Publications by authors named "Lihua Li"

417 Publications

Generation of Marker-Free Transgenic Rice Resistant to Rice Blast Disease Using Transposon-Mediated Transgene Reintegration System.

Front Plant Sci 2021 20;12:644437. Epub 2021 Apr 20.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Rice blast is one of the most serious diseases of rice and a major threat to rice production. Breeding disease-resistant rice is one of the most economical, safe, and effective measures for the control of rice blast. As a complement to traditional crop breeding, the transgenic method can avoid the time-consuming process of crosses and multi-generation selection. In this study, maize () Activator ()/Dissociation () transposon vectors carrying green fluorescent protein (GFP) and red fluorescent protein (mCherry) genetic markers were used for generating marker-free transgenic rice. Double fluorescent protein-aided counterselection against the presence of T-DNA was performed together with polymerase chain reaction (PCR)-based positive selection for the gene of interest (GOI) to screen marker-free progeny. We cloned an RNAi expression cassette of the rice gene that negatively regulates resistance to rice blast as a GOI into the element in the vector and obtained marker-free T1 rice plants from 13 independent transgenic lines. Marker-free and /GOI-homozygous rice lines were verified by PCR and Southern hybridization analysis to be completely free of transgenic markers and T-DNA sequences. qRT-PCR analysis and rice blast disease inoculation confirmed that the marker-free transgenic rice lines exhibited decreased expression levels and increased resistance to rice blast. TAIL-PCR results showed that the (-RNAi) transgenes in two rice lines were reintegrated in intergenic regions in the rice genome. The vector with dual fluorescent protein markers offers more reliable screening of marker-free transgenic progeny and can be utilized in the transgenic breeding of rice disease resistance and other agronomic traits.
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http://dx.doi.org/10.3389/fpls.2021.644437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095379PMC
April 2021

Examining the role of healthcare access in racial/ethnic disparities in receipt of provider-patient discussions about smoking: A latent class analysis.

Prev Med 2021 Apr 27;148:106584. Epub 2021 Apr 27.

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America; Tisch Cancer Institute, New York, NY, United States of America; Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.

Using insurance as a single indicator of healthcare access in examining the association between race/ethnicity and healthcare encounter-based interventions for smoking may not be adequate. In this study, we assessed the role of healthcare access using multifactorial measures in accounting for racial/ethnic disparities in the receipt of provider-patient discussions, defined as either being asked about smoking or advised to quit smoking by providers. We identified adult current smokers from the 2015 National Health Interview Survey. We first conducted a latent class analysis (LCA) to identify the underlying patterns of healthcare access measured by 13 indicators of healthcare access and utilization. We then used a propensity score - based weighting approach to examine racial/ethnic disparities in receiving provider-patient discussions about smoking or quitting in stratified groups by the distinct healthcare access clusters. Out of the 4134 adult current smokers who visited a doctor or a healthcare provider during the past 12 months, 3265 (79.90%) participants were classified as having high healthcare access and 869 (20.10%) participants as having low healthcare access. Compared to non-Hispanic whites, Hispanics had significantly lower odds of being asked about smoking (OR 0.46, 95% CI (0.27-0.77)) and being advised to quit (OR 0.57, 95% CI (0.34-0.97)) in the low access group, but neither association was significant in the high access group. In addition to increasing health insurance coverage, reducing other healthcare access barriers for Hispanics will likely facilitate provider-patient discussion and promote tobacco cessation among Hispanic smokers.
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http://dx.doi.org/10.1016/j.ypmed.2021.106584DOI Listing
April 2021

The Influence of Increasing Levels of Provider-Patient Discussion on Quit Behavior: An Instrumental Variable Analysis of a National Survey.

Int J Environ Res Public Health 2021 Apr 26;18(9). Epub 2021 Apr 26.

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.

Objective: We aimed to examine the influence of increasing levels of discussion (both asked and advised, either asked or advised but not both, and neither asked nor advised) on quit behavior.

Methods: We included 4133 adult current smokers from the 2015 National Health Interview Survey. The primary outcomes were quit intent and quit attempt, and the secondary outcomes were methods used for quitting. We used an instrumental variable analysis, as well as propensity score weighted and multivariable logistic regressions.

Results: Compared to no discussion, having both or only one discussion, respectively, increased quit intent (OR = 1.65, 95% CI = 1.63-1.66 and OR = 1.02, 95% CI = 0.99-1.05), quit attempt (OR = 1.76, 95% CI = 1.75-1.77 and OR = 1.60, 95% CI = 1.57-1.63). Among those who attempted to quit (n = 1536), having both or only one discussion increased the use of pharmacologic (OR = 1.99, 95% CI = 1.97-2.02 and OR = 1.56, 95% CI = 1.49-1.63) or behavioral (OR = 2.01, 95% CI = 1.94-2.08 and OR = 2.91, 95% CI = 2.74-3.08) quit methods.

Conclusions: Increasing levels of provider-patient discussion encourages quit behavior, and should be an integral part of reducing the health and economic burden of smoking. Strategies that promote the adherence and compliance of providers to communicate with patients may help increase the success of smoking cessation.
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http://dx.doi.org/10.3390/ijerph18094593DOI Listing
April 2021

Hemostatic performance of chitosan-based hydrogel and its study on biodistribution and biodegradability in rats.

Carbohydr Polym 2021 Jul 26;264:117965. Epub 2021 Mar 26.

Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, PR China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, PR China. Electronic address:

Hemostasis is of great significance regardless of the smooth operation or postoperative recovery. Therefore, it is urgent to develop a hemostatic material with excellent biodegradability and biocompatibility. It is well known that both carboxymethyl chitosan and hyaluronic acid with biodegradability and biocompatibility have wound healing promoting property. Here, a degradable chitosan-based hydrogel was prepared based on carboxymethyl chitosan and cross-linked by oxidized hyaluronic acid. The hemostatic performance of the hydrogel in rat liver resection injury was evaluated which results showed that the hydrogel exhibited comparable hemostatic properties compared with Fibrin Sealant. In addition, the hydrogel proved to be rapidly absorbed by the body without significant accumulation in vivo, demonstrating good biodegradability and biocompatibility. The overall results suggested the hydrogel will be a promising hemostatic hydrogel for controlling bleeding.
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http://dx.doi.org/10.1016/j.carbpol.2021.117965DOI Listing
July 2021

Depletion of CIP2A inhibits the proliferation, migration, invasion and epithelial-mesenchymal transition of glioma cells.

Brain Res Bull 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurosurgery, The second Affiliated Hospital of Kunming Medical University, Kunming, 650223, China. Electronic address:

CIP2A is an oncoprotein that is overexpressed in multiple solid tumours and some malignant haematologic disorders. However, its function in glioma is poorly understood. In this study, our results demonstrated that the expression of CIP2A was higher in glioma tissues than in normal tissues. Using tissue microarrays for immunohistochemistry, we found that the intensity of CIP2A expression was higher in high-grade gliomas (grade III-IV) than in low-grade gliomas (grade I-II). In addition, we found that depletion of CIP2A inhibited glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Taken together, our findings revealed that CIP2A was involved in glioma progression, indicating that CIP2A could be used as a potential therapeutic target in the future.
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http://dx.doi.org/10.1016/j.brainresbull.2021.04.009DOI Listing
April 2021

Paricalcitol inhibits oxidative stress-induced cell senescence of the bile duct epithelium dependent on modulating Sirt1 pathway in cholestatic mice.

Free Radic Biol Med 2021 Apr 16;169:158-168. Epub 2021 Apr 16.

Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, PR China. Electronic address:

Background: Clinical studies indicate that vitamin D receptor (VDR) expression is reduced in primary biliary cirrhosis patient livers. However, the mechanism by which activated VDR effect cholestatic liver injury remains unclear.

Methods: Mice were injected intraperitoneally with the VDR agonist paricalcitol or a vehicle 3 days prior to bile duct ligation (BDL) and for 5 or 28 days after surgery. The analyses of liver morphology and necrotic areas were based on H&E staining. Serum biochemical indicators of liver damage were analyzed by commercial kits. The mechanisms of paricalcitol on cholestatic liver injury were determined by Western blot analysis.

Results: Paricalcitol ameliorated the BDL-induced liver damage in mice. Paricalcitol increased the proliferation of BECs to promote the repair of the bile duct. Paricalcitol also reduced the BDL-induced oxidative stress level in the mice. Mechanistic analysis revealed that paricalcitol decreased the number of SA-β-gal-positive cells and downregulated the expression of p53, p21 and p16 proteins which was associated with reducing oxidative stress. Additionally, paricalcitol exerted the inhibitory effect of cell senescence was through reducing DNA damage and promoting DNA repair. Interesting, we found that paricalcitol prevented the downregulation of oxidative stress-induced Sirt1 expression in the BDL mice and t-BHP-induced BECs models. Moreover, paricalcitol suppressed cell senescence through a Sirt1-dependent pathway. These results were confirmed by antioxidant ALCAR and the Sirt1 inhibitor EX-527.

Conclusion: Paricalcitol alleviated cholestatic liver injury through promoting the repair of damaged bile ducts and reducing oxidative stress-induced cell senescence of the bile duct via modulating Sirt1 pathway.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.019DOI Listing
April 2021

Radiomics of Tumor Heterogeneity in Longitudinal Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer.

Front Mol Biosci 2021 22;8:622219. Epub 2021 Mar 22.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.

Breast tumor morphological and vascular characteristics can be changed during neoadjuvant chemotherapy (NACT). The early changes in tumor heterogeneity can be quantitatively modeled by longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is useful in predicting responses to NACT in breast cancer. In this retrospective analysis, 114 female patients with unilateral unifocal primary breast cancer who received NACT were included in a development ( = 61) dataset and a testing dataset ( = 53). DCE-MRI was performed for each patient before and after treatment (two cycles of NACT) to generate baseline and early follow-up images, respectively. Feature-level changes (delta) of the entire tumor were evaluated by calculating the relative net feature change (deltaRAD) between baseline and follow-up images. The voxel-level change inside the tumor was evaluated, which yielded a Jacobian map by registering the follow-up image to the baseline image. Clinical information and the radiomic features were fused to enhance the predictive performance. The area under the curve (AUC) values were assessed to evaluate the prediction performance. Predictive models using radiomics based on pre- and post-treatment images, Jacobian maps and deltaRAD showed AUC values of 0.568, 0.767, 0.630 and 0.726, respectively. When features from these images were fused, the predictive model generated an AUC value of 0.771. After adding the molecular subtype information in the fused model, the performance was increased to an AUC of 0.809 (sensitivity of 0.826 and specificity of 0.800), which is significantly higher than that of the baseline imaging- and Jacobian map-based predictive models ( = 0.028 and 0.019, respectively). The level of tumor heterogeneity reduction (evaluated by texture feature) is higher in the NACT responders than in the nonresponders. The results suggested that changes in DCE-MRI features that reflect a reduction in tumor heterogeneity following NACT could provide early prediction of breast tumor response. The prediction was improved when the molecular subtype information was combined into the model.
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http://dx.doi.org/10.3389/fmolb.2021.622219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044916PMC
March 2021

Evaluating the association between extreme heat and mortality in urban Southwestern Ontario using different temperature data sources.

Sci Rep 2021 Apr 14;11(1):8153. Epub 2021 Apr 14.

ICES, Toronto, ON, Canada.

