Publications by authors named "Yunlong Zhang"

165 Publications

Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays.

Front Oncol 2021 20;11:782981. Epub 2021 Dec 20.

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

Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein-protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, , , , , , , , , , and were identified as candidate central genes. According to the survival analysis, the high expression of was related to the poor overall survival (OS) of patients with BC. may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of in BC cells was confirmed . Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC.
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http://dx.doi.org/10.3389/fonc.2021.782981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721040PMC
December 2021

Research on drivers' hazard perception in plateau environment based on visual characteristics.

Accid Anal Prev 2021 Dec 24;166:106540. Epub 2021 Dec 24.

Tibet University, No.36 Jiangsu, Lhasa, Tibet 850000, PR China.

A good visual search mode is an important prerequisite for a driver to perceive the hazard in the traffic environment timely and accurately. However, hypoxia conditions in the plateau environment might affect drivers' cognitive and judgment ability, posing potential threats to safe driving. This study analyzed the eye movement behaviors of drivers when faced with traffic hazards in the plateau environment, to examine the impact level of altitude on drivers' perception and reaction. Nine typical traffic hazard scenarios were investigated at four locations with four different altitudes, including Linzhi, Lhasa, Naqu, and Yanghu Scenic Area based on UC-WIN / ROAD driving simulation software. Then, drivers' visual search modes were analyzed according to drivers' eye movement data collected by ASL Mobile Eye monocular eye tracker. As the altitude increased, the drivers' first fixation time and the average saccade amplitude decreased, while the fixation duration percentage increased. Drivers with fewer years of driving experience had a larger percentage of fixation duration and a smaller saccade amplitude. In addition, a shorter acclimation period also negatively influenced the percentage of fixation time. The increase of altitude would weaken the drivers' visual sensitivity and cognitive processing ability of hazard information, which would reduce drivers' hazard perception skills, and the increase of driving experience might help alleviate such negative impacts to some extent. Based on the visual characteristics of traffic hazard scenarios obtained in this paper, the training of highly accident-prone drivers can be guided specifically to improve their visual search strategies, thereby improving driving safety.
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http://dx.doi.org/10.1016/j.aap.2021.106540DOI Listing
December 2021

A Gas-Phase Migration Strategy to Synthesize Atomically Dispersed Mn-N-C Catalysts for Zn-Air Batteries.

Small Methods 2021 Jun 22;5(6):e2100024. Epub 2021 Apr 22.

Department of Chemical Engineering, Waterloo Institute for Nanotechnology, Waterloo Institute for Sustainable Energy, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.

Mn and N codoped carbon materials are proposed as one of the most promising catalysts for the oxygen reduction reaction (ORR) but still confront a lot of challenges to replace Pt. Herein, a novel gas-phase migration strategy is developed for the scale synthesis of atomically dispersed Mn and N codoped carbon materials (g-SA-Mn) as highly effective ORR catalysts. Porous zeolitic imidazolate frameworks serve as the appropriate support for the trapping and anchoring of Mn-containing gaseous species and the synchronous high-temperature pyrolysis process results in the generation of atomically dispersed Mn-N active sites. Compared to the traditional liquid phase synthesis method, this unique strategy significantly increases the Mn loading and enables homogeneous dispersion of Mn atoms to promote the exposure of Mn-N active sites. The developed g-SA-Mn-900 catalyst exhibits excellent ORR performance in the alkaline media, including a high half-wave potential (0.90 V vs reversible hydrogen electrode), satisfactory durability, and good catalytic selectivity. In the practical application, the Zn-air battery assembled with g-SA-Mn-900 catalysts shows high power density and prominent durability during the discharge process, outperforming the commercial Pt/C benchmark. Such a gas-phase synthetic methodology offers an appealing and instructive guide for the logical synthesis of atomically dispersed catalysts.
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http://dx.doi.org/10.1002/smtd.202100024DOI Listing
June 2021

Different fusion tags affect the activity of ubiquitin overexpression on spastin protein stability.

Eur J Histochem 2021 Dec 7;65(4). Epub 2021 Dec 7.

Department of Orthopaedics, The First Affiliated Hospital of Jinan University, Guangzhou.

Spastin is one of the proteins which lead to hereditary spastic paraplegia (HSP), whose dysfunction towards microtubule severing and membrane transporting is critically important. The present study is to elucidate the mechanisms of the protein stability regulation of spastin. The ubiquitin encoding plasmids are transfected into COS-7 cells with different fusion tags including Green Fluorescent Protein (GFP), mCherry and Flag. The expression level of spastin was detected, microtubule severing activity and neurite outgrowth were quantified. The data showed that ubiquitin overexpression significantly induced the decreased expression of spastin, suppressed the activity of microtubule severing in COS-7 cells and inhibited the promoting effect on neurite outgrowth in cultured hippocampal neurons. Furthermore, when modulating the overexpression experiments of ubiquitin, it was found that relatively small tag like Flag, but not large tags such as GFP or mCherry fused with ubiquitin, retained the activity on spastin stability. The present study investigated the effects of small/large tags addition to ubiquitin and the novel mechanisms of post-transcriptional modifications of spastin on regulating neurite outgrowth, in the attempt to experimentally elucidate the mechanisms that control the level or stability of spastin in hereditary spastic paraplegia.
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http://dx.doi.org/10.4081/ejh.2021.3352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678624PMC
December 2021

Inclusion of phone use while driving data in predicting distraction-affected crashes.

