proved that AFB disrupted the BTB integrity. Then, AFB decreased BTB-related junction protein expression and elevated Sertoli cell apoptosis, which were associated with oxidative stress. Additionally, AFB upregulated the p-p38 MAPK/p38 MAPK ratio. These results collectively indicated that AFB disrupted the BTB via reducing the expression of BTB-related junction protein and promoting apoptosis in mice testes, which were associated with the oxidative stress-mediated p38 MAPK signaling pathway.
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http://dx.doi.org/10.1016/j.fct.2021.111972DOI Listing
February 2021

Short-Term Intake of Hesperetin-7--Glucoside Affects Fecal Microbiota and Host Metabolic Homeostasis in Mice.

J Agric Food Chem 2021 Feb 22;69(5):1478-1486. Epub 2020 Dec 22.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy of Precision Measurement Science and Technology, CAS, Wuhan 430071, China.

Hesperetin-7--glucoside (Hes-7-G) is a typical flavonoid monoglucoside isolated from Citri Reticulatae Pericarpium (CRP), which is commonly used as a food adjuvant and exhibits potential biological activities. To explore the interaction between Hes-7-G ingestion and microbiome and host metabolism, here, 16S rRNA gene sequencing was first used to analyze the alteration of fecal microbiome in mice after Hes-7-G intake. Metabolic homeostasis in mice was subsequently investigated using untargeted H NMR-based metabolomics and targeted metabolite profiling. We found that dietary Hes-7-G significantly regulated fecal microbiota and its derived metabolites, including short-chain fatty acids (SCFAs) and tryptophan metabolites (indole and its derivatives), in feces of mice. Regulation of microbiota was further confirmed by the significantly changed urinary hippurate and trimethylamine -oxide (TMAO), co-metabolites of the microbe and host. We also found that dietary Hes-7-G modulated the host tricarboxylic acid cycle (TCA) involved in energy metabolism. These findings suggested that Hes-7-G exhibits potential beneficial effects for human health.
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http://dx.doi.org/10.1021/acs.jafc.0c05921DOI Listing
February 2021

Prognostic immunohistochemical markers for small cell lung cancer: A review.

Pathol Res Pract 2021 Jan 4;217:153311. Epub 2020 Dec 4.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China; 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, 100021, PR China. Electronic address:

Background: Small Cell Lung Cancer (SCLC) is one of the most aggressive thoracic malignancies and has been very challenging in developing personalized medicine. While immunohistochemistry (IHC) markers have established role in pathology diagnosis of SCLC, it is particularly important to apply early and simple methods to effectively determine the prognosis. This study aimed to review and identify prognostic protein markers that have potential to be incorporated into clinical care for SCLC.

Methods: we systematically reviewed PubMed, Embase, Web of Science and Cochrane Library until October 19th, 2019 that reported prognostic IHC markers in SCLC. In this review, we focused on markers evaluated in at least two independent studies to compile the most forthcoming prognostic markers.

Results: According to their function in the tumor, including proliferation-related markers, growth suppression-related markers, invasion- and metastasis-related markers, apoptosis-related markers, angiogenesis-related markers, immune regulation-related markers. Extensive reports into informative tables based on sufficiencies of evidence were summarized as some easy-to-use literature reservoirs for further referring.

Conclusions: Strong evidence supports that the 24 emerging markers or their combinations may be useful in predicting prognosis, helping personalized therapy decision-making for SCLC patients.
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http://dx.doi.org/10.1016/j.prp.2020.153311DOI Listing
January 2021

Primary Hyperparathyroidism in Pregnancy: Insights From a Case of a 28-Year-Old Woman With Miscarriages and Hyperemesis Gravidarum.

Ann Lab Med 2021 05;41(3):336-338

Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.3343/alm.2021.41.3.336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748091PMC
May 2021

Insulin binding to the analytical antibody sandwich pair OXI-005 and HUI-018: Epitope mapping and binding properties.

Protein Sci 2021 Feb 15;30(2):485-496. Epub 2020 Dec 15.

Novo Nordisk A/S, Måløv, Denmark.

