Publications by authors named "Fei Wang"

4,188 Publications

  • Page 1 of 1

Socioeconomic variation in characteristics, outcomes, and healthcare utilization of COVID-19 patients in New York City.

PLoS One 2021 29;16(7):e0255171. Epub 2021 Jul 29.

Department of Population Health Sciences, Weill Cornell Medical College, New York, NY, United States of America.

Objectives: There is limited evidence on how clinical outcomes differ by socioeconomic conditions among patients with coronavirus disease 2019 (COVID-19). Most studies focused on COVID-19 patients from a single hospital. Results based on patients from multiple health systems have not been reported. The objective of this study is to examine variation in patient characteristics, outcomes, and healthcare utilization by neighborhood social conditions among COVID-19 patients.

Methods: We extracted electronic health record data for 23,300 community dwelling COVID-19 patients in New York City between March 1st and June 11th, 2020 from all care settings, including hospitalized patients, patients who presented to the emergency department without hospitalization, and patients with ambulatory visits only. Zip Code Tabulation Area-level social conditions were measured by the Social Deprivation Index (SDI). Using logistic regressions and Cox proportional-hazards models, we examined the association between SDI quintiles and hospitalization and death, controlling for race, ethnicity, and other patient characteristics.

Results: Among 23,300 community dwelling COVID-19 patients, 60.7% were from neighborhoods with disadvantaged social conditions (top SDI quintile), although these neighborhoods only account for 34% of overall population. Compared to socially advantaged patients (bottom SDI quintile), socially disadvantaged patients (top SDI quintile) were older (median age 55 vs. 53, P<0.001), more likely to be black (23.1% vs. 6.4%, P<0.001) or Hispanic (25.4% vs. 8.5%, P<0.001), and more likely to have chronic conditions (e.g., diabetes: 21.9% vs. 10.5%, P<0.001). Logistic and Cox regressions showed that patients with disadvantaged social conditions had higher risk for hospitalization (odds ratio: 1.68; 95% confidence interval [CI]: [1.46, 1.94]; P<0.001) and mortality (hazard ratio: 1.91; 95% CI: [1.35, 2.70]; P<0.001), adjusting for other patient characteristics.

Conclusion: Substantial socioeconomic disparities in health outcomes exist among COVID-19 patients in NYC. Disadvantaged neighborhood social conditions were associated with higher risk for hospitalization, severity of disease, and death.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255171PLOS
July 2021

Predicting Intensive Care Unit Length of Stay After Acute Type A Aortic Dissection Surgery Using Machine Learning.

Front Cardiovasc Med 2021 12;8:675431. Epub 2021 Jul 12.

Department of Radiology, the First Affiliated Hospital, Jinan University, Guangzhou, China.

Patients with acute type A aortic dissection are usually transferred to the intensive care unit (ICU) after surgery. Prolonged ICU length of stay (ICU-LOS) is associated with higher level of care and higher mortality. We aimed to develop and validate machine learning models for predicting ICU-LOS after acute type A aortic dissection surgery. A total of 353 patients with acute type A aortic dissection transferred to ICU after surgery from September 2016 to August 2019 were included. The patients were randomly divided into the training dataset (70%) and the validation dataset (30%). Eighty-four preoperative and intraoperative factors were collected for each patient. ICU-LOS was divided into four intervals (<4, 4-7, 7-10, and >10 days) according to interquartile range. Kendall correlation coefficient was used to identify factors associated with ICU-LOS. Five classic classifiers, Naive Bayes, Linear Regression, Decision Tree, Random Forest, and Gradient Boosting Decision Tree, were developed to predict ICU-LOS. Area under the curve (AUC) was used to evaluate the models' performance. The mean age of patients was 51.0 ± 10.9 years and 307 (87.0%) were males. Twelve predictors were identified for ICU-LOS, namely, D-dimer, serum creatinine, lactate dehydrogenase, cardiopulmonary bypass time, fasting blood glucose, white blood cell count, surgical time, aortic cross-clamping time, with Marfan's syndrome, without Marfan's syndrome, without aortic aneurysm, and platelet count. Random Forest yielded the highest performance, with an AUC of 0.991 (95% confidence interval [CI]: 0.978-1.000) and 0.837 (95% CI: 0.766-0.908) in the training and validation datasets, respectively. Machine learning has the potential to predict ICU-LOS for acute type A aortic dissection. This tool could improve the management of ICU resources and patient-throughput planning, and allow better communication with patients and their families.
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http://dx.doi.org/10.3389/fcvm.2021.675431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310912PMC
July 2021

Left Bundle Branch Conduction Recovery Following Left Bundle Branch Pacing in a Heart Failure Patient.

JACC Case Rep 2019 Dec 6;1(4):592-596. Epub 2019 Nov 6.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

This report presents the application of left bundle branch pacing as a cardiac resynchronization therapy in a patient with systolic heart failure and complete left bundle branch block. At the 3-month follow-up, the patient had significant improvement in cardiac function accompanied by the recovery of left bundle branch conduction. ().
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http://dx.doi.org/10.1016/j.jaccas.2019.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288571PMC
December 2019

Comorbid neuropsychiatric and autonomic features in REM sleep behavior disorder.

Clin Park Relat Disord 2020 22;3:100044. Epub 2020 Feb 22.

Weill Cornell Medical College, New York, NY, United States of America.

Objective: Our aim is to define the extent of comorbidities in order to improve clinical care of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) utilizing the REM Sleep Behavior Disorder Associations with Parkinson's Disease Study (RAPiDS) cohort.

Methods: Consecutive adult study participants with iRBD confirmed on polysomnogram (PSG) were prospectively recruited from the Weill Cornell Center for Sleep Medicine. Evaluations comprised multiple facets of sleep, neurological, autonomic, and psychiatric function.

