Publications by authors named "Nana Wang"

159 Publications

Low Roll-Off and High Stable Electroluminescence in Three-Dimensional FAPbI Perovskites with Bifunctional-Molecule Additives.

Nano Lett 2021 Apr 28. Epub 2021 Apr 28.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Three-dimensional (3D) perovskites have been demonstrated as an effective strategy to achieve efficient light-emitting diodes (LEDs) at high brightness. However, most 3D perovskite LEDs still suffer from serious efficiency roll-off. Here, using FAPbI as a model system, we find that the main reason for efficiency droop and degradation in 3D perovskite LEDs is defects and the ion migration under electrical stress. By introducing bifunctional-molecule 3-chlorobenzylamine additive into the perovskite precursor solution, the detrimental effects can be significantly suppressed through the growth of high crystalline perovskites and defect passivation. This approach leads to bright near-infrared perovskite LEDs with a peak external quantum efficiency of 16.6%, which sustains 80% of its peak value at a high current density of 460 mA cm, corresponding to a high brightness of 300 W sr m. Moreover, the device exhibits a record half-lifetime of 49 h under a constant current density of 100 mA cm.
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http://dx.doi.org/10.1021/acs.nanolett.0c04900DOI Listing
April 2021

Polystyrene microplastics induce blood-testis barrier disruption regulated by the MAPK-Nrf2 signaling pathway in rats.

Environ Sci Pollut Res Int 2021 Apr 25. Epub 2021 Apr 25.

College of Basic Medicine & Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, People's Republic of China.

As a persistent pollutant, microplastics (MPs) have been reported to induce sperm quantity decrease in mice. However, the related mechanism remains obscure. Therefore, this study is intended to explore the effects of polystyrene microplastics (PS-MPs) on male reproduction and its related mechanism of blood-testis barrier (BTB) impairment. Thirty-two adult male Wistar rats were divided randomly into four groups fed with PS-MPs for 90 days at doses of 0 mg/day (control group), 0.015 mg/day, 0.15 mg/day, and 1.5 mg/day, respectively. The present results have shown that PS-MP exposure led to the damage of seminiferous tubule, resulted in apoptosis of spermatogenic cells, and decreased the motility and concentration of sperm, while the abnormality of sperm was elevated. Meanwhile, PS-MPs could induce oxidative stress and activate the p38 MAPK pathway and thus deplete the nuclear factor erythroid-2 related factor 2 (Nrf2). Noteworthily, PS-MPs led to the BTB-related protein expression decrease. All these results demonstrated that PS-MP exposure may lead to the destruction of BTB integrity and the apoptosis of spermatogenic cells through the activation of the MAPK-Nrf2 pathway. The current study provided novelty evidence for elucidating the effects of PS-MPs on male reproductive toxicity and its potential mechanism.
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http://dx.doi.org/10.1007/s11356-021-13911-9DOI Listing
April 2021

Analysis of Approaches in the Microsurgical Treatment of 102 Cases of Petroclival Meningioma in a Single Center.

Front Neurol 2021 19;12:627736. Epub 2021 Mar 19.

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

We identified the optimal approaches for treating the diverse tumor subtypes of petroclival meningioma (PM) by analyzing the clinical benefits of various surgical approaches adopted for each subtype. Tumors in 102 PM patients from a single center who underwent surgical treatment were classified as upper clivus (UC), cavernous sinus (CS), tentorium (TE), or petrous apex (PA) types based on the attachment site of the tumor base and the displacement of the trigeminal nerve. The therapeutic effects of different surgical approaches among the subtypes were evaluated according to the patient outcomes. The subtemporal (33.33%), retrosigmoid (16.67%), and Kawase approaches (50%) were used for the UC type. Simpson I/II resection was achieved in 46.66% of patients with the Kawase approach. Significant differences were found between the other two approaches ( = 0.044) and in the follow-up Karnofsky performance scale (KPS) scores ( = 0.008). The subtemporal (60%) and Kawase approaches (40%) were used for the CS type; neither approach achieved Simpson I/II resection. The retrosigmoid (25.81%) and Kawase approaches (74.19%) were used for the TE type. The Simpson I/II resection rates of the two approaches were 55.55 and 86.95%, respectively, and a significant difference was observed between them ( = 0.039). The retrosigmoid (43.75%) and Kawase approaches (56.25%) were used for the PA type. The Simpson I/II resection rates of the two approaches were 31.25 and 50%, respectively. The resection degrees of the two approaches and the KPS scores at follow-up were significantly different ( = 0.034). The individual microsurgical approaches adopted for the various PM tumor subtypes can provide maximal safe resection and good KPS scores. The Kawase approach is more suitable for PM, especially for UC- and PA-type PM tumors.
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http://dx.doi.org/10.3389/fneur.2021.627736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018277PMC
March 2021

Role of the Type VI Secretion System in the Pathogenicity of pv. , the Causative Agent of Kiwifruit Bacterial Canker.

Front Microbiol 2021 19;12:627785. Epub 2021 Feb 19.

State Key Laboratory of Crop Stress Biology for Arid Areas, Northwest A&F University, Yangling, China.

