Publications by authors named "Jingjing Yang"

279 Publications

5-hydroxymethylcytosine is dynamically regulated during forebrain organoid development and aberrantly altered in Alzheimer's disease.

Cell Rep 2021 Apr;35(4):109042

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address:

5-hydroxymethylcytosine (5hmC) undergoes dynamic changes during mammalian brain development, and its dysregulation is associated with Alzheimer's disease (AD). The dynamics of 5hmC during early human brain development and how they contribute to AD pathologies remain largely unexplored. We generate 5hmC and transcriptome profiles encompassing several developmental time points of healthy forebrain organoids and organoids derived from several familial AD patients. Stage-specific differentially hydroxymethylated regions demonstrate an acquisition or depletion of 5hmC modifications across developmental stages. Additionally, genes concomitantly increasing or decreasing in 5hmC and gene expression are enriched in neurobiological or early developmental processes, respectively. Importantly, our AD organoids corroborate cellular and molecular phenotypes previously observed in human AD brains. 5hmC is significantly altered in developmentally programmed 5hmC intragenic regions in defined fetal histone marks and enhancers in AD organoids. These data suggest a highly coordinated molecular system that may be dysregulated in these early developing AD organoids.
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http://dx.doi.org/10.1016/j.celrep.2021.109042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106871PMC
April 2021

Superatomic solid solutions.

Nat Chem 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, Columbia University, New York, NY, USA.

In atomic solids, substitutional doping of atoms into the lattice of a material to form solid solutions is one of the most powerful approaches to modulating its properties and has led to the discovery of various metal alloys and semiconductors. Herein we have prepared solid solutions in hierarchical solids that are built from atomically precise clusters. Two geometrically similar metal chalcogenide clusters, CoSe(PEt) and CrTe(PEt), were combined as random substitutional mixture, in three different ratios, in a crystal lattice together with fullerenes. This does not alter the underlying crystalline structure of the [cluster][C] material, but it influences its electronic and magnetic properties. All three solid solutions showed increased electrical conductivities compared with either the Co- or Cr-based parent material, substantially so for two of the Co:Cr ratios (up to 100-fold), and lowered activation barriers for electron transport. We attribute this to the existence of additional energy states arising from the materials' structural heterogeneity, which effectively narrow transport gaps.
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http://dx.doi.org/10.1038/s41557-021-00680-8DOI Listing
April 2021

Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis.

Exp Eye Res 2021 Apr 19:108585. Epub 2021 Apr 19.

The School of Public Health, Kunming Medical University, No. 1168 Chunrong West Road, Kunming, 650500, Yunnan, China. Electronic address:

Diabetic retinopathy (DR), characterized by intraretinal vessel formation, is a major complication in diabetes. Neovascularization is an important characteristic of DR, but its formation mechanism remains unclear. In this research, Malat1, miR-205-5p, and VEGF-A levels in high glucose (HG) treat-human retinal microvascular endothelial cells (hRMECs) was detected with qRT-PCR. CCK-8 assay, transwell assay, and tube formation assay was applied to access hRMEC viability, migration, and angiogenesis. Expression level of endothelial-mesenchymal transition (EndMT) markers (VE-cadherin, FSP1, and α-SMA) was detected by western blotting assay. Interaction among Malat1, miR-205-5p, and VEGF-A was confirmed by dual-luciferase reporter assay. Furthermore, in vivo DR mouse model was induced, and the effect of Malat1 on DR and EndMT markers was confirmed through hematoxylin-eosin (HE) staining and western blotting. As a result, Malat1 and VEGF-A was upregulated while miR-205-5p was suppressed under HG conditions. Malat1 could sponge miR-205-5p to regulate VEGF-A expression. Malat1 knockdown inhibited hRMEC proliferation, migration, and tube formation by targeting miR-205-5p under HG conditions. Furthermore, inhibition of Malat1 prevented the HG-induced EndMT process. In summary, Malat1 knockdown diminished hRMEC dysfunctions by regulating miR-205-5p/VEGF-A, providing a useful insight for exploring new therapeutic target for DR.
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http://dx.doi.org/10.1016/j.exer.2021.108585DOI Listing
April 2021

Genome-wide identification and comparative analysis of the WRKY gene family in aquatic plants and their response to abiotic stresses in giant duckweed (Spirodela polyrhiza).

Genomics 2021 Apr 20;113(4):1761-1777. Epub 2021 Apr 20.

The State Key Laboratory of Freshwater Ecology and Biotechnology, The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

WRKY is one of the largest transcription factor families across higher plant species and is involved in important biological processes and plant responses to various biotic/abiotic stresses. However, only a few investigations on WRKYs have been conducted in aquatic plants. This study first systematically analyzed the gene structure, protein properties, and phylogenetic relationship of 693 WRKYs in nine aquatic and two wetland plants at the genome-wide level. The pattern of WRKY groups in two aquatic ferns provided new evidence for the origin and evolution of WRKY genes. ARE cis-regulatory elements show an unusual high frequency in the promoter region of WRKY genes, indicating the adaptation to the aquatic habitat in aquatic plants. The WRKY gene family experienced a series of gene loss events in aquatic plants, especially group III. Further studies were conducted on the interaction network of SpWRKYs, their target genes, and non-coding RNAs. The expression profile of SpWRKYs under phosphate starvation, cold, and submergence conditions revealed that most SpWRKYs are involved in the response to abiotic stresses. Our investigations lay the foundation for further study on the mechanism of WRKYs responding to abiotic stresses in aquatic plants.
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http://dx.doi.org/10.1016/j.ygeno.2021.03.035DOI Listing
April 2021

Risk factors for pregnancy morbidity in women with antiphospholipid syndrome.