J Safety Res 2021 Dec 13;79:321-328. Epub 2021 Oct 13.

Zachry Department of Civil and Environmental Engineering, Texas A&M University, 3136 TAMU, College Station, TX 77843-3136, United States. Electronic address:

Introduction: Given the tremendous number of lives lost or injured, distracted driving is an important safety area to study. With the widespread use of cellphones, phone use while driving has become the most common distracted driving behavior. Although researchers have developed safety performance functions (SPFs) for various crash types, SPFs for distraction-affected crashes are rarely studied in the literature. One possible reason is the lack of critical distracted behavior information in the commonly used safety data (i.e., roadway inventory, traffic, and crash counts). Recently, the frequency of phone use while driving (referred to as phone use data) is recorded by mobile application companies and has become available to safety researchers. The primary objective of this study is to examine if phone use data can potentially predict distracted-affected crashes.

Method: The authors first integrated phone use data with roadway inventory, traffic, and crash data in Texas. Then, the Random Forest (RF) algorithm was applied to assess the significance of the feature - phone use while driving - for predicting the number of distraction-affected crashes on a road segment. Further, this study developed two SPFs for distraction-affected crashes with and without the phone use data, separately. Both SPFs were assessed in terms of model fitting and prediction performances.

Results: RF results rank the frequency of phone use as an important factor contributing to the number of distraction-affected crashes. Performance evaluations indicated that the inclusion of phone use data in the SPFs consistently improved both fitting and prediction abilities to predict distracted-affected crashes. Practical Applications: The phone use data provide new insights into the safety analyses of distraction-affected crashes, which cannot be achieved by only using the conventional roadway inventory and crash data. Therefore, safety researchers and practitioners are encouraged to incorporate the emerging data sources in reducing distraction-affected crashes.
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http://dx.doi.org/10.1016/j.jsr.2021.09.013DOI Listing
December 2021

Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer.

Cancer Cell Int 2021 Nov 20;21(1):611. Epub 2021 Nov 20.

Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South of Wanping Road, Xuhui District, Shanghai, China.

Background: The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear.

Methods: Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein-protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan-Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database.

Results: In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues.

Conclusion: We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.
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http://dx.doi.org/10.1186/s12935-021-02278-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605517PMC
November 2021

He-Chan Pian inhibits the metastasis of non-small cell lung cancer via the miR-205-5p-mediated regulation of the GREM1/Rap1 signaling pathway.

Phytomedicine 2022 Jan 24;94:153821. Epub 2021 Oct 24.

Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518000, China. Electronic address:

Background: He-Chan Pian (HCP), a traditional Chinese medicinal formula, shows promising efficacy for the treatment of lung cancer.

Purpose: Gremlin (GREM1) plays an important role in gastrointestinal tumor metastasis; however, little is known about its role in lung cancer. We determined the mechanism underlying the protective effect of HCP against metastasis in a mouse model of non-small cell lung cancer (NSCLC) and demonstrated the role of GREM1.

Methods: Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the herbal components and metabolites from the serum of HCP-treated mice. The tumor, liver, and kidney were examined histologically, and the antitumor effects and toxicity of HCP were evaluated. Levels of epithelial-mesenchymal transition (EMT)-associated transcription factors were measured using western blotting in tumors from five groups (i.e., model, HCP [L], HCP [M], HCP [H], and positive control [cisplatin, DDP]). Differentially expressed proteins and genes were identified using protein chip and sequencing analyzes, respectively. Short hairpin RNAs and overexpression plasmids were introduced into cells to evaluate the effects of GREM1. To evaluate proliferation, migration, and invasion, the expression levels of proteins involved in the Rap1 pathway and EMT were measured in vitro. Xenograft tumors with overexpression-GREM1 (OE-GREM1) in A549 cells were examined for cell proliferation. A dual-luciferase assay was performed to verify the direct interaction of GREM1 with miR-205-5p in lung cancer.

Results: Thirty-six ingredients and bioactive constituents detected in the serum of HCP-treated mice were identified as the key compounds involved in the inhibition of tumor growth. Animal experiments revealed that HCP significantly decreased tumor volumes and had no adverse effects on the liver or kidney or side effects. GREM1 upregulation was closely related to tumor metastasis and was regulated by miR-205-5p, as confirmed using a dual-luciferase reporter assay. OE-GREM1 promoted A549 cell migration and invasion, promoted EMT, and increased the expression of Rap1 pathway intermediaries, whereas shGREM1 had the opposite effects. Furthermore, the effects of OE-GREM1 on proliferation in the A549 xenograft mouse model were attenuated, although HCP has an inhibitory effect on tumors.

Conclusion: Our results suggest that HCP contributes to the inhibition of NSCLC metastasis via the Gremlin/Rap1 signaling pathway regulated by miR-205-5p.
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http://dx.doi.org/10.1016/j.phymed.2021.153821DOI Listing
January 2022

Breaking a dative bond with mechanical forces.

Nat Commun 2021 Sep 24;12(1):5635. Epub 2021 Sep 24.

Princeton Institute for the Science and Technology of Materials, Princeton University, Princeton, NJ, 08540-8211, USA.