The insulin epitopes for two monoclonal antibodies (mAbs), OXI-005 and HUI-018, commonly used in combination for insulin concentration determination in sandwich assays, were determined using X-ray crystallography. The crystal structure of the HUI-018 Fab in complex with human insulin (HI) was determined and OXI-005 Fab crystal structures were determined in complex with HI and porcine insulin (PI) as well as on its own. The OXI-005 epitope comprises insulin residues 1,3,4,19-21 (A-chain) and 25-30 (B-chain) and for HUI-018 residues 7,8,10-14,17 (A-chain) and 5-7, 10, 14 (B-chain). The areas of insulin involved in interactions with the mAb are 20% (OXI-005) and 24% (HUI-018) of the total insulin surface. Based on the Fab complex crystal structures with the insulins a molecular model for simultaneous binding of the Fabs to PI was built and this model was validated by small angle X-ray scattering measurements for the ternary complex. The epitopes for the mAbs on insulin were found well separated from each other as expected from luminiscent oxygen channeling immunoassay results for different insulins (HI, PI, bovine insulin, DesB30 HI, insulin glargine, insulin lispro). The affinities of the OXI-005 and HUI-018 Fabs for HI, PI, and DesB30 HI were determined using surface plasmon resonance. The K s were found to be in the range of 1-4 nM for the HUI-018 Fab, while more different for the OXI-005 Fab (50 nM for HI, 20 nM for PI and 400 nM for DesB30 HI) supporting the importance of residue B30 for binding to OXI-005.
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http://dx.doi.org/10.1002/pro.4009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784758PMC
February 2021

Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles.

Biosci Rep 2021 Jan;41(1)

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The gut microbiota-host co-metabolites are good indicators for representing the cross-talk between host and gut microbiota in a bi-direct manner. There is increasing evidence that levels of aromatic amino acids (AAAs) are associated with the alteration of intestinal microbial community though the effects of long-term microbial disturbance remain unclear. Here we monitored the gut microbiota composition and host-microbiota co-metabolites AAA profiles of mice after gentamicin and ceftriaxone treatments for nearly 4 months since their weaning to reveal the relationship between host and microbiome in long- term microbial disturbances. The study was performed employing targeted LC-MS measurement of AAA-related metabolites and 16S RNA sequence of mice cecal contents. The results showed obvious decreased gut microbial diversity and decreased Firmicutes/Bacteroidetes ratio in the cecal contents after long-term antibiotics treatment. The accumulated AAA (tyrosine, phenylalanine and tryptophan) and re-distribution of their downstreaming metabolites that produced under the existence of intestinal flora were found in mice treated with antibiotics for 4 months. Our results suggested that the long-term antibiotic treatment significantly changed the composition of the gut microbiota and destroyed the homeostasis in the intestinal metabolism. And the urinary AAA could be an indicator for exploring interactions between host and gut microbiota.
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http://dx.doi.org/10.1042/BSR20203498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786327PMC
January 2021

Development and validation of an LC-MS/MS method for quantifying nine antimicrobials in human serum and its application to study the exposure of Chinese pregnant women to antimicrobials.

J Clin Lab Anal 2021 Mar 20;35(3):e23658. Epub 2020 Nov 20.

Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Background: To study the prevalence of the exposure of pregnant women to antimicrobials, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine nine antimicrobials, namely sulfadimidine, sulfapyridine, sulfadiazine, sulfathiazole, ofloxacin, ciprofloxacin, norfloxacin, tetracycline, and lincomycin, in human serum.

Methods: The sample preparation procedure included protein precipitation followed by a cleanup step with solid phase extraction (SPE). Separation was carried out using a CORTECS T3 column (100 × 2.1 mm, 2.7 µm) by gradient elution with a runtime of 8.0 min. Detection was performed on a triple quadruple tandem mass spectrometer with scheduled multiple reaction monitoring (sMRM) in positive ion scan mode.

Results: The calibration curves were linear over the concentration range of 0.5-50 ng/ml, and the limit of quantitation was between 0.01 and 0.2 ng/ml. For each level of quality control samples, the inter- and intra-assay precision values were less than 12.0%, and the accuracy ranged from 86.1% to 109.0%. No significant matrix effect or carryover was observed. The antimicrobials of interest were stable under all investigated conditions. The validated method was applied to analyze clinical samples from pregnant women in China, and 10 out of 500 samples showed the presence of antimicrobial residues. Moreover, compared with the time-resolved fluoro-immunoassay (TRFIA) method, the developed method showed greater sensitivity and specificity.