J Reprod Immunol 2021 Mar 29;145:103315. Epub 2021 Mar 29.

Obstetrics and Gynecology Department, Peking University People's Hospital, Beijing, China. Electronic address:

Antiphospholipid syndrome (APS) increases the risk of obstetric complications, but risk factors for pregnancy morbidity in women with APS remain incompletely characterized. This retrospective study included pregnant women with APS and a control group without APS admitted to Peking University People's Hospital between January 2013 and September 2019. Clinical data were extracted from medical records. Univariate and multivariate logistic regression analyses were used to identify factors associated with adverse pregnancy outcomes (fetal loss, premature birth, fetal growth restriction [FGR], preeclampsia and neonatal death). We included 64 pregnancies in 59 patients with APS (age, 32.3 ± 4.3 years) and 256 pregnancies in 256 women without APS (age, 30.4 ± 3.3 years). Compared with the control group, the APS group had higher incidence rates of preeclampsia (10.9 % vs. 2.3 %, P = 0.002), premature rupture of membranes (17.2 % vs. 3.9 %, P < 0.001), postpartum hemorrhage (23.4 % vs. 4.3 %, P < 0.001), fetal loss (4.7 % vs. 0.8 %, P = 0.024) and premature delivery at ≤34 weeks (7.8 % vs. 2.3 %, P = 0.047). The incidence rates of hypertension during pregnancy, HELLP syndrome, gestational diabetes, oligohydramnios and FGR were similar in both groups. Multivariate logistic regression revealed that three or more prior spontaneous miscarriages (odds ratio [OR], 6.162; 95 % confidence interval [CI], 1.271-29.882; P = 0.024) and double-positivity for antiphospholipid antibodies (OR, 4.024; 95 %CI, 1.025-15.794; P = 0.046) were independently associated with adverse pregnancy outcomes. APS increases the risks of adverse maternal and fetal outcomes during pregnancy. Three or more spontaneous miscarriages and double-positivity for antiphospholipid antibodies are risk factors for adverse pregnancy outcomes in women with APS.
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http://dx.doi.org/10.1016/j.jri.2021.103315DOI Listing
March 2021

In silico analysis of the potential mechanism of a preventive Chinese medicine formula on coronavirus disease 2019.

J Ethnopharmacol 2021 Apr 5;275:114098. Epub 2021 Apr 5.

Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, China; Hunan Engineering Technology Research Center for Medicinal and Functional Food, Hunan University of Chinese Medicine, Changsha, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation, Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, China. Electronic address:

Ethnopharmacological Relevance: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19.

Aim Of The Study: To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study.

Materials And Methods: Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1.

Results: According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P < 0.0001).

Conclusion: The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.
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http://dx.doi.org/10.1016/j.jep.2021.114098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020622PMC
April 2021

Author Correction: A new SNP genotyping technology Target SNP-seq and its application in genetic analysis of cucumber varieties.

Sci Rep 2021 Apr 7;11(1):8010. Epub 2021 Apr 7.

Beijing Vegetable Research Center, Beijing Academy of Agricultural and Forestry Sciences, National Engineering Research Center for Vegetables, Beijing, 100097, China.

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http://dx.doi.org/10.1038/s41598-021-86981-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027622PMC
April 2021

Novel Variance-Component TWAS method for studying complex human diseases with applications to Alzheimer's dementia.

PLoS Genet 2021 Apr 2;17(4):e1009482. Epub 2021 Apr 2.

Center for Computational and Quantitative Genetics, Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Transcriptome-wide association studies (TWAS) have been widely used to integrate transcriptomic and genetic data to study complex human diseases. Within a test dataset lacking transcriptomic data, traditional two-stage TWAS methods first impute gene expression by creating a weighted sum that aggregates SNPs with their corresponding cis-eQTL effects on reference transcriptome. Traditional TWAS methods then employ a linear regression model to assess the association between imputed gene expression and test phenotype, thereby assuming the effect of a cis-eQTL SNP on test phenotype is a linear function of the eQTL's estimated effect on reference transcriptome. To increase TWAS robustness to this assumption, we propose a novel Variance-Component TWAS procedure (VC-TWAS) that assumes the effects of cis-eQTL SNPs on phenotype are random (with variance proportional to corresponding reference cis-eQTL effects) rather than fixed. VC-TWAS is applicable to both continuous and dichotomous phenotypes, as well as individual-level and summary-level GWAS data. Using simulated data, we show VC-TWAS is more powerful than traditional TWAS methods based on a two-stage Burden test, especially when eQTL genetic effects on test phenotype are no longer a linear function of their eQTL genetic effects on reference transcriptome. We further applied VC-TWAS to both individual-level (N = ~3.4K) and summary-level (N = ~54K) GWAS data to study Alzheimer's dementia (AD). With the individual-level data, we detected 13 significant risk genes including 6 known GWAS risk genes such as TOMM40 that were missed by traditional TWAS methods. With the summary-level data, we detected 57 significant risk genes considering only cis-SNPs and 71 significant genes considering both cis- and trans- SNPs, which also validated our findings with the individual-level GWAS data. Our VC-TWAS method is implemented in the TIGAR tool for public use.
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http://dx.doi.org/10.1371/journal.pgen.1009482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046351PMC
April 2021

Advances in Endovascular Intervention Using Biomaterials: Study on Heat Efficiency of Scissor-Type Ultrasonic Catheter Device.