Bond breaking and forming are essential components of chemical reactions. Recently, the structure and formation of covalent bonds in single molecules have been studied by non-contact atomic force microscopy (AFM). Here, we report the details of a single dative bond breaking process using non-contact AFM. The dative bond between carbon monoxide and ferrous phthalocyanine was ruptured via mechanical forces applied by atomic force microscope tips; the process was quantitatively measured and characterized both experimentally and via quantum-based simulations. Our results show that the bond can be ruptured either by applying an attractive force of ~150 pN or by a repulsive force of ~220 pN with a significant contribution of shear forces, accompanied by changes of the spin state of the system. Our combined experimental and computational studies provide a deeper understanding of the chemical bond breaking process.
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http://dx.doi.org/10.1038/s41467-021-25932-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463581PMC
September 2021

An integrated strategy for target SSR genotyping with toleration of nucleotide variations in the SSRs and flanking regions.

BMC Bioinformatics 2021 Sep 8;22(1):429. Epub 2021 Sep 8.

Maize Research Center, Beijing Academy of Agricultural and Forest Sciences (BAAFS)/Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding, Beijing, 100097, China.

Background: With the broad application of high-throughput sequencing and its reduced cost, simple sequence repeat (SSR) genotyping by sequencing (SSR-GBS) has been widely used for interpreting genetic data across different fields, including population genetic diversity and structure analysis, the construction of genetic maps, and the investigation of intraspecies relationships. The development of accurate and efficient typing strategies for SSR-GBS is urgently needed and several tools have been published. However, to date, no suitable accurate genotyping method can tolerate single nucleotide variations (SNVs) in SSRs and flanking regions. These SNVs may be caused by PCR and sequencing errors or SNPs among varieties, and they directly affect sequence alignment and genotyping accuracy.

Results: Here, we report a new integrated strategy named the accurate microsatellite genotyping tool based on targeted sequencing (AMGT-TS) and provide a user-friendly web-based platform and command-line version of AMGT-TS. To handle SNVs in the SSRs or flanking regions, we developed a broad matching algorithm (BMA) that can quickly and accurately achieve SSR typing for ultradeep coverage and high-throughput analysis of loci with SNVs compatibility and grouping of typed reads for further in-depth information mining. To evaluate this tool, we tested 21 randomly sampled loci in eight maize varieties, accompanied by experimental validation on actual and simulated sequencing data. Our evaluation showed that, compared to other tools, AMGT-TS presented extremely accurate typing results with single base resolution for both homozygous and heterozygous samples.

Conclusion: This integrated strategy can achieve accurate SSR genotyping based on targeted sequencing, and it can tolerate single nucleotide variations in the SSRs and flanking regions. This method can be readily applied to divergent sequencing platforms and species and has excellent application prospects in genetic and population biology research. The web-based platform and command-line version of AMGT-TS are available at https://amgt-ts.plantdna.site:8445 and https://github.com/plantdna/amgt-ts , respectively.
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http://dx.doi.org/10.1186/s12859-021-04351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424866PMC
September 2021

Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria.

Life (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC 27695-7615, USA.

Tolyporphins A-R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains sp. 106C, sp. RF31YmG, sp. FACHB-892, UFV-OR1, UFV-E1, CENA114 and sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.
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http://dx.doi.org/10.3390/life11080758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401325PMC
July 2021

Patterns of near-crash events in a naturalistic driving dataset: Applying rules mining.

Accid Anal Prev 2021 Oct 17;161:106346. Epub 2021 Aug 17.

Texas A&M University, 3136 TAMU, College Station, TX 77843, United Stated.

This study aims to explore the associations between near-crash events and road geometry and trip features by investigating a naturalistic driving dataset and a corresponding roadway inventory dataset using an association rule mining method - the Apriori algorithm. To provide more insights into near-crash behavior, this study classified near-crash events into two severity levels: trivial near-crash events (-7.5 g ≤ deceleration rate ≤ -4.5 g) and non-trivial near-crash events (≤-7.5 g). From the perspective of descriptive statistics, the frequency of the itemsets, a set of categories of various variables, generated by the Apriori algorithm suggests that near-crash events are highly associated with several factors, including roadways without access control, driving during non-peak hours, roadways without a shoulder or a median, roadways with the minor arterial functional class, and roadways with a speed limit between 30 and 60 mph. By comparing the frequency of the occurrence of the itemset during trivial and non-trivial near-crash events, the results indicate that the length of the trip is a strong indicator of the near-crash event type. The results show that non-trivial near-crash events are more likely to occur if the trip is longer than 2 h. After applying the association rule mining algorithm, more interesting patterns for the two near-crash events were generated through the rules. The main findings include: 1) trivial near-crash events are more likely to occur on roadways without a median and shoulder that have a relatively lower functional class; 2) relatively higher functional roadways with relatively wide medians and shoulders could be an intriguing combination for non-trivial near-crash events; 3) non-trivial near-crash events often occur on long trips (more than 2 h); 4) congestion on roadways that have a lower functional class is a dominant rule associating with the high frequency of non-trivial near-crash events. This study associates near-crash events and the corresponding road geometry and trip features to provide a unique understanding of near-crash events.
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http://dx.doi.org/10.1016/j.aap.2021.106346DOI Listing
October 2021

Insulin Resistance, Serum Calcium and Hypertension: A Cross-Sectional Study of a Multiracial Population, and a Similarity Assessment of Results from a Single-Race Population's Study.