The type VI secretion system (T6SS), a macromolecular machine, plays an important role in the pathogenicity of many Gram-negative bacteria. However, the role of T6SS in the pathogenicity of pv. (), the pathogen of kiwifruit bacterial canker, is yet to be studied. Here, we found a T6SS gene cluster consisting of 13 core genes (A-J) in the genome of M228 based on a genome-wide analysis. To determine whether the T6SS gene cluster affects the pathogenicity of M228, T6SS and its 13 core gene deletion mutants were constructed and their pathogenicity was determined. The deletion mutants showed different degrees of reduction in pathogenicity compared with the wild-type strain M228; in and mutants, pathogenicity was significantly reduced by 78.7 and 71.3%, respectively. The pathogenicity results were also confirmed by electron microscopy. To further confirm that the reduction in pathogenicity is related to the function of T6SS, we selected the T6SS gene cluster, comprising and , for further analyses. Western blot results revealed that and were necessary for hemolytic co-regulatory protein secretion, indicating that they encode a functional T6SS. Further, we explored the mechanism by which T6SS affects the pathogenicity of M228. The ability of bacterial competition, biofilm formation, hydrogen peroxide tolerance, and proteolytic activity were all weakened in the deletion mutants M228ΔT6SS, M228ΔtssM, and M228ΔtssJ. All these properties of the two gene complementation mutants were restored to the same levels as those of the wild-type strain, M228. Quantitative real-time results showed that during the interaction between the deletion mutant M228ΔT6SS and the host, expression levels of T3SS transcriptional regulatory gene , structural genes , , , and effector genes and were down-regulated at different levels. Taken together, our data provide evidence for the first time that the T6SS plays an important role in the pathogenicity of , probably via effects on bacterial competition, biofilm formation, and environmental adaptability. Moreover, a complicated relationship exists between T6SS and T3SS.
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http://dx.doi.org/10.3389/fmicb.2021.627785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933208PMC
February 2021

Efficient and bright warm-white electroluminescence from lead-free metal halides.

Nat Commun 2021 Mar 3;12(1):1421. Epub 2021 Mar 3.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, China.

Solution-processed metal-halide perovskites are emerging as one of the most promising materials for displays, lighting and energy generation. Currently, the best-performing perovskite optoelectronic devices are based on lead halides and the lead toxicity severely restricts their practical applications. Moreover, efficient white electroluminescence from broadband-emission metal halides remains a challenge. Here we demonstrate efficient and bright lead-free LEDs based on cesium copper halides enabled by introducing an organic additive (Tween, polyethylene glycol sorbitan monooleate) into the precursor solutions. We find the additive can reduce the trap states, enhancing the photoluminescence quantum efficiency of the metal halide films, and increase the surface potential, facilitating the hole injection and transport in the LEDs. Consequently, we achieve warm-white LEDs reaching an external quantum efficiency of 3.1% and a luminance of 1570 cd m at a low voltage of 5.4 V, showing great promise of lead-free metal halides for solution-processed white LED applications.
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http://dx.doi.org/10.1038/s41467-021-21638-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930043PMC
March 2021

Halide Homogenization for High-Performance Blue Perovskite Electroluminescence.

Research (Wash D C) 2020 24;2020:9017871. Epub 2020 Dec 24.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Metal halide perovskite light-emitting diodes (LEDs) have achieved great progress in recent years. However, bright and spectrally stable blue perovskite LED remains a significant challenge. Three-dimensional mixed-halide perovskites have potential to achieve high brightness electroluminescence, but their emission spectra are unstable as a result of halide phase separation. Here, we reveal that there is already heterogeneous distribution of halides in the as-deposited perovskite films, which can trace back to the nonuniform mixture of halides in the precursors. By simply introducing cationic surfactants to improve the homogeneity of the halides in the precursor solution, we can overcome the phase segregation issue and obtain spectrally stable single-phase blue-emitting perovskites. We demonstrate efficient blue perovskite LEDs with high brightness, e.g., luminous efficacy of 4.7, 2.9, and 0.4 lm W and luminance of over 37,000, 9,300, and 1,300 cd m for sky blue, blue, and deep blue with Commission Internationale de l'Eclairage (CIE) coordinates of (0.068, 0.268), (0.091, 0.165), and (0.129, 0.061), respectively, suggesting real promise of perovskites for LED applications.
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http://dx.doi.org/10.34133/2020/9017871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877380PMC
December 2020

Modulation effect of chenpi extract on gut microbiota in high-fat diet-induced obese C57BL/6 mice.

J Food Biochem 2021 Apr 11;45(4):e13541. Epub 2021 Feb 11.

Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China.

The current study employed high-fat diet (HFD) induced murine model to assess the relationship between the lipid-lowering effect of aged citrus peel (chenpi) extract and the alterations of gut microbiota. The results showed that intake of chenpi extract for 12 week dose-dependently suppressed HFD-induced body weight, food intake, Lee's index, together with decreased the level of fasting blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Moreover, chenpi extract administration up-regulated the abundance and diversity of fecal microbiota and down-regulated the ratio of Firmicutes-to-Bacteroidetes, which was characterized by the lower family of Lachnospiraceae, Helicobacteraceae, and Desulfovibrionaceae, and higher family of Bacteroidales_S24-7, Bacteroidaceae, Rikenellaceae, and Ruminococcaceae. Consistently, at the genus levels, chenpi extract treatment reversed the expansions of Helicobacter, Lachnospiraceae_UCG-006, and Desulfovibrio, while increased the abundance of Bacteroides, Rikenellaceae_RC9_gut_group, and Alistipes (belonging to Rikenellaceae family), Anaerotruncus and Odoribacter (belonging to Ruminococcaceae family), which were significantly negatively correlated with the levels of the serum lipid parameters. In conclusion, our findings indicated that anti-obesity ability of chenpi extract might be related to the improvement of gut microbiota imbalance. PRACTICAL APPLICATIONS: With the improvement of living standards, the incidence of metabolic diseases such as obesity, hypertension, and diabetes has increased significantly, and it has become a public health problem that seriously affects the health of the people. Chenpi contains a large amount of active ingredients, flavonoids, and other compounds, which can promote the absorption of the digestive system and have good effects on diseases such as the cardiovascular system. Our previous study has confirmed that the chenpi extract effectively regulated the glucose and lipid metabolism disorder induced by high-fat diet. However, it is not clear whether the effect is closely related to the improvement of gut microbiota. Accordingly, our result would provide a theoretical basis for future research on the relationship between obesity, chenpi extract, and gut microbiota, and support additional understanding of its potential anti-obesity effects.
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http://dx.doi.org/10.1111/jfbc.13541DOI Listing
April 2021

Identification and sequencing of 59 highly polymorphic microhaplotypes for analysis of DNA mixtures.