Biomed Res Int 2021 9;2021:5543520. Epub 2021 Mar 9.

Yamaguchi University, Tokiwadai 2-16-1, Ube, Yamaguchi, Japan.

To improve the performance of the ultrasonic device during the endovascular operation, a scissor-type ultrasonic catheter device with compound vibration was developed. The heat generated by friction between the target and the device affects its coagulation mechanism while the actuator contacts the tissue. The scissor-type ultrasonic catheter device proposed in this study is expected to improve heat generation performance because it has the action of rubbing the object when it is pushed by combined vibration. In addition, since it is constructed by simple notch processing, it can be miniaturized and can be expected to be introduced into catheters. However, the observation of ultrasonic vibration during frictional heating is difficult, which is an issue for device design. In this paper, a thermal-structure coupling analysis was done using the finite element method to calculate the heat generation efficiency and evaluate its coagulation performance.
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http://dx.doi.org/10.1155/2021/5543520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969089PMC
March 2021

Phenotypic, Nutritional, and Antioxidant Characterization of Blanched for Preferable Cultivar.

Front Plant Sci 2021 19;12:639639. Epub 2021 Feb 19.

The State Key Laboratory of Freshwater Ecology and Biotechnology, The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Blanching is a technique used in blocking sunlight for the production of tender, sweet, and delicious stems in the field. This technique is also used in water dropwort (), an important vegetable in East Asia. In China, the steamed stems of water dropwort are prepared with boiled rice. However, the effect of blanching on the nutritional level and antioxidant capacity of water dropwort has not been explored yet. The current study aims to determine the nutrient contents and antioxidant capacities of five cultivars and select the best cultivar. They were mainly compared in terms of phenotypic, physiological, nutritional, and antioxidant levels after blanch cultivation. Results indicate that blanching significantly influenced the phenotype, physiology, and nutritional level of water dropwort in all cultivars. Although few parameters decreased with blanching, starch, sugars, vitamins, minerals, and antioxidant activities increased significantly in the blanched stems in mid- and post-blanching periods. The most noticeable changes were detected in post-blanching samples. Furthermore, the best cultivar (V11E0012) was identified among them. Therefore, blanched water dropwort could be consumed for achieving more nutraceuticals and antioxidants, and cultivar V11E0012 could be recommend for blanching cultivation.
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http://dx.doi.org/10.3389/fpls.2021.639639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933200PMC
February 2021

CRISPR/Cas9-Engineered Universal CD19/CD22 Dual-Targeted CAR-T Cell Therapy for Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia.

Clin Cancer Res 2021 Feb 24. Epub 2021 Feb 24.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China.

Purpose: Autologous chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed/refractory acute lymphoblastic leukemia (r/r ALL). However, certain characteristics of autologous CAR-T cells can delay treatment availability. Relapse caused by antigen escape after single-targeted CAR-T therapy is another issue. Therefore, we aim to develop CRISPR-edited universal off-the-shelf CD19/CD22 dual-targeted CAR-T cells as a novel therapy for r/r ALL.

Patients And Methods: In this open-label dose-escalation phase I study, universal CD19/CD22-targeting CAR-T cells (CTA101) with a CRISPR/Cas9-disrupted region and gene to avoid host immune-mediated rejection were infused in patients with r/r ALL. Safety, efficacy, and CTA101 cellular kinetics were evaluated.

Results: CRISPR/Cas9 technology mediated highly efficient, high-fidelity gene editing and production of universal CAR-T cells. No gene editing-associated genotoxicity or chromosomal translocation was observed. Six patients received CTA101 infusions at doses of 1 (3 patients) and 3 (3 patients) × 10 CAR T cells/kg body weight. Cytokine release syndrome occurred in all patients. No dose-limiting toxicity, GvHD, neurotoxicity, or genome editing-associated adverse events have occurred to date. The complete remission (CR) rate was 83.3% on day 28 after CTA101 infusion. With a median follow-up of 4.3 months, 3 of the 5 patients who achieved CR or CR with incomplete hematologic recovery (CR/CRi) remained minimal residual disease (MRD) negative.

Conclusions: CRISPR/Cas9-engineered universal CD19/CD22 CAR-T cells exhibited a manageable safety profile and prominent antileukemia activity. Universal dual-targeted CAR-T cell therapy may offer an alternative therapy for patients with r/r ALL.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3863DOI Listing
February 2021

Microscopic Tumour Classification by Digital Mammography.

J Healthc Eng 2021 4;2021:6635947. Epub 2021 Feb 4.