Diabetes Metab Syndr Obes 2021 24;14:3361-3373. Epub 2021 Jul 24.

Department of Nutrition and Food Hygiene, The National Key Discipline, School of Public Health, Harbin Medical University, Harbin, People's Republic of China.

Background: Recent research suggests the need to assess more ethnic disparities in hypertension (HTN). On the other hand, studies reveal impressive mortality rates due to cardiovascular diseases for some race and ethnic groups compared to others.

Methods: We referred to a recent study on serum calcium (SC) and insulin resistance associated with HTN incidence to compare different race groups in the latter found relationship. We compare the current study outcomes with those from the Wu et al study.

Results: From 425 participants of the National Health and Nutrition Examination Survey (NHANES) data, we found a significant association between race and hypertension; Cramer's V (0.006) = 0.21 when adjusted with non-hypertensives and hypertensives. Mc Auley index (McA) was negatively related to hypertension, (355) = -0.24, < 0.0001. SC associated with HTN in all race groups significance persisted only in non-Hispanic Whites after multivariate adjustments of 74.1 ( = 0.03). McA was a mediator on SC-HTN in non-Hispanic Whites (NHW) (Coef = 13.25, [CI] = 1.42-32.13), and a moderator in other Hispanics interaction (0.04) = 0.27 and NHW interaction (0.001) = 0.028.

Conclusion: SC was associated with hypertension, similarly to the baseline study. SC and HTN association persisted in NHW compared to other race groups. Homeostasis model assessment (HOMA-IR) was not a mediator on SC-HTN, but with McA, this in NHW only. McA played a moderator role in OH and NHW. We suggest that race is a factor implicated in our findings, which may be investigated further in future research.
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http://dx.doi.org/10.2147/DMSO.S259409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318711PMC
July 2021

4,4'-Dimethoxychalcone regulates redox homeostasis by targeting riboflavin metabolism in Parkinson's disease therapy.

Free Radic Biol Med 2021 10 28;174:40-56. Epub 2021 Jul 28.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, 510260, China. Electronic address:

Oxidative stress damage plays a pivotal role in Parkinson's disease (PD) pathogenesis. Previously, we developed a blood brain barrier-penetrating peptide-based "Trojan Horse" strategy to deliver 4,4'-dimethoxychalcone (DMC) for PD therapy and revealed neuroprotective properties of DMC in a PD model; however, the underlying mechanisms remained unclear. Here, we report that DMC attenuated motor impairment, degeneration of DA neurons and α-synuclein aggregation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and exogenous human α-synuclein-induced PD mouse models. Mechanistically, DMC increased the expression of two critical intermediates in riboflavin metabolism: riboflavin kinase (RFK) and its metabolic product, flavin mononucleotide (FMN). We provide the first direct evidence that FMN ameliorated oxidative stress damage and dopaminergic neuron degeneration both in vitro and in vivo and that riboflavin metabolism was required for DMC-mediated neuroprotection. DMC-induced restoration of redox homeostasis was mediated via the activation of protein kinase Cθ (PKCθ) signaling. Together, our findings reveal that DMC may serve as a novel antioxidant in PD intervention and also define a novel mechanism that underlies its therapeutic activity.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.07.038DOI Listing
October 2021

Programmable Site-Specific Functionalization of DNA Origami with Polynucleotide Brushes.

Angew Chem Int Ed Engl 2021 10 24;60(43):23241-23247. Epub 2021 Aug 24.

Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Combining surface-initiated, TdT (terminal deoxynucleotidyl transferase) catalyzed enzymatic polymerization (SI-TcEP) with precisely engineered DNA origami nanostructures (DONs) presents an innovative pathway for the generation of stable, polynucleotide brush-functionalized DNA nanostructures. We demonstrate that SI-TcEP can site-specifically pattern DONs with brushes containing both natural and non-natural nucleotides. The brush functionalization can be precisely controlled in terms of the location of initiation sites on the origami core and the brush height and composition. Coarse-grained simulations predict the conformation of the brush-functionalized DONs that agree well with the experimentally observed morphologies. We find that polynucleotide brush-functionalization increases the nuclease resistance of DONs significantly, and that this stability can be spatially programmed through the site-specific growth of polynucleotide brushes. The ability to site-specifically decorate DONs with brushes of natural and non-natural nucleotides provides access to a large range of functionalized DON architectures that would allow for further supramolecular assembly, and for potential applications in smart nanoscale delivery systems.
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http://dx.doi.org/10.1002/anie.202107829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511278PMC
October 2021

Unique Biomarker Characteristics in Gestational Diabetes Mellitus Identified by LC-MS-Based Metabolic Profiling.

J Diabetes Res 2021 9;2021:6689414. Epub 2021 Jun 9.

Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.

Background: Gestational diabetes mellitus (GDM) is a type of glucose intolerance disorder that first occurs during women's pregnancy. The main diagnostic method for GDM is based on the midpregnancy oral glucose tolerance test. The rise of metabolomics has expanded the opportunity to better identify early diagnostic biomarkers and explore possible pathogenesis.

Methods: We collected blood serum from 34 GDM patients and 34 normal controls for a LC-MS-based metabolomics study.