Int J Legal Med 2021 Jan 27. Epub 2021 Jan 27.

Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.

Mixture detection remains one of the major challenges within a forensic science context. In recent years, microhaplotypes were proposed to have great potential in mixture detection, although many of them are not as polymorphic as widely used short tandem repeat (STR) markers. In this study, 59 new highly polymorphic microhaplotypes were identified and sequenced with the NextSeq 500 Sequencer. Based on the whole 1000 Genomes Project dataset, the average effective number of alleles (Ae) of the 59 microhaplotypes was 5.44, and the Ae values of 36 of these microhaplotypes were > 5.00. Their genetic variations in 187 Han Chinese individuals were evaluated. The average allele coverage ratio (ACR) of heterozygotes across all loci was 0.96 ± 0.05. The number of observed alleles varied from 4 to 23, with an average of 8.8 alleles per microhaplotype locus. The average observed heterozygosity (Ho) of 59 loci was 0.77 ± 0.05, and the Ho values of 15 of these loci were > 0.80. All loci showed high polymorphisms with a discrimination power (DP) ranging from 0.80 to 0.97, and the average DP was 0.92 ± 0.03. The analysis of simulated mixtures demonstrated that the microhaplotypes reported here were highly polymorphic and performed well in forensic DNA mixture analysis. This study not only demonstrated the applicability of microhaplotypes in mixture analysis but also provided new choices for highly polymorphic microhaplotypes because after adding the markers identified here, the number of microhaplotypes with Ae values of > 4.00 will increase from ~ 50 to ~ 110.
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http://dx.doi.org/10.1007/s00414-020-02483-xDOI Listing
January 2021

Eradication of solid tumors by chemodynamic theranostics with HO-catalyzed hydroxyl radical burst.

Theranostics 2021 1;11(5):2334-2348. Epub 2021 Jan 1.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, P.R. China.

Activatable theranostics, integrating high diagnostic accuracy and significant therapeutic effect, holds great potential for personalized cancer treatments; however, their chemodynamic modality is rarely exploited. Herein, we report a new activatable chemodynamic theranostics PAsc/Fe@Cy7QB to specifically recognize and eradicate cancer cells with HO-catalyzed hydroxyl radical (•OH) burst cascade. The nanomicelles PAsc/Fe@Cy7QB were constructed by self-assembly of acid-responsive copolymers incorporating ascorbates and acid-sensitive Schiff base-Fe complexes as well as HO-responsive adjuvant Cy7QB. Upon systematic delivery of PAsc/Fe@Cy7QB into cancer cells, the acidic microenvironment triggered disassembly of the nanomicelles. The released Fe catalyzed the oxidation of ascorbate monoanion (AscH) to efficiently produce HO. The released HO, together with the endogenous HO, could be converted into highly active •OH the Fenton reaction, resulting in enhanced Fe-mediated T magnetic resonance imaging (MRI). The synchronously released Cy7QB was activated by HO to produce a glutathione (GSH)-scavenger quinone methide to boost the •OH yield and recover the Cy7 dye for fluorescence and photoacoustic imaging. The biodegradable PAsc/Fe@Cy7QB designed for tumor-selective multimodal imaging and high therapeutic effect provides an exemplary paradigm for precise chemodynamic theranostic.
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http://dx.doi.org/10.7150/thno.49277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797687PMC
January 2021

Assessment of heavy metals mobility and correlative recovery and decontamination from MSWI fly ash: Mechanism and hydrometallurgical process evaluation.

Sci Total Environ 2021 May 9;768:145050. Epub 2021 Jan 9.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China; Linköping University - Guangzhou University Research Center on Urban Sustainable Development, Guangzhou University, Guangzhou 510006, China.

Fly ash from municipal solid waste incineration (MSWI) enriches many leachable toxic metals which readily migrate into the environment, posing serious risks to the ecosystem and human. In this study, the elements mobility, leaching availability as well as the potential maximum amounts of heavy metals in fly ash were thoroughly evaluated. To decontaminate the toxic elements from resulting fly ash leachates, The aqueous zinc (Zn) was recovered using Cyanex 572, cadmium (Cd) and copper (Cu) were effectively removed through adsorption process by a self-assembled hierarchical hydroxyapatite (HAP) nanostructure. The removal mechanism of Cd, Cu and Zn by leaching, extraction and adsorption was revealed with the results from XRD, ICP-MS and SEM. The results showed that fly ash has a high mobility under maximum availability leaching test (95% of fly ash was dissolved), a recovery rate of 91% for Zn can be obtained using Cyanex 572, and a high adsorption rate (> 95% for both Cu and Cd) was reached using HAP for the pristine fly ash leachate. The outcomes from isothermal and kinetic study revealed that Langmuir isotherm and pseudo-second order model can well describe the Cd and Cu adsorption behavior. Economic assessment suggested that the application of HAP for the removal of Cd and Cu is a technically sound and economically feasible approach. The findings of this study demonstrated that this comprehensive process integrated leaching, solvent extraction and consequential decontamination can be a practical strategy for MSWI fly ash treatment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145050DOI Listing
May 2021

MYC promotes cancer progression by modulating m A modifications to suppress target gene translation.

EMBO Rep 2021 Mar 11;22(3):e51519. Epub 2021 Jan 11.

Guangzhou First People's Hospital, School of Medicine, Institutes for Life Sciences, South China University of Technology, Guangzhou, China.