School of Medical Technology, Qiqihar Medical College, Heilongjiang, Qiqihar 161006, China.

In this paper, we investigate the classification of microscopic tumours using full digital mammography images. Firstly, to address the shortcomings of traditional image segmentation methods, two different deep learning methods are designed to achieve the segmentation of uterine fibroids. The deep lab model is used to optimize the lesion edge detailed information by using the void convolution algorithm and fully connected CRF, and the two semantic segmentation networks are compared to obtain the best results. The Mask RCNN case segmentation model is used to effectively extract features through the ResNet structure, combined with the RPN network to achieve effective use and fusion of features, and continuously optimize the network training to achieve a fine segmentation of the lesion area, and demonstrate the accuracy and feasibility of the two models in medical image segmentation. Histopathology was used to obtain ER, PR, HER scores, and Ki-67 percentage values for all patients. The Kaplan-Meier method was used for survival estimation, the Log-rank test was used for single-factor analysis, and Cox proportional risk regression was used for multifactor analysis. The prognostic value of each factor was calculated, as well as the factors affecting progression-free survival. This study was done to compare the imaging characteristics and diagnostic value of mammography and colour Doppler ultrasonography in nonspecific mastitis, improve the understanding of the imaging characteristics of nonspecific mastitis in these two examinations, improve the accuracy of the diagnosis of this type of disease, improve the ability of distinguishing it from breast cancer, and reduce the rate of misdiagnosis.
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http://dx.doi.org/10.1155/2021/6635947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878100PMC
February 2021

Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change.

J Mol Med (Berl) 2021 Feb 21. Epub 2021 Feb 21.

Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Tamoxifen resistance remains the major obstacle to the estrogen receptor positive breast cancer endocrine therapy. Placenta-specific 8 (PLAC8) has been implicated in epithelial-mesenchymal transition and tumorigenesis. However, the molecular mechanisms underlying PLAC8 function in the context of tamoxifen resistance are unclear. Curcumin has attracted considerable attention in the last decades. It is isolated from Curcuma longa and has beneficial effects in cancer therapy. We studied this property by using MCF-7 and tamoxifen-resistant breast cancer cells (MCF-7/TAM) cell lines. PLAC8 can regulate MCF-7/TAM cell drug sensitivity through the MAPK/ERK pathway and shows the potential effects of curcumin or as a possible druggable target against tamoxifen failure.
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http://dx.doi.org/10.1007/s00109-021-02047-5DOI Listing
February 2021

Magnetic Colloid Antibodies Accelerate Small Extracellular Vesicles Isolation for Point-of-Care Diagnostics.

Nano Lett 2021 03 16;21(5):2001-2009. Epub 2021 Feb 16.

College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, National Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210023, China.

Small extracellular vesicles (sEVs) are increasingly recognized as noninvasive diagnostic markers for many diseases. Hence, it is highly desirable to isolate sEVs rapidly for downstream molecular analyses. However, conventional methods for sEV isolation (such as ultracentrifugation and immune-based isolation) are time-consuming and expensive and require large sample volumes. Herein, we developed artificial magnetic colloid antibodies (MCAs) via surface imprinting technology for rapid isolation and analysis of sEVs. This approach enabled the rapid, purification-free, and low-cost isolation of sEVs based on size and shape recognition. The MCAs presented a higher capture yield in 20 min with more than 3-fold enrichment of sEVs compared with the ultracentrifugation method in 4 h. Moreover, the MCAs also proposed a reusability benefiting from the high stability of the organosilica recognition layer. By combining with volumetric bar-chart chip technology, this work provides a sensitive, rapid, and easy-to-use sEV detection platform for point-of-care (POC) diagnostics.
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http://dx.doi.org/10.1021/acs.nanolett.0c04476DOI Listing
March 2021

Research progress on the effects of nickel on hormone secretion in the endocrine axis and on target organs.

Ecotoxicol Environ Saf 2021 Apr 11;213:112034. Epub 2021 Feb 11.

The Second Clinical Medical College, Lanzhou University, Lanzhou, 730030 Gansu, China; Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, 730030 Gansu, China. Electronic address:

Background: Nickel, as one of the most abundant elements in the earth's crust, plays many roles in human reproduction and life. It is an essential trace element for the human body, but can be harmful in excess amounts. Nickel has a significant impact on endocrine hormones in humans and animals, potentially causing abnormal secretions and changing the structure and function of endocrine organs. This article systematically reviews the effects of nickel on hormone secretion and target organs in the endocrine system and identifies areas of insufficient research.

Methods: All data in this article were extracted from peer-reviewed articles. The PubMed, SciFinder, Google Scholar, Web of Science, and China National Knowledge Infrastructure databases were searched for relevant articles. Data on nickel's effect on endocrine system hormones and target organs were retrieved, and manually sorted prior to inclusion in this review.

Results: Nickel acts on the endocrine system and affects the release and regulation of endocrine hormones. Disorders of endocrine hormones may lead to retardation of human growth and mental development, disturbance of water and salt regulation, and even a decline in reproductive ability. Nickel affects the hypothalamus and pituitary gland by regulating organs upstream of the endocrine axis; it can cause abnormal secretion of pituitary hormones, which affects target organs of the endocrine axis, resulting in dysfunction therein and abnormal secretion of related hormones. Nickel also damages target organs, mainly by inducing apoptosis, which triggers oxidative stress, cell autophagy, free radical release, and DNA damage. However, there are few studies on the endocrine axis, and some of the data are contradictory. Nevertheless, it is clear that nickel affects the endocrine system.

