Publications by authors named "Qingqing Wu"

165 Publications

Aortic dissection during pregnancy and postpartum.

J Card Surg 2021 Apr 29. Epub 2021 Apr 29.

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

Background: Patients with aortic dissection during pregnancy and postpartum period exhibit a high mortality. At present, a complete overview of aortic dissection during pregnancy and postpartum period is lacking. ​Methods: This systematic review included 80 reports published from 2000 to 2020, comprising a total study population of 103 patients with aortic dissection. ​Results: We found that Stanford Type A aortic dissection was more common in prepartum cases, especially in the third trimester, while postpartum cases of aortic dissection were more common in Stanford Type B. The most common risk factor was connective tissue disease, with no other known risk factors. The mode of delivery had no significant effect on the type of postpartum aortic dissection. Reduced maternal and fetal mortality was observed when patients with Stanford Type A aortic dissection occurring after 28 gestational weeks underwent cesarean section followed by aortic replacement. Patients with Stanford Type B aortic dissection were treated mainly with medication and/or endovascular repair. ​Conclusion: Contemporary management of patients during pregnancy and within 12 weeks postpartum requires multidisciplinary cooperation and includes serial, noninvasive imaging, biomarker testing, and genetic risk profiling for aortopathy. Early diagnosis and accurate treatment are essential to reduce maternal and fetal mortality.
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http://dx.doi.org/10.1111/jocs.15575DOI Listing
April 2021

Necrotizing funisitis and calcification of umbilical vein: case report and review.

BMC Pregnancy Childbirth 2021 Apr 12;21(1):296. Epub 2021 Apr 12.

Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yaojiayuan Road, Beijing, 100026, China.

Background: Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF is characterized by yellow-white bands running parallel to the umbilical blood vessels. These bands consist of inflammatory cells, necrotic debris, and calcium deposits. Calcification is visible in ultrasonography, which makes it possible to suspect NF when umbilical vascular wall calcification is detected by prenatal ultrasonography.

Case Presentation: Ultrasonography revealed calcification of the umbilical venous wall in an expectant 31-year-old woman who was gravida 1, para 0. The woman required emergency cesarean section because of fetal distress and suspected umbilical cord torsion at 31 weeks gestation. The root of the umbilical cord was quite fragile and broke during the operation. The pathological results on the placenta showed histologic chorioamnionitis and NF. The infant was diagnosed to have neonatal sepsis and acidosis after delivery but was discharged without severe complications after a one-month hospitalization that included antibiotic and supportive therapy.

Conclusion: NF is a rare and severe inflammation of the umbilical cord. Umbilical vascular wall calcification discovered in prenatal ultrasonography is diagnostically helpful.
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http://dx.doi.org/10.1186/s12884-021-03743-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042875PMC
April 2021

Plasma glycerophospholipid profile, erythrocyte n-3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women.

Am J Clin Nutr 2021 Apr 7. Epub 2021 Apr 7.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Background: Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce.

Objectives: We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort.

Methods: A total of 1243 community-dwelling Chinese aged 50-70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.

Results: After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16-1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n-3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05].

Conclusions: Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.
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http://dx.doi.org/10.1093/ajcn/nqab050DOI Listing
April 2021

The distorted power of medical surgical masks for changing the human thermal psychology of indoor personnel in summer.

Indoor Air 2021 Apr 5. Epub 2021 Apr 5.

School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai, China.

The medical surgical mask (MSM) has been the essential protective equipment in people's daily work. The experimental purpose is to explore the effects of wearing MSM on human thermal sensation, thermal comfort, and breathing comfort in office buildings in summer. A total of 30 healthy college students were recruited for the testing. The experiment was carried out in a climate chamber, which can simulate the office buildings in summer. The experiment collects the subjects' skin temperature, microclimate in the mask, and subjective votes, including thermal sensory votes (TSV), thermal comfort votes (TCV), and respiratory comfort votes (BCV). Experimental results show that wearing MSM has no significant effect on the skin temperature of the human body. The microclimate temperature inside the MSM reaches over 34℃, and the relative humidity reaches over 70%. The high-temperature and high-humidity microclimate put human beings in an uneven thermal environment, which leads to poor human tolerance to the thermal environment and becomes the main reason for destroying human thermal comfort. Wearing MSM has a significant impact on the subjective thermal sensation, thermal comfort, and breathing comfort of the human body, and the impact becomes more significant as the environmental temperature increases. Once the mask is taken off, the human body will enter an extremely comfortable environment, resulting in an excessively high vote value. The difference in voting values before and after removing the mask becomes larger with the environmental temperature. By fitting the voting results and perform data processing, it can be found that wearing MSM will reduce the neutral temperature by 1.5°C, and the environmental temperature with the optimal thermal comfort by 1.4°C, and as the temperature increases, the respiratory discomfort will become more and more intense. Regardless of whether wearing a MSM, the subjects preferred a slight warmer environment. In conclusion, with the increase of ambient temperature, wearing MSM can cause the human worse tolerance to the thermal environment, and this disturbance will become more and more intense.
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http://dx.doi.org/10.1111/ina.12830DOI Listing
April 2021

Establishment of interleukin-18 time-resolved fluorescence immunoassay and its preliminary application in liver disease.

J Clin Lab Anal 2021 Mar 15:e23758. Epub 2021 Mar 15.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.