Results: 184 metabolites were increased and 86 metabolites were decreased in the positive ion mode, and 65 metabolites were increased and 71 were decreased in the negative ion mode. Also, it was found that the unsaturated fatty acid metabolism was disordered in GDM. Ten metabolites with the most significant differences were selected for follow-up studies. Since the diagnostic specificity and sensitivity of a single differential metabolite are not definitive, we combined these metabolites to prepare a ROC curve. We found a set of metabolite combination with the highest sensitivity and specificity, which included eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, arachidonic acid, citric acid, -ketoglutaric acid, and genistein. The area under the curves (AUC) value of those metabolites was 0.984 between the GDM and control group.

Conclusions: Our results provide a direction for the mechanism of GDM research and demonstrate the feasibility of developing a diagnostic test that can distinguish between GDM and normal controls clearly. Our findings were helpful to develop novel biomarkers for precision or personalized diagnosis for GDM. In addition, we provide a critical insight into the pathological and biological mechanisms for GDM.
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http://dx.doi.org/10.1155/2021/6689414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211500PMC
January 2022

The Outcomes of Minimally Invasive Percutaneous Nephrolithotomy with Different Access Sizes for the Single Renal Stone ≤25 mm: A Randomized Prospective Study.

Urol Int 2021 Jul 1:1-6. Epub 2021 Jul 1.

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

Objectives: The aim of this study was to provide a randomized controlled trial comparing the outcomes of different access sizes used in the solo ultrasonic-guided minimally invasive percutaneous nephrolithotomy (mini-PCNL).

Methods: From January 2018 to December 2019, a total of 160 cases with single renal stones of <25 mm were randomized to undergo mini-PCNLs with Fr16, Fr18, Fr20, or Fr22 accesses. All accesses were established with the axis of the target calyx as the marker for puncture location and then expanded to the desired size. Hemoglobin reduction, operative time, stone-free rate, complications, etc., were all recorded and assessed.

Results: The demographic data were similar, and there were no significantly intergroup differences in stone-free rate, complications, and hospital stay time. The hemoglobin reduction was comparable and was 0.9 ± 0.6, 0.9 ± 0.7, 1.0 ± 0.5, and 1.1 ± 0.7 g/dL for the groups Fr16, Fr18, Fr20, and Fr22, respectively. The operative time was 53.4 ± 14.5, 48.5 ± 15.2, 42.8 ± 13.3, and 43.3 ± 13.1 min for the 4 groups, which decreased significantly from group Fr16 to Fr20, but there was no significant difference between Fr20 and Fr22 groups.

Conclusions: The axis of target calyx is a reliable marker for establishment of percutaneous renal access under ultrasonic guidance. The surgical outcomes of different access sizes were comparable, but the operation time was significantly shortened with the increase of size. However, Fr22 was not more efficient than Fr20.
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http://dx.doi.org/10.1159/000516914DOI Listing
July 2021

Mining patterns of near-crash events with and without secondary tasks.

Accid Anal Prev 2021 Jul 11;157:106162. Epub 2021 May 11.

Zachry Department of Civil & Environmental Engineering, Texas A&M University, 3136 TAMU, College Station, TX, 77843-3136, United States. Electronic address:

The engagement of secondary tasks, like using a phone or talking to passengers while driving, could introduce considerable risks to driving safety. This study utilizes a near-crash dataset extracted from a naturalistic driving study to explore the patterns of near-crash events with or without the involvement of secondary tasks as a surrogate approach to understand the impact of these behaviors on traffic safety. The dataset contains information about driver behaviors, such as secondary tasks, vehicle maneuvers, other conflict vehicles' maneuvers before and during near-crash events, and the driving environment. The patterns for near-crashes with or without the involvement of secondary tasks are mined by adopting the apriori association rule algorithm. Finally, the mined rules for the near-crash events with or without the involvement of the secondary tasks are analyzed and compared. The results demonstrate that near-crashes with the involvement of secondary tasks often occur with drivers in a relatively stable and presumably predictable environment, such as an interstate highway with a constant speed. This type of near-crash is highly associated with the leading vehicle's sudden slowing or stopping since there is no expectation of any interruptions for these drivers performing the secondary tasks. The most common evasive maneuver in this kind of emergency is braking. Near-crashes without the involvement of secondary tasks is often associated with lane-changing behavior and sideswipe incidents. With shorter reaction time and awareness of the driving environment, the drivers in this type of near-crash can often make more complex maneuvers, like braking and steering, to avoid a collision. Understanding the patterns of these two types of near-crash incidents could help safety researchers, traffic engineers, and even vehicle designers/engineers develop countermeasures for minimizing potential collisions caused by secondary tasks or improper lane changing behaviors.
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http://dx.doi.org/10.1016/j.aap.2021.106162DOI Listing
July 2021

Trojan Horse Delivery of 4,4'-Dimethoxychalcone for Parkinsonian Neuroprotection.

Adv Sci (Weinh) 2021 05 3;8(9):2004555. Epub 2021 Mar 3.

Key Laboratory of Neurological Function and Health School of Basic Medical Sciences Guangzhou Medical University Guangzhou 511436 China.