Conclusions: Nickel can damage organs in the endocrine system, such as the hypothalamus and pituitary. It also affects the secretion of hormones and damages the target organs of these hormones; this can result in endocrine system dysfunction. However, the results have been equivocal and further research is needed.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112034DOI Listing
April 2021

Cloning and Expression of Four Aquaporin Homologs from the Chinese Black Sleeper (Bostrychus sinensis): The Effects of Salinity Acclimation.

Biochem Genet 2021 Feb 5. Epub 2021 Feb 5.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316004, China.

Several fish species are known to possess mechanisms that allow them to adapt to environments with different salinities. The aim of this study was to investigate the effects of salinity on the expression of aquaporins (aqp1a, aqp3a, aqp8a, and aqp9a) in the gills and intestines of Chinese black sleeper. After 30 days of acclimation, the expression of aqp1a, aqp3a, and aqp9a in the gills was significantly higher in fish transferred to 5 ppt than in those transferred to 40 ppt seawater, whereas aqp8 expression was lower. In contrast, aqp1a, aqp3a, and aqp8a expression in the intestines was higher in fish acclimated in 40 ppt than in those acclimated in 5 ppt. During abrupt salinity acclimation, the levels of aqp1a and aqp9a in the gills varied over time in fish acclimated in 5 ppt, but not in 40 ppt. The aqp3a levels in gills were higher in the 5 ppt group after 24 h than in the 40 ppt. The expression level of aqp8a in gills was higher in 40 ppt than in 5 ppt, except for that at 12 h. In the intestines, expression level of aqp1a and aqp8a were significantly upregulated from 12 to 48 h following acclimation in 40 ppt and aqp3a was higher in 40 ppt group than in 5 ppt, while aqp9a expression exhibited an opposite trend. These findings suggest that aqp1a, aqp3a, aqp8a and aqp9a may play a major osmoregulatory role in water transport in the gills and intestines during acclimation to different salinity environment.
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http://dx.doi.org/10.1007/s10528-021-10033-2DOI Listing
February 2021

Multi-omic and multi-species meta-analyses of nicotine consumption.

Transl Psychiatry 2021 Feb 4;11(1):98. Epub 2021 Feb 4.

The Jackson Laboratory, Bar Harbor, ME, USA.

Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a model organism geneset by collecting results from five animal models of nicotine exposure (RNA expression changes in brain) and then tested the relevance of these genes and flanking genetic variation using genetic data from human cigarettes per day (UK BioBank N = 123,844; all European Ancestry). We tested three hypotheses: (1) DNA variation in, or around, the 'model organism geneset' will contribute to the heritability to human tobacco consumption, (2) that the model organism genes will be enriched for genes associated with human tobacco consumption, and (3) that a polygenic score based off our model organism geneset will predict tobacco consumption in the AddHealth sample (N = 1667; all European Ancestry). Our results suggested that: (1) model organism genes accounted for ~5-36% of the observed SNP-heritability in human tobacco consumption (enrichment: 1.60-31.45), (2) model organism genes, but not negative control genes, were enriched for the gene-based associations (MAGMA, H-MAGMA, SMultiXcan) for human cigarettes per day, and (3) polygenic scores based on our model organism geneset predicted cigarettes per day in an independent sample. Altogether, these findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption.
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http://dx.doi.org/10.1038/s41398-021-01231-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862377PMC
February 2021

Shining light on transition metal sulfides: New choices as highly efficient antibacterial agents.

Nano Res 2021 Jan 21:1-23. Epub 2021 Jan 21.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials Ministry of Education, Shandong University, Jinan, 250061 China.

Globally, millions of people die of microbial infection-related diseases every year. The more terrible situation is that due to the overuse of antibiotics, especially in developing countries, people are struggling to fight with the bacteria variation. The emergence of super-bacteria will be an intractable environmental and health hazard in the future unless novel bactericidal weapons are mounted. Consequently, it is critical to develop viable antibacterial approaches to sustain the prosperous development of human society. Recent researches indicate that transition metal sulfides (TMSs) represent prominent bactericidal application potential owing to the meritorious antibacterial performance, acceptable biocompatibility, high solar energy utilization efficiency, and excellent photo-to-thermal conversion characteristics, and thus, a comprehensive review on the recent advances in this area would be beneficial for the future development. In this review article, we start with the antibacterial mechanisms of TMSs to provide a preliminary understanding. Thereafter, the state-of-the-art research progresses on the strategies for TMSs materials engineering so as to promote their antibacterial properties are systematically surveyed and summarized, followed by a summary of the practical application scenarios of TMSs-based antibacterial platforms. Finally, based on the thorough survey and analysis, we emphasize the challenges and future development trends in this area.
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http://dx.doi.org/10.1007/s12274-021-3293-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818700PMC
January 2021

Exercise and Circulating Microparticles in Healthy Subjects.

J Cardiovasc Transl Res 2021 Jan 25. Epub 2021 Jan 25.