Urban areas have complex thermal distribution. We examined the association between extreme temperature and mortality in urban Ontario, using two temperature data sources: high-resolution and weather station data. We used distributed lag non-linear Poisson models to examine census division-specific temperature-mortality associations between May and September 2005-2012. We used random-effect multivariate meta-analysis to pool results, adjusted for air pollution and temporal trends, and presented risks at the 99th percentile compared to minimum mortality temperature. As additional analyses, we varied knots, examined associations using different temperature metrics (humidex and minimum temperature), and explored relationships using different referent values (most frequent temperature, 75th percentile of temperature distribution). Weather stations yielded lower temperatures across study months. U-shaped associations between temperature and mortality were observed using both high-resolution and weather station data. Temperature-mortality relationships were not statistically significant; however, weather stations yielded estimates with wider confidence intervals. Similar findings were noted in additional analyses. In urban environmental health studies, high-resolution temperature data is ideal where station observations do not fully capture population exposure or where the magnitude of exposure at a local level is important. If focused upon temperature-mortality associations using time series, either source produces similar temperature-mortality relationships.
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http://dx.doi.org/10.1038/s41598-021-87203-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046761PMC
April 2021

Donor Family History of ESKD and Long-term Outcomes Among African American Living Kidney Donors: A Retrospective Cohort Study.

Kidney Med 2021 Mar-Apr;3(2):223-230.e1. Epub 2021 Feb 6.

Division of Nephrology, University of Michigan, Ann Arbor, MI.

Rationale & Objective: Live kidney donation is associated with a small increased risk for kidney disease and hypertension in African American donors. We investigated a possible association between donor family history of end-stage kidney disease (ESKD) and their postdonation kidney function and the development of hypertension. We tested whether this association was modified by kidney donation.

Study Design: Retrospective cohort.

Setting & Participants: Former African American live kidney donors between 1993 and 2010. Healthy nondonors were selected from the Coronary Artery Disease in Young Adults (CARDIA) Study.

Exposure: Family history of ESKD in a first-degree relative.

Outcomes: Kidney function and blood pressure ≥ 140/90 mm Hg or use of antihypertensive medications at follow-up.

Analytical Approach: Donors were grouped based on family history of ESKD. Outcomes were first compared between donor groups and then between donors and healthy nondonors matched for demographics, follow-up time, and family history. A mixed-effect model was used to compare outcomes.

Results: Of 179 donors, 139 (78%) had a first degree relative with ESKD. Predonation characteristics were similar between the 2 groups. At a median follow-up of 11 years postdonation, there was no difference in postdonation estimated glomerular filtration rates (68 ± 19 vs 69 ± 13 mL/min/1.73 m;  = 0.71) and the presence of albuminuria ( = 0.16). There was a trend toward a higher incidence of hypertension (51% vs 35%;  = 0.08) among donors with a family history of ESKD than for those without. Although there was no difference in annual change in estimated glomerular filtration rate ( = 0.17), the risk for hypertension was higher in donors than nondonors (relative risk, 2.44 [95% CI, 1.56-3.84]), but there was no interaction by family history ( = 0.11).

Limitations: Retrospective small study. Lack of data across donor-recipient specific biological relationship.

Conclusions: Family history of ESKD is not associated with postdonation kidney function among African American kidney donors. Live kidney donation is associated with an increased risk for hypertension among African Americans, independent of donor family history of ESKD.
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http://dx.doi.org/10.1016/j.xkme.2020.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039402PMC
February 2021

Hsa-miR-155 regulates the cell cycle and barrier function of corneal endothelial cells through E2F2.

Am J Transl Res 2021 15;13(3):1505-1515. Epub 2021 Mar 15.

Department of Optometry Center, Tianjin Eye Hospital Tianjin 300022, China.

This study was aimed to determine the role of has-miR-155 and E2F2 on corneal endothelial cells. Real-time quantitative PCR and Western blot assays were carried out to determine the levels of has-miR-155 and E2F2, and Flow cytometry assay was conducted to detect cell cycle. In addition, Targetscan7.2 was adopted to analyze the internal connection between hsa-miR-155 and E2F2, and a dual luciferase reporter gene assay to determine predicted site between has-miR-155 and E2F2. Increased hsa-miR-155 resulted in decreased E2F2, while decreased hsa-miR-155 increased the level of E2F2. In addition, both increased hsa-miR-155 and decreased E2F2 led to an increase in S-phase cells and a decrease in G1-phase cells. Also, they induced an increase in the activity of barrier-related proteins MLCK and ZO-1, an up-regulation of Cyclin D1 and Cyclin E1, and a down-regulation of apoptosis proteins (Caspase 3/Bax/Bim/Bid) whereas decreased hsa-miR-155 led to an opposite change in cells, and decreased E2F2 could offset cell changes caused by increased has-miR-155. In conclusion, Has-miR-155 regulates the cell cycle of corneal endothelial cells and improves their barrier function by down regulating E2F2.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014374PMC
March 2021

The effect of the Affordable Care Act dependent coverage provision on HPV vaccine uptake in young adult women, National Health and Nutrition Examination Survey 2007-2016.

Prev Med 2021 Mar 30;148:106536. Epub 2021 Mar 30.

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America; Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.

The human papillomavirus (HPV) vaccine protects against cancers caused by HPV. The study objective was to examine the effect of the Affordable Care Act (ACA) dependent child coverage provision on HPV vaccination initiation, HPV vaccine completion, HPV infection, and health insurance coverage among young women. Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2172 female participants were included. The impact of the dependent coverage provision on the four outcomes was examined using difference-in-difference analyses with linear probability regressions, controlling for race/ethnicity, age, income, head of household education, and family employment. ACA exposure group was operationalized by age, with those targeted by the dependent coverage provision (ages 19-25) serving as the intervention group and those similar in age but not targeted (ages 18 and 26) serving as the control group. From 2007 to 2016, HPV vaccine initiation, HPV vaccine completion, and health insurance prevalence increased and HPV infection prevalence decreased. In the difference-in-difference adjusted models, ACA exposure was not associated with HPV vaccine initiation (0.045 percentage points [95% CI -0.087, 0.178]), completion (-0.044 percentage points [95% CI -0.152, 0.063]), HPV 16/18 infection (-0.051 percentage points [95% CI -0.123, 0.021]), or health insurance (0.065 percentage points [95% CI -0.032, 0.162]) among women aged 19 to 25. The dependent coverage provision may not have addressed relevant barriers to HPV vaccination. However, given that the effect of the dependent coverage provision on HPV vaccination and health insurance has been demonstrated previously, small sample size is a concern.
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http://dx.doi.org/10.1016/j.ypmed.2021.106536DOI Listing
March 2021

Role of NFAT in the Progression of Diabetic Atherosclerosis.