Parkinson's disease (PD) is characterized by the progressive deterioration of dopamine (DA) neurons, and therapeutic endeavors are aimed at preventing DA loss. However, lack of effective brain delivery approaches limits this strategy. In this study, a "Trojan horse" system is used for substantia nigra-targeted delivery of a blood brain barrier-penetrating peptide (RVG29) conjugated to the surface of nanoparticles loaded with the natural autophagy inducer 4,4'-dimethoxychalcone (DMC) (designated as RVG-nDMC). Here, the neuroprotective effects of DMC are demonstrated in PD. Specifically, RVG-nDMC penetrates the blood brain barrier with enhanced brain-targeted delivery efficiency and is internalized by DA neurons and microglia. In vivo studies demonstrate that RVG-nDMC ameliorates motor deficits and nigral DA neuron death in PD mice without causing overt adverse effects in the brain or other major organs. Moreover, RVG-nDMC reverses tyrosine hydroxylase ubiquitination and degradation, alleviates oxidative stress in DA neurons, and exerts antiinflammatory effects in microglia. The "Trojan horse" strategy for targeted delivery of DMC thus provides a potentially powerful and clinically feasible approach for PD intervention.
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http://dx.doi.org/10.1002/advs.202004555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097374PMC
May 2021

An electrochemical sensor based on the modification of platinum nanoparticles and ZIF-8 membrane for the detection of ascorbic acid.

Talanta 2021 May 16;226:122105. Epub 2021 Jan 16.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, People's Republic of China. Electronic address:

In this manuscript, a layer of 2-methylimidazole zinc salt (ZIF-8) membrane is deposited on the surface of glassy carbon electrode (GCE) modified with platinum nanoparticles (Pt NPs) by reduction electrochemical method to obtain ZIF-8/Pt NPs/GCE, and then used for the detection of ascorbic acid (AA). The deposition of Pt NPs on the surface of GCE can not only guide the nucleation and growth of ZIF-8 membrane, but also exert a synergistic effect with it to enhance conductivity. For ZIF-8 membrane, it can increase the active area of electrode and thus improve the electrochemical response of the sensor for AA. Influence factors such as the deposition current density, deposition time on the surface morphology of the modified electrode, and the detection performance of the modified electrode during the electrochemical deposition of ZIF-8 membrane were explored to get the best performance. In addition, influence of conditions such as sweep speed and pH of the test solution on the electrochemical response signal of AA were also studied. Under the best conditions, the linear range of AA detection by this sensor is from 10 μmol L to 2500 μmol L, and the detection limit is 5.2 μmol L based on S/N = 3. What's more, the modified electrode also has good anti-interference ability, reproducibility and stability, and has achieved satisfactory results in the detection for AA in real samples.
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http://dx.doi.org/10.1016/j.talanta.2021.122105DOI Listing
May 2021

Berberine Protects Against NLRP3 Inflammasome via Ameliorating Autophagic Impairment in MPTP-Induced Parkinson's Disease Model.

Front Pharmacol 2020 27;11:618787. Epub 2021 Jan 27.

Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome was reported to be regulated by autophagy and activated during inflammatory procession of Parkinson's disease (PD). Berberine (BBR) is well-studied to play an important role in promoting anti-inflammatory response to mediate the autophagy activity. However, the effect of Berberine on NLRP3 inflammasome in PD and its potential mechanisms remain unclear. Hence, in this study, we investigated the effects of BBR on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, by evaluating their behavioral changes, dopaminergic (DA) neurons loss, neuroinflammation, NLRP3 inflammasome and autophagic activity. BBR was also applied in BV2 cells treated with 1-methyl-4-pehnyl-pyridine (MPP+). The autophagy inhibitor 3-Methyladenine (3-MA) was administrated to block autophagy activity both and . In our studies, compared to MPTP group, mice in MPTP + BBR group showed significant amelioration of behavioral disorders, mitigation of neurotoxicity and NLRP3-associated neuroinflammation, enhancement of the autophagic process in substantia nigra (SN). , compared to MPP+ group, BBR significantly decreased the level of NLRP3 inflammasome including the expressions of NLRP3, PYD and CARD domain containing (PYCARD), cleaved caspase 1 (CASP1), and mature interleukin 1 beta (IL1B), via enhancing autophagic activity. Furthermore, BBR treatment increased the formation of autophagosomes in MPP+-treated BV2 cells. Taken together, our data indicated that BBR prevents NLRP3 inflammasome activation and restores autophagic activity to protect DA neurons against degeneration and , suggesting that BBR may be a potential therapeutic to treat PD.
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http://dx.doi.org/10.3389/fphar.2020.618787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872967PMC
January 2021

Characterizing phone usage while driving: Safety impact from road and operational perspectives using factor analysis.

Accid Anal Prev 2021 Mar 9;152:106012. Epub 2021 Feb 9.

Zachry Department of Civil & Environmental Engineering, 3136 TAMU, College Station, TX 77843-3136, United States. Electronic address:

Phone use while driving (PUWD) is one of the most crucial factors of distraction related traffic crashes. This study utilized an unsupervised learning method, known as factor analysis, on a unique distracted driving dataset to understand PUWD behavior from the roadway geometry and operational perspectives. The results indicate that the presence of a shoulder, median, and access control on the relatively higher functional class roadways could encourage more PUWD events. The roadways with relatively lower speed limits could have high PUWD event occurrences if the variation in operating speed is high. The results also confirm the correlations between the frequency of PUWD events and the frequency of distracted crashes. This relationship is strong on urban roadways. For rural roadways, this correlation is only strong on the roadways with a large amount of PUWD events. The findings could help transportation agencies to identify suitable countermeasures in reducing distraction related crashes. Moreover, this study provides researchers a new perspective to study PUWD behavior rather than only focus on drivers' personalities.
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http://dx.doi.org/10.1016/j.aap.2021.106012DOI Listing
March 2021

The Role of Methyl Groups in the Early Stage of Thermal Polymerization of Polycyclic Aromatic Hydrocarbons Revealed by Molecular Imaging.