The MYC oncoprotein activates and represses gene expression in a transcription-dependent or transcription-independent manner. Modification of mRNA emerges as a key gene expression regulatory nexus. We sought to determine whether MYC alters mRNA modifications and report here that MYC promotes cancer progression by down-regulating N6-methyladenosine (m A) preferentially in transcripts of a subset of MYC-repressed genes (MRGs). We find that MYC activates the expression of ALKBH5 and reduces m A levels in the mRNA of the selected MRGs SPI1 and PHF12. We also show that MYC-regulated m A controls the translation of MRG mRNA via the specific m A reader YTHDF3. Finally, we find that inhibition of ALKBH5, or overexpression of SPI1 or PHF12, effectively suppresses the growth of MYC-deregulated B-cell lymphomas, both in vitro and in vivo. Our findings uncover a novel mechanism by which MYC suppresses gene expression by altering m A modifications in selected MRG transcripts promotes cancer progression.
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http://dx.doi.org/10.15252/embr.202051519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926262PMC
March 2021

Hypoxia-Induced Suppression of Alternative Splicing of MBD2 Promotes Breast Cancer Metastasis via Activation of FZD1.

Cancer Res 2021 03 5;81(5):1265-1278. Epub 2021 Jan 5.

Department of General Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.

Metastasis is responsible for the majority of breast cancer-related deaths, however, the mechanisms underlying metastasis in this disease remain largely elusive. Here we report that under hypoxic conditions, alternative splicing of MBD2 is suppressed, favoring the production of MBD2a, which facilitates breast cancer metastasis. Specifically, MBD2a promoted, whereas its lesser known short form MBD2c suppressed metastasis. Activation of HIF1 under hypoxia facilitated MBD2a production via repression of SRSF2-mediated alternative splicing. As a result, elevated MBD2a outcompeted MBD2c for binding to promoter CpG islands to activate expression of FZD1, thereby promoting epithelial-to-mesenchymal transition and metastasis. Strikingly, clinical data reveal significantly correlated expression of MBD2a and MBD2c with the invasiveness of malignancy, indicating opposing roles for MBD2 splicing variants in regulating human breast cancer metastasis. Collectively, our findings establish a novel link between MBD2 switching and tumor metastasis and provide a promising therapeutic strategy and predictive biomarkers for hypoxia-driven breast cancer metastasis. SIGNIFICANCE: This study defines the opposing roles and clinical relevance of MBD2a and MBD2c, two MBD2 alternative splicing products, in hypoxia-driven breast cancer metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/5/1265/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2876DOI Listing
March 2021

Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats.

Toxicology 2021 02 24;449:152665. Epub 2020 Dec 24.

Department of Histology and Embryology, Binzhou Medical University, Yantai, PR China; College of Basic Medicine & Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, PR China. Electronic address:

Microplastics (MPs) are receiving increased attention as a harmful environmental pollutant. Studies have investigated that MPs have reproductive toxicity, but the mechanism is little known. Here, we aimed to investigate the effects of polystyrene microplastics (PS-MPs) on ovary in rats and the underlying molecular mechanisms. in vivo, thirty-two female Wistar rats were exposed to 0.5 μm PS-MPs at different concentrations (0, 0.015, 0.15 and 1.5 mg/d) for 90 days. And then, all animals were sacrificed, ovaries and blood were collected for testing. in vitro, granulosa cells (GCs) were separated from rat ovary and treated with 0、1、5、25 μg/mL PS-MPs and reactive oxygen species (ROS) inhibitor N-Acetyl-l-cysteine (NAC) respectively. Our results showed that PS-MPs could enter into GCs and result in the reducing of growing follicles number. And the Enzyme-linked immunosorbent assay (ELISA) manifested that PS-MPs could obviously decrease the level of anti-Müllerian hormone (AMH). In addition, PS-MPs induced oxidative stress, apoptosis of GCs and ovary fibrosis evidenced by assay kits, flow cytometry, immunohistochemistry, Masson's trichrome and Sirius red staining. Moreover, the western blot assay manifested that PS-MPs exposure significantly increased the expression levels of Wnt/β-Catenin signaling pathways-related proteins (Wnt, β-catenin, p-β-catenin) and the main fibrosis markers (transforming growth factor-β (TGF-β), fibronectin, α-smooth muscle actin (α-SMA). Additionally, the expression levels of Wnt and p-β-catenin, apoptosis of GCs decreased after NAC treatment. In summary, polystyrene microplastics cause fibrosis via Wnt/β-Catenin signaling pathway activation and granulosa cells apoptosis of ovary through oxidative stress in rats, both of which ultimately resulted in decrease of ovarian reserve capacity.
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http://dx.doi.org/10.1016/j.tox.2020.152665DOI Listing
February 2021

One-step synthesis of cake-like biosorbents from plant biomass for the effective removal and recovery heavy metals: Effect of plant species and roles of xanthation.

Chemosphere 2021 Mar 30;266:129129. Epub 2020 Nov 30.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou, 510006, China; School of Environmental Science and Engineering, Guangzhou University, Guangzhou, 510006, China. Electronic address:

The continuous production of plant wastes and heavy metal pollution of waters have become widespread unavoidable challenges. Reutilization of plant wastes to treat toxic metal-contaminated water is an eco-friendly way to simultaneously solve these problems. Herein, three cake-like biosorbents were synthesized from tea waste, trimmed lawn grass and Nephrolepis cordifolia leaves through a one-step xanthation modification method combined with lyophilization, respectively. The plant species affected the appearance, structure and mechanical strength of the biosorbents due to the different contents of hydrocarbons and inorganic substances, which influenced the gel-like degree and thus the ability of the particles to pack between water molecules. The maximum adsorption capacities of the modified materials for Pb(II), Cu(II) and Cd(II) were 247.20, 85.80 and 265.31 mg/g, respectively, far higher than those of the original wastes, and the adsorption was selective. These results were mainly attributed to newly introduced -(CS)-S-Na groups, which triggered ion exchange, complexation and microprecipitation between heavy metal ions and functional groups. As-prepared biosorbents owned an excellent regenerability, which contributed to recovery heavy metals. The physicochemical properties and adsorption performances of the modified materials indicated that xanthation is a universal modification method suited to different plant biomasses with great potential to purify heavy metal-contaminated water. These biosorbents with excellent separability and regenerability might be promising for continuous-flow sewage treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129129DOI Listing
March 2021

HSCCC Separation of Three Main Compounds from the Crude Extract of Dracocephalum Tanguticum by Using Dimethyl Sulfoxide as Cosolvent.