Front Cardiovasc Med 2021 11;8:635172. Epub 2021 Mar 11.

Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Nuclear factor of activated T cells (NFAT) is a transcription factor with a multidirectional regulatory function, that is widely expressed in immune cells, including cells in the cardiovascular system, and non-immune cells. A large number of studies have confirmed that calcineurin/NFAT signal transduction is very important in the development of vascular system and cardiovascular system during embryonic development, and plays some role in the occurrence of vascular diseases such as atherosclerosis, vascular calcification, and hypertension. Recent and studies have shown that NFAT proteins and their activation in the nucleus and binding to DNA-related sites can easily ɨnduce the expression of downstream target genes that participate in the proliferation, migration, angiogenesis, and vascular inflammation of vascular wall related cells in various pathophysiological states. NFAT expression is regulated by various signaling pathways, including CD137-CD137L, and OX40-OX40L pathways. As a functionally diverse transcription factor, NFAT interacts with a large number of signaling molecules to modulate intracellular and extracellular signaling pathways. These NFAT-centered signaling pathways play important regulatory roles in the progression of atherosclerosis, such as in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. NFAT and related signaling pathways provide new therapeutic targets for vascular diseases such as atherosclerosis. Hence, further studies of the mechanism of NFAT in the occurrence and evolution of atherosclerosis remain crucial.
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http://dx.doi.org/10.3389/fcvm.2021.635172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006278PMC
March 2021

A Retrospective Study on the Use of Chinese Patent Medicine in 24 Medical Institutions for COVID-19 in China.

Front Pharmacol 2020 30;11:574562. Epub 2020 Nov 30.

Beijing University of Traditional Chinese Medicine, Beijing, China.

This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20-22, February 16-18, March 01-03, April 01-03, 2020), and explore its contribution to combating the disease. 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software. 1) The heat-clearing medicine was the main use category nationwide during January 20-22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16-18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions ( < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01-03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01-03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( < 0.01). Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.
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http://dx.doi.org/10.3389/fphar.2020.574562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990099PMC
November 2020

Role of PI3K in the Progression and Regression of Atherosclerosis.

Front Pharmacol 2021 9;12:632378. Epub 2021 Mar 9.

Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.
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http://dx.doi.org/10.3389/fphar.2021.632378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985550PMC
March 2021

Artesunate alleviates diabetic retinopathy by activating autophagy via the regulation of AMPK/SIRT1 pathway.

Arch Physiol Biochem 2021 Mar 4:1-8. Epub 2021 Mar 4.

Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, China.

Context: Artesunate (ART), an antimalarial drug, possesses the ability to induce autophagy and exhibits a protective effect on diabetes.

Objective: This study aimed to evaluate the effects of ART on diabetic retinopathy (DR) and to explore the underlying mechanisms.

Methods: Rats with streptozotocin-induced DR were given intravitreal injection of ART.

Results: ART administration inhibited the increase in retinal thickness and prevented blood-retinal barrier in diabetic rats. Further, vascular leukocyte adherence, microglial activation, inflammatory cytokine, and ROS production in the retinas of diabetic rats were also inhibited by ART. Additionally, ART enhanced autophagy in the retinas of diabetic rats as demonstrated by up-regulated Beclin-1 expression and LC3II/I ratio and down-regulated p62. ART also activated AMP-activated protein kinase (AMPK)/sensor class III histone deacetylase sirtuin 1 (SIRT1) pathway.

Conclusions: ART, as an autophagy activator, has therapeutic potential in DR treatment.
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http://dx.doi.org/10.1080/13813455.2021.1887266DOI Listing
March 2021

Three Statistical Approaches for Assessment of Intervention Effects: A Primer for Practitioners.

Risk Manag Healthc Policy 2021 22;14:757-770. Epub 2021 Feb 22.

Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Introduction: Statistical methods to assess the impact of an intervention are increasingly used in clinical research settings. However, a comprehensive review of the methods geared toward practitioners is not yet available.

Methods And Materials: We provide a comprehensive review of three methods to assess the impact of an intervention: difference-in-differences (DID), segmented regression of interrupted time series (ITS), and interventional autoregressive integrated moving average (ARIMA). We also compare the methods, and provide illustration of their use through three important healthcare-related applications.

Results: In the first example, the DID estimate of the difference in health insurance coverage rates between expanded states and unexpanded states in the post-Medicaid expansion period compared to the pre-expansion period was 5.93 (95% CI, 3.99 to 7.89) percentage points. In the second example, a comparative segmented regression of ITS analysis showed that the mean imaging order appropriateness score in the emergency department at a tertiary care hospital exceeded that of the inpatient setting with a level change difference of 0.63 (95% CI, 0.53 to 0.73) and a trend change difference of 0.02 (95% CI, 0.01 to 0.03) after the introduction of a clinical decision support tool. In the third example, the results from an interventional ARIMA analysis show that numbers of creatinine clearance tests decreased significantly within months of the start of eGFR reporting, with a magnitude of drop equal to -0.93 (95% CI, -1.22 to -0.64) tests per 100,000 adults and a rate of drop equal to 0.97 (95% CI, 0.95 to 0.99) tests per 100,000 per adults per month.

