Publications by authors named "Di Yang"

479 Publications

Synthesis of an organic-inorganic hybrid with short organic molecular chains by sol-gel chemistry.

J Mech Behav Biomed Mater 2021 Apr 29;120:104567. Epub 2021 Apr 29.

College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, China. Electronic address:

An oligomer with short organic molecular chains was successfully synthesized with KH550 and KH560. This oligomer was combined with tetraethyl orthosilicate and calcium chloride to prepare an organic-inorganic hybrid biological material (OI-BM) by sol-gel chemistry. The hybrid was fully characterized by a series of instrumental characterizations including nuclear magnetic resonance spectrometry, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray energy spectroscopy and inductively coupled plasma spectrometry. OI-BM presented elastic deformation under compression. The elastic modulus and ultimate stress of OI-BM were 0.4 ± 0.1 GPa and 23.0 ± 4.0 MPa, respectively, lower than those of 45S5 bioactive glass (45S5-BG), whereas the strain at failure and modulus of toughness of OI-BM was about 4.5 times and 4 times higher. The hybrid is easy to form due to the improved mechanical property, suggesting excellent machining properties. The hybrid OI-BM produced hydroxyapatite in 1 h in simulated body fluid due to its excellent bioactivity. CCK-8 assay further demonstrated the desirable cytocompatibility of the hybrid. Thus, the hybrid can be a potential material for satisfying the mechanical property requirement of an implant.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104567DOI Listing
April 2021

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets.

Eye Vis (Lond) 2021 May 1;8(1):15. Epub 2021 May 1.

Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan Province, China.

Diabetic retinopathy (DR), one of the common complications of diabetes, is the leading cause of visual loss in working-age individuals in many industrialized countries. It has been traditionally regarded as a purely microvascular disease in the retina. However, an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina. Deterioration of neural retina could precede microvascular abnormalities in the DR, leading to microvascular changes. Furthermore, disruption of interactions among neurons, vascular cells, glia and local immune cells, which collectively form the neurovascular unit, is considered to be associated with the progression of DR early on in the disease. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration, neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR. Here, we present current perspectives on the pathophysiology of DR as a neurovascular disease, especially at the early stage. Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.
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http://dx.doi.org/10.1186/s40662-021-00239-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088070PMC
May 2021

Early and consecutive RT-PCR tests with both oropharyngeal swabs and sputum could improve testing yield for patients with COVID-19: An Observation Cohort Study in China.

Int J Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China. Electronic address:

Objective: The real-time polymerase chain reaction (RT-PCR) test is recommended for diagnosis of COVID-19 and provides a powerful tool to identify new infections and contact tracing. In fact, as COVID-19 prevalence decreases, this remains the main preventive measure to avoid rebound. However, inconsistent results due to biological sample variability in collection timing post infection and sampling procedures, misleads our application in clinic.

Methods: We applied Kaplan-Meier method and multivariate Logistic regression on the RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the negative percentages among patients who had tested twice or more and compared the proportions by oropharyngeal swab, sputum and combined double testing, respectively.

Main Results: The proportion of negative conversion was 6.7% at the 4 day, 16.4% at the 7 day, 41.0% at two weeks and 61.0% at three-weeks post-admission. We also found 34.1% and 60.3% with at least one negative RT-PCR result at the 7 days and 14 days after symptom onset, respectively. The negative proportion in sputum was higher than that in oropharyngeal swab in the early stage but lowered after symptoms.

Conclusion: In the absence of effective treatments or vaccines, efficient testing strategies are critical to control COVID-19 epidemic. According to this study, early, consecutive and combined double testing will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases, and minimize misdiagnosis and ineffective isolation of infected patients.
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http://dx.doi.org/10.1016/j.ijid.2021.04.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079261PMC
April 2021

Atorvastatin reverses high cholesterol-induced cardiac remodeling and regulates mitochondrial quality-control in a cholesterol-independent manner: an experimental study.

Clin Exp Pharmacol Physiol 2021 Apr 23. Epub 2021 Apr 23.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China.

Mitochondria are key regulators of cell fate, maintaining self-stability by a fine-tuned quality-control network including mitophagy, biogenesis, fission and fusion processes. Myocardial mitochondria can be impaired by hypercholesterolemia. Statins, such as atorvastatin, are considered the cornerstone in the management of hypercholesterolemia primarily due to their marked cholesterol-lowering ability. The direct effect of atorvastatin on myocardial mitochondria remains unclear. We aimed to explore whether atorvastatin could attenuate myocardial mitochondrial defects induced by high cholesterol, and whether cycloastragenol, a potent telomerase activator, could be used as a potential complementary bioactive compound for obesity and hypercholesterolemia treatment. We found that atorvastatin at a low dose (3 mg/kg) did not reduce elevated serum cholesterol, but reversed cardiac remodeling and dysfunction in C57BL/6J mice fed with high-fat diet (HFD). Atorvastatin reversed the upregulated mitophagy, mitochondrial fission and fusion, accompanied by mitochondrial biogenesis activation in HFD-fed mice hearts. Mitochondrial structural impairments were attenuated by atorvastatin in HFD-fed mice and oxidized low-density lipoprotein (ox-LDL) exposed HL-1 cardiomyocytes. The depolarized mitochondrial membrane potential and increased mitochondrial oxygen consumption rates in ox-LDL exposed HL-1 cells were recovered by atorvastatin. Furthermore, atorvastatin co-treated with cycloastragenol had better effects on reducing body weight, improving cardiac remodeling and dysfunction, and protecting mitochondria in high cholesterol. Conclusively, low-dose atorvastatin exhibited a cholesterol-independent cardioprotective effect through improving the mitochondrial quality-control network and repairing mitochondrial ultrastructure in high cholesterol. Atorvastatin plus cycloastragenol supplement therapy has a better effect on treating obesity and hypercholesterolemia.
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http://dx.doi.org/10.1111/1440-1681.13507DOI Listing
April 2021