J Chromatogr Sci 2021 Jan;59(2):175-181

Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, 52 Sanlihe Rd Xining 810001, P.R. China.

Separation of natural compounds directly from the crude extract is a challenging work for traditional column chromatography. In the present study, an efficient method for separation of three main compounds from the crude extract of Dracocephalum tanguticum has been successfully established by high-speed counter-current chromatography (HSCCC). The crude extract was directly introduced into HSCCC by using dimethyl sulfoxide as cosolvent. Ethyl acetate/n-butyl alcohol/0.3% glacial acetic acid (4: 1: 5, v/v) system was used and three target compounds with purity higher than 80% were obtained. Preparative HPLC was used for further purification and three target compounds with purity higher than 98% were obtained. The compounds were identified as chlorogenic acid, pedaliin and pedaliin-6″-acetate.
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http://dx.doi.org/10.1093/chromsci/bmaa094DOI Listing
January 2021

LaeA Controls Virulence and Secondary Metabolism in Apple Canker Pathogen .

Front Microbiol 2020 5;11:581203. Epub 2020 Nov 5.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, China.

Apple Valsa canker is a destructive disease caused by the ascomycete and poses a serious threat to apple production. Toxins synthesized by secondary metabolite biosynthetic gene clusters (SMBGCs) have been proven to be crucial for pathogen virulence. A previous study showed that genome contains remarkably expanded SMBGCs and some of their genes were significantly upregulated during infection. In this study, we focus on LaeA, a known regulator of secondary metabolism, for its role in SMBGC regulation, toxin production, and virulence of . Deletion of led to greatly reduced virulence with lesion length reduced by 48% on apple twigs. Toxicity tests proved that toxicity of secondary metabolites (SMs) produced by deletion mutant (Δ) was markedly decreased in comparison with wild-type (WT). Transcriptomic and proteomic analyses of WT and Δ indicated that a portion of transporters and about half (31/60) SMBGCs are regulated by Function analysis of eight gene clusters including , , , , , , , and that were differentially expressed at both transcriptional and translational levels showed that four of them (i.e., , , , and ) were involved in pigment production and contributed to virulence. Our findings will provide new insights and gene resources for understanding the role of pathogenicity-related toxins in .
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http://dx.doi.org/10.3389/fmicb.2020.581203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674932PMC
November 2020

In Situ-Fabricated Perovskite Nanocrystals for Deep-Blue Light-Emitting Diodes.

J Phys Chem Lett 2020 Dec 24;11(24):10348-10353. Epub 2020 Nov 24.

Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Efficient and stable deep-blue emission from perovskite light-emitting diodes (LEDs) is required for their application in lighting and displays. However, this is difficult to achieve due to the phase segregation issue of mixed halide perovskites and the challenge of synthesizing high-quality single-halide deep-blue perovskite nanocrystals through a traditional method. Here, we show that an antisolvent treatment can facilitate the in situ formation of perovskite nanocrystals using a facile spin-coating method. We find that the dropping time of the antisolvent can significantly affect the constitution of nanocrystal perovskite films. With a delay in the start time of the antisolvent treatment, small single-halide perovskite nanocrystals can be achieved, exhibiting efficient deep-blue emission. The LED device shows a stable electroluminescence (EL) peak at 465 nm, with a peak external quantum efficiency and a peak current efficiency of 2.4% and 2.5 cd A, respectively. This work provides a facile approach to changing the size of perovskite nanocrystals, thus effectively tuning their EL emission spectra.
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http://dx.doi.org/10.1021/acs.jpclett.0c03120DOI Listing
December 2020

Protective effects of tryptophan-catabolizing Lactobacillus plantarum KLDS 1.0386 against dextran sodium sulfate-induced colitis in mice.

Food Funct 2020 Dec 24;11(12):10736-10747. Epub 2020 Nov 24.

Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.

Tryptophan is an essential amino acid for the human body, whose intake is through the diet. Several studies support the theory that microbiota-derived tryptophan metabolite played a crucial role in maintaining the balance between gut microbiota and the mucosal immune system. Previously, we selected the Lactobacillus plantarum KLDS 1.0386 strain with high tryptophan-metabolic activity after the screening of 16 Lactobacillus strains. The current study aimed to assess the effects of L. plantarum KLDS 1.0386 combination with tryptophan in improving ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) and the potential mechanisms involved. Our results showed that L. plantarum KLDS 1.0386 combined with tryptophan (LAB + Trp) decreased DAI score, MPO level, and pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) concentration. It also increased anti-inflammatory cytokine (IL-10) production, tight junction proteins (claudin-1, occludin, and ZO-1), and mucin (MUC1 and MUC2) mRNA expressions. The level of indole-3-acetic acid (IAA), an important tryptophan metabolite in the liver, serum, and colon, was elevated after LAB + Trp treatment, which further upregulated aryl hydrocarbon receptor (AHR) mRNA expression to activate the IL-22/STAT3 signaling pathway. Moreover, the supplementation with LAB + Trp modulated gut microbiota composition. The present study provided novel insights that can be used to reduce the number of UC patients by employing a method utilizing tryptophan-catabolizing Lactobacillus strains.
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http://dx.doi.org/10.1039/d0fo02622kDOI Listing
December 2020

The Effects of Silicon and Different Types of Acid Rain on Root Growth and Physiology Activity of Oryza Sativa L. Seedlings.

Bull Environ Contam Toxicol 2020 Dec 19;105(6):967-971. Epub 2020 Nov 19.

School of Environment, Xuzhou Institute of Technology, No. 2, Lishui Road, 221018, Xuzhou, Jiangsu, China.

