Publications by authors named "Junyi Chen"

140 Publications

A dual-emissive europium-based metal-organic framework for selective and sensitive detection of Fe and Fe.

Dalton Trans 2021 Sep 14. Epub 2021 Sep 14.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, P. R. China.

A dual-emissive optical material as a ratiometric fluorescent probe has been demonstrated to be remarkably superior in precise and quantitative analyses. Herein, a novel dual-emissive fluorescent probe Eu-BDC-OH was designed and successfully synthesized using Eu and 2-hydroxyterephthalic acid (HBDC-OH) at room temperature. Eu-BDC-OH has a three-dimensional interpenetrating network structure with a large number of exposed hydroxyl functional groups, providing abundant active sites for molecular recognition. In particular, the as-obtained Eu-BDC-OH serves as a unique fluorescent probe, and the double emission peaks of both the ligand and Eu are completely quenched by Fe. However, it is worth noting that the dual emissions of Eu-BDC-OH enable the ratiometric detection of Fe, which leads to an increase in ligand emission and a decrease in Eu emission, accompanied by a distinct red to blue color transition. The relative fluorescence intensity ratio (/) decreased linearly with increasing Fe concentration in the 0-50 μM range with a superior detection limit of 0.32 μM. In this work, a fluorescent probe based on a MOF was developed for the recognition of Fe and Fe, providing a promising strategy for the synthesis of novel dual-emission materials by integrating suitable luminescent ligands with lanthanide metal ions.
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http://dx.doi.org/10.1039/d1dt02249kDOI Listing
September 2021

SnO nanoparticles based highly sensitive gas sensor for detection of CFN: A new eco-friendly gas insulating medium.

J Hazard Mater 2021 Aug 10;422:126882. Epub 2021 Aug 10.

School of Electrical Engineering and Automation, Wuhan University, Wuhan 430072, China; Hubei Engineering Research Center for Safety Monitoring of New Energy and Power Grid Equipment, Hubei University of Technology, Wuhan 430068, China; State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing 400044, China. Electronic address:

As a novel eco-friendly gas insulation medium, perfluoroisobutyronitrile (CFN) has been utilized in various gas insulated equipment. Considering the biological toxicity of CFN, it is of great engineering significance to develop highly sensitive sensors for leakage detection scenarios. Herein, we fabricated the first SnO nanoparticles based highly sensitive CFN gas sensor that realized a superior response of 65.01% within 21 s for 50 ppm CFN exposure and a detection limit of 0.25 ppm. Meanwhile, successive response-recovery tests were performed to confirm its durability and stability. We also explored the sensing mechanism of SnO nanoparticles towards CFN and explained the superior sensing performance compared with other gases based on the density functional theory. It was found that the O vacancy demonstrates strong interaction with the -CN group in CFN that promotes the detection response, which was also confirmed by sensing experiments for SnO with different O vacancy density. We believe this paper provides convincing support for lowering the potential operation risk brought by CFN in electrical engineering and the application scenarios of SnO based gas sensors.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126882DOI Listing
August 2021

Machine Learning Aids Classification and Discrimination of Noncanonical DNA Folding Motifs by an Arrayed Host:Guest Sensing System.

J Am Chem Soc 2021 Aug 4;143(32):12791-12799. Epub 2021 Aug 4.

An arrayed host:guest fluorescence sensor system can discriminate among and classify multiple different noncanonical DNA structures by exploiting selective molecular recognition. The sensor is highly selective and can discriminate between folds as similar as native G-quadruplexes and those with bulges or vacancies. The host and guest can form heteroternary complexes with DNA strands, with the host acting as mediator between the DNA and dye, modulating the emission. By applying machine learning algorithms to the sensing data, prediction of the folding state of unknown DNA strands is possible with high fidelity.
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http://dx.doi.org/10.1021/jacs.1c06031DOI Listing
August 2021

Correction to: Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study.

Graefes Arch Clin Exp Ophthalmol 2021 Aug;259(8):2389-2390

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s00417-021-05260-7DOI Listing
August 2021

A Versatile Method for Preparing Polysaccharide Conjugates via Thiol-Michael Addition.

Polymers (Basel) 2021 Jun 8;13(12). Epub 2021 Jun 8.

Department of Sustainable Biomaterials, Virginia Tech, Blacksburg, VA 24061, USA.