CCL2 regulation of MST1-mTOR-STAT1 signaling axis controls BCR signaling and B-cell differentiation.

Cell Death Differ 2021 Apr 20. Epub 2021 Apr 20.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Chemokines are important regulators of the immune system, inducing specific cellular responses by binding to receptors on immune cells. In SLE patients, decreased expression of CCL2 on mesenchymal stem cells (MSC) prevents inhibition of B-cell proliferation, causing the characteristic autoimmune phenotype. Nevertheless, the intrinsic role of CCL2 on B-cell autoimmunity is unknown. In this study using Ccl2 KO mice, we found that CCL2 deficiency enhanced BCR signaling by upregulating the phosphorylation of the MST1-mTORC1-STAT1 axis, which led to reduced marginal zone (MZ) B cells and increased germinal center (GC) B cells. The abnormal differentiation of MZ and GC B cells were rescued by in vivo inhibition of mTORC1. Additionally, the inhibition of MST1-mTORC1-STAT1 with specific inhibitors in vitro also rescued the BCR signaling upon antigenic stimulation. The deficiency of CCL2 also enhanced the early activation of B cells including B-cell spreading, clustering and signalosome recruitment by upregulating the DOCK8-WASP-actin axis. Our study has revealed the intrinsic role and underlying molecular mechanism of CCL2 in BCR signaling, B-cell differentiation, and humoral response.
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http://dx.doi.org/10.1038/s41418-021-00775-2DOI Listing
April 2021

TTP-mediated regulation of mRNA stability in immune cells contributes to adaptive immunity, immune tolerance and clinical applications.

RNA Biol 2021 Apr 27:1-7. Epub 2021 Apr 27.

Institute of Immunology, PLA, Third Military Medical University (Army Medical University), Chongqing, PR China.

Dendritic cells (DCs) form a sentinel network to induce protective immunity against pathogens or self-tolerance. mRNA stability is an important part of the post-transcriptional regulation (PTR) that controls the maturation and function of DCs. In this review, we summarize the effects of TTP-mediated regulation of mRNA stability in DCs, focusing on DC maturation and antigen presentation, T cell activation and differentiation, immune tolerance and inflammation. We also discuss the potential DC-based immune treatment for HIV patients through regulation of mRNA stability. This review proposes the regulation of mRNA stability as a novel immune therapy for various inflammatory diseases, such as arthritis and dermatitis.
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http://dx.doi.org/10.1080/15476286.2021.1917185DOI Listing
April 2021

Unprecedented Migratory Bird Die-Off: A Citizen-Based Analysis on the Spatiotemporal Patterns of Mass Mortality Events in the Western United States.

Geohealth 2021 Apr 1;5(4):e2021GH000395. Epub 2021 Apr 1.

Department of Forest and Wildlife Ecology University of Wisconsin-Madison Madison WI USA.

Extensive, severe wildfires, and wildfire-induced smoke occurred across the western and central United States since August 2020. Wildfires resulting in the loss of habitats and emission of particulate matter and volatile organic compounds pose serious threatens to wildlife and human populations, especially for avian species, the respiratory system of which are sensitive to air pollutions. At the same time, the extreme weather (e.g., snowstorms) in late summer may also impact bird migration by cutting off their food supply and promoting their migration before they were physiologically ready. In this study, we investigated the environmental drivers of massive bird die-offs by combining socioecological earth observations data sets with citizen science observations. We employed the geographically weighted regression models to quantitatively evaluate the effects of different environmental and climatic drivers, including wildfire, air quality, extreme weather, drought, and land cover types, on the spatial pattern of migratory bird mortality across the western and central US during August-September 2020. We found that these drivers affected the death of migratory birds in different ways, among which air quality and distance to wildfire were two major drivers. Additionally, there were more bird mortality events found in urban areas and close to wildfire in early August. However, fewer bird deaths were detected closer to wildfires in California in late August and September. Our findings highlight the important impact of extreme weather and natural disasters on bird biology, survival, and migration, which can provide significant insights into bird biodiversity, conservation, and ecosystem sustainability.
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http://dx.doi.org/10.1029/2021GH000395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029984PMC
April 2021

Prevalence of psychiatric diagnosis and related psychopathological symptoms among patients with COVID-19 during the second wave of the pandemic.

Global Health 2021 04 8;17(1):44. Epub 2021 Apr 8.

Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China.

Background: The possibility of psychopathological symptoms and related risk factors among normal persons and patients infected during the outbreak of COVID-19 has been widely investigated. The mental health outcomes of the second wave of the pandemic remain unclear, especially those of patients with an infection. Thus, this study aims to explore the prevalence of and related risk factors associated with psychopathological symptoms among patients infected with COVID-19 during the second wave.

Method: A cross-sectional survey was conducted in five isolated wards of a designated hospital in Beijing, China, from July 1 to July 15, 2020. The Mini International Neuropsychiatric Interview (MINI) was conducted to assess psychiatric disorders, and a series of scales were used to measure self-reported psychopathological symptoms and psychosomatic factors. Multivariate regression analysis was used to analyze the risk factors associated with psychopathological symptoms.

Results: Among 119 participants with infections, the prevalence of generalized anxiety symptoms (51.3%), depressive symptoms (41.2%), and posttraumatic stress symptoms (PTSS)/posttraumatic stress disorder (PTSD) symptoms (33.6%) was observed. Loneliness, hope, coping strategies, and history of mental disorders were the shared risk or protective factors across several psychopathological symptoms. The perceived impact of COVID-19 is the specific risk factor associated with state anxiety symptoms.

Conclusions: The prevalence of symptoms of depression, anxiety, and PTSS/PTSD is high among patients with infections during the second wave of the pandemic in Beijing. Clinical doctors must realize that these patients will probably experience depressive disorder, anxiety disorders, and PTSS/PTSD, as well as some neuropsychiatric syndromes. Specific mental health care is urgently required to help patients manage the virus during the second wave of the pandemic.
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http://dx.doi.org/10.1186/s12992-021-00694-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027973PMC
April 2021

H3K4 Methyltransferase Smyd3 Mediates Vascular Smooth Muscle Cell Proliferation, Migration, and Neointima Formation.

Arterioscler Thromb Vasc Biol 2021 Apr 8:ATVBAHA121314689. Epub 2021 Apr 8.

State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau (D.Y., Y.Z.Z.).

Objective: Smyd3 (SET and MYND domain-containing protein 3) is an H3K4 (histone H3 lysine 4) dimethyltransferase and trimethyltransferase that activates the transcription of oncogenes and cell cycle genes in human cancer cells. We discovered its overexpression in proliferative vascular smooth muscle cells (VSMCs). However, whether Smyd3 plays a role in vascular remodeling remains unanswered. The objective of this study is to investigate the role and underlying mechanism of Smyd3 in phenotypic transition of VSMCs (such as proliferation and migration) and vascular remodeling (such as neointima formation). Approach and Results: We discovered upregulation of Smyd3 in both PDGF (platelet-derived growth factor) BB-induced vascular cell proliferation model and balloon injury-induced neointima formation model. Knockdown of Smyd3 or blockade of its enzymatic activity suppressed VSMCs proliferation and migration ability, whereas Smyd3 overexpression promoted VSMC migration and proliferation. Mechanistically, RNA-seq and ChIP-seq analysis revealed Smyd3 promoted neointimal formation by directly binding and increasing H3K4me3 to the promoter regions of target genes that are associated with cell proliferation and migration, cell cycle control. Furthermore, knockout of Smyd3 in mice profoundly suppressed carotid artery ligation-induced neointimal hyperplasia, consistently, local knocking down Smyd3 in rats relieved balloon injury-induced neointimal formation, while restored VSMC contractile protein expression, suggesting that Smyd3 plays a critical role in vivo.

Conclusions: Our results demonstrate that Smyd3 promotes VSMC proliferation and migration during injury-induced vascular remodeling, which provide a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.
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http://dx.doi.org/10.1161/ATVBAHA.121.314689DOI Listing
April 2021

5-Substituted isatin thiosemicarbazones as inhibitors of tyrosinase: Insights of substituent effects.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 9;255:119669. Epub 2021 Mar 9.

College of Chemistry and Environmental Engineering, Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Xiwang Avenue South Rd. 2, Yancheng 224007, PR China. Electronic address:

Seven isatin-thiosemicarbazone analogues bearing different substituents (R) attached at C-5 of the indoline ring, TSC-ISA-R (R = -H, -CH, -OCH, -OCF, -F, -Cl and -NO), were synthesized and evaluated as inhibitors of mushroom tyrosinase (TYR). The inhibitory behaviour and performance of TSC-ISA-R were investigated spectroscopically in relation to the substituent modifications through examining their inhibition against the diphenolase activity of TYR using L-DOPA as a substrate. The IC values of TSC-ISA-R were determined to be in the range of 81-209 μM. The kinetic analysis showed that TSC-ISA-R were reversible and mixed type inhibitors. Three potential non-covalent interactions rather than complexation including the binding of TSC-ISA-R with free TYR, TYR-L-DOPA complex, and with substrate L-DOPA were found to be involved in the inhibition. The substituent modifications affected these interactions by varying the characters of the resulting TSC-ISA-R in different degrees. The thiosemicarbazido moiety of each TSC-ISA-R contributed predominantly to the inhibition, and the isatin moiety seemed to play a regulatory role in the binding of TSC-ISA-R to the target molecules. The results of theoretical calculations using density functional theory method indicated a different effect of -R on the electron distribution in HOMO of TSC-ISA-R. The LUMO-HOMO energy gap of TSC-ISA-R almost accords with the trend of their experimental inhibition potency.
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http://dx.doi.org/10.1016/j.saa.2021.119669DOI Listing
July 2021

Exploring spatiotemporal variation characteristics of China's industrial carbon emissions on the basis of multi-source data.