Results: Participants evaluated included 30 individuals with iRBD, with mean 1.5 ± 2.3 years from PSG to neuropsychiatric evaluation. Mean age was 59.5 ± 16.0 years at time of PSG, and 6/30 were women. Urinary difficulties were reported in 14/30 (47%): slight 7 (23%), mild 4 (13%), moderate 2 (7%), and severe 1 (3.0%). Ten out of 29 (34%) had abnormal Montreal Cognitive Assessment (MoCA) scores and the mean was 26.5 ± 3.2. The distribution of MoCA scores was significantly associated with urinary problems insofar as the more severe urinary problems were, the lower the MoCA scores (p = 0.04).

Conclusions: In this RAPiDS cohort, we detected an unexpectedly high occurrence of non-motor dysfunction. Our results point to the need for screening patients with iRBD for complaints that are actionable, for example those affecting mood, cognition, urinary function, and bowel function. We propose the term RBD+ to be used to identify such individuals. For the quality of life in patients diagnosed with RBD, a closer look by the clinician should be enacted, with appropriate referrals and workup.
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http://dx.doi.org/10.1016/j.prdoa.2020.100044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298794PMC
February 2020

Quantitative MRI-based radiomics for noninvasively predicting molecular subtypes and survival in glioma patients.

NPJ Precis Oncol 2021 Jul 26;5(1):72. Epub 2021 Jul 26.

Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Gliomas can be classified into five molecular groups based on the status of IDH mutation, 1p/19q codeletion, and TERT promoter mutation, whereas they need to be obtained by biopsy or surgery. Thus, we aimed to use MRI-based radiomics to noninvasively predict the molecular groups and assess their prognostic value. We retrospectively identified 357 patients with gliomas and extracted radiomic features from their preoperative MRI images. Single-layered radiomic signatures were generated using a single MR sequence using Bayesian-regularization neural networks. Image fusion models were built by combing the significant radiomic signatures. By separately predicting the molecular markers, the predictive molecular groups were obtained. Prognostic nomograms were developed based on the predictive molecular groups and clinicopathologic data to predict progression-free survival (PFS) and overall survival (OS). The results showed that the image fusion model incorporating radiomic signatures from contrast-enhanced T1-weighted imaging (cT1WI) and apparent diffusion coefficient (ADC) achieved an AUC of 0.884 and 0.669 for predicting IDH and TERT status, respectively. cT1WI-based radiomic signature alone yielded favorable performance in predicting 1p/19q status (AUC = 0.815). The predictive molecular groups were comparable to actual ones in predicting PFS (C-index: 0.709 vs. 0.722, P = 0.241) and OS (C-index: 0.703 vs. 0.751, P = 0.359). Subgroup analyses by grades showed similar findings. The prognostic nomograms based on grades and the predictive molecular groups yielded a C-index of 0.736 and 0.735 in predicting PFS and OS, respectively. Accordingly, MRI-based radiomics may be useful for noninvasively detecting molecular groups and predicting survival in gliomas regardless of grades.
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http://dx.doi.org/10.1038/s41698-021-00205-zDOI Listing
July 2021

3D Printing of a PDMS Cylindrical Microlens Array with 100% Fill-Factor.

ACS Appl Mater Interfaces 2021 Jul 23. Epub 2021 Jul 23.

Shandong Engineering Research Center for Additive Manufacturing, Qingdao University of Technology, Qingdao 266520, China.

Cylindrical microlens arrays (CMLAs) play a key role in many optoelectronic devices, and 100% fill-factor CMLAs also have the advantage of improving the signal-to-noise ratio and avoiding stray-light effects. However, the existing preparation technologies are complicated and costly, which are not suitable for mass production. Herein, we propose a simple, efficient, and low-cost manufacturing method for CMLAs with a high fill-factor via the electric-field-driven (EFD) microscale 3D printing of polydimethylsiloxane (PDMS). By adjusting the printing parameters, the profile and the fill-factor of the CMLAs can be controlled to improve their optical performance. The optical performance test results show that the printed PDMS CMLAs have good image-projecting and light-diffraction properties. Using the two printing modes of this EFD microscale 3D-printing technology, a cylindrical dual-microlens array with a double-focusing function is simply prepared. At the same time, we print a series of specially shaped microlenses, proving the flexible manufacturing capabilities of this technology. The results show that the prepared CMLAs have good morphology and optical properties. The proposed method may provide a viable route for manufacturing large-area CMLAs with 100% fill-factor in a very simple, efficient, and low-cost manner.
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http://dx.doi.org/10.1021/acsami.1c08652DOI Listing
July 2021

Artificial Intelligence-Enabled Caregiving Walking Stick Powered by Ultra-Low-Frequency Human Motion.

ACS Nano 2021 Jul 26. Epub 2021 Jul 26.

Department of Electrical & Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117576, Singapore.

The increasing population of the elderly and motion-impaired people brings a huge challenge to our social system. However, the walking stick as their essential tool has rarely been investigated into its potential capabilities beyond basic physical support, such as activity monitoring, tracing, and accident alert. Here, we report a walking stick powered by ultra-low-frequency human motion and equipped with deep-learning-enabled advanced sensing features to provide a healthcare-monitoring platform for motion-impaired users. A linear-to-rotary structure is designed to achieve highly efficient energy harvesting from the linear motion of a walking stick with ultralow frequency. Besides, two kinds of self-powered triboelectric sensors are proposed and integrated to extract the motion features of the walking stick. Augmented sensing functionalities with high accuracies have been enabled by deep-learning-based data analysis, including identity recognition, disability evaluation, and motion status distinguishing. Furthermore, a self-sustainable Internet of Things (IoT) system with global positioning system tracing and environmental temperature and humidity amenity sensing functions is obtained. Combined with the aforementioned functionalities, this walking stick is demonstrated in various usage scenarios as a caregiver for real-time well-being status and activity monitoring. The caregiving walking stick shows the potential of being an intelligent aid for motion-impaired users to help them live life with adequate autonomy and safety.
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http://dx.doi.org/10.1021/acsnano.1c04464DOI Listing
July 2021

AlO Dispersion-Induced Micropapillae in an Epoxy Composite Coating and Implications in Thermal Conductivity.