Background: To establish a time-resolved fluorescence immunoassay of interleukin (IL)-18 (IL-18-TRFIA) and detect its concentration in different liver disease serum samples.

Methods: The IL-18 coating antibody and the Eu -labeled detection antibody were used for the IL-18-TRFIA to detect serum IL-18 concentration in patients with liver cancer, hepatitis B, hepatitis C, autoimmune hepatitis, fatty liver disease, and healthy controls. The double-antibody sandwich method was used and methodological evaluation was performed.

Results: The average intra- and inter-assay coefficient of variation for IL-18-TRFIA was 4.80% and 5.90%, respectively. The average recovery rate was 106.19 ± 3.44%. The sensitivity (10.96 pg/mL) was higher than that obtained using the ELISA method (62.5 pg/mL). The detection range was 10.96-1000 pg/mL. IL-6 and galectin-3 did not cross-react with IL-18-TRFIA. The serum concentration of IL-18 was (776.99; 653.48-952.39 pg/mL) in hepatitis C, (911; 775.55-1130.03 pg/mL) in fatty liver, (1048.88; 730.04-1185.10 pg/mL) in liver cancer, and (949.12; 723.70-1160.28 pg/mL) in hepatitis B. Moreover, IL-18 serum levels were significantly higher in patients than the healthy controls (483.09; 402.52-599.70/mL) (p < 0.0001). Autoimmune hepatitis with a serum IL-18 concentration of 571.62; 502.47-730.31 pg/mL was not significantly different from the healthy controls (p > 0.05).

Conclusion: We established a highly sensitive IL-18-TRFIA method that successfully detected serum IL-18 concentrations in different liver diseases. Furthermore, IL-18 serum concentration was higher in patients with liver cancer, hepatitis C, hepatitis B, and fatty liver disease compared to healthy controls.
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http://dx.doi.org/10.1002/jcla.23758DOI Listing
March 2021

Circulating Glycerolipids, Fatty Liver Index and Incidence of Type 2 Diabetes: A Prospective Study among Chinese.

J Clin Endocrinol Metab 2021 Mar 12. Epub 2021 Mar 12.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Context: Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the glycerolipids-T2D associations.

Objective: We aimed to assess associations between plasma glycerolipids and incident T2D, and explore a potential role of liver fat accumulation in the associations.

Design: A prospective cohort study with 6-year of follow-up.

Participants: This work included 1,781 Chinese aged 50-70 years.

Main Outcome Measures: T2D.

Results: At 6-year resurvey, 463 participants developed T2D. At the false-discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs)(16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs)(46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% confidence intervals [CIs]) ranging from 1.16 (1.05 to 1.27) to 1.23 (1.11 to 1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index (FLI) largely attenuated these findings (RRs [95% CIs] were 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the FLI explained 12%-28% glycerolipids-T2D associations (all p < 0.01).

Conclusions: Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.
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http://dx.doi.org/10.1210/clinem/dgab165DOI Listing
March 2021

Inhibition of 5-lipoxygenase is associated with downregulation of the leukotriene B4 receptor 1/ Interleukin-12p35 pathway and ameliorates sepsis-induced myocardial injury.

Free Radic Biol Med 2021 Apr 9;166:348-357. Epub 2021 Mar 9.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China. Electronic address:

Sepsis rapidly contributed to multiorgan failure affecting most commonly of the cardiovascular and respiratory systems and yet there were no effective therapies. The current study aimed at providing evidence on the cardioprotection of suppression of 5-Lipoxygenase (5-Lox) and identifying the possible mechanism in the mouse model of sepsis. The cecal ligation-perforation (CLP) model was applied to C57BL/6 wild-type (WT) and 5-Lox deficient (5-Lox) mice to induce sepsis. 5-Lox expression was up-regulated in mouse myocardium and leukotriene B4 (LTB4) level was increased in serum after sepsis. Subsequently, we utilized a recombinant adenoviral expression vector (rAAV9) to overexpress Alox5 gene in adult mice. Compared to WT mice, 5-Lox overexpression accelerated CLP-induced myocardial injury and cardiac dysfunction. Oppositely, 5-Lox deficiency offered protection against myocardial injury in a mouse model of sepsis and attenuated sepsis-mediated inflammation, oxidative stress and apoptosis in the mouse heart. Mechanically, 5-Lox promoted LTB4 production, which in turn contributed to the activation of leukotriene B4 receptor 1 (BLT1)/interleukin-12p35 (IL-12p35) pathway and enhanced M1 macrophage polarization. However, the suppression of BLT1 by either gene mutation or antagonist U75302 significantly inhibited the adverse effect of 5-Lox in sepsis. Further study demonstrated that pharmacological inhibition of 5-Lox prevented CLP-induced septic cardiomyopathy (SCM). Our study identified 5-Lox exacerbated sepsis-associated myocardial injury through activation of LTB4 production and promoting BLT1/IL-12p35 pathway. Hence, inhibition of 5-Lox may be a potential candidate strategy for septic cardiac dysfunction treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.034DOI Listing
April 2021

Allyl isothiocyanate increases MRP1 expression in cigarette smoke extract-stimulated human bronchial epithelial cells via the JNK/Nrf2 pathway.

Exp Ther Med 2021 Apr 25;21(4):409. Epub 2021 Feb 25.

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.