Environ Sci Pollut Res Int 2021 Mar 27. Epub 2021 Mar 27.

Beijing Research Center for Information Technology in Agriculture, Beijing, 100097, China.

Spatiotemporal variations of industrial carbon emissions (IE) must be scientifically understood, which will be helpful to formulate reasonable emission reduction strategies. Given that spatial distribution of IE is irrelevant to space agents commonly used (such as population and nighttime light), estimation and spatialization methods for total carbon dioxide (CO) emissions are not entirely suitable for IE. Therefore, this paper used greenhouse gases observing satellite level 4A product to estimate IE at the city level and used industrial land density to obtain the distribution of IE within the administrative districts. Sectoral emission inventories of 182 cities and a mosaic Asian anthropogenic emission inventory named MIX were used to verify the results. Then, spatiotemporal variation characteristics of China's IE were analyzed from multiple levels. Results showed that (1) the mean relative error of estimation results was 56.11%, among which 62 cities had relative error of less than 30%. Gridded IE in this paper had high consistency with MIX. (2) Cities with high IE experienced rapid growth from 2009 to 2012, followed by slower growth from 2012 to 2017. (3) Centroid of significant cold and hot spots moved to the southeast and northwest, respectively. Most cities with high annual IE growth had relatively low emission efficiency, mainly located in Inner Mongolia and Xinjiang. Aggregation of medium and high IE grids may represent high emission efficiency. Significant differences still exist between cities in IE, and sustainable development strategies should be formulated according to local conditions. Regions with high annual growth or low emission efficiency are the key to achieving IE reduction targets in future.
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http://dx.doi.org/10.1007/s11356-021-13092-5DOI Listing
March 2021

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.

Rapid Commun Mass Spectrom 2021 Jun;35(11):e9083

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China.

Rationale: Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes.

Methods: An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap MS).

Results: The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1-M5) of glimepiride were found, and they were named 3N-hydroxyglimepiride, hydroxyglimepiride, 1,2-epoxy ether-3-hydroxyglimepiride, 1N-hydroxyglimepiride and 1N,2C,S,O,O-epoxy ether-3-hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2.

Conclusions: An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.
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http://dx.doi.org/10.1002/rcm.9083DOI Listing
June 2021

Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway.

J Extracell Vesicles 2021 Mar 10;10(5):e12060. Epub 2021 Mar 10.

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

Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC) and associated with their poor prognosis. However, its underlying mechanisms remain elusive. Here, we developed an ESCC-induced cachexia mouse model using human xenograft ESCC cell lines and found that ESCC-derived extracellular vesicles (EVs) containing prolyl 4-hydroxylase subunit beta (P4HB) induced apoptosis of skeletal muscle cells. We further identified that P4HB promoted apoptotic response through activating ubiquitin-dependent proteolytic pathway and regulated the stability of phosphoglycerate dehydrogenase (PHGDH) and subsequent antiapoptotic protein Bcl-2. Additionally, we proved that the P4HB inhibitor, CCF642, not only rescued apoptosis of muscle cells in vitro, but also prevented body weight loss and muscle wasting in ESCC-induced cachexia mouse model. Overall, these findings demonstrate a novel pathway for ESCC-induced muscle wasting and advocate for the development of P4HB as a potential intervention target for cachexia in patients with ESCC.
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http://dx.doi.org/10.1002/jev2.12060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944388PMC
March 2021

Low Molecular Weight Oligosaccharide from C.A. Meyer against UV-Mediated Apoptosis and Inhibits Tyrosinase Activity In Vitro and In Vivo.

Evid Based Complement Alternat Med 2021 26;2021:8879836. Epub 2021 Feb 26.

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.

To find new anti-UV and whitening agents, 21 fractions isolated from three preparations of ginseng (white, red, and black ginseng) were screened, and their antioxidant effects on AAPH- or HO-induced damage were investigated. Furthermore, the protective effect against UV-mediated apoptosis and the tyrosinase inhibitory activity of the targeted fractions were evaluated in vitro and in a zebrafish model. Among all fractions, F10 from white ginseng was selected as having the strongest anti-UV and antimelanogenesis activities. This fraction exhibited excellent inhibitory effects on the pigmentation of zebrafish, which may be due to its potential tyrosinase inhibitory activity. Additionally, the chemical composition of F10 was evaluated by UPLC-MS and NMR instruments. The results indicated that F10 had a carbohydrate content of more than 76%, and the weight-average molecular weight was approximately 239 Da. Disaccharide sucrose was the main active compound in F10. These results suggest that F10 could be used as an ingredient for whitening cosmetics and regarded as an anti-UV filter in the future.
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http://dx.doi.org/10.1155/2021/8879836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935584PMC
February 2021

Effect of short-term exposure to particulate air pollution on heart rate variability in normal-weight and obese adults.