ACS Omega 2021 Jul 8;6(28):17870-17879. Epub 2021 Jul 8.

Institute of Resources and Environmental Engineering & Shanxi Collaborative Innovation Center of High Value-Added Utilization of Coal-Related Wastes, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi 030006, China.

AlO particles with different sizes were dispersed into an epoxy precursor to improve the thermal conductivity (TC) of the epoxy coating. AlO particles tend to aggregate in epoxy, and the aggregation becomes more apparent (formation of micropapillae when the particle size is larger than 1 μm) with the increase of particle size. The calculated fast aggregation rates of various-size AlO particles in epoxy showed that the fast aggregation rate increased to a maximum rate of 6.37 × 10 m·s at a particle size of 200 nm and then decreased to a plateau value with the increase of particle size. The high fast aggregation rate caused the aggregation and the formation of nano- and micropapillae, causing the heterogeneous distribution of AlO particles. These micropapillae were separated by epoxy, which made formation of continuous pathways fail, causing the reduction of TC and heterogeneous heat distribution. The highest thermal conductivity of 2.52 W/m·K and uniform heat distribution were observed at the optimum filler size of 30 nm. The research findings provide the knowledge of optimizing particle size on constructing a thermally conductive polymer composite.
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http://dx.doi.org/10.1021/acsomega.1c01282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295999PMC
July 2021

Effect of a Topical Nonsteroidal Anti-Inflammatory Drug (0.1% Pranoprofen) on VEGF and COX-2 Expression in Primary Pterygium.

Front Pharmacol 2021 9;12:709251. Epub 2021 Jul 9.

Department of Ophthalmology, Nanjing Lishui District People's Hospital, Lishui Branch of Southeast University Affiliated Zhongda Hospital, Nanjing, China.

To evaluate the effect of a topical nonsteroidal anti-inflammatory drug (0.1% pranoprofen) on the expression of VEGF and Cox-2 in primary pterygium. This was a prospective, randomized study. Between January 2019 and April 2020, 120 patients diagnosed with primary pterygium were enrolled and randomly divided into three groups before operation: 1) 40 patients in group 1 received topical pranoprofen 0.1% four times daily for 4 weeks, 2) 40 patients in group 2 received topical fluorometholone 0.1% four times daily for 4 weeks, and 3) patients in group 3 did not receive treatment. For each group, the age, sex, eye type, best-corrected visual acuity (BCVA), intraocular pressure (IOP), duration of onset, combined systemic diseases, and the results regarding vascular endothelial growth factor (VEGF) and cyclo-oxygen-ase-2 (COX-2) in postoperative pterygial tissues were evaluated in detail. There were no significant differences regarding age, sex, eye type, combined systemic diseases, duration of onset, IOP, and BCVA within the three groups ( > 0.05). The reduction of VEGF and CoX-2 expression of pterygial vascular endothelial cells in group 1 were statistically significant compared to group 2 and group 3 ( < 0.05). There were significant correlations between COX-2 and VEGF expression of pterygial tissues within the three groups ( < 0.05). The present findings suggested that the topical pranoprofen 0.1% could reduce the expression of VEGF and COX-2 in primary pterygium. We confirmed that treatment with pranoprofen offers advantages in early intervention and has therapeutic potential in reducing the postoperative recurrence of primary pterygium patients. : The study was registered with the Chinese Clinical Trial Registry. (http://www.chictr.org.cn/index.aspx, Registration Number: ChiCTR2100047726).
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http://dx.doi.org/10.3389/fphar.2021.709251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298757PMC
July 2021

Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nat Commun 2021 07 23;12(1):4501. Epub 2021 Jul 23.

State key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin, China.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.
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http://dx.doi.org/10.1038/s41467-021-24804-3DOI Listing
July 2021

Carbon/Silicone Nanocomposite-Enabled Soft Pressure Sensors with a Liquid-Filled Cell Structure Design for Low Pressure Measurement.

Sensors (Basel) 2021 Jul 10;21(14). Epub 2021 Jul 10.

Research Institute of Intelligent Wearable Systems, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, China.

In the fields of humanoid robots, soft robotics, and wearable electronics, the development of artificial skins entails pressure sensors that are low in modulus, high in sensitivity, and minimal in hysteresis. However, few sensors in the literature can meet all the three requirements, especially in the low pressure range (<10 kPa). This article presents a design for such pressure sensors. The bioinspired liquid-filled cell-type structural design endows the sensor with appropriate softness (Young's modulus < 230 kPa) and high sensitivity (highest at 0.7 kPa) to compression forces below 0.65 N (6.8 kPa). The low-end detection limit is ~0.0012 N (13 Pa), only triple the mass of a bee. Minimal resistance hysteresis of the pressure sensor is 7.7%. The low hysteresis is attributed to the study on the carbon/silicone nanocomposite, which reveals the effect of heat treatment on its mechanical and electromechanical hysteresis. Pressure measurement range and sensitivity of the sensor can be tuned by changing the structure and strain gauge parameters. This concept of sensor design, when combined with microfluidics technology, is expected to enable soft, stretchable, and highly precise touch-sensitive artificial skins.
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http://dx.doi.org/10.3390/s21144732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309609PMC
July 2021

Identification of Groundwater Pollution Characteristics and Health Risk Assessment of a Landfill in a Low Permeability Area.

Int J Environ Res Public Health 2021 Jul 20;18(14). Epub 2021 Jul 20.

Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu 610031, China.