Conclusion: This study provides a simple and rapid LC-MS/MS method for the simultaneous measurement of nine antimicrobials in serum samples, which could be a useful tool in clinical utilization.
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http://dx.doi.org/10.1002/jcla.23658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958000PMC
March 2021

Benchmark Examination of Blood Amino Acids Patterns in Phenylketonuria Neonates and Young Children on Phenylalanine-Restricted Dietary Treatment.

Fetal Pediatr Pathol 2020 Nov 16:1-8. Epub 2020 Nov 16.

Department of Laboratory Medicine, Capital Medical University, Beijing Obstetrics and Gynecology Hospital, Beijing, China.

Background: Phenylalanine-restricted diets have been the basis of therapy for phenylketonuria; however, little is known how this treatment effects homeostasis of other amino acids. This study aimed to assess blood amino acid alterations in phenylketonuric neonates before and after treatment to identify any residual amino acid alterations with phenylalanine restriction in these treated children. Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry performed on dried blood spots. Elevated blood phenylalanine, arginine, citrulline, valine, methionine concentrations and decreased tyrosine, proline concentrations were observed in phenylketonuria neonates relative to controls, of which phenylalanine, arginine, methionine, tyrosine, and proline levels could be either partially or completely restored with dietary intervention, whereas citrulline and valine were not restored and remained higher. Blood amino acid homeostasis is disrupted in phenylketonuria. Although dietary intervention adjusts amino acid homeostasis in the direction of a healthy equilibrium, complete restoration is not achieved.
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http://dx.doi.org/10.1080/15513815.2020.1846647DOI Listing
November 2020

Laser irradiation method to prepare polyethylene porous fiber membrane with ultrahigh xylene gas filtration capacity.

J Hazard Mater 2021 Apr 9;407:124395. Epub 2020 Nov 9.

Key Laboratory of Advanced Civil Engineering Materials, School of Materials Science & Engineering, Tongji University, Shanghai 201804, China. Electronic address:

In recent years, volatile organic compound (VOC) gases have caused potential harm to people's health. This study reveals the preparation of polyethylene porous fiber membrane with excellent low-concentration VOCs filtration performance via laser irradiation technology. A neodymium-doped yttrium aluminum garnet (Nd:YAG) pulsed laser beam was used to scan the laser-sensitive low-density polyethylene/carbon black (LDPE/CB) fibers prepared by nanolayer coextrusion in the air. The controllable thermal energy generated by laser irradiation makes the surface of the fiber membrane to produce a porous carbon layer in situ. Laser power and scanning speed are important parameters for controlling laser-induced carbonization. The results indicate that the rich "fluffy" carbon structures on the surface of the porous fiber membrane can efficiently adsorb xylene gas. This study can provide a positive reference for the large-scale preparation of polyolefin porous fiber membrane with VOCs filtration by simple and efficient laser irradiation method.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124395DOI Listing
April 2021

Flexible multicamera calibration method with a rotating calibration plate.

Opt Express 2020 Oct;28(21):31397-31413

Camera calibration is necessary for accurate image measurements, particularly in multicamera systems. The calibration process involves corresponding the coordinates of 3D calibration points with a 2D image and requires the establishment of a reliable 3D world coordinate system. This paper presents a convenient multicamera calibration method that uses a rotating calibration plate and multi-view stereo vision to calculate 3D points and their relationship with the image coordinates. Despite simple implementation, the rotation of the calibration plate presents numerous calibration points from various planes, increasing the stability of the solution and the noise reduction. The relocation accuracy and reprojection error are experimentally verified.
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http://dx.doi.org/10.1364/OE.402761DOI Listing
October 2020

Bobath therapy is inferior to task-specific training and not superior to other interventions in improving lower limb activities after stroke: a systematic review.

J Physiother 2020 10 14;66(4):225-235. Epub 2020 Oct 14.

School of Health Sciences, University of Manchester, Manchester, UK.