Environ Health 2021 Mar 16;20(1):29. Epub 2021 Mar 16.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, China.

Background: The adverse effects of particulate air pollution on heart rate variability (HRV) have been reported. However, it remains unclear whether they differ by the weight status as well as between wake and sleep.

Methods: A repeated-measure study was conducted in 97 young adults in Beijing, China, and they were classified by body mass index (BMI) as normal-weight (BMI, 18.5-24.0 kg/m) and obese (BMI ≥ 28.0 kg/m) groups. Personal exposures to fine particulate matter (PM) and black carbon (BC) were measured with portable exposure monitors, and the ambient PM/BC concentrations were obtained from the fixed monitoring sites near the subjects' residences. HRV and heart rate (HR) were monitored by 24-h Holter electrocardiography. The study period was divided into waking and sleeping hours according to time-activity diaries. Linear mixed-effects models were used to investigate the effects of PM/BC on HRV and HR in both groups during wake and sleep.

Results: The effects of short-term exposure to PM/BC on HRV were more pronounced among obese participants. In the normal-weight group, the positive association between personal PM/BC exposure and high-frequency power (HF) as well as the ratio of low-frequency power to high-frequency power (LF/HF) was observed during wakefulness. In the obese group, personal PM/BC exposure was negatively associated with HF but positively associated with LF/HF during wakefulness, whereas it was negatively correlated to total power and standard deviation of all NN intervals (SDNN) during sleep. An interquartile range (IQR) increase in BC at 2-h moving average was associated with 37.64% (95% confidence interval [CI]: 25.03, 51.51%) increases in LF/HF during wakefulness and associated with 6.28% (95% CI: - 17.26, 6.15%) decreases in SDNN during sleep in obese individuals, and the interaction terms between BC and obesity in LF/HF and SDNN were both statistically significant (p <  0.05). The results also suggested that the effects of PM/BC exposure on several HRV indices and HR differed in magnitude or direction between wake and sleep.

Conclusions: Short-term exposure to PM/BC is associated with HRV and HR, especially in obese individuals. The circadian rhythm of HRV should be considered in future studies when HRV is applied.
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http://dx.doi.org/10.1186/s12940-021-00707-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968215PMC
March 2021

Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats.

World J Gastroenterol 2021 Feb;27(8):708-724

Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China.

Background: A recent investigation showed that the prevalence of type 2 diabetes mellitus (T2DM) is 12.8% among individuals of Han ethnicity. Gut microbiota has been reported to play a central role in T2DM. Goto-Kakizaki (GK) rats show differences in gut microbiota compared to non-diabetic rats. Previous studies have indicated that berberine could be successfully used to manage T2DM. We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.

Aim: To determine whether berberine can regulate glucose metabolism in GK rats the gut microbiota.

Methods: GK rats were acclimatized for 1 wk. The GK rats were randomly divided into three groups and administered saline (Mo), metformin (Me), or berberine (Be). The observation time was 8 wk, and weight, fasting blood glucose (FBG), insulin, and glucagon-like peptide-1 (GLP-1) were measured. Pancreatic tissue was observed for pathological changes. Additionally, we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.

Results: Compared with the Mo group, the Me and Be groups displayed significant differences in FBG ( < 0.01) and GLP-1 ( < 0.05). A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group ( < 0.01). The pancreatic islets of the Me- and Be-treated rats showed improvement in number, shape, and necrosis compared with those of Mo-treated rats. A total of 580 operational taxonomic units were obtained in the three groups. Compared to the Mo group, the Me and Be groups showed a shift in the structure of the gut microbiota. Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014 ( < 0.01) and negatively correlated with ( < 0.01). Body weight showed a positive correlation with ( < 0.01) and a negative correlation with ( < 0.01). Importantly, our results demonstrated that Me and Be could significantly decrease ( < 0.01) and the / ratio ( < 0.01). Furthermore, ( < 0.01; < 0.05) was significantly decreased in the Me and Be groups, and ( < 0.01) was significantly increased.

Conclusion: Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.
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http://dx.doi.org/10.3748/wjg.v27.i8.708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934002PMC
February 2021

Environmental enrichment implies GAT-1 as a potential therapeutic target for stroke recovery.

Theranostics 2021 27;11(8):3760-3780. Epub 2021 Jan 27.

Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation. We used multifaceted approaches combining electrophysiology, chemogenetics, optogenetics, and floxed mice in a mouse photothrombotic stroke model to reveal the key target of EE-mediated stroke recovery. EE reduced tonic gamma-aminobutyric acid (GABA) inhibition and facilitated phasic GABA inhibition in the peri-infarct cortex, thereby promoting network excitability and stroke recovery. These beneficial effects depended on GAT-1, a GABA transporter regulating both tonic and phasic GABA signaling, as EE positively regulated GAT-1 expression, trafficking, and function. Furthermore, GAT-1 was necessary for EE-induced network plasticity, including structural neuroplasticity, input synaptic strengthening in the peri-infarct cortex, output synaptic strengthening in the corticospinal tract, and sprouting of uninjured corticospinal axons across the midline into the territory of denervated spinal cord, and functional recovery from stroke. Moreover, restoration of GAT-1 function in the peri-infarct cortex by its overexpression showed similar beneficial effects on stroke recovery as EE exposure. GAT-1 is a key molecular substrate of the effects of EE on network excitability and consequent stroke recovery and can serve as a novel therapeutic target for stroke treatment during the repair phase.
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http://dx.doi.org/10.7150/thno.53316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914370PMC
January 2021

The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity.