Multidrug resistance-related protein 1 (MRP1) is involved in the biological transport of several molecules with diverse structural characteristics outside of the cell. In addition to its transport activity, MRP1 exhibits multiple defense mechanisms . MRP1 is highly expressed in normal lung tissues and plays a protective role in the process of chronic obstructive pulmonary disease. In the present study, human bronchial epithelial cells (16HBE14o-cells) were stimulated by cigarette smoke extract (CSE) to simulate a smoking environment. On this basis, the mechanism of Allyl isothiocyanate (AITC) administration on the expression of MRP1 in CSE-stimulated 16HBE14o-cells was investigated. The effects of CSE on the viability of 16 HBE14o-cells were investigated by an MTT assay. The changes in the mRNA expression levels of nuclear erythroid factor 2 (Nrf2) and MRP1 were investigated in CSE-stimulated 16HBE14o-cells using western blotting and reverse transcription quantitative PCR (RT-qPCR). Immunofluorescence analysis was used to detect Nrf2 nuclear translocation. Incubation of the cells with 5% CSE for 24 h had minor effects on cell viability and resulted in the activation of the JNK and p38MAPK signaling pathways. AITC activated the JNK pathway, inhibited the activation of the p38MAPK pathway in 16HBE14o-cells stimulated by 5% CSE and upregulated the expression levels of Nrf2 and MRP1 in a time-dependent manner. The upregulation of Nrf2, MRP1 and of Nrf2, and MRP1 mRNA expression levels in CSE-stimulated cells was inhibited by pretreatment with SP600125 (a JNK pathway inhibitor). Furthermore, the fluorescence intensity in the nucleus was significantly enhanced following AITC pretreatment and the analysis indicated nuclear translocation of Nrf2 in the cells. These results indicated that Nrf2 and MRP1 expression levels in CSE-stimulated cells were altered following AITC pretreatment. Thus demonstrating that the primary mechanism may be associated with activation of the JNK pathway, while the p38MAPK pathway may not be involved.
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http://dx.doi.org/10.3892/etm.2021.9840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938453PMC
April 2021

Microalgae Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice.

Front Cell Dev Biol 2020 9;8:600575. Epub 2021 Feb 9.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan.

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae sp. as a nutraceutical. To test neuroprotection by the ethanol extract of (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.
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http://dx.doi.org/10.3389/fcell.2020.600575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900145PMC
February 2021

In situ mapping identifies distinct vascular niches for myelopoiesis.

Nature 2021 02 10;590(7846):457-462. Epub 2021 Feb 10.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Medical Center, Cincinnati, OH, USA.

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF). Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.
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http://dx.doi.org/10.1038/s41586-021-03201-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020897PMC
February 2021

Establishment and Application of a Dual-Labeling Time-Resolved Fluorescence Immunoassay Method for Simultaneous Detection of the Troponin I-C Complex and Full-Size-Troponin I.

Front Cardiovasc Med 2020 14;7:596051. Epub 2021 Jan 14.

Clinical Lab, Wuxi No.5 People's Hospital, Wuxi, China.

The measurement of cardiac troponin I (cTnI) is widely used in the diagnosis of acute myocardial infarction (AMI). Although existing cTnI detection methods measure total cTnI, the significance of undegraded full-size-cTnI levels is still not well-understood. In this study, we have established a novel dual-labeling time-resolved fluorescence immunoassay (TRFIA) technique that simultaneously detects the cTnI-C complex and full-size-cTnI, allowing us to explore the clinical value of full-size-cTnI determination. An antibody against the 23-43 amino acid region of cTnI protected by endogenous cTnC is coupled to magnetic beads to provide a solid-phase antibody for capturing all cTnI. An antibody against cTnC in the cTnI-C complex labeled with Eu was used to detect the cTnI-C complex, and an antibody labeled with Sm near the C-terminal 190-203 amino acids of cTnI was used to detect full-size-cTnI. Through dual-labeling TRFIA, cTnI-C complex, full-size-cTnI, and the full-size-cTnI/cTnI-C ratio can be detected simultaneously. The dual-labeling TRFIA technique was used to analyze serum samples collected at different times during treatment and compare their full-size-cTnI/cTnI-C ratios. The sensitivity for the cTnI-C-TRFIA complex was 0.02 ng/mL, the measurement range was 0.02-40 ng/mL, the average intra-batch coefficient of variation (CV) was 4.35%, and the inter-average CV was 6.23%. The correlation coefficient between cTnI-C-TRFIA and commercial cTnI-CLIA methods was = 0.8887. The sensitivity for full-size-cTnI-TRFIA was 0.04 ng/mL, the measurement range was 0.04-40 ng/mL, the average intra-batch CV was 4.95%, and the average inter-batch CV was 7.79%. The correlation coefficient between full-size-cTnI-TRFIA and commercial cTnI-CLIA methods was = 0.7247. Dual-labeling full-size-cTnI/cTnI-C-TRFIA analysis is helpful for determining the length of time of chest pain before admission and the degree of continuous release of cTnI in the myocardium. Thus, it is more for early prognosis than just detecting cTnI.
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http://dx.doi.org/10.3389/fcvm.2020.596051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840586PMC
January 2021

Identification and Characterization of Chemical Constituents in HuaTanJiangQi Capsule by UPLC-QTOF-MS Method.

J AOAC Int 2021 Jan 23. Epub 2021 Jan 23.

Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China.

Background: HuaTanJiangQi capsule (HTJQ) is a classical Chinese medicine compound preparation, mainly used for clinically treating and improving the Chronic Obstructive Pulmonary Disease (COPD) in China.