The shallow weathering fissure groundwater in the red-bed area of Southwest China is usually the only drinking water source for most rural residents. In this study, a typical landfill with surrounding residents drinking unpurified groundwater in red-bed area was selected and water quality detection, groundwater numerical simulation and human health risk assessment were used to identify and assess groundwater pollution in the region. The chemical type evolved from HCO-SO-Ca-Mg and HCO-SO-Ca to Na-Ca-Cl-HCO contaminated by the landfill. Na and Cl were selected as factors for rapid identification of groundwater pollution. Subsequent analyses using these factors showed that the leachate pollution plume boundary was 190 m downstream of the landfill. Analysis of the redox conditions revealed that the area from the landfill to 5 m downstream was the reduction zone, while the area beyond 5 m was the oxidation zone. The migration and attenuation patterns of inorganic salts (such as SO) and heavy metals (such as Fe and Mn) in the oxidation and reduction zones differed obviously. Meanwhile, the organic pollutants in the leachate were reduced and decomposed into organic acids, which caused the groundwater 80 m downstream of the landfill to become weakly acidic (pH ranged from 6.51 to 6.83), and promoted re-entry of adsorbed heavy metals (such as Pb) into the groundwater. The groundwater risk assessment based on human health revealed that lead, manganese, chlorobenzene, dichloroethane and chloroform constituted a major health threat to the residents. The rank of non-carcinogenic risk was lead >manganese, and the maximum area of non-carcinogenic risk was 15,485 m. The total carcinogenic risk caused by organic pollutants was 7.9 × 10, and the area of the carcinogenic risk zone was 11,414 m. Overall, the results of this study provide a scientific basis for management of drinking water and groundwater remediation in the red-bed area with low permeability.
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http://dx.doi.org/10.3390/ijerph18147690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307002PMC
July 2021

The Antiviral Molecule 5-Pyridoxolactone Identified Post BmNPV Infection of the Silkworm, .

Int J Mol Sci 2021 Jul 10;22(14). Epub 2021 Jul 10.

Biological Science Research Center, Southwest University, Chongqing 400715, China.

nucleopolyhedrovirus (BmNPV) is a pathogen that causes great economic losses in sericulture. Many genes play a role in viral infection of silkworms, but silkworm metabolism in response to BmNPV infection is unknown. We studied BmE cells infected with BmNPV. We performed liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomics analysis of the cytosolic extract and identified 36, 76, 138, 101, 189, and 166 different molecules at 3, 6, 12, 24, 48, and 72 h post BmNPV infection (hpi) compared with 0 hpi. Compounds representing different areas of metabolism were increased in cells post BmNPV infection. These areas included purine metabolism, aminoacyl-tRNA biosynthesis, and ABC transporters. Glycerophosphocholine (GPC), 2-hydroxyadenine (2-OH-Ade), gamma-glutamylcysteine (γ-Glu-Cys), hydroxytolbutamide, and 5-pyridoxolactone glycerophosphocholine were continuously upregulated in BmE cells post BmNPV infection by heat map analysis. Only 5-pyridoxolactone was found to strongly inhibit the proliferation of BmNPV when it was used to treat BmE cells. Fewer infected cells were detected and the level of BmNPV DNA decreased with increasing 5-pyridoxolactone in a dose-dependent manner. The expression of BmNPV genes ie1, helicase, GP64, and VP39 in BmE cells treated with 5-pyridoxolactone were strongly inhibited in the BmNPV infection stage. This suggested that 5-pyridoxolactone may suppress the entry of BmNPV. The data in this study characterize the metabolism changes in BmNPV-infected cells. Further analysis of 5-pyridoxolactone, which is a robust antiviral molecule, may increase our understanding of antiviral immunity.
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http://dx.doi.org/10.3390/ijms22147423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307608PMC
July 2021

HDAC6-mediated Hsp90 deacetylation reduces aggregation and toxicity of the protein alpha-synuclein by regulating chaperone-mediated autophagy.

Neurochem Int 2021 Jul 20:105141. Epub 2021 Jul 20.

Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Histone deacetylase 6 (HDAC6) has been shown to control major cell response pathways to the cytotoxic ubiquitinated aggregates in some protein aggregation diseases. However, it is not well known whether HDAC6 affects the aggregation process of α-synuclein (α-syn) in Parkinson's disease (PD). Previously, we demonstrated that HDAC6 inhibition exacerbated the nigrostriatal dopamine neurodegeneration and up-regulated α-syn oligomers in a heat shock protein 90 (Hsp90)-dependent manner in PD mouse model. Here, we further showed that HDAC6 overexpression partly improved the behavior deficits of the PD model and alleviated the nigrostriatal dopamine (DA) neurons injury. Furthermore, HDAC6 was found to regulate α-syn oligomers levels through activation of chaperone-mediated autophagy (CMA). During this process, Hsp90 deacetylation mediated the crosstalk between HDAC6 and lysosome-associated membrane protein type 2A. Liquid chromatography-tandem mass spectrometry and mutational analysis showed that acetylation status Hsp90 at the K489 site was a strong determinant for HDAC6-induced CMA activation, α-syn oligomers levels, and cell survival in the cell model of PD. Therefore, our findings uncovered the mechanism of HDAC6 in the PD model that HDAC6 regulated α-syn oligomers levels and DA neurons survival partly through modulating CMA, and Hsp90 deacetylation at the K489 site mediated the crosstalk between HDAC6 and CMA. HDAC6 and its downstream effectors appear as key modulators of the cytotoxic α-syn aggregates, which deserve further investigations to evaluate their values as potential therapeutic targets in PD.
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http://dx.doi.org/10.1016/j.neuint.2021.105141DOI Listing
July 2021

study of enhanced photodynamic cancer cell killing effect by nanometer-thick gold nanosheets.

Nano Res 2020 Dec 14;13:3217-3223. Epub 2020 Aug 14.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Wisconsin 53706, USA.

Photodynamic therapy (PDT) by near-infrared (NIR) irradiation is a promising technique for treating various cancers. Here, we reported the development of free-standing wafer-scale Au nanosheets (NSs) that exhibited an impressive PDT effect. The Au NSs were synthesized by ionic layer epitaxy at the air-water interface with a uniform thickness in the range from 2 to 8.5 nm. These Au NSs were found very effective in generating singlet oxygen under NIR irradiation. cellular study showed that the Au NSs had very low cytotoxicity and high PDT efficiency due to their uniform 2D morphology. Au NSs could kill cancer cells after 5 min NIR irradiation with little heat generation. This performance is comparable to using 10 times mass loading of Au nanoparticles (NPs). This work suggests that two-dimensional (2D) Au NSs could be a new type of biocompatible nanomaterial for PDT of cancer with an extraordinary photon conversion and cancer cell killing efficiency.
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http://dx.doi.org/10.1007/s12274-020-2990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291290PMC
December 2020

Identification of Potential Signatures and Their Functions for Acute Lymphoblastic Leukemia: A Study Based on the Cancer Genome Atlas.