Cell Metab 2021 Mar;33(3):565-580.e7

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China. Electronic address:

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.
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http://dx.doi.org/10.1016/j.cmet.2021.02.007DOI Listing
March 2021

The Effect of Infection on CD86 Expression in THP-1 Cells.

Infect Drug Resist 2021 19;14:651-660. Epub 2021 Feb 19.

Department of Dermatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.

Background: () is a destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of mainly depends on the innate immune response.

Objective: To investigate whether can inhibit the expression of CD86 in THP-1 cells after infection and discuss the potential mechanisms.

Methods: Western blot and immunoelectron microscopy were used to detect the CD86 expression on cultured on BHI medium at 37°C. Western blot, enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with . Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on incubating with macrophages.

Results: did not express CD86 when cultured separately at 37°C detected by Western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by Western blot, enzyme-linked immunoassay and immunofluorescence.

Conclusion: 1) After infection, CD86 expression on THP-1 decreased, and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared; 2) may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.
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http://dx.doi.org/10.2147/IDR.S297160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903953PMC
February 2021

Troxerutin Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

J Agric Food Chem 2021 Mar 23;69(9):2729-2744. Epub 2021 Feb 23.

Department of Cell Biology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221009, Jiangsu, China.

Screening potential compounds for improving ulcerative colitis (UC) from clinical medication is an effective strategy for drug repurposing. We applied bioinformatics and network pharmacology to the drug screening process in this study, which helped us to screen out troxerutin that could improve UC. Troxerutin belongs to flavonoids and is used clinically as an anticoagulant and thrombolytic agent. This study found a new pharmacological activity of troxerutin, that is, it had a significant improvement effect on UC in mice. Experimental results of and levels showed that troxerutin could effectively reduce the level of oxidative stress that caused damages in intestinal epithelial cells and colonic tissue, maintain the distribution and expression of tight junction-related proteins, and protect the barrier function of colon tissue. In addition to the oxidative stress, severe inflammatory response is also an important pathological factor that aggravates UC. However, troxerutin could reduce the infiltration of inflammatory cells in the colon tissue and decrease the expression of inflammation-related proteins and proinflammatory cytokines. Due to its antioxidant and anti-inflammatory effects, troxerutin inhibited the process of cell apoptosis in the colon tissue and relieved the degree of colonic fibrosis. Bioinformatics analysis showed that the ameliorating effect of troxerutin on UC was probably related to its network regulation of signaling pathways. In summary, we discovered a new pharmacological activity of the flavonoid troxerutin against UC, which is conducive to the expansion and application of flavonoids in the treatment of human diseases.
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http://dx.doi.org/10.1021/acs.jafc.0c06755DOI Listing
March 2021

Two PGPR strains from the rhizosphere of Haloxylon ammodendron promoted growth and enhanced drought tolerance of ryegrass.

Plant Physiol Biochem 2021 Apr 5;161:74-85. Epub 2021 Feb 5.

State Key Laboratory of Grassland Agro-ecosystems, Center of Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730000, PR China. Electronic address:

Haloxylon ammodendron, a typical xerophyte, tolerates various abiotic stresses and is widely distributed in desert areas. Two PGPR strains, Bacillus sp. WM13-24 and Pseudomonas sp. M30-35, were previously isolated from the rhizosphere of H. ammodendron in Tengger Desert, Gansu province, northwest China. The aim of this study was to investigate the role of M30-35 and WM13-24 in drought stress alleviation of ryegrass (Lolium perenne L.). Under normal condition, both M30-35 and WM13-24 increased shoot fresh and dry weight, chlorophyll content, total nitrogen and phosphorus contents and altered phytohormone distribution compared to control. Moreover, after 7 days of drought stress, WM13-24 and M30-35 enhanced photosynthetic capacity, relative water content, the activities of catalase (CAT) and peroxidase (POD) and proline content, resulted in decreased malondialdehyde (MDA) content, relative membrane permeability (RMP) and HO accumulation; interestingly, the two strains decreased ABA content in leaves. This study demonstrated that the two PGPR strains promoted ryegrass growth and root development via regulating plant hormone distribution and enhanced drought tolerance of ryegrass through improving the activities of antioxidant enzymes, regulating ABA signaling and maintaining plant growth. Our results indicated that PGPR strains from rhizosphere of the desert plant species could be considered as promising bioinoculants for grass plants.
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http://dx.doi.org/10.1016/j.plaphy.2021.02.003DOI Listing
April 2021

Erratum to comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms' tumor.

Ann Transl Med 2021 Jan;9(1):96

Department of Pediatric Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

[This corrects the article DOI: 10.21037/atm-20-6047.].
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http://dx.doi.org/10.21037/atm-2020-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859745PMC
January 2021

Economic and social drivers of antibiotic dispensing practices among community pharmacies in Nepal.