Objective: To establish a rapid and efficient analytical method for the identification and characterization of chemical constituents in HTJQ based on ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS).

Methods: UPLC-QTOF-MS was used to rapidly separate and identify the chemical constituents of HTJQ via gradient elution system. The accurate mass data of the protonated and deprotonated molecules and fragment ions was detected in positive and negative ion modes. Compounds of HTJQ can be identified and assigned by analyzing accurate mass measurements and ion fragmentation mechanisms and comparing them with the chemical compositions database.

Results: A total of 61 compounds in HTJQ were separated and identified, including 14 flavonoids, 16 organic acids, 4 isothiocyanic acids, 8 butyl phthalides, 2 alkaloids, 10 terpenoids, 4 methoxyphenols and furanocoumarins, 3 other compounds. The chemical compounds of HTJQ were identified and elucidated comprehensively for the first time.

Conclusions: A rapid, accurate, and efficient UPLC-QTOF-MS method has been developed for the identification of the chemical components and applied to simultaneously evaluate the quality and effectiveness of the HTJQ.

Highlights: Systematic identification of chemical constituents in HTJQ can provide a scientific and reasonable basis for the application of HTJQ in the clinical treatment of COPD.
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http://dx.doi.org/10.1093/jaoacint/qsab004DOI Listing
January 2021

Activation of Toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction.

Clin Transl Med 2021 01;11(1):e266

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.

Background: As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy.

Methods: We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7-knockout (TLR7 ), wild-type (WT) mice, cardiac-specific TLR7-transgenic (cTG-TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad-TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca imaging, western blotting, immunostaining, and quantitative real-time polymerase chain reaction (qPCR).

Results: We found that TLR7 knockout markedly exacerbated sepsis-induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7 mice displayed weaker Ca handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS-induced systolic dysfunction, and loxoribine (TLR7-specific agonist) improved LPS-induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)-protein kinase A (PKA) pathway, which upregulated phosphorylate-phospholamban (p-PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca handling in response to sepsis. While improved Ca handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG-TLR7 mice. Consistently, TLR7 overexpression improved LPS-induced Ca -handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype.

Conclusions: Our data demonstrated that activation of TLR7 protected against sepsis-induced cardiac dysfunction through promoting cAMP-PKA-PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.
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http://dx.doi.org/10.1002/ctm2.266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775988PMC
January 2021

Extracellular Vesicles in the Treatment of Parkinson's Disease: A Review.

Curr Med Chem 2021 Jan 13. Epub 2021 Jan 13.

Department of Rehabilitation Medicine, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, Zhejiang. China.

Background: Parkinson's disease (PD) is one of the most common neurological disorders that can severely affect the ability to perform daily activities. The clinical presentation of PD includes motor and nonmotor symptoms. The motor symptoms generally involve movement conditions like tremors, rigidity, slowness, and impaired balance. In contrast, the nonmotor symptoms are often not apparent but can affect various organ systems, such as the urinary and gastrointestinal systems, and mental health. Gene mutations and toxic environmental factors have contributed significantly to PD; nevertheless, its cause and underlying mechanism remain unknown. Currently, treatments such as dopamine agonists, RNA molecules, and antioxidants can, to some extent, alleviate the motor symptoms triggered by PD. However, these medicines cannot effectively halt ongoing dopaminergic damage, mainly because the blood-brain barrier (BBB) lowers the efficiency of drug delivery. Recently, extracellular vesicles (EVs), a novel drug delivery platform, have been widely used in various neurological diseases, including stroke and brain tumors, because of their excellent biocompatibility, their ability to penetrate the BBB without toxicity, and their target specificity. EVs thus provide a promising therapeutic for treating PD.

Objective: This review focuses on novel therapies based on EVs in practice. Herein, we briefly introduce the biogenesis, composition, isolation, and characterization of EVs, and we discuss strategies for loading therapeutic agents onto EVs and recent applications for PD treatment. Moreover, we discuss perspectives on the direction of preclinical and clinical studies regarding novel and effective therapies.

Methods: A literature search regarding PD treatment based on extracellular vesicles was performed in PubMed (updated in June 2020). Treatment, therapy, drug delivery, extracellular vesicles, and their combinations were the search queries. Both systematic reviews and original publications were included. Searched results were selected and compared based on relevance. Articles published in the last five years were given top priority.

Conclusion: PD is a heterogeneous disease that can be treated by using pharmacologic approaches (e.g., dopamine agonists and levodopa) and nonpharmacologic approaches (e.g., music), based on symptoms and progression level in patients. Even though current treatments have demonstrated effectiveness, clinical challenges remain because the BBB reduces medication received and lowers the efficacy of drug delivery, which impairs the treatment's effect. Therefore, EVs, as an emerging delivery platform, are highly promising for PD treatment since they can readily cross the BBB with high therapeutic efficiency through the loading or functionalization process. However, defining a safe source of EVs, reliably purifying and isolating EVs with high yield, and improving the efficacy of therapeutic loading in EVs remain challenging in this field. Therefore, future investigations should focus on generating large-scale exosomal carriers and designing new effective drugs encapsulated in EVs for better efficacy.
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http://dx.doi.org/10.2174/0929867328666210113170941DOI Listing
January 2021

International values for haemoglobin distributions in healthy pregnant women.