Dongzhimen Hospital, Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100700, People's Republic of China.

This study aimed to explore the relationship between exercise and circulating microparticles (CMPs). PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until August 13, 2020, using the terms "exercise" and "cell-derived microparticles." The Cochrane tool of risk of bias and the Methodological Index for Non-Randomized Studies were used to grade the studies. Twenty-six studies that met criteria were included in this review, including one before-after self-control study, 2 cohort studies, 4 randomized control trials, 5 case-control studies, and 14 descriptive studies. The studies were divided into a single bout and long-term exercise. The types of MPs contained endothelium-derived microparticles (EMPs), leukocyte-derived microparticles (LMPs), platelet-derived microparticles (PMPs), and erythrocyte-derived microparticles (ErMPs). This first systematic review found that the levels of CMPs continued to increase after a single bout of exercise in untrained subjects and were lower in trained subjects. PMPs expressed a transient increase after a single bout of exercise, and the proportion and duration of PMPs increment reduced in long-term exercise. Most studies showed a decline in LMPs in trained subjects after a single bout and long-term exercise, and variable changes were found in EMPs and ErMPs after exercise. A single bout of exercise drives the vessels exposed to high shear stress that promotes the formation of CMPs. However, the decline in CMPs in trained subjects may be attributed to the fact that they have a better ability to adapt to changes in hemodynamics and cellular function during exercise.
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http://dx.doi.org/10.1007/s12265-021-10100-4DOI Listing
January 2021

Mechanisms of the Morphological Plasticity Induced by Phytohormones and the Environment in Plants.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

The State Key Laboratory of Freshwater Ecology and Biotechnology, The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Plants adapt to environmental changes by regulating their development and growth. As an important interface between plants and their environment, leaf morphogenesis varies between species, populations, or even shows plasticity within individuals. Leaf growth is dependent on many environmental factors, such as light, temperature, and submergence. Phytohormones play key functions in leaf development and can act as molecular regulatory elements in response to environmental signals. In this review, we discuss the current knowledge on the effects of different environmental factors and phytohormone pathways on morphological plasticity and intend to summarize the advances in leaf development. In addition, we detail the molecular mechanisms of heterophylly, the representative of leaf plasticity, providing novel insights into phytohormones and the environmental adaptation in plants.
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http://dx.doi.org/10.3390/ijms22020765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828791PMC
January 2021

Lw-CNN-Based Myoelectric Signal Recognition and Real-Time Control of Robotic Arm for Upper-Limb Rehabilitation.

Comput Intell Neurosci 2020 28;2020:8846021. Epub 2020 Dec 28.

College of Information Science and Engineering, Hebei North University, Zhang Jiakou 075000, China.

Deep-learning models can realize the feature extraction and advanced abstraction of raw myoelectric signals without necessitating manual selection. Raw surface myoelectric signals are processed with a deep model in this study to investigate the feasibility of recognizing upper-limb motion intents and real-time control of auxiliary equipment for upper-limb rehabilitation training. Surface myoelectric signals are collected on six motions of eight subjects' upper limbs. A light-weight convolutional neural network (Lw-CNN) and support vector machine (SVM) model are designed for myoelectric signal pattern recognition. The offline and online performance of the two models are then compared. The average accuracy is (90 ± 5)% for the Lw-CNN and (82.5 ± 3.5)% for the SVM in offline testing of all subjects, which prevails over (84 ± 6)% for the online Lw-CNN and (79 ± 4)% for SVM. The robotic arm control accuracy is (88.5 ± 5.5)%. Significance analysis shows no significant correlation ( = 0.056) among real-time control, offline testing, and online testing. The Lw-CNN model performs well in the recognition of upper-limb motion intents and can realize real-time control of a commercial robotic arm.
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http://dx.doi.org/10.1155/2020/8846021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785339PMC
December 2020

Expression of JWA and XRCC1 as prognostic markers for gastric cancer recurrence.

Int J Clin Exp Pathol 2020 1;13(12):3120-3127. Epub 2020 Dec 1.

Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yangzhou University Yixing, Jiangsu, China.

Gastric cancer is one of the common gastrointestinal tumors. Tumor recurrence leads to a high death rate of gastric cancer. It is very important to find markers to effectively predict gastric cancer recurrence. We constructed a gastric cancer tissue microarray containing 89 tumors and corresponding normal tissues to explore the relationship between some proteins' expression and gastric cancer recurrence. The expression of JWA, Cullin1, p53, XRCC1, CHIP, FAK, MMP-2, MDM2 and p21 was determined on the microarray by immunohistochemistry. The relationship between the expression of these proteins and gastric cancer recurrence was analyzed. Tumor diameter, lymph node metastasis, and TNM stage were closely related with gastric cancer recurrence by Fisher's exact test (P<0.05). We used the univariate Cox regression analysis to find that JWA, XRCC1 were related to gastric cancer recurrence (P<0.05); Lymph node metastasis and TNM stage were closely related to gastric cancer recurrence (P<0.05). Multivariate Cox regression analysis revealed that XRCC1 or lymph node metastasis were independent risk factors of gastric cancer recurrence (P<0.05). Kaplan-Meier survival curve assay indicated that patients with low JWA or XRCC1 expression in gastric cancer had significantly shorter DFS than those with high-expressed proteins (P<0.05). JWA or XRCC1 may be effective markers to predict gastric cancer recurrence.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791389PMC
December 2020

Adsorption of Organic Compounds by Biomass Chars: Direct Role of Aromatic Condensation (Ring Cluster Size) Revealed by Experimental and Theoretical Studies.