The effect of silicon (Si) and different types of acid rain (AR) on rice seedling roots was elucidated. The results showed different types of AR had different effects. Nitrate AR at pH 3.0 could promote the growth of rice roots, increased the dry weight, improved root phenotype, boosted HO contents and increased peroxidase, catalase and ascorbate peroxidase activities. Sulfate AR at pH 3.0 could significantly inhibit the growth of rice roots, decreased the dry weight, root phenotype, increased HO content and autioxidant enzyme activities. Sulfate-nitrate AR at pH 3.0 spraying had no significant effect on rice roots. Under different types of AR stress, the addition of exogenous Si could significantly promote the growth of rice seedling roots. This results indicated that the effects of rice root caused by AR might be due to not only the types of AR but also the content of Si in soil.
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http://dx.doi.org/10.1007/s00128-020-03046-xDOI Listing
December 2020

[Investigation of benzo(a)pyrene contamination in edible vegetable oil sold in Henan Province from 2017 to 2019].

Wei Sheng Yan Jiu 2020 Sep;49(5):759-794

Kaifeng Institute for Food and Drug Control, Kaifeng 475000, China.

Objective: To investigate the contamination of benzo(a)pyrene in edible vegetable oil from Henan Province.

Methods: A total of 1190 edible vegetable oil samples from Henan Province were collected. The concentration of benzo(a)pyrene was examined by high performance liquid chromatography.

Results: The concentration of benzo(a)pyrene in prepackaged edible vegetable oils was <0. 3-63. 5 μg/kg with an average of 1. 5 μg/kg. The detection rate of benzo(a)pyrene in samples was 80. 0%, and the over standard rate was 0. 6%. In terms of subclasses of vegetable oil, the sesame seed oil samples were most seriously contaminated with benzo(a)pyrene. The risk of the benzo(a)pyrene contamination of sesame seed oil produced by aqueous extraction method was higher than that by mechanical pressed method. The risk of benzo(a)pyrene contamination in sesame seed oil and rapeseed oil increased as the decrease of quality grade.

Conclusion: The result suggested that the sesame seed oil produced by aqueous extraction method had high risk in benzo(a)pyrene contamination in Henan Province.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2020.05.011DOI Listing
September 2020

Caduet enhances connexin 43 phosphorylation in left ventricular and thoracic aorta of SH model rats.

Exp Ther Med 2020 Nov 11;20(5):80. Epub 2020 Sep 11.

Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.

Caduet, also known as amlodipine besylate and atorvastatin calcium (AM + AT) tablet, can improve cardiac and vascular remodeling in patients with spontaneous hypertension (SH), but the underlying mechanism remains unknown. The present study aimed to explore whether AM + AT improved hypertensive left ventricular and thoracic aortic remodeling by regulating connexin 43 (Cx43) phosphorylation. A total of 32 male spontaneous hypertension model rats (SHR) were randomly divided into four groups: SHR control group, amlodipine-alone group (SHR-AM), atorvastatin-alone (SHR-AT) and AM + AT group (SHR-AM + AT); 8 Wistar-Kyoto (WKY) rats with normal blood pressure were used as the normal control. Drugs were orally administered for 8 weeks; subsequently, body weight, heart rate (HR), left ventricular mass index (LVMI), blood pressure (BP), plasma lipid levels and morphological changes of myocardial tissue in each group were analyzed. The expression of total (T)-Cx43 and phosphorylated (P)-Cx43 protein in the left ventricular and thoracic aortic tissues was determined using western blotting and immunofluorescence double labeling. The results revealed that AM + AT significantly decreased LVMI and cardiomyocyte cross-sectional area compared with SHR-AM and SHR-AT group. The western blotting results demonstrated that AM + AT could inhibit the expression of T-Cx43 protein, but increased the expression of P-Cx43 in the left ventricular and thoracic aorta. Moreover, immunofluorescence results indicated AM + AT could also decrease the expression T-Cx43, and increase that of P-Cx43 in the left ventricular and thoracic aorta compared with AM and AT alone. Therefore, it was concluded that AM + AT may mitigate left ventricular and thoracic aorta remodeling in SH rats by enhancing Cx43 phosphorylation, and the efficacy of AM + AT was superior to that of AM and AT alone.
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http://dx.doi.org/10.3892/etm.2020.9207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500004PMC
November 2020

Large Organic Cations in Quasi-2D Perovskites for High-Performance Light-Emitting Diodes.

J Phys Chem Lett 2020 Oct 24;11(20):8502-8510. Epub 2020 Sep 24.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Quasi-two-dimensional (quasi-2D) layered perovskites have received considerable attention because of their potential for high-performance perovskite optoelectronics. Among them, chemical modifications of large organic cations provide great opportunities to control the morphology, defect density, and stability of perovskite films. This Perspective mainly focuses on the design of large organic cations in quasi-2D perovskites and their effects on the performance of light-emitting diodes (LEDs). Potential candidates and challenges of large organic cations for high-performance perovskite LEDs are also discussed.
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http://dx.doi.org/10.1021/acs.jpclett.0c02476DOI Listing
October 2020

Synthesis of 7-hydroxy-6H-naphtho[2,3-c]coumarin via a TsOH-mediated tandem reaction.

Chem Commun (Camb) 2020 Sep 7;56(71):10369-10372. Epub 2020 Aug 7.

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, School of Chemistry and Chemical Engineering, and Basic Experimental Teaching Center, Shaanxi Normal University, Xi'an 710119, China.