Polysaccharide conjugates are important renewable materials. If properly designed, they may for example be able to carry drugs, be proactive (e.g., with amino acid substituents) and can carry a charge. These aspects can be particularly useful for biomedical applications. Herein, we report a simple approach to preparing polysaccharide conjugates. Thiol-Michael additions can be mild, modular, and efficient, making them useful tools for post-modification and the tailoring of polysaccharide architecture. In this study, hydroxypropyl cellulose (HPC) and dextran (Dex) were modified by methacrylation. The resulting polysaccharide, bearing α,β-unsaturated esters with tunable DS (methacrylate), was reacted with various thiols, including 2-thioethylamine, cysteine, and thiol functional quaternary ammonium salt through thiol-Michael addition, affording functionalized conjugates. This click-like synthetic approach provided several advantages including a fast reaction rate, high conversion, and the use of water as a solvent. Among these polysaccharide conjugates, the ones bearing quaternary ammonium salts exhibited competitive antimicrobial performance, as supported by a minimum inhibitory concentration (MIC) study and tracked by SEM characterization. Overall, this methodology provides a versatile route to polysaccharide conjugates with diverse functionalities, enabling applications such as antimicrobial activity, gene or drug delivery, and biomimicry.
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http://dx.doi.org/10.3390/polym13121905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228737PMC
June 2021

Preparation of Superhydrophobic Metal-Organic Framework/Polymer Composites as Stable and Efficient Catalysts.

ACS Appl Mater Interfaces 2021 Jul 29;13(27):32175-32183. Epub 2021 Jun 29.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, P.R. China.

Metal-organic frameworks (MOFs), as a chemical platform, combined with multifunctional polymers are of interest in catalytic applications, which can not only inherit the outstanding properties of the two components but also lead to unique synergistic effects. Nonetheless, most MOFs possess varying degrees of water instability, which limits their real application. Herein, we fabricated highly hydrophobic MOF/polymer composites a universal post-synthetic polymerization strategy as efficient catalysts. Polyaniline (PANI) was first hybridized with MOFs by vapor deposition polymerization, and then, hydrophobic molecules were grafted to the PANI by a covalent linking process, thereby forming a superhydrophobic MOF/PANI hybrid material (MOF/PANI-shp). The resultant MOF/PANI-shp not only obtains superior moisture/water resistance without significantly disturbing the original features but also exhibits a novel catalytic selectivity in styrene oxidation because of the accessible sites and synergistic effects. Such a synthetic strategy for the MOF/polymer catalyst opens a new avenue for the design of a unique catalyst with outstanding catalytic efficiency, selectivity, and stability.
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http://dx.doi.org/10.1021/acsami.1c07188DOI Listing
July 2021

Prevalence of short stature among children in China: A systematic review.

Pediatr Investig 2021 Jun 25;5(2):140-147. Epub 2021 Jan 25.

Department of Child Development and Behavior Children's Hospital of Gansu Province Lanzhou University Second Hospital Lanzhou Gansu China.

Importance: The prevalence and characteristics of short stature (SS) among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies. Thus far, there have been no accurate estimates of the prevalence of SS in China.

Objective: To analyze the prevalence of SS among children in China and to explore the influences of sex, area, age, study year, and study site on prevalence rates.

Methods: Relevant literature was identified by searching the following databases: PubMed, Embase, The Cochrane Library, Chinese Biomedical Literature, China Knowledge Resource Integrated, WeiPu, and WanFang databases. Meta-analysis was carried out using STATA 11.2.

Results: This meta-analysis included 39 studies with 348 326 Chinese participants; the studies covered 20 provinces, municipalities, and autonomous regions. The pooled prevalence of SS was 3.2% (95% confidence interval [], 2.6%-3.7%; = 99.8%). The prevalence of SS in boys and girls were 3.1% (95% , 2.5%-3.7%) and 3.2% (95% , 2.6%-3.9%), respectively. The sex difference was not statistically significant ( 0.05). The prevalence of SS was higher in rural areas than in urban areas (4.7% [95% , 3.6%-5.8%] vs. 2.8% [95% , 2.2%-3.4%]; 0.001). The prevalence of SS was higher in West China (5.2%; 95% , 4.4%-6.0%) than in Northeast China (0.6%; 95% , 0.3%-0.8%), East China (2.3%; 95% , 1.9%-2.8%), or Central China (2.9%; 95% , 1.9%-3.9%).

Interpretation: The prevalence of SS among children was higher in western and rural areas of China. Close attention to children's growth and development is needed to prevent the occurrence of SS.
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http://dx.doi.org/10.1002/ped4.12233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212717PMC
June 2021

Synergistic enhancement of the emergency treatment effect of organophosphate poisoning by a supramolecular strategy.

Chem Sci 2021 Mar 1;12(14):5202-5208. Epub 2021 Mar 1.

College of Environmental and Chemical Engineering, Shanghai University Shanghai 200444 P. R. China.