Front Genet 2021 6;12:656042. Epub 2021 Jul 6.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Objective: Acute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL.

Methods: Differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA-microRNA (miRNA) and miRNA-DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein-protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR.

Results: A total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA-mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples.

Conclusion: Our results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.
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http://dx.doi.org/10.3389/fgene.2021.656042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290159PMC
July 2021

Colon-Targeted Adhesive Hydrogel Microsphere for Regulation of Gut Immunity and Flora.

Adv Sci (Weinh) 2021 Jul 22:e2101619. Epub 2021 Jul 22.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.

Intestinal immune homeostasis and microbiome structure play a critical role in the pathogenesis and progress of inflammatory bowel disease (IBD), whereas IBD treatment remains a challenge as the first-line drugs show limited therapeutic efficiency and great side effect. In this study, a colon-targeted adhesive core-shell hydrogel microsphere is designed and fabricated by the ingenious combination of advanced gas-shearing technology and ionic diffusion method, which can congregate on colon tissue regulating the gut immune-microbiota microenvironment in IBD treatment. The degradation experiment indicates the anti-acid and colon-targeted property of the alginate hydrogel shell, and the in vivo imaging shows the mucoadhesive ability of the thiolated-hyaluronic acid hydrogel core of the microsphere, which reduces the systematic exposure and prolongs the local drug dwell time. In addition, both in vitro and in vivo study demonstrate that the microsphere significantly reduces the secretion of pro-inflammatory cytokines, induces specific type 2 macrophage differentiation, and remarkably alleviates colitis in the mice model. Moreover, 16S ribosomal RNA sequencing reveals an optimized gut flora composition, probiotics including Bifidobacterium and Lactobacillus significantly augment, while the detrimental communities are inhibited, which benefits the intestinal homeostasis. This finding provides an ideal clinical candidate for IBD treatment.
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http://dx.doi.org/10.1002/advs.202101619DOI Listing
July 2021

Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice.

Neurosci Bull 2021 Jul 22. Epub 2021 Jul 22.

Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, 400038, China.

Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER; Tau-mGFP), we found that myelinogenesis was highly active in most brain regions, such as the motor cortex and corpus callosum. After exposure to hypoxia (10% oxygen) 12 h per day for 4 weeks, myelinogenesis was largely inhibited in the 4-month old brain and the mice displayed motor coordination deficits revealed by the beam-walking test. To determine the relationship between the inhibited myelination and functional impairment, we induced oligodendroglia-specific deletion of the transcription factor Olig2 by tamoxifen (NG2-CreER; Tau-mGFP; Olig2 fl/fl) in adult mice to mimic the decreased myelinogenesis caused by hypoxia. The deletion of Olig2 inhibited myelinogenesis and consequently impaired motor coordination, suggesting that myelinogenesis is required for motor function in adult mice. To understand whether enhancing myelination could protect brain functions against hypoxia, we treated hypoxic mice with the myelination-enhancing drug-clemastine, which resulted in enhanced myelogenesis and improved motor coordination. Taken together, our data indicate that chronic hypoxia inhibits myelinogenesis and causes functional deficits in the brain and that enhancing myelinogenesis protects brain functions against hypoxia-related deficits.
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http://dx.doi.org/10.1007/s12264-021-00745-1DOI Listing
July 2021

Two-Step Chemical Vapor Deposition-Synthesized Lead-Free All-Inorganic CsSbBr Perovskite Microplates for Optoelectronic Applications.

ACS Appl Mater Interfaces 2021 Jul 21. Epub 2021 Jul 21.

Department of Physics, City University of Hong Kong, Kowloon, Hong Kong SAR, China.

Lead-based halide perovskites (APbX, where A = organic or inorganic cation, X = Cl, Br, I) are suitable materials for many optoelectronic devices due to their many attractive properties. However, the concern of lead toxicity and the poor ambient and operational stability of the organic cation group greatly limit their practical utilization. Therefore, there has recently been great interest in lead-free, environment-friendly all-inorganic halide perovskites (IHPs). Sb and Sn are common species suggested to replace Pb for Pb-free IHPs. However, the large difference in the melting points of the precursor materials (e.g., CsBr and SbBr precursors for CsSbBr) makes the chemical vapor deposition (CVD) growth of high-quality Pb-free IHPs a very challenging task. In this work, we developed a two-step CVD method to overcome this challenge and successfully synthesized Pb-free CsSbBr perovskite microplates. CsSbBr microplates ∼25 μm in size with the exciton absorption peak at ∼2.8 eV and a band gap of ∼2.85 eV were obtained. The microplates have a smooth hexagonal morphology and show a large Stokes shift of ∼450 meV and exciton binding energy of ∼200 meV. To demonstrate the applications of these microplates in optoelectronics, simple photoconductive devices were fabricated. These photodetectors exhibit a current on/off ratio of 2.36 × 10, a responsivity of 36.9 mA/W, and a detectivity of 1.0 × 10 Jones with a fast response of rise and decay time of 61.5 and 24 ms, respectively, upon 450 nm photon irradiation. Finally, the CsSbBr microplates also show good stability in ambient air without encapsulation. These results demonstrate that the 2-step CVD process is an effective approach to synthesize high-quality all-inorganic lead-free CsSbBr perovskite microplates that have the potential for future high-performance optoelectronic device applications.
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http://dx.doi.org/10.1021/acsami.1c07839DOI Listing
July 2021

Distribution characteristics of per- and polyfluoroalkyl substances (PFASs) in human urines of acrylic fiber plant and chemical plant.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, 510632, China.