Question: In adults with stroke, does Bobath therapy improve lower limb activity performance, strength or co-ordination when compared with no intervention or another intervention?

Design: Systematic review of randomised trials with meta-analyses.

Participants: Adults after stroke.

Intervention: Bobath therapy compared with another intervention or no intervention.

Outcome Measures: Lower limb activity performance (eg, sit to stand, walking, balance), lower limb strength and lower limb co-ordination. Trial quality was assessed using the PEDro scale.

Results: Twenty-two trials were included in the review and 17 in the meta-analyses. The methodological quality of the trials varied, with PEDro scale scores ranging from 2 to 8 out of 10. No trials compared Bobath therapy to no intervention. Meta-analyses estimated the effect of Bobath therapy on lower limb activities compared with other interventions, including: task-specific training (nine trials), combined interventions (four trials), proprioceptive neuromuscular facilitation (one trial) and strength training (two trials). The pooled data indicated that task-specific training has a moderately greater benefit on lower limb activities than Bobath therapy (SMD 0.48), although the true magnitude of the benefit may be substantially larger or smaller than this estimate (95% CI 0.01 to 0.95). Bobath therapy did not clearly improve lower limb activities more than a combined intervention (SMD -0.06, 95% CI -0.73 to 0.61) or strength training (SMD 0.35, 95% CI -0.37 to 1.08). In one study, Bobath therapy was more effective than proprioceptive neuromuscular facilitation for improving standing balance (SMD -1.40, 95% CI -1.92 to -0.88), but these interventions did not differ on any other outcomes. Bobath therapy did not improve strength or co-ordination more than other interventions.

Conclusions: Bobath therapy was inferior to task-specific training and not superior to other interventions, with the exception of proprioceptive neuromuscular facilitation. Prioritising Bobath therapy over other interventions is not supported by current evidence.

Registration: PROSPERO CRD42019112451.
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http://dx.doi.org/10.1016/j.jphys.2020.09.008DOI Listing
October 2020

Thromboelastography (TEG) in normal pregnancy and its diagnostic efficacy in patients with gestational hypertension, gestational diabetes mellitus, or preeclampsia.

J Clin Lab Anal 2021 Feb 17;35(2):e23623. Epub 2020 Oct 17.

Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Background: Thromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α-angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE).

Methods: With specified including and excluding criteria, non-pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory.

Results: The RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α-angle were 4.0-7.7, 1.2-3.2, 51.9-70.1, and 41.4-74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50).

Conclusions: Thromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.
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http://dx.doi.org/10.1002/jcla.23623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891543PMC
February 2021

[Application of quadriceps snip in complex total knee arthroplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Sep;34(9):1096-1100

Department of Orthopedics, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, P.R.China.

Objective: To explore the safety and effectiveness of quadriceps snip in complex total knee arthroplasty (TKA).

Methods: A clinical data of 19 cases (29 knees) with complex TKA assisted with quadriceps snip between January 2016 and May 2017 were retrospectively analyzed. There were 9 males (13 knees) and 10 females (16 knees). The age of patients ranged from 34 to 66 years (mean, 50.2 years). Four patients (8 knees) were ankylosing spondylitis, 5 patients (7 knees) were rheumatoid arthritis, and 10 patients (14 knees) were knee osteoarthritis. The average disease duration was 10.9 years (range, 8-15 years). There were 12 knees of Kellgren-Lawrence grade Ⅲ and 17 knees of Kellgren-Lawrence grade Ⅳ. The range of motion (ROM) of knee was (19.86±7.23)°. The clinical and function scores of knee society score (KSS) were 47.86±11.26 and 15.52±11.21, respectively. Postoperative complications, ROM, KSS scores, extensor lag, and prosthesis loosening were observed to evaluate the effectiveness.

Results: All incisions healed by first intention, and no infection or cardiovascular and cerebrovascular accidents occurred. All patients were followed up 25-39 months (mean, 30.3 months). At last follow-up, the ROM of knee was (91.03±7.30) °, the KSS clinical score was 83.62±9.99 and functional score was 66.38±7.89, showing significant differences when compared with preoperative ones ( <0.05). Postoperative extensor lag (10°, 10°, 15°) occurred in 3 cases. There was no evidence of prosthesis loosening or osteolysis on X-ray films during follow-up.