Discussion: When choosing the appropriate method to model the intervention effect, it is necessary to consider the structure of the data, the study design, availability of an appropriate comparison group, sample size requirements, whether other interventions occur during the study window, and patterns in the data.
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http://dx.doi.org/10.2147/RMHP.S275831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910529PMC
February 2021

Role of histone deacetylase Sirt3 in the development and regression of atherosclerosis.

Life Sci 2021 May 19;272:119178. Epub 2021 Feb 19.

Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. Electronic address:

Atherosclerosis (AS) is the most common cause of death in cardiovascular diseases and poses severe challenges to human life and safety. Epigenetics plays a vital role in every single link of AS. Whereas, how epigenetics regulates its development and regression is still unknown. Sirt3, a recognized histone deacetylase, having been reported to be involved in other acylation processes in recent years, is broadening its role in epigenetic modifications. Sirt3 is an important factor in the normal physiology of blood vessels through deacetylation of mitochondrial proteins and participates in various metabolic activities. Besides, medical research targeting Sirt3 is in full swing as well. This review combining histone deacetylase Sirt3 with AS, aims to clarify the latest progress in the significant role of Sirt3 in the development and regression of AS and to provide a novel prospect for a new regulatory factor and potential intervention target for AS.
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http://dx.doi.org/10.1016/j.lfs.2021.119178DOI Listing
May 2021

Screening of hypolipidemic active components in Jiang-Zhi-Ning and its preliminary mechanism research based on "active contribution value" study.

J Ethnopharmacol 2021 May 14;272:113926. Epub 2021 Feb 14.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. Electronic address:

Ethnopharmacological Relevance: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect.

Aim Of The Study: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula.

Materials And Methods: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MS) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN.

Results: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside.

Conclusions: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.
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http://dx.doi.org/10.1016/j.jep.2021.113926DOI Listing
May 2021

HMD-ARG: hierarchical multi-task deep learning for annotating antibiotic resistance genes.

Microbiome 2021 02 8;9(1):40. Epub 2021 Feb 8.

Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955, Saudi Arabia.

Background: The spread of antibiotic resistance has become one of the most urgent threats to global health, which is estimated to cause 700,000 deaths each year globally. Its surrogates, antibiotic resistance genes (ARGs), are highly transmittable between food, water, animal, and human to mitigate the efficacy of antibiotics. Accurately identifying ARGs is thus an indispensable step to understanding the ecology, and transmission of ARGs between environmental and human-associated reservoirs. Unfortunately, the previous computational methods for identifying ARGs are mostly based on sequence alignment, which cannot identify novel ARGs, and their applications are limited by currently incomplete knowledge about ARGs.

Results: Here, we propose an end-to-end Hierarchical Multi-task Deep learning framework for ARG annotation (HMD-ARG). Taking raw sequence encoding as input, HMD-ARG can identify, without querying against existing sequence databases, multiple ARG properties simultaneously, including if the input protein sequence is an ARG, and if so, what antibiotic family it is resistant to, what resistant mechanism the ARG takes, and if the ARG is an intrinsic one or acquired one. In addition, if the predicted antibiotic family is beta-lactamase, HMD-ARG further predicts the subclass of beta-lactamase that the ARG is resistant to. Comprehensive experiments, including cross-fold validation, third-party dataset validation in human gut microbiota, wet-experimental functional validation, and structural investigation of predicted conserved sites, demonstrate not only the superior performance of our method over the state-of-art methods, but also the effectiveness and robustness of the proposed method.

Conclusions: We propose a hierarchical multi-task method, HMD-ARG, which is based on deep learning and can provide detailed annotations of ARGs from three important aspects: resistant antibiotic class, resistant mechanism, and gene mobility. We believe that HMD-ARG can serve as a powerful tool to identify antibiotic resistance genes and, therefore mitigate their global threat. Our method and the constructed database are available at http://www.cbrc.kaust.edu.sa/HMDARG/ . Video abstract (MP4 50984 kb).
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http://dx.doi.org/10.1186/s40168-021-01002-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871585PMC
February 2021

[Comparative analysis of clinical features of primary and secondary laryngeal tuberculosis].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 01;35(1):38-41

Department of Otorhinolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Nanchang University,Nanchang,330006,China.

The aim of this study was to analyze and compare the clinical pattern, diagnosis and treatment in primary and secondary laryngeal and pharyngeal TB. A retrospective analysis was carried out on 103 patients diagnosed laryngeal tuberculosis in our department. Characteristics of demography, life-style, clinical features, diagnosis and treatment were obtained from medical case records. Clinical analysis of 103 patients with pathologically confirmed laryngeal TB was carried out retrospectively in the second affiliated hospital of Nanchang university in Jiangxi province. Among 103 patients, 64 cases were diagnosed as primary laryngeal TB and 39 cases were diagnosed as secondary laryngeal TB. The most common complaints were hoarseness and odynophagia. The true and the false vocal cords were most commonly involved. Most patients with primary tuberculosis of the larynx present a single, hyperplastic lesion.Secondary laryngeal TB of larynx was characterized by ulcers, edema effusive, multiple sites lesions. The anti-TB treatment was given systemically to all patients. The surgery should be considered if the patient has a laryngeal obstruction. The clinical manifestations and signs of primary and secondary tuberculosis of the larynx are different. Laryngeal tuberculosis is easy to be misdiagnosed as laryngitis and laryngeal tumors. Pathological examination should be performed to confirm the diagnosis.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.01.009DOI Listing
January 2021

Evaluation of Warpage and Residual Stress of Precision Glass Micro-Optics Heated by Carbide-Bonded Graphene Coating in Hot Embossing Process.

Authors:
Lihua Li Jian Zhou

Nanomaterials (Basel) 2021 Feb 1;11(2). Epub 2021 Feb 1.