Poisoning by organophosphorus agents (OPs) is a serious public health issue across the world. These compounds irreversibly inhibit acetylcholinesterase (AChE), resulting in the accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. A supramolecular detoxification system (SDS) has been designed with a view to deliver pyridine-2-aldoxime methochloride (PAM) with a synergistic inhibition effect on the ACh-induced hyperstimulation through host-guest encapsulation. NMR and fluorescence titration served to confirm the complexation between carboxylatopillar[6]arene (CP6A) and PAM as well as ACh with robust affinities. Patch-clamp studies proved that CP6A could exert an inhibition effect on the ACh-induced hyperstimulation of ACh receptors. Support for the feasibility of this strategy came from fluorescence imaging results. studies revealed that complexation by CP6A serves to increase the AChE reactivation efficiency of PAM. The formation of the PAM/CP6A complex contributed to enhance in a statistically significant way the ability of PAM not only to relieve symptoms of seizures but also to improve the survival ratio in paraoxon-poisoned model rats. These favorable findings are attributed to synergistic effects that PAM reactivates AChE to hydrolyze ACh and excess ACh is encapsulated in the cavity of CP6A to relieve cholinergic crisis symptoms.
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http://dx.doi.org/10.1039/d1sc00426cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179580PMC
March 2021

An Open-Label, Randomized, 2-Way, Crossover Bioequivalence Study of Cefradine Capsules in Healthy Chinese Volunteers.

Clin Pharmacol Drug Dev 2021 Jun 20. Epub 2021 Jun 20.

Phase I Clinical Trial Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.

The purpose of this study was to evaluate whether test cefradine capsules and reference cefradine capsules were bioequivalent in healthy Chinese volunteers. An open-label, randomized, biperiodic, crossover design was used. In each of the 2 study periods (separated by a 1-week washout period), 250-mg single doses of either the test or reference cefradine capsule were administered to study participants under fasted and fed conditions. Blood samples were collected at intervals from predose to 8 hours afterward. In the fasting study, the 90% confidence intervals (90%CI) of the C , AUC , and AUC for the test and reference preparations were 93.7%-112.2%, 94.6%-100.8%, and 94.7%-100.9%, respectively. In the fed study, the 90%CI of the C , AUC , and AUC for the test and reference preparations was 81.0%-99.1%, 100.5%-106.3%, and 100.5%-105.9%, respectively. The results showed that the test cefradine capsules and the reference formulation are bioequivalent under both fasting and fed conditions.
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http://dx.doi.org/10.1002/cpdd.991DOI Listing
June 2021

Serum Metabolic Profiling Identifies a Biomarker Panel for Improvement of Prostate Cancer Diagnosis.

Front Oncol 2021 7;11:666320. Epub 2021 May 7.

Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

Objectives: To identify and validate a biomarker panel by serum metabolic profiling for improvement of PCa diagnosis.

Materials And Methods: Totally, 134 individuals were included in this study. Among them, 39 PCa patients and 45 control patients (negative prostate biopsy) were involved in the discovery phase and 50 healthy controls were enrolled for validation phase of metabolomics study. LC-MS Analysis was used for the identification of the serum metabolites of patients.

Results: Logistics regression analysis shows that 5 metabolites [dMePE(18:0/18:2), PC(16:0/20:2), PS(15:0/18:2), SM(d16:0/24:1], Carnitine C14:0) were significantly changed in PCa patients compared with control patients. A metabolic panel (MET) was calculated, showing a significantly higher diagnostic performance than PSA in differentiating PCa from control patients [AUC (MET . PSA): 0.823 ± 0.046 . 0.712 ± 0.057, p<0.001]. Moreover, this panel was superior to PSA in distinguishing PCa from negative prostate biopsies when PSA levels were less than 20 ng/ml [AUC (MET . PSA]: 0.836 ± 0.050 . 0.656 ± 0.067, p<0.001]. In the validation set, the MET panel yielded an AUC of 0.823 in distinguishing PCa patients from healthy controls, showing a significant improvement of PCa detection.

Conclusions: The metabolite biomarker panel discovered in this study presents a good diagnostic performance for the detection of PCa.
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http://dx.doi.org/10.3389/fonc.2021.666320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138432PMC
May 2021

Mobilization and geochemistry of nutrients in sediment evaluated by diffusive gradients in thin films: Significance for lake management.

J Environ Manage 2021 Aug 18;292:112770. Epub 2021 May 18.

State Environmental Protection Key Laboratory for Lake Pollution Control, Institute of Lake Environment, Chinese Research Academy of Environmental Sciences (CRAES), Beijing, 100012, China; College of Water Science, Beijing Normal University, Beijing, 100875, China.