Conclusion: The application of quadriceps snip in complex TKA can effectively improve the operative field exposure and reduce incidence of complications such as patella tendon tearing, patella fracture, and quadriceps tendon injury. The surgical technique of Krackow tendon suture can effectively guarantee early rehabilitation without occurrence of other complications.
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http://dx.doi.org/10.7507/1002-1892.202001075DOI Listing
September 2020

An Antioxidant Enzyme Therapeutic for COVID-19.

Adv Mater 2020 Oct 13;32(43):e2004901. Epub 2020 Sep 13.

Department of Chemical and Biomolecular Engineering, Microbiology, Immunology and Molecular Genetics, and the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. Herein it is a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process, is reported. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.
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http://dx.doi.org/10.1002/adma.202004901DOI Listing
October 2020

Shear stress improves the endothelial progenitor cell function via the CXCR7/ERK pathway axis in the coronary artery disease cases.

BMC Cardiovasc Disord 2020 09 7;20(1):403. Epub 2020 Sep 7.

Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.

Background: Dysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients.

Methods: The human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR.

Result: Compared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs.

Conclusion: Up-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.
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http://dx.doi.org/10.1186/s12872-020-01681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487552PMC
September 2020

Elevating bioavailable iron levels in mitochondria suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila melanogaster.

Biochem Biophys Res Commun 2020 11 29;532(2):285-291. Epub 2020 Aug 29.

Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China. Electronic address:

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron deposit was found in the SNpc of PD patients and animal models, however, the mechanisms involved in disturbed iron metabolism remain unknown. Identifying the relationship between iron metabolism and PD is important for finding new therapeutic strategies. In this study, we found that transgenic overexpression (OE) of Drosophila mitoferrin (dmfrn) or knockdown of Fer3HCH significantly mitigated the reduced mitochondrial aconitase activity, abnormal wing posture, flight deficits and mitochondrial morphology defects associated with PINK1 loss-of-function (LOF). Further work demonstrated that dmfrn OE or Fer3HCH knockdown significantly rescued the impaired mitochondrial respiration in PINK1 LOF flies, indicating that dmfrn or Fer3HCH may rescue PINK1 LOF phenotypes through elevating mitochondrial bioavailable iron levels to promote mitochondrial respiration.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.002DOI Listing
November 2020

Neighborhood greenness associated with chronic obstructive pulmonary disease: A nationwide cross-sectional study in China.

Environ Int 2020 11 19;144:106042. Epub 2020 Aug 19.

National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Differential findings have been reported on the association between neighborhood greenness and chronic obstructive pulmonary disease (COPD). The underlying reasons might be the different types of vegetation and the diagnosis methods used in different studies. In this nationwide cross-sectional study in China, we examined the linkage between neighborhood greenness and COPD prevalence among 66,752 adults aged 40 years and above. Neighborhood greenness was estimated using the normalized difference vegetation index (NDVI) based on satellite imagery within buffers of 100, 300, 500, 1000, 2000, 3000 and 5000 m of residential community of the participants. COPD was defined according to the 2017 Global Initiative for Chronic Obstructive Lung Disease lung function criteria. A two-level logistic regression model was applied to estimate the associations. Finally, 9134 adults were classified as COPD. We observed significant positive associations between neighborhood greenness and COPD prevalence. The odds ratio for each interquartile range increase in NDVI within 100 m buffer was 1.08 (95% CI: 1.01, 1.15) after adjustment for potential confounders. Consistent associations were observed across all other NDVI buffer sizes. Stratified analyses revealed that younger adults (40-65 years) and urban residents might be the vulnerable subpopulations. Further regional analyses found that residents from the Northeastern and Northern China were more likely to have this association. Our results indicated that neighborhood greenness might be one risk factor of COPD prevalence. Our study have important public health implications for allocating the surrounding green spaces among living areas, especially for those with respiratory illness; however, the findings and the underlying mechanisms warrant further examinations in longitudinal settings.
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http://dx.doi.org/10.1016/j.envint.2020.106042DOI Listing
November 2020