A concise and efficient method for the synthesis of 7-hydroxy-6H-naphtho[2,3-c]coumarin using available 1-(2-hydroxyphenyl)-2-phenylethanone and Meldrum's acid has been developed. This transformation involved a tandem aldol reaction/lactonization/Friedel-Crafts reaction to form a lactone ring and a benzene ring. It showed high atom economy with water and acetone as the byproducts. Mechanism studies demonstrated two roles of Meldrum's acid: (i) as the reagent for the tandem reaction, and (ii) as the catalyst for the Friedel-Crafts reaction. Moreover, the hydroxyl group of 7-hydroxy-6H-naphtho[2,3-c]coumarin was further functionalized efficiently by arylethynyl, aryl, and cyano groups to furnish D-π-A compounds with excellent fluorescence emissions (Φ = 0.14-0.78).
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http://dx.doi.org/10.1039/d0cc04452kDOI Listing
September 2020

Wogonin preventive impact on hippocampal neurodegeneration, inflammation and cognitive defects in temporal lobe epilepsy.

Saudi J Biol Sci 2020 Aug 22;27(8):2149-2156. Epub 2020 May 22.

Department of Neurology, The First Affiliated Hospital of Air Force Military Medical University, No.127 Changle West Road, Xincheng District, Xi'an, Shaanxi 710032, China.

Previous studies demonstrated that the pathophysiological changes after temporal lobe epilepsy (TLE) such as oxidative stress, inflammatory reaction contribute to cognitive defect and neuronal damage. The present study was conducted to evaluate the anticonvulsant effect of wogonin ameliorates kainate-induced TLE, and to investigate the mechanism underlying these effects. Rats were divided into control, wogonin, kainate, and wogonin-pretreated kainate groups. The rat model of TLE was induced by unilateral intrahippocampal injection of 0.4 ug/ul of kainate. The results showed that the cognitive function in TLE rats was significantly impaired, and wogonin treatment improved cognitive function in the Morris water maze (MWM). H & E staining and TUNEL staining showed obvious damage in the hippocampus of TLE rats, and wogonin alleviated the damage. To evaluate the oxidative stress, the expression of MDA and GSH in plasma were detected. Nrf-2 and HO-1 mRNA expression in the hippocampus were detected. The levels of MDA in plasma increased in TLE rats, and the levels of GSH in plasma and Nrf-2, HO-1 in the brain decreased. Treatment with wogonin alleviated these changes. We also detected the mRNA expression of inflammatory mediators like IL-1β, TNF-α, and NF kB in the brain. The inflammatory reaction was significantly activated in the brain of TLE rats, and wogonin alleviated neuroinflammation. We detected the mRNA expression of Bcl-2, Bax, caspase-3, in the hippocampus. The levels of Bcl-2 decreased in TLE rats, Bax and caspase-3 increased, while wogonin alleviated these changes. The present study indicated that wogonin exerted a noticeable neuroprotective effect in kainate-induced TLE rats.
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http://dx.doi.org/10.1016/j.sjbs.2020.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384362PMC
August 2020

Identification of sequence polymorphisms at 58 STRs and 94 iiSNPs in a Tibetan population using massively parallel sequencing.

Sci Rep 2020 07 22;10(1):12225. Epub 2020 Jul 22.

Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.

Massively parallel sequencing (MPS) has rapidly become a promising method for forensic DNA typing, due to its ability to detect a large number of markers and samples simultaneously in a single reaction, and sequence information can be obtained directly. In the present study, two kinds of forensic genetic markers, short tandem repeat (STR) and identity-informative single nucleotide polymorphism (iiSNP) were analyzed simultaneously using ForenSeq DNA Signature Prep Kit, a commercially available kit on MPS platform. A total of 152 DNA markers, including 27 autosomal STR (A-STR) loci, 24 Y chromosomal STR (Y-STR) loci, 7 X chromosomal STR (X-STR) loci and 94 iiSNP loci were genotyped for 107 Tibetan individuals (53 males and 54 females). Compared with length-based STR typing methods, 112 more A-STR alleles, 41 more Y-STR alleles, and 24 more X-STR alleles were observed at 17 A-STRs, 9 Y-STRs, and 5 X-STRs using sequence-based approaches. Thirty-nine novel sequence variations were observed at 20 STR loci. When the flanking regions were also analyzed in addition to target SNPs at the 94 iiSNPs, 38 more alleles were identified. Our study provided an adequate genotype and frequencies data of the two types of genetic markers for forensic practice. Moreover, we also proved that this panel is highly polymorphic and informative in Tibetan population, and should be efficient in forensic kinship testing and personal identification cases.
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http://dx.doi.org/10.1038/s41598-020-69137-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376188PMC
July 2020

Myc-mediated SDHA acetylation triggers epigenetic regulation of gene expression and tumorigenesis.

Nat Metab 2020 03 16;2(3):256-269. Epub 2020 Mar 16.

Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.

The transcriptional role of cMyc (or Myc) in tumorigenesis is well appreciated; however, it remains to be fully established how extensively Myc is involved in the epigenetic regulation of gene expression. Here, we show that by deactivating succinate dehydrogenase complex subunit A (SDHA) via acetylation, Myc triggers a regulatory cascade in cancer cells that leads to H3K4me3 activation and gene expression. We find that Myc facilitates the acetylation-dependent deactivation of SDHA by activating the SKP2-mediated degradation of SIRT3 deacetylase. We further demonstrate that Myc inhibition of SDH-complex activity leads to cellular succinate accumulation, which triggers H3K4me3 activation and tumour-specific gene expression. We demonstrate that acetylated SDHA at Lys 335 contributes to tumour growth in vitro and in vivo, and we confirm increased tumorigenesis in clinical samples. This study illustrates a link between acetylation-dependent SDHA deactivation and Myc-driven epigenetic regulation of gene expression, which is critical for cancer progression.
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http://dx.doi.org/10.1038/s42255-020-0179-8DOI Listing
March 2020

A Geomorphological Regionalization using the Upscaled DEM: the Beijing-Tianjin-Hebei Area, China Case Study.

Sci Rep 2020 Jun 29;10(1):10532. Epub 2020 Jun 29.

Sichuan Provincial Engineering Laboratory of Monitoring and Controlling for Soil Erosion on Dry Valleys, China West Normal University, Nanchong, Sichuan, 637009, China.