EClinicalMedicine 2020 Dec 2;29-30:100660. Epub 2020 Dec 2.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Background: Anaemia in pregnancy is a global health problem with associated morbidity and mortality.

Methods: A secondary analysis of prospective, population-based study from 2009 to 2016 to generate maternal haemoglobin normative centiles in uncomplicated pregnancies in women receiving optimal antenatal care. Pregnant women were enrolled <14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21 Project which involved eight geographically diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, United Kingdom and United States. At each 5 ± 1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care that complemented the study's requirements, including haemoglobin values.

Findings: A total of 3502 (81%) of 4321 women who delivered a live, singleton newborn with no visible congenital anomalies, contributed at least one haemoglobin value. Median haemoglobin concentrations ranged from 114.6 to 121.4 g/L, 94 to 103 g/L at the 3 centile, and from 135 to 141 g/L at the 97 centile. The lowest values were seen between 31 and 32 weeks' gestation, representing a mean drop of 6.8 g/L compared to 14 weeks' gestation. The percentage variation in maternal haemoglobin within-site was 47% of the total variance compared to 13% between sites.

Interpretation: We have generated International, gestational age-specific, smoothed centiles for maternal haemoglobin concentration compatible with better pregnancy outcomes, as well as adequate neonatal and early childhood morbidity, growth and development up to 2 years of age.

Funding: Bill & Melinda Gates Foundation Grant number 49038.
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http://dx.doi.org/10.1016/j.eclinm.2020.100660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788439PMC
December 2020

Conformation and Quantum-Interference-Enhanced Thermoelectric Properties of Diphenyl Diketopyrrolopyrrole Derivatives.

ACS Sens 2021 02 31;6(2):470-476. Epub 2020 Dec 31.

Physics Department, Lancaster University, LA1 4YB Lancaster, United Kingdom.

Manipulating the connectivity of external electrodes to central rings of carbon-based molecules in single molecule junctions is an effective route to tune their thermoelectrical properties. Here we investigate the connectivity dependence of the thermoelectric properties of a series of thiophene-diketopyrrolopyrrole (DPP) derivative molecules using density functional theory and tight-binding modeling, combined with quantum transport theory. We find a significant dependence of electrical conductance on the connectivity of the two thiophene rings attached to the DPP core. Interestingly, for connectivities corresponding to constructive quantum interference (CQI), different isomers obtained by rotating the thiophene rings possess the same electrical conductance while those corresponding to destructive quantum interference (DQI) show huge conductance variations upon ring rotation. Furthermore, we find that DQI connectivity leads to enhanced Seebeck coefficients, which can reach 500-700 μV/K. After including the contribution to the thermal conductance from phonons, the full figure of merit () for the CQI molecules could reach 1.5 at room temperature and it would further increase to 2 when temperature elevates to 400 K. Finally, we demonstrate that doping with tetracyanoquinodimethane can change the sign of the Seebeck coefficients by forming a charge-transfer system with the DPP.
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http://dx.doi.org/10.1021/acssensors.0c02043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021221PMC
February 2021

Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene-related peptide and substance P.

Ann N Y Acad Sci 2021 03 10;1487(1):56-73. Epub 2020 Dec 10.

Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of systematic administration of bisphosphonates (BPs). Sensory innervation is crucial for bone healing. We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression in the IANI and IANT models by decreasing calcitonin gene-related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. In vitro, RAW 264.7 cells were treated with BPs and then CGRP and/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.
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http://dx.doi.org/10.1111/nyas.14540DOI Listing
March 2021

Associations among circulating sphingolipids, β-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

PLoS Med 2020 12 9;17(12):e1003451. Epub 2020 Dec 9.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

Background: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms.

Methods And Findings: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication.

Conclusions: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
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http://dx.doi.org/10.1371/journal.pmed.1003451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725305PMC
December 2020

S100A8/A9 in Myocardial Infarction: A Promising Biomarker and Therapeutic Target.

Front Cell Dev Biol 2020 12;8:603902. Epub 2020 Nov 12.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Myocardial infarction (MI), the main cause of cardiovascular-related deaths worldwide, has long been a hot topic because of its threat to public health. S100A8/A9 has recently attracted an increasing amount of interest as a crucial alarmin that regulates the pathogenesis of cardiovascular disease after its release from myeloid cells. However, the role of S100A8/A9 in the etiology of MI is not well understood. Here, we elaborate on the critical roles and potential mechanisms of S100A8/A9 driving the pathogenesis of MI. First, cellular source of S100A8/A9 in infarcted heart is discussed. Then we highlight the effect of S100A8/A9 heterodimer in the early inflammatory period and the late reparative period of MI as well as myocardial ischemia/reperfusion (I/R) injury. Moreover, the predictive value of S100A8/A9 for the risk of recurrence of cardiovascular events is elucidated. Therefore, this review focuses on the molecular mechanisms of S100A8/A9 in MI pathogenesis to provide a promising biomarker and therapeutic target for MI.
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http://dx.doi.org/10.3389/fcell.2020.603902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688918PMC
November 2020

Touch-induced seedling morphological changes are determined by ethylene-regulated pectin degradation.

Sci Adv 2020 Nov 27;6(48). Epub 2020 Nov 27.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.