Environ Sci Technol 2021 02 7;55(3):1594-1603. Epub 2021 Jan 7.

School of Environment and Energy, South China University of Technology, Guangzhou 510006, P. R. China.

Biomass chars are a major component of the soil environmental black carbon pool and prepared forms are a potentially useful tool in remediation. A function critical to the roles of both environmental and prepared chars is sorption of organic compounds. Char properties known to control sorption include surface area, porosity, functional group composition, and percent aromatic carbon. Here, we show that sorption affinity (but not maximum capacity) of organic compounds is directly related to the degree of condensation of the aromatic fraction. The Dubinin-Ashtakov characteristic sorption energy (, kJ mol) of 22 compounds on a thermoseries of bamboo chars correlates strongly with the DP/MAS-C NMR-determined bridgehead aromatic carbon fraction (χ), which relates to the mean ring cluster size. Density functional theory-computed binding energy () for five of the compounds on a representative series of polybenzenoid hydrocarbon open-face sheets also correlates positively with χ, leveling off for rings larger than ∼C. The , in turn, correlates strongly with . An increase in with cluster size is also found for sorption, both monolayer and bilayer, between parallel sheets representing slit micropores. The increasing sorption energy with cluster size is shown to be due to increasing cluster polarizability, which strengthens dispersion forces with the sorbate. The findings underscore a previously overlooked explicit role of aromatic condensation in sorption energy, and illustrate the utility of - comparison for predicting sorption.
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http://dx.doi.org/10.1021/acs.est.0c04852DOI Listing
February 2021

Chirality Amplified: Long, Discrete Helicene Nanoribbons.

J Am Chem Soc 2021 01 30;143(2):983-991. Epub 2020 Dec 30.

Department of Chemistry, Columbia University, New York 10027, United States.

Here we report the synthesis of two polyhelicene frameworks consisting, from end-to-end, of 18 and 24 fused benzene rings. The latter exhibits the largest electronic circular dichroism in the visible spectrum of any molecule. These shape-persistent helical nanoribbons incorporate multiple helicenes, a class of contorted polycyclic aromatic molecules consisting of -annulated rings. These conjugated, chiral molecules have interesting chemical, biological, and chiroptical properties; however, there are very few helicenes with extraordinary chiroptical response over a broad range of the visible spectrum-a key criterion for applications such as chiral optoelectronics. In this report, we show that coupling the polyhelicene framework with multiple perylene-diimide subunits elicits a significant chiroptic response. Notably, the molar circular dichroism increases faster than the absorptivity of these molecules as their helical axis lengthens. Computational analysis reveals that the greatly amplified circular dichroism arises from exciton-like interactions between the perylene-diimide and the helicene moieties. We predict that even greater chiroptic enhancement will result from further axial elongation of these nanoribbons, which can be readily enabled via the iterative synthetic method presented herein.
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http://dx.doi.org/10.1021/jacs.0c11260DOI Listing
January 2021

Mesopore to Macropore Transformation of Metal-Organic Framework for Drug Delivery in Inflammatory Bowel Disease.

Adv Healthc Mater 2021 02 28;10(3):e2000973. Epub 2020 Dec 28.

College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210093, China.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation-targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation-responsive metal-organic framework material (Ce-MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce-MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce-MOF@PSS delivery system exhibits excellent inflammation-targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. Accordingly, by targeting intestinal inflammation, increasing local drug concentrations, scavenging ROS, reducing systemic exposure, and exhibiting excellent safety profiles, it is considered that the Ce-MOF drug delivery platform can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.
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http://dx.doi.org/10.1002/adhm.202000973DOI Listing
February 2021

Protective Effect of Quercetin against HO-Induced Oxidative Damage in PC-12 Cells: Comprehensive Analysis of a lncRNA-Associated ceRNA Network.

Oxid Med Cell Longev 2020 1;2020:6038919. Epub 2020 Dec 1.

Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Quercetin is a bioflavonoid with potential antioxidant properties. However, the mechanisms underlying its effects remain unclear. Herein, we focused on integrating long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) sequencing of PC-12 cells treated with quercetin. We treated PC-12 cells with hydrogen peroxide to generate a validated oxidative damage model. We evaluated the effects of quercetin on PC-12 cells and established the lncRNA, miRNA, and mRNA profiles of these cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of these RNAs were conducted to identify the key pathways. Quercetin significantly protected PC-12 neuronal cells from hydrogen peroxide-induced death. We identified 297, 194, and 14 significantly dysregulated lncRNAs, miRNAs, and mRNAs, respectively, associated with the antioxidant effect of quercetin. Furthermore, the phosphatidylinositol-3-kinase/protein kinase B pathway was identified as the crucial signalling pathway. Finally, we constructed a lncRNA-associated competing endogenous RNA (ceRNA) network by utilizing oxidative damage mechanism-matched miRNA, lncRNA, and mRNA expression profiles and those changed by quercetin. In conclusion, quercetin exerted a protective effect against oxidative stress-induced damage in PC-12 cells. Our study provides novel insight into ceRNA-mediated gene regulation in the progression of oxidative damage and the action mechanisms of quercetin.
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http://dx.doi.org/10.1155/2020/6038919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725564PMC
December 2020

The APETALA2 transcription factor LsAP2 regulates seed shape in lettuce.