Trop Med Int Health 2021 May 4;26(5):557-571. Epub 2021 Mar 4.

Global Health Initiative, Henry Ford Health System, Detroit, MI, USA.

Objective: To assess economic and social drivers of dispensing antibiotics without prescription by community pharmacies in Nepal.

Method: A survey was conducted among 111 pharmacy owners and managers in five districts. Information on demographic and economic characteristics of the pharmacies (e.g. revenue and profits from antibiotics) and their inclination to sell antibiotics without a physician's prescription under various scenarios (e.g. diarrhoea in a child) was collected. Univariate analysis was conducted to assess the demographic and economic characteristics. Bivariate analysis was conducted to examine the relationship between dispensing antibiotics without prescription and economic and social factors.

Results: Azithromycin and amoxicillin were the most commonly dispensed antibiotics. The proportions of pharmacies reporting that they would 'most likely' or 'likely' dispense antibiotics without prescription to adult patients ranged from 36.9% (sore throat) to 67.6% (cough). The proportions for paediatric patients ranged from 62.2% (sore throat) to 80.2% (cough or diarrhoea). There was no consistent relationship between the likelihood of dispensing antibiotics and revenues, profits or the number of patients. Instead, dispensing behaviour was influenced by the pressure from the patient; the respondents were more likely to dispense antibiotics when the patient specifically asked for 'an antibiotic' rather than for 'a medicine', and 68.5% respondents ranked 'customer satisfaction' as the most important factor motivating their work.

Conclusions: In Nepal, inappropriate sale of antibiotics by community pharmacists is high, particularly for paediatric patients. Additional research is needed to establish key drivers of this behaviour and to help design effective approaches to reducing AMR.
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http://dx.doi.org/10.1111/tmi.13555DOI Listing
May 2021

Fusing crash data and surrogate safety measures for safety assessment: Development of a structural equation model with conditional autoregressive spatial effect and random parameters.

Accid Anal Prev 2021 Mar 25;152:105971. Epub 2021 Jan 25.

Department of Computational Modeling and Simulation Engineering, Old Dominion University, 4700 Elkhorn Ave, Norfolk, VA, 23529, USA. Electronic address:

Most existing efforts to assess safety performance require sufficient crash data, which generally takes a few years to collect and suffers from certain limitations (such as long data collection time, under-reporting issue and so on). Alternatively, the surrogate safety measure (SSMs) based approach that can assess traffic safety by capturing the more frequent "near-crash" situations have been developed, but it is criticized for the potential sampling and measurement errors. This study proposes a new safety performance measure-Risk Status (RS), by fusing crash data and SSMs. Real-world connected vehicle data collected in the Safety Pilot Model Deployment (SPMD) project in Ann Arbor, Michigan is used to extract SSMs. With RS treated as a latent variable, a structural equation model with conditional autoregressive spatial effect and corridor-level random parameters is developed to model the interrelationship among RS, crash frequency, risk identified by SSMs, and contributing factors. The modeling results confirm the proposed interrelationship and the necessity to account for both spatial autocorrelation and unobserved heterogeneity. RS can integrate both crash frequency and SSMs together while controlling for observed and unobserved factors. RS is found to be a more reliable criterion for safety assessment in an implementation case of hotspot identification.
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http://dx.doi.org/10.1016/j.aap.2021.105971DOI Listing
March 2021

Potential Effects of Nutraceuticals in Retinopathy of Prematurity.

Life (Basel) 2021 Jan 22;11(2). Epub 2021 Jan 22.

Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Retinopathy of prematurity (ROP), the most common cause of childhood blindness, is a hypoxia-induced eye disease characterized by retinal neovascularization. In the normal retina, a well-organized vascular network provides oxygen and nutrients as energy sources to maintain a normal visual function; however, it is disrupted when pathological angiogenesis is induced in ROP patients. Under hypoxia, inadequate oxygen and energy supply lead to oxidative stress and stimulate neovasculature formation as well as affecting the function of photoreceptors. In order to meet the metabolic needs in the developing retina, protection against abnormal vascular formation is one way to manage ROP. Although current treatments provide beneficial effects in reducing the severity of ROP, these invasive therapies may also induce life-long consequences such as systemic structural and functional complications as well as neurodevelopment disruption in the developing infants. Nutritional supplements for the newborns are a novel concept for restoring energy supply by protecting the retinal vasculature and may lead to better ROP management. Nutraceuticals are provided in a non-invasive manner without the developmental side effects associated with current treatments. These nutraceuticals have been investigated through various in vitro and in vivo methods and are indicated to protect retinal vasculature. Here, we reviewed and discussed how the use of these nutraceuticals may be beneficial in ROP prevention and management.
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http://dx.doi.org/10.3390/life11020079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912639PMC
January 2021

SOX-5 activates a novel RORγt enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation.

Nat Commun 2021 01 20;12(1):481. Epub 2021 Jan 20.

Institute of Immunology, PLA, Third Military Medical University (Army Medical University), 400038, Chongqing, People's Republic of China.