Characterizing geomorphological patterns based on digital elevation models (DEMs) has become a basic focus of current geomorphology. A new DEM upscaling method based on the high-accuracy surface modelling method (HASM-US method) has been developed to improve the accuracy of current models and the subjectivity of macroscopic geomorphological patterns. The topographic variables of elevation (EL), slope (SL), aspect (AS), relief amplitude (RA), surface incision (SI), surface roughness (SR), and profile curvature (PC) with a spatial resolution of 1 km × 1 km in the Beijing-Tianjin-Hebei (BTH) area of China have been obtained by using the HASM-US method combined with the principal component analysis (PCA) method in terms of the elevation data of the SRTM-4 DEM, meteorological station location information, and field measurements with a GPS receiver. A geomorphological regionalization pattern has been developed to quantitatively classify the geomorphological types in the BTH area by combining the seven topographic factors of EL, SL, AS, RA, SI, SR, and PC that have significant spatial variation. The results show that the upscaling accuracy of elevation (mean difference only -2.32 m) with the HASM-US method is higher than that with the bilinear interpolation method and nearest neighbour interpolation method. The geomorphologic distribution in the BTH area includes 11 types: low plain, low tableland, low hill, low basin, middle plain, middle hill, low mountain with low RA values, low mountain with medium RA values, middle mountain with low RA values, middle mountain with medium RA values, and middle mountain with high RA values. The low plain is the dominant geomorphological type that covers 40.58% of the whole BTH area. The geomorphological distribution shows the different significant characteristics: the elevation rapidly decreases from the Taihang Mountains to the eastern area, gradually decreases from the Yanshan Mountains to the southern area, and first increases and then decreases from the Bashang Plateau to the southeastern area in the whole BTH area.
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http://dx.doi.org/10.1038/s41598-020-66993-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324369PMC
June 2020

Characterization of genetic polymorphisms in Nigerians residing in Guangzhou using massively parallel sequencing.

Forensic Sci Int Genet 2020 09 5;48:102323. Epub 2020 Jun 5.

Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address:

African populations exhibit extensive linguistic and cultural diversity but are less studied from a population genetic standpoint. Although much genetic data on admixed African individuals, such as African Americans, have been published, genetic polymorphism data, especially that based on sequence-based typing, are still insufficient in indigenous Africans. In this study, we examined the genetic diversity of 85 Nigerians residing in Guangzhou, China. Forensically relevant genetic markers, including autosomal short tandem repeats (A-STRs), X-chromosomal STRs (X-STRs), Y-chromosomal STRs (Y-STRs), and identity-informative single nucleotide polymorphisms (iiSNPs) were genotyped to uncover the genetic polymorphisms of this population. Sequence-based allelic variations were observed in 22 A-STRs, ten Y-STRs, and four X-STRs. Using massively parallel sequencing (MPS), the allele number increased from 475 length-based alleles to 683 sequence-based alleles. Compared to other populations, the overall observed heterozygosity of the 27 A-STRs was the highest in Nigerians, which reflected the higher genetic diversity of this population. The combined match probability of the 27 A-STRs was low at 9.06 × 10. When both A-STRs and iiSNPs were considered, the cumulative discrimination power, and combined power of exclusion for duo and trio paternity testing was 1-2.97 × 10, 1-2.20 × 10 and 1-4.61 × 10, respectively, which demonstrated that the STRs and SNPs analyzed here can be applied to forensic investigations. In summary, this study uncovers the genetic features of the Nigerian population and provides valuable frequency data for forensic applications.
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http://dx.doi.org/10.1016/j.fsigen.2020.102323DOI Listing
September 2020

Microcavity top-emission perovskite light-emitting diodes.

Light Sci Appl 2020 22;9:89. Epub 2020 May 22.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, 211816 China.

Light-emitting diodes (LEDs) based on perovskites show great potential in lighting and display applications. However, although perovskite films with high photoluminescence quantum efficiencies are commonly achieved, the efficiencies of perovskite LEDs are largely limited by the low light out-coupling efficiency. Here, we show that high-efficiency perovskite LEDs with a high external quantum efficiency of 20.2% and an ultrahigh radiant exitance up to 114.9 mW cm can be achieved by employing the microcavity effect to enhance light extraction. The enhanced microcavity effect and light out-coupling efficiency are confirmed by the study of angle-dependent emission profiles. Our results show that both the optical and electrical properties of the device need to be optimized to achieve high-performance perovskite LEDs.
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http://dx.doi.org/10.1038/s41377-020-0328-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242415PMC
May 2020

Cell-penetrating peptide enhanced insulin buccal absorption.

Int J Pharm 2020 Jun 26;584:119469. Epub 2020 May 26.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.

Non-injectable delivery of peptides and proteins is not feasible due to the limitations of large molecular mass, high hydrophilic properties, and gastrointestinal degradation. Therefore, proposing a new method to solve this problem is a burning issue. The objective of this study was to propose a novel protein delivery strategy to overcome the poor efficacy and irritation of buccal insulin delivery. In this study, we applied a conjugate of cell-penetrating peptides (LMWP) and insulin (INS-PEG-LMWP) for buccal delivery. INS-PEG-LMWP was prepared using insulin solution and mixture as references. The transport behaviour, in vivo bioactivity, hypoglycaemic effect, and safety of INS-PEG-LMWP were systematically characterised. An in vitro study demonstrated that the uptake and transportation of INS-PEG-LMWP across buccal mucosal multilayers significantly increased. By comparing the effects of different endocytic inhibitors on INS-PEG-LMWP uptake, the conjugate might be delivered via an energy independent, electrostatically adsorbed pathway. INS-PEG-LMWP's relative pharmacological bioavailability was high and its relative bioavailability was up to 26.86%, demonstrating no visible mucosal irritation. Cell-penetrating peptides are likely to become a reliable and safe tool for overcoming insulin's low permeability through the epithelial multilayers, the major barrier to buccal delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119469DOI Listing
June 2020