Energy Fuels 2021 Feb 12;35(3):2224-2233. Epub 2021 Jan 12.

Corporate Strategic Research, ExxonMobil Research and Engineering Company, 1545 Route 22 E., Annandale, New Jersey 08801, United States.

The initial thermal reactions of aromatic hydrocarbons are relevant to many industrial applications. However, tracking the growing number of heavy polycyclic aromatic hydrocarbon (PAH) products is extremely challenging because many reactions are unfolding in parallel from a mixture of molecules. Herein, we studied the reactions of 2,7-dimethylpyrene (DMPY) to decipher the roles of methyl substituents during mild thermal treatment. We found that the presence of methyl substituents is key for reducing the thermal severity required to initiate chemical reactions in natural molecular mixtures. A complex mixture of thermal products including monomers, dimers, and trimers was characterized by NMR, mass spectrometry, and noncontact atomic force microscopy (nc-AFM). A wide range of structural transformations including methyl transfer and polymerization reactions were identified. A detailed mechanistic understanding on the roles of H radicals during the polymerization of polycyclic aromatic hydrocarbons was obtained.
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http://dx.doi.org/10.1021/acs.energyfuels.0c04016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869141PMC
February 2021

DNA Origami Guided Self-Assembly of Plasmonic Polymers with Robust Long-Range Plasmonic Resonance.

Nano Lett 2020 12 13;20(12):8926-8932. Epub 2020 Nov 13.

Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.

Plasmonic polymers consisting of metallic nanoparticles (NPs) are able to squeeze light into the deep-subwavelength space and transfer along a highly confined nanoscale path in long range. DNA nanotechnology, particularly benefiting from the molecular programmability of DNA origami, has provided otherwise nearly impossible platforms for constructing plasmonic nanoparticle polymers with designer configurations and nanoscale gaps. Here, we design and assemble a DNA origami hashtag tile that is able to polymerize into one-dimensional chains with high rigidity. The DNA origami hashtag chains are used as frames to enable robust, versatile, and precise arrangement of metallic NPs into micrometer-long chiral and magnetic plasmonic polymers, which are capable of efficiently transporting plasmonic angular momentum and magnetic surface plasmonic polaritons at the deep-subwavelength scale. Our work provides a molecular platform for the fabrication of long, straight, and structurally complex nanoparticle polymers with emerging plasmonic properties that are appealing to a variety of fields.
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http://dx.doi.org/10.1021/acs.nanolett.0c04055DOI Listing
December 2020

Dietary iron and vitamins in association with mortality.

Clin Nutr 2021 04 23;40(4):2401-2409. Epub 2020 Oct 23.

Department of Nutrition and Food Hygiene, The National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China. Electronic address:

Background & Aims: Although disorders of iron metabolism are among the most common diseases and dietary intakes of vitamin A, B, B, C, E, and folic acid are known to affect the absorption or oxidation of iron, limited data are available on the association of dietary iron and these vitamins with mortality in the same population. Specifically, the holistic dietary vitamins intake and its combined effect with iron on mortality are unclear. The purpose of this study was to evaluate the association of dietary iron, holistic dietary vitamins, and their interactive effect with total and cause-specific mortality.

Methods: We evaluated the effects of dietary total/heme/non-heme iron, vitamins, and their interaction on all-cause/cardiovascular disease (CVD)/cancer mortality among 14,826 US adults in the National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative study. We developed a vitamin score to represent the holistic dietary intakes of vitamin A, B, B, C, E, and folic acid.

Results: A total of 2154 deaths occurred during a median follow-up of 9.3 years. Results from multivariate Cox proportional hazards models showed that higher vitamin score was associated lower risk of all-cause mortality (P-trend = 0.027). Negative interactions between dietary heme iron and vitamin score were observed on all-cause/CVD mortality. Dietary higher vitamins combined with lower heme iron was associated with lower risk of all-cause and CVD mortality (HR (95% confidence intervals (CIs)): 0.80 (0.64-0.98) and 0.55 (0.31-0.98), respectively). Higher dietary vitamins combined with higher total/non-heme iron was associated with lower risk of CVD mortality (HR (95%CIs): 0.69 (0.48-0.99) and 0.70 (0.48-0.99), respectively). These results remained significant even excluding participants with iron supplementation.

Conclusion: Our findings suggested that interactive effect of holistic dietary vitamins and iron play a protective role in decreasing all-cause and CVD mortality. Future studies, including cohort studies and clinical trials, are necessary to confirm these findings.
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http://dx.doi.org/10.1016/j.clnu.2020.10.038DOI Listing
April 2021

Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease.

Cell Death Dis 2020 10 22;11(10):897. Epub 2020 Oct 22.

Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, China.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.
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http://dx.doi.org/10.1038/s41419-020-03043-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582183PMC
October 2020

Ciliary localization of folliculin mediated via a kinesin-2-binding motif is required for its functions in mTOR regulation and tumor suppression.

FEBS Lett 2021 01 20;595(1):123-132. Epub 2020 Nov 20.

Department of Pharmacology and Chemical Biology, University of Pittsburgh, PA, USA.

Folliculin (FLCN) is a tumor suppressor protein involved in many cellular processes, including cell signaling, apoptosis, and autophagy. In ciliated cells, FLCN localizes to primary cilia and controls mTORC1 signaling in response to flow stress. Here, we show that the ciliary localization of FLCN requires its interaction with kinesin-2, the motor protein for anterograde intraflagellar transport. FLCN binds to kinesin-2 through a loop region in the middle of the protein. Single point mutations within this region of FLCN disrupt its kinesin-2 binding and ciliary entry. The mutants lose the ability to suppress the abnormal mTORC1/2 signaling activities and anchorage-independent growth of FLCN-deficient tumor cells. These observations suggest that ciliary localization of FLCN is essential for its function as a tumor suppressor.
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http://dx.doi.org/10.1002/1873-3468.13959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980781PMC
January 2021

Regulation of the cathode for amphi-charge storage in a redox electrolyte for high-energy lithium-ion capacitors.

Chem Commun (Camb) 2020 Oct 23;56(84):12777-12780. Epub 2020 Sep 23.

State Key Laboratory of Heavy Oil Processing, Institute of New Energy, College of Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.

Operating the cathodes of lithium-ion capacitors in an extended potential window for amphi-charge storage was proposed to be combined with a redox electrolyte-enabled capacity for balancing the typical gap between the capacity of the anode and that of the cathode. As a result, the as-obtained lithium-ion capacitors showed a three-fold increase in energy density.
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http://dx.doi.org/10.1039/d0cc04106hDOI Listing
October 2020

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

Ther Adv Neurol Disord 2020 3;13:1756286420947973. Epub 2020 Sep 3.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Panyu District, Xinzao, Guangzhou, 510260, China.

Background: Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer's disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood.

Methods: The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aβ), Aβ, and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson's correlation was used to examine the association between cognitive indicators and differential metabolites.

Results: We found significantly decreased MMSE scores, elevated plasma Aβ, and decreased Aβ/Aβ ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aβ/Aβ ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls.

Conclusions: Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.
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http://dx.doi.org/10.1177/1756286420947973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476355PMC
September 2020

Neutrophil extracellular traps increased by hyperglycemia exacerbate ischemic brain damage.

Neurosci Lett 2020 11 13;738:135383. Epub 2020 Sep 13.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address:

Hyperglycemia is common and associated with poor outcome in acute ischemic stroke patients. Neutrophil extracellular traps (NETs) are increased either in diabetes or ischemic stroke. We aimed to determine the role of NETs in acute ischemic stroke with hyperglycemia as it has not been clarified. NETs were observed in thrombi retrieved from ischemic stroke patients undergoing endovascular treatment. Citrullinated histone H3 was much more abundant in thrombi from hyperglycemic patients than in those from normoglycemic patients. BKS-db/db and wild-type mice injected with glucose were used to establish the permanent middle cerebral artery occlusion model with hyperglycemia. NETs induced by hyperglycemia were detected in the peri-ischemic brain tissue. Inhibition of NET formation decreased the infarction volume both in db/db and wild-type mice with hyperglycemia. Neurological function deficits were alleviated by blocking NET formation. These findings suggest that NETs increased by hyperglycemia play a role in exacerbation of ischemic brain damage.
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http://dx.doi.org/10.1016/j.neulet.2020.135383DOI Listing
November 2020

Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis.

J Cell Mol Med 2020 10 29;24(20):11742-11754. Epub 2020 Aug 29.

Department of Orthopedics, Shanghai Fengxian District Central Hospital/Southern Medical University Affiliated Fengxian Hospital, Shanghai, China.

Mesenchymal stem cell (MSCs)-based therapies have shown a promised result for intervertebral disc degeneration (IVDD) treatment. However, its molecular mechanisms remain unclear. Exosomes involve cell-cell communication via transference of its contents among different cells, and the present potential effect on cell death regulation. This study aimed to investigate the role of MSCs-derived exosomes on IVDD formation. Here, we first found the NLRP3-mediated nucleus pulposus cell (NP cell) pyroptosis was activated in the IVDD mice model and lipopolysaccharide (LPS)-induced model. However, MSCs treatment could inhibit NP cell pyroptosis in vitro. We then isolated MSCs-derived exosomes by differential centrifugation and identified the characteristics. Secondly, we investigated the function of MSCs-derived exosomes on LPS-induced NP cell pyroptosis. Finally, we presented evidence that MSCs-derived exosomal miR-410 was a crucial regulator of pyroptosis. Results showed that MSCs-derived exosomes play an anti-pyroptosis role by suppressing the NLRP3 pathway. Moreover, it suggested that this effect was attributed to miR-410, which was derived from MSCs-exosomes and could directly bind to NLRP3mRNA. In conclusion, for the first time, we demonstrated that MSCs-exosome treatment may inhibit pyroptosis and could be a promising therapeutic strategy for IVDD.
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http://dx.doi.org/10.1111/jcmm.15784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579702PMC
October 2020
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