T helper type 17 (Th17) cells have important functions in the pathogenesis of inflammatory and autoimmune diseases. Retinoid-related orphan receptor-γt (RORγt) is necessary for Th17 cell differentiation and functions. However, the transcriptional regulation of RORγt expression, especially at the enhancer level, is still poorly understood. Here we identify a novel enhancer of RORγt gene in Th17 cells, RORCE2. RORCE2 deficiency suppresses RORγt expression and Th17 differentiation, leading to reduced severity of experimental autoimmune encephalomyelitis. Mechanistically, RORCE2 is looped to RORγt promoter through SRY-box transcription factor 5 (SOX-5) in Th17 cells, and the loss of SOX-5 binding site in RORCE abolishes RORCE2 function and affects the binding of signal transducer and activator of transcription 3 (STAT3) to the RORγt locus. Taken together, our data highlight a molecular mechanism for the regulation of Th17 differentiation and functions, which may represent a new intervening clue for Th17-related diseases.
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http://dx.doi.org/10.1038/s41467-020-20786-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817841PMC
January 2021

Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy.

Stem Cells 2021 Apr 18;39(4):467-481. Epub 2021 Jan 18.

Department of Orthopaedics, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China.

Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)-derived exosomes (N-Exos) and degenerated CESC-derived exosomes (D-Exos) in vitro and in vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N-Exos and D-Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. N-Exos were more conducive to autophagy activation than D-Exos. The apoptotic rate of NPCs decreased obviously after treatment with N-Exos compared to D-Exos. N-Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP.
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http://dx.doi.org/10.1002/stem.3322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048856PMC
April 2021

Corrigendum to "A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma" [EBioMedicine 41 (2019) 244-255].

EBioMedicine 2021 Jan 6;63:103041. Epub 2021 Jan 6.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2020.103041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804599PMC
January 2021

3D modeling of coherence scanning interferometry on 2D surfaces using FEM.

Opt Express 2020 Dec;28(26):39807-39826

Despite the fact that optical profilers, such as coherence scanning interferometers, are frequently used for fast and contactless topography measurements in various fields of application, measured profiles still suffer from the wave characteristics of light, which leads to systematic deviations that are still not sufficiently investigated. In order to analyze these systematic deviations and their physical relations, we apply a rigorous simulation model considering both the transfer characteristics of the measurement instrument as well as the geometry and material of different measurement objects. Simulation results are compared to measurement results for different polarizations, wavelengths and interferometer types, considering surface structures including edges, slopes and different materials as the main reasons for those deviations. Compared to former publications, a full three-dimensional (3D) modeling of the image formation with regard to two-dimensional (2D) surface structures is provided. The advantages of 3D modeling in contrast to a time efficient 2D approach are discussed. Further, an extract of an atomic force microscope (AFM) measurement result is used as the basis for the FEM simulation in one example in order to achieve most realistic simulation results.
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http://dx.doi.org/10.1364/OE.411167DOI Listing
December 2020

The burden of serious non-AIDS-defining events among admitted cART-naive AIDS patients in China: An observational cohort study.

PLoS One 2020 22;15(12):e0243773. Epub 2020 Dec 22.

Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

The objective of this study was to elucidate the burden, risk factors, and prognosis of serious non-AIDS-defining events among admitted cART-naive AIDS patients in China. The evaluation of the burden, risk factors and prognosis of serious NADEs was carried out among 1309 cART-naive AIDS patients (median age: 38.2 years, range: 18-78 years) admitted in Beijing Ditan Hospital between January 2009 and December 2018. Among 1309 patients, 143 patients (10.9%) had at least one serious NADEs, including 49 (3.8%) with cerebrovascular diseases, 37 (2.8%) with non-AIDS-defining cancers, 28 (2.1%) with chronic kidney diseases, 26 (2.0%) with cardiovascular diseases, and 18 (1.4%) with liver cirrhosis. Serious NADEs distributed in different age and CD4 levels, especially with age ≥50 years and CD4 ≤350 cells/ul. Other traditional risk factors, including cigarette smoking (OR = 1.9, 95%CI = 1.3-2.8, p = 0.002), hypertension (OR = 2.5, 95%CI = 1.7-3.7, p<0.001), chronic HCV infection (OR = 2.8, 95%CI = 1.4-5.6, p = 0.004), and hypercholesterolemia (OR = 4.1, 95% CI = 1.2-14.1, p = 0.026), were also associated with serious NADEs. Seventeen cases (1.3%) with serious NADEs died among hospitalized cART-naive AIDS patients, and severe pneumonia (HR = 5.5, 95%CI = 1.9-15.9, p<0.001) and AIDS-defining cancers (HR = 3.8, 95%CI = 1.1-13.2, p = 0.038) were identified as risk factors associated with an increased hazard of mortality among these patients with serious NADEs. Serious NADEs also occurred in cART-naive AIDS patients in China with low prevalence. Our results reminded physicians that early screening of serious NADEs, timely intervention of their risk factors, management of severe AIDS-defining events, multi-disciplinary cooperation, and early initiation of cART were essential to reduce the burden of serious NADEs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243773PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755215PMC
January 2021