Investigation of in-situ mobilization of both nitrogen (N) and phosphate (PO) in sediment is important for lake management strategy. In this paper, diffusion gradients in thin films (DGT) and DGT induced flux in sediments (DIFS) model are newly designed for in-situ measurement of iron (Fe), PO, nitrate (NO-N) and ammonium (NH-N), and nutrients' mobility in sediment in Lake Nanhu (China). According to DGT profiles together with physicochemical properties in sediment, (I) PO is released from (i) Fe-bound P plus loosely sorbed P in anoxic sediment and (ii) the loosely sorbed P in oxic sediment; (II) anoxic sediment inhibits nitrification and NO-N release, but it favors denitrification and dissimilatory nitrate reduction to ammonium (DNRA), leading to NH-N release; (III) Eh and organic matter are two key influence factors on mobility of PO, NO-N and NH-N. According to DIFS calculation, the dynamics of desorption and diffusion at two sites belong to (i) slow rate of resupply and (ii) fast resupply cases, respectively. Internal loadings are estimated to be 92.74 (PO), 268.1 (NH-N) and -2466 kg a (NO-N), which reflects sediment mainly acts as a source for PO and NH-N, and a sink for NO-N in water. Based on sediment P release risk index (SPRRI), P release risks in lake sediments are estimated, ranging from light to relative high level. DGT and SPRRI aid choice of restoration methods for sediment, including sediment dredging, phytoremediation and in-situ inactivation.
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http://dx.doi.org/10.1016/j.jenvman.2021.112770DOI Listing
August 2021

Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome.

Front Pediatr 2021 29;9:544925. Epub 2021 Apr 29.

Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Gitelman syndrome (GS, OMIM 263800) is a genetic congenital tubulopathy associated with salt loss, which is characterized by hypokalemic metabolic toxicity, hypocalciuria, and hypomagnesemia. GS, which is typically detected in adolescence or adulthood, has long been considered a benign tubular lesion; however, the disease is associated with a significant decrease in the quality of life. In this study, we assessed the genotype-phenotype correlations based on the medical histories, clinical symptoms, laboratory test results, and whole-exome sequencing profiles from pediatric patients with GS. Between January 2014 and December 2020, all 31 consecutively enrolled patients complained of fatigue, salt craving, and muscle weakness. Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in were detected in 4, 24, and 3 patients, respectively. GS patients often present with muscle weakness and fatigue caused by hypokalemia and hypomagnesemia. Therefore, early diagnosis of GS is important in young children to reduce the possibility of growth retardation, tetany, and seizures. Next-generation sequencing such as whole-exome or whole-genome sequencing provides a practical tool for the early diagnosis and improvement of GS prognosis. Further whole-genome sequencing is expected to reveal more variants in among GS patients with single heterozygous mutations.
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http://dx.doi.org/10.3389/fped.2021.544925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116576PMC
April 2021

Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy.

Front Pharmacol 2021 14;12:621146. Epub 2021 Apr 14.

Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3'-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.
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http://dx.doi.org/10.3389/fphar.2021.621146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080440PMC
April 2021

Correction: A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

J Mater Chem B 2021 Apr;9(16):3595

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China and NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031, China.

Correction for 'A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy' by Chen Tan et al., J. Mater. Chem. B, 2021, DOI: 10.1039/d0tb02881a.
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http://dx.doi.org/10.1039/d1tb90052hDOI Listing
April 2021

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

J Mater Chem B 2021 04 30;9(15):3335-3345. Epub 2021 Mar 30.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.
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http://dx.doi.org/10.1039/d0tb02881aDOI Listing
April 2021

Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 19;259(8):2379-2387. Epub 2021 Apr 19.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Purpose: To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese.

Methods: Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts.

Results: A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan's syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat's disease, and neurofibromatosis.

Conclusions: We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.
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http://dx.doi.org/10.1007/s00417-021-05172-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352827PMC
August 2021

High-Throughput Cell Trapping in the Dentate Spiral Microfluidic Channel.

Micromachines (Basel) 2021 Mar 9;12(3). Epub 2021 Mar 9.

Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093, China.

Cell trapping is a very useful technique in a variety of cell-based assays and cellular research fields. It requires a high-throughput, high-efficiency operation to isolate cells of interest and immobilize the captured cells at specific positions. In this study, a dentate spiral microfluidic structure is proposed for cell trapping. The structure consists of a main spiral channel connecting an inlet and an out and a large number of dentate traps on the side of the channel. The density of the traps is high. When a cell comes across an empty trap, the cell suddenly makes a turn and enters the trap. Once the trap captures enough cells, the trap becomes closed and the following cells pass by the trap. The microfluidic structure is optimized based on the investigation of the influence over the flow. In the demonstration, 4T1 mouse breast cancer cells injected into the chip can be efficiently captured and isolated in the different traps. The cell trapping operates at a very high flow rate (40 μL/s) and a high trapping efficiency (>90%) can be achieved. The proposed high-throughput cell-trapping technique can be adopted in the many applications, including rapid microfluidic cell-based assays and isolation of rare circulating tumor cells from a large volume of blood sample.
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http://dx.doi.org/10.3390/mi12030288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000121PMC
March 2021

Selective discrimination and classification of G-quadruplex structures with a host-guest sensing array.