Per- and polyfluoroalkyl substances (PFASs) are persistent and bioaccumulative substances that have many adverse effects on human bodies. This study investigated the PFASs distribution characteristics in urine samples of workers from an acrylic fiber plant and a chemical plant. It was found that perfluorobutanoic acid (PFBA) was the predominant PFASs both in urine samples from the chemical plant (detection frequency: 86.52%; median value: 39.01 ng/mL) and the acrylic fiber plant (detection frequency: 88.16%; median value: 44.36 ng/mL). Meanwhile, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were detected with very low frequencies and low concentrations. Furthermore, the results showed that PFASs levels in urine samples of workers from different units of the plants were quite different. PFASs concentrations of urine samples in males were higher than those in females, especially for PFBA, PFHxA, and PFDoA. The age had limited effects on the PFASs distribution in urine samples in this study, as short-chain PFASs were the dominant compounds. The correlations between PFASs concentrations in urine and gender/ages of workers were finally analyzed by Pearson correlation. The overall results may indicate that short-chain PFASs (such as: PFBA and PFBS) were becoming dominant for human exposure, especially occupational workers.
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http://dx.doi.org/10.1007/s11356-021-15355-7DOI Listing
July 2021

Mitochondrial Protein Translation: Emerging Roles and Clinical Significance in Disease.

Front Cell Dev Biol 2021 1;9:675465. Epub 2021 Jul 1.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.

Mitochondria are one of the most important organelles in cells. Mitochondria are semi-autonomous organelles with their own genetic system, and can independently replicate, transcribe, and translate mitochondrial DNA. Translation initiation, elongation, termination, and recycling of the ribosome are four stages in the process of mitochondrial protein translation. In this process, mitochondrial protein translation factors and translation activators, mitochondrial RNA, and other regulatory factors regulate mitochondrial protein translation. Mitochondrial protein translation abnormalities are associated with a variety of diseases, including cancer, cardiovascular diseases, and nervous system diseases. Mutation or deletion of various mitochondrial protein translation factors and translation activators leads to abnormal mitochondrial protein translation. Mitochondrial tRNAs and mitochondrial ribosomal proteins are essential players during translation and mutations in genes encoding them represent a large fraction of mitochondrial diseases. Moreover, there is crosstalk between mitochondrial protein translation and cytoplasmic translation, and the imbalance between mitochondrial protein translation and cytoplasmic translation can affect some physiological and pathological processes. This review summarizes the regulation of mitochondrial protein translation factors, mitochondrial ribosomal proteins, mitochondrial tRNAs, and mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in the mitochondrial protein translation process and its relationship with diseases. The regulation of mitochondrial protein translation and cytoplasmic translation in multiple diseases is also summarized.
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http://dx.doi.org/10.3389/fcell.2021.675465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280776PMC
July 2021

Nomograms to predict ipsilateral and contralateral central lymph node metastasis in clinically lymph node-negative patients with solitary isthmic classic papillary thyroid carcinoma.

Surgery 2021 Jul 15. Epub 2021 Jul 15.

Department of Thyroid Surgery, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, Jiangsu, China. Electronic address:

Background: Isthmus-originating papillary thyroid carcinoma has unique clinicopathological characteristics. There are no specific guidelines regarding the extent of surgery for isthmic papillary thyroid carcinoma. We aimed to evaluate the characteristics of clinically lymph node-negative patients with solitary isthmic papillary thyroid carcinoma and to determine the best surgical protocol for these patients.

Methods: A total of 904 patients diagnosed with solitary papillary thyroid carcinoma who underwent surgery were retrospectively reviewed. These patients were divided into the isthmic group (246 patients) or lobar group (658 patients). We compared the 2 groups and conducted a multivariate analysis to assess risk factors for ipsilateral and contralateral central lymph node metastasis in isthmic papillary thyroid carcinoma patients. Nomograms for predicting central lymph node metastasis in isthmic papillary thyroid carcinoma patients were developed and internal calibration was performed for these models.

Results: Isthmic papillary thyroid carcinoma patients have a significantly higher incidence of extrathyroidal extension and central lymph node metastasis than do lobar papillary thyroid carcinoma patients. For isthmic papillary thyroid carcinoma patients, sex, BRAF V600E mutation, chronic lymphocytic thyroiditis, tumor size, margin, and extrathyroidal extension were independent risk factors of ipsilateral central lymph node metastasis. Body mass index, BRAF V600E mutation, tumor size, location, and extrathyroidal extension were independent risk factors of contralateral central lymph node metastasis. All the above factors were incorporated into nomograms, which showed the perfect discriminative ability.

Conclusion: Based on the predictive nomograms, we proposed a risk stratification scheme and corresponding individualized surgical treatment based on different nomogram scores. In the debate about prophylactic central neck dissection among clinically lymph node-negative patients with solitary isthmic papillary thyroid carcinoma, our nomograms provide the balance to avoid overtreatment and undertreatment through personal risk assessment.
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http://dx.doi.org/10.1016/j.surg.2021.06.027DOI Listing
July 2021

A tubby-like protein CsTLP8 acts in the ABA signaling pathway and negatively regulates osmotic stresses tolerance during seed germination.

BMC Plant Biol 2021 Jul 17;21(1):340. Epub 2021 Jul 17.

Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, College of Horticulture, China Agricultural University, Beijing, 100193, China.

Background: TLPs (Tubby-like proteins) are widespread in eukaryotes and highly conserved in plants and animals. TLP is involved in many biological processes, such as growth, development, biotic and abiotic stress responses, while the underlying molecular mechanism remains largely unknown. In this paper we characterized the biological function of cucumber (Cucumis sativus L.) Tubby-like protein 8 (CsTLP8) in Arabidopsis.