School of Mechanical Engineering, Hefei University of Technology, Hefei 230009, China.

A newly developed hot embossing technique which uses the localized rapid heating of a thin carbide-bonded graphene (CBG) coating, greatly reduces the energy consumption and promotes the fabrication efficiency. However, because of the non-isothermal heat transfer process, significant geometric deviation and residual stress could be introduced. In this paper, we successfully facilitate the CBG-heating-based hot embossing into the fabrication of microlens array on inorganic glass N-BK7 substrate, where the forming temperature is as high as 800 °C. The embossed microlens array has high replication fidelity, but an obvious geometric warpage along the glass substrate also arises. Thermo-mechanical coupled finite element modelling of the embossing process is conducted and verified by the experimental results. Based on trial and error simulations, an appropriate compensation curvature is determined and adopted to modify the geometrical design of the silicon wafer mold. The warpage of the re-embossed microlens array is significantly decreased using the compensated mold, which demonstrates the feasibility of the simulation-oriented compensation scheme. Our work would contribute to improving the quality of optics embossed by this innovative CBG-heating-based hot embossing technique.
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http://dx.doi.org/10.3390/nano11020363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912754PMC
February 2021

Evaluating the Impact of New York's Executive Order on Face Mask Use on COVID-19 Cases and Mortality: a Comparative Interrupted Times Series Study.

J Gen Intern Med 2021 04 26;36(4):985-989. Epub 2021 Jan 26.

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: On April 17, 2020, the State of New York (NY) implemented an Executive Order that requires all people in NY to wear a face mask or covering in public settings where social distancing cannot be maintained. Although the Centers for Disease Control and Prevention recommended face mask use by the general public, there is a lack of evidence on the effect of face mask policies on the spread of COVID-19 at the state level.

Objective: To assess the impact of the Executive Order on face mask use on COVID-19 cases and mortality in NY.

Design: A comparative interrupted time series analysis was used to assess the impact of the Executive Order in NY with Massachusetts (MA) as a comparison state.

Participants: We analyzed data on COVID-19 in NY and MA from March 25 to May 6, 2020.

Intervention: The Executive Order on face mask use in NY.

Main Measures: Daily numbers of COVID-19 confirmed cases and deaths.

Key Results: The average daily number of confirmed cases in NY decreased from 8549 to 5085 after the Executive Order took effect, with a trend change of 341 (95% CI, 187-496) cases per day. The average daily number of deaths decreased from 521 to 384 during the same two time periods, with a trend change of 52 (95% CI, 44-60) deaths per day. Compared to MA, the decreasing trend in NY was significantly greater for both daily numbers of confirmed cases (P = 0.003) and deaths (P < 0.001).

Conclusions: The Executive Order on face mask use in NY led to a significant decrease in both daily numbers of COVID-19 confirmed cases and deaths. Findings from this study provide important evidence to support state-level policies that require face mask use by the general public.
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http://dx.doi.org/10.1007/s11606-020-06476-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837644PMC
April 2021

Transcriptomic analysis identifies organ-specific metastasis genes and pathways across different primary sites.

J Transl Med 2021 01 7;19(1):31. Epub 2021 Jan 7.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, 310000, China.

Background: Metastasis is the most devastating stage of cancer progression and often shows a preference for specific organs.

Methods: To reveal the mechanisms underlying organ-specific metastasis, we systematically analyzed gene expression profiles for three common metastasis sites across all available primary origins. A rank-based method was used to detect differentially expressed genes between metastatic tumor tissues and corresponding control tissues. For each metastasis site, the common differentially expressed genes across all primary origins were identified as organ-specific metastasis genes.

Results: Pathways enriched by these genes reveal an interplay between the molecular characteristics of the cancer cells and those of the target organ. Specifically, the neuroactive ligand-receptor interaction pathway and HIF-1 signaling pathway were found to have prominent roles in adapting to the target organ environment in brain and liver metastases, respectively. Finally, the identified organ-specific metastasis genes and pathways were validated using a primary breast tumor dataset. Survival and cluster analysis showed that organ-specific metastasis genes and pathways tended to be expressed uniquely by a subgroup of patients having metastasis to the target organ, and were associated with the clinical outcome.

Conclusions: Elucidating the genes and pathways underlying organ-specific metastasis may help to identify drug targets and develop treatment strategies to benefit patients.
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http://dx.doi.org/10.1186/s12967-020-02696-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791985PMC
January 2021

A multi-omics view of the complex mechanism of vascular calcification.

Biomed Pharmacother 2021 Mar 2;135:111192. Epub 2021 Jan 2.

Department of Cardiology, Affiliated Hospital of Jiangsu University, 212000, Zhenjiang, China. Electronic address:

Vascular calcification is a high incidence and high risk disease with increasing morbidity and high mortality, which is considered the consequence of smooth muscle cell transdifferentiation initiating the mechanism of accumulation of hydroxyl calcium phosphate. Vascular calcification is also thought to be strongly associated with poor outcomes in diabetes and chronic kidney disease. Numerous studies have been accomplished; however, the specific mechanism of the disease remains unclear. Development of the genome project enhanced the understanding of life science and has entered the post-genomic era resulting in a variety of omics techniques used in studies and a large amount of available data; thus, a new perspective on data analysis has been revealed. Omics has a broader perspective and is thus advantageous over a single pathway analysis in the study of complex vascular calcification mechanisms. This paper reviews in detail various omics studies including genomics, proteomics, transcriptomics, metabolomics and multiple group studies on vascular calcification. Advances and deficiencies in the use of omics to study vascular calcification are presented in a comprehensive view. We also review the methodology of the omics studies and omics data analysis and processing. In addition, the methodology and data processing presented here can be applied to other areas. An omics landscape perspective across the boundaries between genomics, transcriptomics, proteomics and metabolomics is used to examine the mechanisms of vascular calcification. The perspective combined with various technologies also provides a direction for the subsequent exploration of clinical significance.
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http://dx.doi.org/10.1016/j.biopha.2020.111192DOI Listing
March 2021

Discrete Element Modelling of the Mechanical Behavior of Sand-Rubber Mixtures under True Triaxial Tests.