Nat Chem 2021 05 1;13(5):488-495. Epub 2021 Apr 1.

Environmental Toxicology Graduate Program, University of California, Riverside, CA, USA.

The secondary structures of nucleic acids have an important influence on their cellular functions but can be difficult to identify and classify quickly. Here, we show that an arrayed suite of synthetic hosts and dyes is capable of fluorescence detection of oligonucleotide secondary structures. Multivariate analysis of different fluorescence enhancements-generated using cationic dyes that show affinity for both DNA G-quadruplexes and the synthetic hosts-enables discrimination between G-quadruplex structures of identical length and highly similar topological types. Different G-quadruplexes that display the same folding topology can also be easily differentiated by the number of G-quartets and sequence differences at the 3' or 5' ends. The array is capable of both differentiation and classification of the G-quadruplex structures at the same time. This simple non-invasive sensing method does not require the discovery and synthesis of specific G-quadruplex binding ligands, but employs a simple multicomponent approach to ensure wide applicability.
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http://dx.doi.org/10.1038/s41557-021-00647-9DOI Listing
May 2021

Analyzing High-Order Epistasis from Genotype-Phenotype Maps Using 'Epistasis' Package.

Methods Mol Biol 2021 ;2212:265-275

Department of Computer Science, City University of Hong Kong, Kowloon Tong, Hong Kong.

Epistasis is the phenomenon about the interactions between genes, leading to complex phenotypic effects. The interactions between three or more mutations called "high-order epistasis" aroused significant interests in recent studies. However, there are still debates for analysis of high-order epistasis due to the non-linear model complexity and statistical artifacts. A recent "epistasis" Python package was therefore developed to characterize high-order epistasis by estimating non-linear scaling for mutation effects to extract high-order epistasis using linear models. This method successfully discovered statistically significant high-order epistasis on several real genotype-phenotype maps. We provided a concise and step-by-step guide to apply the "epistasis" by reproducing the high-order epistasis discoveries on real genotype-phenotype data using the latest API of the package.
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http://dx.doi.org/10.1007/978-1-0716-0947-7_16DOI Listing
April 2021

Complexation of an Antimicrobial Peptide by Large-Sized Macrocycles for Decreasing Hemolysis and Improving Stability.

Angew Chem Int Ed Engl 2021 05 9;60(20):11288-11293. Epub 2021 Apr 9.

College of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, P. R. China.

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (K ) of (4.20±0.23)×10  M for PXG/WQP3 and (2.46±0.44)×10  M for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.
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http://dx.doi.org/10.1002/anie.202102706DOI Listing
May 2021

Upper Motor Neuron Signs in the Cervical Region of Patients With Flail Arm Syndrome.

Front Neurol 2021 15;12:610786. Epub 2021 Feb 15.

Department of Neurology, Peking University Third Hospital, Beijing, China.

We investigated upper motor neuron (UMN) signs in the cervical region in a Chinese clinic-based cohort of patients with flail arm syndrome (FAS) by clinical examination and neurophysiological tests such as triple stimulation technique (TST) and pectoralis tendon reflex testing. A total of 130 consecutive FAS patients from Peking University Third Hospital underwent physical examination and neurophysiological tests at baseline and 3 months, 6 months, 9 months, and 12 months later. Pyramidal signs, pectoralis tendon reflex and TST results were evaluated to estimate the function of cervical spinal UMNs. At the first visit, weakness of the bilateral proximal upper limbs was found in 99 patients, while weakness of a single proximal upper limb was found in 31 patients. There were 49 patients with tendon hyperreflexia, 42 patients with tendon hyporeflexia and 39 patients with tendon areflexia. All except 4 of the patients had brisk pectoralis tendon reflex. The UMN score of the cervical region was 1.7 ± 0.4, and the lower motor neuron score of that region was 3.5 ± 0.3. The TST/TST amplitude ratio was 65.7 ± 7.5%. The latency of quantitative detection of the pectoralis tendon reflex was 7.7 ± 1.2 ms. In the follow-up study, the UMN score and the TST/TST amplitude ratio decreased, while the lower motor neuron score increased, and the latency of quantitative detection of the pectoralis tendon reflex remained steady. Although the signs of cervical spinal UMN dysfunction in patients with FAS were often concealed by muscle atrophy in the progression of the disease, TST and pectoralis tendon reflex could reveal it.
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http://dx.doi.org/10.3389/fneur.2021.610786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917109PMC
February 2021

F-Boramino acid PET/CT in healthy volunteers and glioma patients.

Eur J Nucl Med Mol Imaging 2021 09 15;48(10):3113-3121. Epub 2021 Feb 15.

Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

Purpose: In this work, the safety, biodistribution, and radiation dosimetry of large neutral amino acid transporter type-1 (LAT-1) targeting PET tracer F-trifluorobborate-derived tyrosine (denoted as F-FBY) has been investigated. It is designed as a first-in-human study in healthy volunteers and to assay LAT-1 expression level in glioma patients.

Methods: Six healthy volunteers (3 M, 3 F) underwent whole-body PET acquisitions at multiple time points after bolus injection of F-FBY. Regions of interest (ROIs) were mapped manually on major organs, and then the time-activity curves (TACs) were obtained. Dosimetry was calculated with the OLINDA/EXM software. Thirteen patients who were suspected of glioma were scanned with PET/CT at 30 min after F-FBY injection. Within 7 days after PET/CT, the tumor was removed surgically, and LAT-1 immunohistochemical staining for LAT-1 was performed on tumor samples and correlated with F-FBY PET imaging.

Results: F-FBY was well tolerated by all healthy volunteers, and no adverse symptoms were observed or reported. F-FBY is rapidly cleared from the blood circulation and excreted mainly through the kidneys and urinary tract. The effective dose (ED) was 0.0039 ± 0.0006 mSv/MBq. In 14 surgical confirmed gliomas (one of the patiens had two gliomas), F-FBY uptake increased consistently with tumor grade, with maximum standard uptake values (SUV) of 0.28 ± 0.14 and 2.84 ± 0.46 and tumor-to-normal contralateral activity (T/N) ratio of 2.30 ± 1.26 and 24.56 ± 6.32 in low- and high-grade tumors, respectively. In addition to the significant difference in the uptakes between low- and high-grade gliomas (P < 0.001), the immunohistochemical staining confirmed the positive correlations between the SUV, LAT-1 expression (r = 0.80, P < 0.001), and Ki-67 labeling index (r = 0.79, P < 0.001).

Conclusion: F-FBY is a PET tracer with favorable dosimetry profile and pharmacokinetics. It has the potential to assay LAT-1 expression in glioma patients and may provide imaging guidance for further boron neutron capture therapy of gliomas.

Trial Registration: clinicaltrials.gov (NCT03980431).
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http://dx.doi.org/10.1007/s00259-021-05212-7DOI Listing
September 2021

Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.

J Am Chem Soc 2021 02 31;143(5):2250-2255. Epub 2021 Jan 31.

Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.
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http://dx.doi.org/10.1021/jacs.0c10399DOI Listing
February 2021

Xanthohumol suppresses inflammation in chondrocytes and ameliorates osteoarthritis in mice.

Biomed Pharmacother 2021 May 28;137:111238. Epub 2021 Jan 28.

Department of Orthopaedics, Affiliated Hospital of Guilin Medical College, Guilin, Guangxi Province, China. Electronic address:

Osteoarthritis (OA), manifested as degeneration and damage of the articular cartilage is a progressive disease of joints. Previous studies have shown that extracellular matrix degradation and inflammation have quite a significant performance in the occurrence and development of OA. In various maladies, an anti-inflammatory effect has been demonstrated for Xanthohumol (XN); while OA is an inflammation related disease. The current in vivo and in vitro study aimed to investigate the therapeutic effect of XN on OA as well as its working mechanism. The results showed that XN has the capability to hinder the expression of nitric oxide synthase (INOS), IL-1β-promoted inducible nitric oxide (NO), necrosis factor-α of tumor (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in vitro. In addition, XN has been found to down-regulate the expression of matrix metalloproteinase-13 and prothrombin stimulated by IL-1β and up-regulates type II collagen and Aggrecan expression. At the same time, it was discovered that XN activates nuclear factor (Nrf2) in chondrocytes stimulated by IL-1β and inhibits nuclear factor B (NF-кB) signal transduction. The DMM model manifests that XN has an inhibitory impact on the progression of osteoarthritis and thus may be a candidate drug to slow down and delay the development of OA.
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http://dx.doi.org/10.1016/j.biopha.2021.111238DOI Listing
May 2021

[Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jan;41(1):75-78

Department of Neurology, Peking University Third Hospital, Beijing 100191, China.

Objective: To explore the association between rare HSPB1 variants and amyotrophic lateral sclerosis (ALS).

Methods: We performed next-generation sequencing for 166 Chinese ALS patients to screen for possible pathogenic rare variants of HSPB1. The control individuals were obtained from 1000 Genome Project and an in-house whole-exome sequencing database. The Sequence Kernel Association Test (SKAT) and the SKAT-optimal test (SKAT-O) were used to identify the association between rare HSPB1 variants and ALS.

Results: We identified 3 possible pathogenic rare variants of HSPB1 (all were missenses), including c.379C>T (p.R127W), c.446A>C (p.D149A) and c.451A>C (p.T151P). Compared with 1000 Genome Project, SKAT p=3.61×10 and SKAT-O p=1.62×10; while compared with the in-house database, SKAT p=9.99×10, SKAT-O p= 1.80×10. We analyzed the phenotypes of rare HSPB1 variant carriers and found no specific clinical characteristics associated with these variants.