How mechanical forces regulate plant growth is a fascinating and long-standing question. After germination underground, buried seedlings have to dynamically adjust their growth to respond to mechanical stimulation from soil barriers. Here, we designed a lid touch assay and used atomic force microscopy to investigate the mechanical responses of seedlings during soil emergence. Touching seedlings induced increases in cell wall stiffness and decreases in cell elongation, which were correlated with pectin degradation. We revealed that , which encodes a polygalacturonase, mediates touch-imposed alterations in the pectin matrix and the mechanics of morphogenesis. Furthermore, we found that ethylene signaling is activated by touch, and the transcription factor EIN3 directly associates with promoter and is required for touch-repressed expression. By uncovering the link between mechanical forces and cell wall remodeling established via the EIN3-PGX3 module, this work represents a key step in understanding the molecular framework of touch-induced morphological changes.
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http://dx.doi.org/10.1126/sciadv.abc9294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695475PMC
November 2020

Effects of protection and restoration on reducing ecological vulnerability.

Sci Total Environ 2021 Mar 22;761:143180. Epub 2020 Oct 22.

School of Finance, Zhongnan University of Economics and Law, Wuhan 430073, China.

Quantitative assessment and long-term analysis of ecological vulnerability can effectively grasp the driving factors of environmental change, which is of great significance for ecological protection and restoration. This study took 381 villages in Jingle County, a typical ecological vulnerable area on the Loess Plateau, as basic evaluation unit, and an ecological vulnerability evaluation index system with 12 evaluation indexes was constructed based on "sensitivity-resilience-pressure" (SRP) conceptual model. Combined with spatial principal component analysis, spatial autocorrelation, cross-sectional and panel regression, the spatio-temporal variation characteristics and driving factors of ecological vulnerability in 2005, 2010 and 2015 were quantitatively analyzed. The results showed that areas classified as not and somewhat vulnerable were expanding, while areas classified as highly and extremely vulnerable were shrinking from 2005 to 2015. The variations of ecological vulnerability were the result of interaction of natural environment and human activities, among which Normalized Difference Vegetation Index (NDVI), distance from main road and distance from river system were conducive to reducing ecological vulnerability, moreover, NDVI has the greatest impact on the probability of ecological vulnerability transition from high to low, with a regression coefficient of 46.66. The impact of social factors decreased relatively, while the role of natural factors increased, and increasing vegetation coverage and economic development helped reduce ecological vulnerability.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143180DOI Listing
March 2021

Sugarcane ( L.) Top Extract Ameliorates Cognitive Decline in Senescence Model SAMP8 Mice: Modulation of Neural Development and Energy Metabolism.

Front Cell Dev Biol 2020 6;8:573487. Epub 2020 Oct 6.

School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.

Age-related biological alterations in brain function increase the risk of mild cognitive impairment and dementia, a global problem exacerbated by aging populations in developed nations. Limited pharmacological therapies have resulted in attention turning to the promising role of medicinal plants and dietary supplements in the treatment and prevention of dementia. Sugarcane ( L.) top, largely considered as a by-product because of its low sugar content, in fact contains the most abundant amounts of antioxidant polyphenols relative to the rest of the plant. Given the numerous epidemiological studies on the effects of polyphenols on cognitive function, in this study, we analyzed polyphenolic constituents of sugarcane top and examined the effect of sugarcane top ethanolic extract (STEE) on a range of central nervous system functions and . Orally administrated STEE rescued spatial learning and memory deficit in the senescence-accelerated mouse prone 8 (SAMP8) mice, a non-transgenic strain that spontaneously develops a multisystemic aging phenotype including pathological features of Alzheimer's disease. This could be correlated with an increased number of hippocampal newborn neurons and restoration of cortical monoamine levels in STEE-fed SAMP8 mice. Global genomic analysis by microarray in cerebral cortices showed multiple potential mechanisms for the cognitive improvement. Gene set enrichment analysis (GSEA) revealed biological processes such as neurogenesis, neuron differentiation, and neuron development were significantly enriched in STEE-fed mice brain compared to non-treated SAMP8 mice. Furthermore, STEE treatment significantly regulated genes involved in neurotrophin signaling, glucose metabolism, and neural development in mice brain. Our results suggest that STEE treatment enhances the metabolic activity of neuronal cells promoting glucose metabolism with significant upregulation of genes, namely , , , and . STEE also stimulated proliferation of human neural stem cells (hNSCs), regulated bHLH factor expression and induced neuronal differentiation and astrocytic process lengthening. Altogether, our findings suggest the potential of STEE as a dietary intervention, with promising implications as a novel nutraceutical for cognitive health.
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http://dx.doi.org/10.3389/fcell.2020.573487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573230PMC
October 2020

Pharmacokinetics and Bioequivalence of Two Formulations of Valsartan 80 mg Capsules: A Randomized, Single Dose, 4-Period Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Drug Des Devel Ther 2020 12;14:4221-4230. Epub 2020 Oct 12.

Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People's Republic of China.

Purpose: To compare the bioequivalence of two formulations of valsartan (80 mg capsules) under fasting and fed conditions in healthy Chinese volunteers using a full-replicate study design.

Methods: A total of 78 Subjects were randomly assigned to fasting cohort (n = 48) or fed cohort (n = 30). Each cohort includes 4 single-dose observation periods and 3-day washout periods. Blood samples were collected at designed time point. Plasma concentration of valsartan was analyzed by a validated LC-MS/MS method. Noncompartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation (S) of the reference formulation, either reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was used to evaluate the bioequivalence of the two formulations.