Materials (Basel) 2020 Dec 15;13(24). Epub 2020 Dec 15.

Institute of Rock and Soil Mechanics, Chinese Academy of Sciences, Wuhan 430071, China.

Sand-rubber mixtures (SRMs) consisting of stiff sand particles and soft rubber particles are typical binary mixture materials that possess a variety of complicated properties. The complexity of the properties of sand-rubber mixtures is increased when complex stress path is involved. This study investigates the mechanical behavior of sand-rubber mixtures under generalized loading conditions using the discrete element method. A series of numerical true triaxial shear tests were conducted on pure sand and sand-rubber mixtures. The effect of rubber content and loading path on both of the macroscopic and microscopic performances of sand-rubber mixtures was investigated, and the associated microscale mechanism was also discussed. Numerical simulations show that the relationship between the peak friction angle ϕp and the intermediate principal stress ratio b is influenced by the addition of rubber particles, and a suggested explanation of this phenomenon is that the rubber particles mainly affect the inherent stability of the strong network. Particle-scale observations, including the coordinate number, the proportion of strong contacts, and the fabric anisotropy, are also presented in this study. Microscopic results confirm the explanation above, and explore the force transmission characteristics of sand-rubber mixtures under generalized loading conditions. This research can provide a reference for the constitutive model development of sand-rubber mixtures.
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http://dx.doi.org/10.3390/ma13245716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765338PMC
December 2020

Facile Synthesis of Formable Alginate Composite Hydrogels with Ca-Induced Healing Ability.

Tissue Eng Part A 2021 Feb 15. Epub 2021 Feb 15.

College of Chemistry and Materials Science, Jinan University, Guangzhou, P.R. China.

Dental caries have plagued humans for many years. At present, photocrosslinking resin is commonly used in clinics to repair narrow tooth defects, but the ultraviolet light used in this process has unavoidable cytotoxicity. hydrogels with a similar structure to that of the natural extracellular matrix have gradually attracted attention in the field of hard tissue repair engineering. The injectable molding properties of hydrogel also give it the potential to fill irregularly shaped or fine tissue defects. Through a rapid and facile Michael addition reaction, we prepared maleic chitosan (CS-maleic anhydride [MA]) and thiolated alginate (sodium alginate [SA]-SH) to form a CS-MA/SA-SH hydrogel. To endue its mineralize ability, β-glycerophosphate calcium phosphate and calcium carbonate as the precursor of hydroxyapatite (HAp) were premixed in the hydrogel at certain ratios. This kind of hydrogel can quickly form into different shapes within 10 min. It is worth noting that external Ca can react with the residual carboxyl groups of SA and provide the hydrogel with a self-healing ability. At the same time, we creatively propose a method that uses alkaline phosphatase to promote the mineralization of HAp in hydrogels, to achieve the purpose of regenerating hard tissue . By examining the properties of hydrogels at different concentrations of calcium and phosphorus salts, we find that the CS-MA/SA-SH hydrogel with 50% (wt.%) inorganic matter presented the best self-healing properties, excellent mineralization of highly crystallized Hap, and has ideal cell compatibility. The potential application of the CS-MA/SA-SH hydrogel in repairing exposed dentin tubules in decayed teeth was explored through preliminary dental restoration experiments. Obviously, the penetration depth through dentin tubules was better than that of commercial dental sensitizers. In addition, the HAp morphology was affected by the local environment. We believe that this hydrogel can utilize tissues for dental regeneration and mineralization, and the healing ability provides the hydrogel flexibility for further application in hard tissue regeneration.
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http://dx.doi.org/10.1089/ten.TEA.2020.0282DOI Listing
February 2021

Galectin-3 mediates cardiac remodeling caused by impaired glucose and lipid metabolism through inhibiting two pathways of activating Akt.

Am J Physiol Heart Circ Physiol 2021 01 4;320(1):H364-H380. Epub 2020 Dec 4.

Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Pathological cardiac remodeling is a leading cause of mortality in patients with diabetes. Given the glucose and lipid metabolism disorders (GLDs) in patients with diabetes, it is urgent to conduct a comprehensive study of the myocardial damage under GLDs and find key mechanisms. Apolipoprotein E knockout (ApoE) mice, low-density lipoprotein receptor heterozygote (Ldlr) Syrian golden hamsters, or H9C2 cells were used to construct GLDs models. GLDs significantly promoted cardiomyocyte fibrosis, apoptosis, and hypertrophy in vivo and in vitro, but inhibition of galectin-3 (Gal-3) could significantly reverse this process. Then, the signal transmission pathways were determined. It was found that GLDs considerably inhibited the phosphorylation of Akt at Thr/Ser, whereas the silencing of Gal-3 could reverse the inhibition of Akt activity through phosphoinositide 3-kinase-Akt (PI3K-Akt) and AMP-activated protein kinase-mammalian target of rapamycin complex 2-Akt (AMPK-mTOR2-Akt) pathways. Finally, the PI3K, mTOR, AMPK inhibitor, and Akt activator were used to investigate the role of pathways in regulating cardiac remodeling. Phospho-Akt could mediate myocardial fibrosis, whereas myocardial apoptosis and hypertrophy were regulated by both phospho-Akt and phospho-Akt. In conclusion, Gal-3 was an important regulatory factor in GLDs-induced cardiac remodeling, and Gal-3 could suppress the phosphorylation of Akt at different sites in mediating cardiomyocyte fibrosis, apoptosis, and hypertrophy. Studies on the pathogenesis of diabetic cardiac remodeling are highly desired. Glucose and lipid metabolism are both disordered in diabetes. Glucose and lipid metabolism disturbances promote myocardial fibrosis, apoptosis, and hypertrophy through galectin-3. Galectin-3 promotes cardiac remodeling by inhibiting phosphorylation of Akt or Akt. The present study finds that glucose and lipid metabolism disorders are important causes for myocardial damage and provides novel ideas for the prevention and treatment of diabetic cardiac remodeling.
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http://dx.doi.org/10.1152/ajpheart.00523.2020DOI Listing
January 2021

Mass Detection and Segmentation in Digital Breast Tomosynthesis Using 3D-Mask Region-Based Convolutional Neural Network: A Comparative Analysis.