J Exp Bot 2021 Mar;72(7):2463-2476

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

Seeds are major vehicles of propagation and dispersal in plants. A number of transcription factors, including APETALA2 (AP2), play crucial roles during the seed development process in various plant species. However, genes essential for seed development and the regulatory networks that operate during seed development remain unclear in lettuce. Here, we identified a lettuce AP2 (LsAP2) gene that was highly expressed during the early stages of seed development. LsAP2 knockout plants obtained by the CRISPR/Cas9 system were used to explore the biological function of LsAP2. Compared with the wild type, the seeds of Lsap2 mutant plants were longer and narrower, and developed an extended tip at the seed top. After further investigating the structural characteristics of the seeds of Lsap2 mutant plants, we proposed a new function of LsAP2 in seed dispersal. Moreover, we identified several interactors of LsAP2. Our results showed that LsAP2 directly interacted with the lettuce homolog of BREVIPEDICELLUS (LsBP) and promoted the expression of LsBP. Transcriptome analysis revealed that LsAP2 might also be involved in brassinosteroid biosynthesis and signaling pathways. Taken together, our data indicate that LsAP2 has a significant function in regulating seed shape in lettuce.
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http://dx.doi.org/10.1093/jxb/eraa592DOI Listing
March 2021

Targeting ferroptosis in breast cancer.

Biomark Res 2020 Nov 5;8(1):58. Epub 2020 Nov 5.

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.

Ferroptosis is a recently discovered distinct type of regulated cell death caused by the accumulation of lipid-based ROS. Metabolism and expression of specific genes affect the occurrence of ferroptosis, making it a promising therapeutic target to manage cancer. Here, we describe the current status of ferroptosis studies in breast cancer and trace the key regulators of ferroptosis back to previous studies. We also compare ferroptosis to common regulated cell death patterns and discuss the sensitivity to ferroptosis in different subtypes of breast cancer. We propose that viewing ferroptosis-related studies from a historical angle will accelerate the development of ferroptosis-based biomarkers and therapeutic strategies in breast cancer.
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http://dx.doi.org/10.1186/s40364-020-00230-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643412PMC
November 2020

Fluorescent sensing film decorated with ratiometric probe for visual and recyclable monitoring of Cu.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 16;249:119217. Epub 2020 Nov 16.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Biomedicine Key Laboratory of Shaanxi Province, Lab of Tissue Engineering, the College of Life Sciences, Faculty of Life Science & Medicine, Northwest University, Xi'an, Shaanxi Province 710069, China. Electronic address:

Specifically, visually, and quantitatively monitor copper ion (Cu) is critical in the area of biological and environmental detection. Herein, a ratiometric fluorescent probe with benzoxazole appended xanthenes skeleton was constructed and further employed to monitor Cu in Hela cells, real water samples, and test strips. An easily distinguishable colorimetric (colorless to red) and fluorescence (green to red) change could be observed by naked eye under the portable UV lamp (365 nm) and the changes could be recovered by adding S. Furthermore, electrospinning technique was employed to fabricate a probe composited fluorescent sensing film (PMMA) for realizing the visual and recyclable monitoring of Cu, indicating that the probe-composited fluorescent sensing film has great potential for on-site and naked-eye detection of Cu in practical.
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http://dx.doi.org/10.1016/j.saa.2020.119217DOI Listing
March 2021

Docking of Cu and Ag in Metal-Organic Frameworks for Adsorption and Separation of Xenon.

Angew Chem Int Ed Engl 2021 Feb 26;60(7):3417-3421. Epub 2021 Jan 26.

Department of Chemistry, University of California-Berkeley, Berkeley, CA, 94720, USA.

We present a metal docking strategy utilizing the precise spatial arrangement of organic struts as metal chelating sites in a MOF. Pairs of uncoordinated N atoms on adjacent pyrazole dicarboxylate linkers distributed along the rod-shaped Al-O secondary building units in MOF-303 [Al(OH)(C H O N )] were used to chelate Cu and Ag with atomic precision and yield the metalated Cu- and Ag-MOF-303 compounds [(CuCl) Al(OH)(C H O N ) and (AgNO ) Al(OH)(C H O N )]. The coordination geometries of Cu and Ag were examined using 3D electron diffraction and extended X-ray absorption fine structure spectroscopy techniques. The resulting metalated MOFs showed pore sizes matching the size of Xe, thus allowing for binding of Xe from Xe/Kr mixtures with high capacity and selectivity. In particular, Ag-MOF-303 exhibited Xe uptake of 59 cm  cm at 298 K and 0.2 bar with a selectivity of 10.4, placing it among the highest performing MOFs.
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http://dx.doi.org/10.1002/anie.202015262DOI Listing
February 2021