Conclusions: Rare variants of HSPB1 are probably associated with the pathogenesis of ALS.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2021.01.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867492PMC
January 2021

An integrated model for evaluation of maternal health care in China.

PLoS One 2021 28;16(1):e0245300. Epub 2021 Jan 28.

Child and Adolescent Physical Examination and Health Management Center, Lanzhou University Second Hospital, Lanzhou, China.

In recent years, in the context of China's continuous medical and health reforms, the health status of Chinese women and children has been significantly improved through the continuous efforts of staff at all levels of maternal and child health care institutions. Many indicators in maternal health care have improved significantly, but the speed and magnitude of changes have varied. The purpose of this study is to evaluate the dynamic changes in China's maternal health status from 2004 to 2018, in order to determine whether China's medical and health reform measures in recent years have improved maternal health. A total of 6 evaluation indicators from the data of China Health Statistics Yearbook 2019 were selected. Then, based on the multi-criteria decision-making (MCDA) methodology, the entropy weighted technique for order preference by similarity to an ideal solution (TOPSIS), entropy weighted rank-sum ratio (RSR) method and the fuzzy comprehensive evaluation were employed in this study. In addition, sensitivity analysis was engaged to validate the stability and accuracy of the achieved results. The study results shows the ranking values of various methods were not exactly the same, but the overall trend was consistent. Overall, the maternal health care in China improved from 2004 to 2018 year by year, of which the top four were ranked from 2015 to 2018, and relatively poor from 2004 to 2006. This means that the policies and measures implemented in China's medical and health reform in the past few decades have effectively promoted China's maternal health care, and this will also provide a theoretical basis for future decisions to promote maternal health care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245300PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842919PMC
May 2021

PET imaging facilitates antibody screening for synergistic radioimmunotherapy with a Lu-labeled αPD-L1 antibody.

Theranostics 2021 1;11(1):304-315. Epub 2021 Jan 1.

Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

The low response rate of immunotherapy, such as anti-PD-L1/PD-1 and anti-CTLA4, has limited its application to a wider population of cancer patients. One widely accepted view is that inflammation within the tumor microenvironment is low or ineffective for inducing the sufficient infiltration and/or activation of lymphocytes. Here, a highly tumor-selective anti-PD-L1 (αPD-L1) antibody was developed through PET imaging screening, and it was radiolabeled with Lu-177 for PD-L1-targeted radioimmunotherapy (RIT) and radiation-synergized immunotherapy. A series of αPD-L1 antibodies were radiolabeled with zirconium-89 for PET imaging to screen the most suitable antibodies for RIT. Mice were divided into an immunotherapy group, a RIT group and a radiation-synergized immunotherapy group to evaluate the therapeutic effect. Alterations in the tumor microenvironment after treatment were assessed using flow cytometry and immunofluorescence microscopy. Radiation-synergistic RIT can achieve a significantly better therapeutic effect than immunotherapy or RIT alone. The dosages of the radiopharmaceuticals and αPD-L1 antibodies were reduced, the infiltration of CD4 and CD8 T cells in the tumor microenvironment was increased, and no side effects were observed. This radiation-synergistic RIT strategy successfully showed a strong synergistic effect with αPD-L1 checkpoint blockade therapy, at least in the mouse model. PET imaging of Zr-labeled antibodies is an effective method for antibody screening. RIT with a Lu-labeled αPD-L1 antibody could successfully upregulate antitumor immunity in the tumor microenvironment and turn "cold" tumors "hot" for immunotherapy.
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http://dx.doi.org/10.7150/thno.45540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681088PMC
August 2021

Study on antimony mobility in a contaminated shallow lake sediment using the diffusive gradients in thin films technique.

Chemosphere 2021 Mar 19;267:128913. Epub 2020 Nov 19.

National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Sciences, Anwai, Beiyuan, Beijing, 100012, China.

Antimony is a priority environmental contaminant. Increasing attention is being paid to the behaviors and mobilities of the various Sb species in the environment. Sb speciation in the environment and the mobilities of Sb species at mining sites have been studied well, but Sb speciation and mobility in shallow lakes requires further study. Here, we studied Sb behavior in sediment of a shallow lake in the plain rivers network in Taihu Basin that suffers continual Sb inputs from textile plants. The diffusive gradients in thin films techniques (DGT) made of zirconium oxide based binding resin gel (ZrO-Chelex), agarose diffusive gel and polyvinylidene fluoride filter were deployed in water and sediment to obtain a high-resolution record in situ. The results indicated that (1) pollutants released by textile plants caused relatively high Sb(Ⅲ), Sb(Ⅴ) and organoantimony concentrations in the eutrophic shallow lake, (2) Sb was seldomly mobile in the oxic layer where Sb(Ⅲ) was sorbed on Fe(Ⅲ) oxides and gradually formed Fe-Sb complexes in the sediment, but in the anoxic environment (oxidation-reduction potential: 366 - -344 mv) Sb(V), Fe(Ⅱ) and P (V) were simultaneously released to resupply the porewater, (3) the release of Sb from solid phase is decided by the redox condition, and the rate of release is dependent on the labile Sb content of the sediment. The mobility of Sb should be given sufficient attention when the potential ecological risk of metal(loid)s in shallow lakes and wetlands sediment are evaluated.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128913DOI Listing
March 2021