Results: In cucumber, the expression of the tubby-like protein CsTLP8 was induced by NaCl treatment, but reduced by PEG (Polyethylene Glycol) and ABA (Abscisic Acid) treatment. Subcellular localization and transcriptional activation activity analysis revealed that CsTLP8 possessed two characteristics of classical transcription factors: nuclear localization and trans-activation activity. Yeast two-hybrid assay revealed interactions of CsTLP8 with CsSKP1a and CsSKP1c, suggesting that CsTLP8 might function as a subunit of E3 ubiquitin ligase. The growth activity of yeast with ectopically expressed CsTLP8 was lower than the control under NaCl and mannitol treatments. Under osmotic and salt stresses, overexpression of CsTLP8 inhibited seed germination and the growth of Arabidopsis seedlings, increased the content of MDA (Malondialdehyde), and decreased the activities of SOD (Superoxide Dismutase), POD (Peroxidase) and CAT (Catalase) in Arabidopsis seedlings. Overexpression of CsTLP8 also increased the sensitivity to ABA during seed germination and ABA-mediated stomatal closure.

Conclusion: Under osmotic stress, CsTLP8 might inhibit seed germination and seedling growth by affecting antioxidant enzymes activities. CsTLP8 acts as a negative regulator in osmotic stress and its effects may be related to ABA.
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http://dx.doi.org/10.1186/s12870-021-03126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286588PMC
July 2021

Pharmacokinetics and Bioequivalence of a Generic Fixed-Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions.

Clin Pharmacol Drug Dev 2021 Jul 17. Epub 2021 Jul 17.

Phase I Clinical Trial Unit, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.

The purpose of this study was to compare the bioequivalence and safety of test and reference preparations of fixed-dose combination tablets of metformin hydrochloride/vildagliptin 850 mg/50 mg in healthy volunteers under fasting and fed conditions for marketing authorization in China. A single-dose, randomized, open-label, 2-way crossover study was conducted. Blood samples were collected up to 36 hours after dosing in each period with a 7-day washout. Pharmacokinetic parameters, including maximum plasma concentration (C ), time to reach C , area under the plasma concentration-time curve (AUC) from time 0 to the last time point of the measurable concentration, AUC from time 0 to infinity, terminal elimination half-life, and apparent clearance, were calculated using noncompartmental methods and compared between the 2 formulations. Safety profiles were assessed, including significant findings of vital signs, electrocardiogram, laboratory tests, physical examination, and adverse events. A total of 30 healthy subjects (19 men, 11 women) were randomized, and 29 subjects were treated under fasting conditions. Likewise, 30 subjects (24 men, 6 women) were randomized and treated under fed conditions. The geometric mean ratio and corresponding 90% confidence intervals of C , AUC from time 0 to the last time point of the measurable concentration , and AUC from time 0 to infinity for both metformin hydrochloride and vildagliptin between the 2 fixed-dose combination formulations were within the bioequivalence acceptance range of 80% to 125% under fasting or fed conditions. Therefore, the generic and branded formulations were bioequivalent and well tolerated in healthy Chinese subjects.
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http://dx.doi.org/10.1002/cpdd.992DOI Listing
July 2021

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer.

J Clin Endocrinol Metab 2021 Jul 17. Epub 2021 Jul 17.

Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.

Context: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined.

Objective: To study whether BRAF V600E affected LNM-associated mortality in PTC.

Design, Setting, Participants: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 (IQR 35-58) years and median follow-up time of 58 (IQR 26-107) months.

Results: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAFV600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAFV600E patients; mortality rates were 2/659 (0.3%) versus 4/321 (1.2%) in non-LNM versus LNM patients (P=0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAFV600E CPTC, morality rates were 7/515 (1.4%) versus 28/363 (7.7%) in non-LNM versus LNM patients (P<0.001), corresponding to HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAFV600E versus absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism.

Conclusions: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.
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http://dx.doi.org/10.1210/clinem/dgab286DOI Listing
July 2021

Suppression of miR-106a-5p expression inhibits tumorigenesis via increasing CELF-2 expression in spinal cord glioma.

Oncol Lett 2021 Aug 30;22(2):627. Epub 2021 Jun 30.

Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230000, P.R. China.

Spinal cord glioma is a tumor characterized by high recurrence and mortality rates, and its treatment remains a major challenge. It has been reported that abnormal expression of microRNAs (miRNAs/miRs) is associated with tumor progression. Therefore, the current study aimed to identify novel miRNAs associated with spinal cord glioma. Herein, the expression levels of several miRNAs were determined in human spinal cord glioma and adjacent non-cancerous tissues by reverse transcription-quantitative (RT-qPCR). The results revealed that miR-106a-5p expression was markedly upregulated in spinal cord glioma tissues compared with in non-cancerous tissues. Furthermore, the biological effects of miR-106a-5p on spinal cord glioma cells were evaluated by MTT, Transwell and flow cytometric assays. In 0231SCG cells transfected with miR-106a-5p inhibitor, cell proliferation, migration and invasion were attenuated, whereas apoptosis was enhanced. A search of the TargetScan database revealed that miR-106a-5p directly targeted CUGBP Elav-like family member 2 (CELF-2). Western blot and RT-qPCR experiments further confirmed the association between miR-106a-5p and CELF-2 expression in spinal cord glioma tissues. The current results demonstrated that CELF-2 was a direct target of miR-106a-5p, and that the expression levels of CELF-2 were negatively associated with those of miR-106a-5p. In addition, overexpression of CELF-2 in spinal cord glioma cells reversed the tumor-promoting effects of miR-106a-5p both and . Overall, the aforementioned findings indicated that miR-106a-5p, which was highly expressed in spinal cord glioma tissues, may affect the proliferation, migration, invasion and apoptosis of spinal cord glioma cells via targeting CELF-2, thus indicating a potential approach to the future clinical management of spinal cord glioma.
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http://dx.doi.org/10.3892/ol.2021.12888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258617PMC
August 2021

Identification of LuxR Family Regulators That Integrate Into Quorum Sensing Circuit in .