Front Mol Biosci 2020 11;7:599333. Epub 2020 Nov 11.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.

Digital breast tomosynthesis (DBT) is an emerging breast cancer screening and diagnostic modality that uses quasi-three-dimensional breast images to provide detailed assessments of the dense tissue within the breast. In this study, a framework of a 3D-Mask region-based convolutional neural network (3D-Mask RCNN) computer-aided diagnosis (CAD) system was developed for mass detection and segmentation with a comparative analysis of performance on patient subgroups with different clinicopathological characteristics. To this end, 364 samples of DBT data were used and separated into a training dataset ( = 201) and a testing dataset ( = 163). The detection and segmentation results were evaluated on the testing set and on subgroups of patients with different characteristics, including different age ranges, lesion sizes, histological types, lesion shapes and breast densities. The results of our 3D-Mask RCNN framework were compared with those of the 2D-Mask RCNN and Faster RCNN methods. For lesion-based mass detection, the sensitivity of 3D-Mask RCNN-based CAD was 90% with 0.8 false positives (FPs) per lesion, whereas the sensitivity of the 2D-Mask RCNN- and Faster RCNN-based CAD was 90% at 1.3 and 2.37 FPs/lesion, respectively. For breast-based mass detection, the 3D-Mask RCNN generated a sensitivity of 90% at 0.83 FPs/breast, and this framework is better than the 2D-Mask RCNN and Faster RCNN, which generated a sensitivity of 90% with 1.24 and 2.38 FPs/breast, respectively. Additionally, the 3D-Mask RCNN achieved significantly ( < 0.05) better performance than the 2D methods on subgroups of samples with characteristics of ages ranged from 40 to 49 years, malignant tumors, spiculate and irregular masses and dense breast, respectively. Lesion segmentation using the 3D-Mask RCNN achieved an average precision (AP) of 0.934 and a false negative rate (FNR) of 0.053, which are better than those achieved by the 2D methods. The results suggest that the 3D-Mask RCNN CAD framework has advantages over 2D-based mass detection on both the whole data and subgroups with different characteristics.
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http://dx.doi.org/10.3389/fmolb.2020.599333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686533PMC
November 2020

Multifunctional chitosan-copper-gallic acid based antibacterial nanocomposite wound dressing.

Int J Biol Macromol 2021 Jan 27;167:10-22. Epub 2020 Nov 27.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, PR China. Electronic address:

Antibacterial wound dressings can effectively avoid the residual of antibacterial nanomaterials for injection in vivo, reduce their biological toxicity to normal cells and tissues, making them be widely applied in biomedical field. Herein, an approach of combining ion-crosslinking, in-situ reduction and microwave-assisted methods was employed to prepare chitosan-copper-gallic acid nanocomposites (CS-Cu-GA NCs) with dual-functional nano-enzyme characteristics (oxidase- and peroxidase-like functions). The oxidase-like activity of CS-Cu-GA NCs can facilitate the production of hydrogen peroxide (HO) when it contacted with physiologically relevant antioxidants (AH) in bacteria. Subsequently, HO was catalyzed to generate hydroxyl radicals (OH) under the peroxidase-like activity of CS-Cu-GA NCs. Furthermore, CS-Cu-GA NCs integrate the inherent antibacterial properties of chitosan, Cu NPs and Cu. Animal experiments revealed that the antibacterial dressing incorporating CS-Cu-GA NCs exhibited its effective promotion of S. aureus-infected wounds healing, as well as no damage to normal tissues. Besides, the antibacterial dressing was prepared to a band aid with excellent water swelling and antibacterial properties, which was further fixed in a medical tape to construct a portable antibacterial product that can be applied to the surface of human skin and showed excellent waterproof performance, providing a new insight for the construction of clinical antibacterial wound healing products.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.153DOI Listing
January 2021

Identifying individuals with autism spectrum disorder based on the principal components of whole-brain phase synchrony.

Neurosci Lett 2021 01 24;742:135519. Epub 2020 Nov 24.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, 310018, China. Electronic address:

Autism spectrum disorder (ASD) is a brain disorder that develops during an early stage of childhood. Previous neuroimaging-based diagnostic models for ASD were based on static functional connectivity (FC). The nonlinear complexity of brain connectivity remains unexplored for ASD diagnosis. This study aimed to build intelligent discriminative models for ASD based on phase synchrony (PS). To this end, data from 49 patients with ASD and 41 healthy controls were obtained from the Autism Brain Imaging Data Exchange (ABIDE) project. PS between brain regions was determined using Hilbert transform. Principal component analysis (PCA) and support vector machines (SVMs) were used to build the discriminative models. PS-based models (AUC = 0.81) outperformed static FC-based models (AUC = 0.71). Furthermore, embedded functional biomarkers were discovered. Moreover, significant correlations were found between PCA-PS and the clinical severity of ASD. Together, intelligent discriminative models based on PS were established for ASD identification. The performance of the diagnostic models suggested the potential benefits of PS for clinical applications. The discriminative patterns indicated that PCA-PS features could be additional biomarkers for ASD research. Furthermore, the significant relationships between the PCA-PS features and clinical scores implied their potential use for personalized medication strategies.
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http://dx.doi.org/10.1016/j.neulet.2020.135519DOI Listing
January 2021