Selective Oxidation of 2-Hydroxypropyl Ethers of Cellulose and Dextran: Simple and Efficient Introduction of Versatile Ketone Groups to Polysaccharides.

Biomacromolecules 2020 12 25;21(12):4835-4849. Epub 2020 Nov 25.

Department of Sustainable Biomaterials, Virginia Tech, Blacksburg, Virginia 24061, United States.

Oxidation of polysaccharides has been a useful approach to new materials. However, selectivity in oxidation of polysaccharide macromolecular polyols remains a significant challenge with few methods for the synthesis of ketone-substituted polysaccharides. We report here a selective, practical, and efficient process, beginning with 2-hydroxypropyl ethers of polysaccharides that are simple and economical to prepare. We demonstrate this approach herein using commercial 2-hydroxypropyl cellulose (HPC) and 2-hydroxypropyl dextran (HPD) that we prepared. We oxidize the terminal, secondary alcohols of the oligo(2-hydroxypropyl) substituents with sodium hypochlorite so that the product has an oligo(2-hydroxypropyl) side chains terminated by a ketone. We demonstrate the high chemo- and regioselectivity of this oxidation by analytical methods including hydrolysis to monosaccharides and mass spectrometry of the resulting mixture. We provide an initial demonstration of the potential utility of these keto-polysaccharides by reacting Ox-HPC with primary amines to form Schiff base imines, providing proactive polymers.
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http://dx.doi.org/10.1021/acs.biomac.0c01045DOI Listing
December 2020

Long Non-Coding RNA SNHG1 Regulates the Wnt/β-Catenin and PI3K/AKT/mTOR Signaling Pathways EZH2 to Affect the Proliferation, Apoptosis, and Autophagy of Prostate Cancer Cell.

Front Oncol 2020 22;10:552907. Epub 2020 Oct 22.

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Background: Prostate cancer (PCa) is the most common malignant cancer in western developed countries, which has seriously threatened the life style and life quality of men. Its pathogenesis and causes remain indistinct. Currently, it is found that lncRNA-SNHG1 (SNHG1) is highly expressed in multiple tumors with proto-oncogene effect, but its function and mechanism in PCa need to be further studied.

Methods: The expression of SNHG1 and EZH2 was detected by RT-qPCR in the 20 pairs of PCa tissue, adjacent tissue and PCa cell lines. They were transfected with siRNA NC, SNHG1 siRNA, EZH2 siRNA, SNHG1 siRNA+empty, and SNHG1 siRNA+EZH2 overexpression. Then, MTT and colony formation assay were used to detect the proliferation and cloning ability of PCa cells LNCaP and PC3. Transwell and flow cytometry were used to measure cell migration and invasion ability and apoptosis level respectively. Immunofluorescence was used to detect the LC3 spot formation. Western blot was used to detect the expression of the autophagy-related proteins, and PI3K/AKT/mTOR and Wnt/β-catenin signaling pathway related proteins. Finally, nude mice tumorigenesis experiment to explore the effect of SNHG1 expression on PCa.

Results: We found that SNHG1 and EZH2 were up-regulated in PCa tissue and cells. The expression of SNHG1 and EZH2 was positively correlated. RNA pull down and RNA IP assay further confirmed that SNHG1 bound to EZH2. The proliferation, colony formation, migration and invasion of LNCaP and PC3 cells were significantly reduced with the interference with SNHG1or EZH2 compared with the control group. The related proteins of Wnt/β-catenin and PI3K/AKT/mTOR signaling pathway were significantly reduced after the interference with SNHG1 or EZH2; after simultaneous interference with SNHG1 and overexpression of EZH2, the functional effects on LNCaP and PC3 cells interfered with SNHG1 were reversed. These results were also confirmed nude mice tumor formation experiments.

Conclusions: This study reveals that lncRNA-SNHG1 regulates Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways via EZH2 gene to affect proliferation, apoptosis and autophagy of PCa cells. This experiment provides ideas and experimental basis for the improvement and treatment of PCa.
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http://dx.doi.org/10.3389/fonc.2020.552907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643000PMC
October 2020
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