Results: Under fasting conditions, the RSABE method was used to evaluate the bioequivalence of C (S>0.294), while ABE method was used to evaluate the bioequivalence of AUC and AUC. The geometric mean ratio (GMR) of the test/reference for C was 99.52%, and the 95% upper confidence bound was <0. For AUC and AUC comparisons, GMRs were 102.07% and 101.92%, and the 90% CIs of the test/reference were 96.28%-108.21%, 96.28%-107.88%, respectively. Under fed conditions, the S value of C, AUC and AUC all exceeded the cutoff value of 0.294 and therefore, the RSABE method was used. The GMRs for C, AUC and AUC were 98.78%, 103.33% and 103.08%, respectively, while the 95% upper confidence bound values were all <0. These results all met the bioequivalence criteria for highly variable drugs. All adverse events were mild and transient.

Conclusion: In this study, the generic formulation of valsartan 80 mg capsule was considered to be bioequivalent to the reference product under both fasting and fed conditions, and satisfied the requirements for marketing in China.

Nmpa Registration No: CTR20181422.
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http://dx.doi.org/10.2147/DDDT.S253078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567554PMC
October 2020

Concerns About Information Regarding COVID-19 on the Internet: Cross-Sectional Study.

J Med Internet Res 2020 11 9;22(11):e20487. Epub 2020 Nov 9.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

Background: Since the outbreak of COVID-19, the Chinese government and the Chinese Center for Disease Control and Prevention have released COVID-19-related information to the public through various channels to raise their concern level of the pandemic, increase their knowledge of disease prevention, and ensure the uptake of proper preventive practices.

Objective: Our objectives were to determine Chinese netizens' concerns related to COVID-19 and the relationship between their concerns and information on the internet. We also aimed to elucidate the association between individuals' levels of concern, knowledge, and behaviors related to COVID-19.

Methods: The questionnaire, which consisted of 15 closed-ended questions, was designed to investigate Chinese netizens' knowledge about COVID-19. The self-selection online survey method of nonprobability sampling was used to recruit participants through Dingxiangyisheng WeChat (a public, medical, and health service platform in China) accounts. Standard descriptive statistics and multivariate logistic regression analyses were conducted to analyze the data.

Results: In total, 10,304 respondents were surveyed on the internet (response rate=1.75%; 10,304/590,000). Nearly all (n=9803, 95.30%) participants were concerned about "confirmed cases" of COVID-19, and 87.70% (n=9036) received information about the outbreak through social media websites. There were significant differences in participants' concerns by sex (P=.02), age (P<.001), educational attainment (P=.001), and occupation (P<.001). All knowledge questions and preventive practices were associated with concerns about COVID-19. The results of the multivariate logistic regression indicated that participants' sex, educational attainment, occupation and employment status, knowledge acquisition, and concern level were significantly associated with the practice of proper preventive behaviors.

Conclusions: This study elucidated Chinese netizens' concerns, information sources, and preventive behaviors related to the COVID-19 pandemic. Sex, educational attainment, occupation and employment status, knowledge acquisition, and level of concern were key factors associated with proper preventive behaviors. This offers a theoretical basis for the government to provide targeted disease prevention and control information to the public.
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http://dx.doi.org/10.2196/20487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655729PMC
November 2020

Methanogenesis Is an Important Process in Controlling MeHg Concentration in Rice Paddy Soils Affected by Mining Activities.

Environ Sci Technol 2020 11 21;54(21):13517-13526. Epub 2020 Oct 21.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, P. R. China.

Rice paddies are agricultural sites of special concern because the potent toxin methylmercury (MeHg), produced in rice paddy soils, accumulates in rice grains. MeHg cycling is mostly controlled by microbes but their importance in MeHg production and degradation in paddy soils and across a Hg concentration gradient remains unclear. Here we used surface and rhizosphere soil samples in a series of incubation experiments in combination with stable isotope tracers to investigate the relative importance of different microbial groups on MeHg production and degradation across a Hg contamination gradient. We showed that sulfate reduction was the main driver of MeHg formation and concentration at control sites, and that methanogenesis had an important and complex role in MeHg cycling as Hg concentrations increased. The inhibition of methanogenesis at the mining sites led to an increase in MeHg production up to 16.6-fold and a decrease in MeHg degradation by up to 77%, suggesting that methanogenesis is associated with MeHg degradation as Hg concentrations increased. This study broadens our understanding of the roles of microbes in MeHg cycling and highlights methanogenesis as a key control of MeHg concentrations in rice paddies, offering the potential for mitigation of Hg contamination and for the safe production of rice in Hg-contaminated areas.
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http://dx.doi.org/10.1021/acs.est.0c00268DOI Listing
November 2020

Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury.

Free Radic Biol Med 2020 11 23;160:303-318. Epub 2020 Aug 23.

Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, PR China. Electronic address:

Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of regulated cell death (RCD), playing critical roles in organ injury and targeting therapy of cancers. Previous studies have demonstrated that ferroptosis participates in the development of cardiomyopathy including cardiac hypertrophy, diabetic cardiomyopathy and doxorubicin-induced cardiotoxicity. However, the role of ferroptosis in sepsis-induced cardiac injury remains unclear. This study aimed to explore the role and underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced cardiac injury. Mice were injected with LPS (10 mg/kg) for 12 h to generate experimental sepsis. Ferrostatin-1 (Fer-1) and Dexrazoxane (DXZ) were used to suppress ferroptosis of mice with sepsis-induced cardiac injury. LPS increased the levels of ferroptotic markers involving prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA) and lipid ROS, apart from resulting in obvious mitochondria damage, which were alleviated by Fer-1 and DXZ. In vitro experiments showed that Fer-1 inhibited LPS-induced lipid peroxidation and injury of H9c2 myofibroblasts while erastin and sorafenib aggravated LPS-induced ferroptosis. Additionally, Fer-1 and DXZ improved survival rate and cardiac function of mice with sepsis. Mechanistically, LPS increased the expression of nuclear receptor coactivator 4 (NCOA4) and the level of intracellular Fe but decreased the level of ferritin. NCOA4 could directly interact with ferritin and degrade it in a ferritinophagy-dependent manner, which subsequently released a great amount of iron. Cytoplasmic Fe further activated the expression of siderofexin (SFXN1) on mitochondrial membrane, which in turn transported cytoplasmic Fe into mitochondria, giving rise to the production of mitochondrial ROS and ferroptosis. Based on these findings, we concluded that ferritinophagy-mediated ferroptosis is one of the critical mechanisms contributing to sepsis-induced cardiac injury. Targeting ferroptosis in cardiomyocytes may be a therapeutic strategy for preventing sepsis in the future.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.009DOI Listing
November 2020

Experimental study on dynamic thermal environment of passenger compartment based on thermal evaluation indexes.

Sci Prog 2020 Jul-Sep;103(3):36850420942991

School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai, China.

In this article, the thermal environment and the human thermal comfort of car cabin under different driving states in summer were studied experimentally. The weighted predictive mean vote model and the weighted equivalent temperature model were used for calculation and compared with the experimental values. The experimental results show that the air temperature and relative humidity distribution in cabin are affected by the space position and driving state. The temperature of the cabin seat, which is affected by solar radiation and crew, in the heating stage is slightly higher than the air temperature, while the cooling rate in the cooling stage is much lower than the air temperature. The predictive mean vote model and the equivalent temperature model are basically consistent with the actual thermal comfort of human body under the idle and driving conditions with the change of time. The prediction accuracy of the two models under the idle condition is higher than that under the driving condition, and the overall prediction accuracy of the equivalent temperature model is higher than that of the predictive mean vote model.
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http://dx.doi.org/10.1177/0036850420942991DOI Listing
August 2020

The sialylation profile of IgG determines the efficiency of antibody directed osteogenic differentiation of iMSCs by modulating local immune responses and osteoclastogenesis.

Acta Biomater 2020 09 6;114:221-232. Epub 2020 Aug 6.

Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400015, China.

Antibody-mediated osseous regeneration (AMOR) has been proved as a promising strategy for osteogenic differentiation of induced pluripotent stem cells derived MSCs (iMSCs). The key characteristic of antibody that determines the AMOR potential is largely unknown. The glycosylation profile of immunoglobulin G (IgG) represents a key checkpoint that determines its effector functions. Herein, we modified the sialylation profile of BMP2 antibodies to investigate the effects of glycosylation on antibody-mediated osteogenic differentiation of iMSCs. We found that over-sialylated BMP2 antibodies stimulated the highest amount of new bone while those non- or low-sialylated led to bone porosity and collapse. The immune response aroused by BMP2 immune complexes (BMP2-ICs) was intensified by desialylation, which contributed to an environment that favored osteoclastogenesis while inhibited osteoblastogenesis. In vitro study further demonstrated that the osteogenic potential of BMP2-ICs was not significantly affected by the degree of sialylation. On the other hand, BMP2-ICs could stimulate osteoclastogenesis by binding FcγRs on preosteoclasts directly, which was significantly intensified by desialylation and attenuated by over-sialylation. Bone defects implanted with alginate microbeads loaded with iMSCs and over-sialylated antibodies showed more bone formation than those sites with non- or low sialylated antibodies. Taken together, our study demonstrated that sialylation profile is one of the traits that decide the AMOR potential of BMP2 antibodies. Enhancement of sialylation may be a promising strategy to optimize antibody for iMSCs application in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Antibody-mediated osseous regeneration (AMOR) is a promising strategy for bone tissue engineering that takes advantage of the specific reactivity of antibodies to sequester endogenous BMP2 and present it to osteoprogenitor cells. We previously demonstrated that BMP2 immune complex can drive iPSCs derived MSCs to osteogenic lineage. In this study, we analyze the effects of glycosylation profile on antibody directed osteogenic differentiation of iMSCs because glycosylation profile represents a key checkpoint that determines the effector functions of antibodies, and it is susceptible to variations in different clones. The results showed that sialylation profile is one of the traits that decides the AMOR potential of BMP2 antibody, and the enhancement of sialylation maybe a promising strategy to optimize antibodies for AMOR.
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http://dx.doi.org/10.1016/j.actbio.2020.07.055DOI Listing
September 2020

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21 Project.

Am J Obstet Gynecol 2021 02 5;224(2):208.e1-208.e18. Epub 2020 Aug 5.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom.

Background: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth.

Objective: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21 Fetal Growth Standards.

Study Design: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21 Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression.

Results: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work.

Conclusion: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21 Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21 tools at https://intergrowth21.tghn.org/standards-tools/.
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http://dx.doi.org/10.1016/j.ajog.2020.07.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858163PMC
February 2021