Front Microbiol 2021 29;12:691842. Epub 2021 Jun 29.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Hangzhou, China.

is one of the most important food-borne pathogens that cause economic and public health problems worldwide. Quorum sensing (QS) is a way for the cell-cell communication between bacteria that controls a wide spectrum of processes and phenotypic behaviors. In this study, we performed a systematic research of LuxR family regulators in and found that they influence the bacterial growth and biofilm formation. We then established a QS reporter plasmid based on bioluminescence CDABE operon of and demonstrated that several LuxR family regulators integrated into QS circuit in . Thereinto, a novel LuxR family regulator, named RobA, was identified as a global regulator by RNA-sequencing analyses, which affected the transcription of 515 genes in . Subsequent studies confirmed that RobA regulated the expression of the exopolysaccharides (EPS) synthesis cluster and thus controlled the biofilm formation. In addition, bioluminescence reporter assays showed that RobA plays a key role in the QS circuit by regulating the expression of , , , , and . We further demonstrated that the regulation of RobA to EPS and MfpABC depended on OpaR and CpsQ, which combined the QS signal with bis-(3'-5')-cyclic dimeric GMP to construct a complex regulatory network of biofilm formation. Our data provided new insights into the bacterial QS mechanisms and biofilm formation in .
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http://dx.doi.org/10.3389/fmicb.2021.691842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276238PMC
June 2021

Clinical subphenotypes in COVID-19: derivation, validation, prediction, temporal patterns, and interaction with social determinants of health.

NPJ Digit Med 2021 Jul 14;4(1):110. Epub 2021 Jul 14.

Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.

The coronavirus disease 2019 (COVID-19) is heterogeneous and our understanding of the biological mechanisms of host response to the viral infection remains limited. Identification of meaningful clinical subphenotypes may benefit pathophysiological study, clinical practice, and clinical trials. Here, our aim was to derive and validate COVID-19 subphenotypes using machine learning and routinely collected clinical data, assess temporal patterns of these subphenotypes during the pandemic course, and examine their interaction with social determinants of health (SDoH). We retrospectively analyzed 14418 COVID-19 patients in five major medical centers in New York City (NYC), between March 1 and June 12, 2020. Using clustering analysis, 4 biologically distinct subphenotypes were derived in the development cohort (N = 8199). Importantly, the identified subphenotypes were highly predictive of clinical outcomes (especially 60-day mortality). Sensitivity analyses in the development cohort, and rederivation and prediction in the internal (N = 3519) and external (N = 3519) validation cohorts confirmed the reproducibility and usability of the subphenotypes. Further analyses showed varying subphenotype prevalence across the peak of the outbreak in NYC. We also found that SDoH specifically influenced mortality outcome in Subphenotype IV, which is associated with older age, worse clinical manifestation, and high comorbidity burden. Our findings may lead to a better understanding of how COVID-19 causes disease in different populations and potentially benefit clinical trial development. The temporal patterns and SDoH implications of the subphenotypes may add insights to health policy to reduce social disparity in the pandemic.
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http://dx.doi.org/10.1038/s41746-021-00481-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280198PMC
July 2021

Association between ambient temperature and atopic dermatitis in Lanzhou, China: a time series analysis.

Environ Sci Pollut Res Int 2021 Jul 12. Epub 2021 Jul 12.

The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Many studies have explored the association between temperature and atopic dermatitis (AD); however, the results are inconsistent. We used a quasi-Poisson function fitted to a distributed lag nonlinear model (DLNM) to evaluate the association between daily average temperature and AD outpatient visits from January 1, 2013, to December 31, 2019, in Lanzhou, China. We found that the exposure-response association curve was inversely "s-shaped," low-temperature effects occurred at a lag of 11 days and then lasted for 10 days, and high-temperature effects occurred on the current day and then significantly decreased. Both low and high ambient temperatures can increase the risk of outpatient visits. Compared with median temperature (12.89°C), the cumulative relative risk (RR) of extreme high temperature and moderate-high temperature were 1.847 (95% confidence interval [CI]: 1.613, 2.114) and 1.447 (95% CI: 1.298, 1.614), respectively, at lag0-7 days, and the cumulative RRs of extremely low temperature and moderate-low temperature were 1.004 (95% CI: 0.904, 1.115) and 1.056 (95% CI: 0.925, 1.205), respectively, at lag0-21 days. Females were more sensitive to high temperatures than males, and high or low temperatures had significant effects on children ≤14 years of age. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-021-15198-2DOI Listing
July 2021

Perfluoroalkyl substances (PFASs) in leachate, fly ash, and bottom ash from waste incineration plants: Implications for the environmental release of PFAS.

Sci Total Environ 2021 Jun 24;795:148468. Epub 2021 Jun 24.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 510632, China.

Perfluoroalkyl substances (PFASs) are a family of chemicals widely distributed in daily use consumer products. Most of these products become municipal solid wastes (MSWs) after they have been used. In the present study, we examined different types of PFASs in leachate, fly ash and bottom ash produced from three MSW incineration plants in southern China. High PFAS levels were found in leachate (mean concentration 215 ng/mL, range 21.4-682 ng/mL) from the incineration plants, which indicated large amounts of PFASs in the wastes leached out. The average quantities of PFASs annually discharged from the leachates of the three plants were estimated to be approximately 384 kg (Plant A), 47.3 kg (Plant B), and 2.82 kg (Plant C). Relatively lower levels of PFASs in fly ash (mean 16.4 ng/g, range 1.46-87.6 ng/g) and bottom ash (mean 14.6 ng/g, range 3.11-77.4 ng/g) indicated that high-temperature incineration destroyed most of the PFASs. The wide array of PFASs concentrations in all three matrices illustrated that some PFASs-containing industrial wastes were still entered into local MSW. In general, short chain PFASs, including perfluorobutyric acid (PFBA) and perfluorobutane sulfonate (PFBS), were the primary PFASs in leachate samples. In addition, PFOS was the predominant PFASs in fly ash samples. The results showed that leachate, fly ash, and bottom ash from MSW incineration plants are important vectors of PFASs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148468DOI Listing
June 2021
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