Publications by authors named "Can Yang"

147 Publications

Photocatalyzed cycloaromatization of vinylsilanes with arylsulfonylazides.

Nat Commun 2021 06 3;12(1):3304. Epub 2021 Jun 3.

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China.

Sila-molecules have recently attracted attention due to their promising applications in medical and industrial fields. Compared with all-carbon parent compounds, the different covalent radius and electronegativity of silicon from carbon generally endow the corresponding sila-analogs with unique biological activity and physicochemical properties. Vinylsilanes feature both silyl-hyperconjugation effect and versatile reactivities, developing vinylsilane-based Smiles rearrangement will therefore provide an efficient platform to assemble complex silacycles. Here we report a practical Ir(III)-catalyzed cycloaromatization of ortho-alkynylaryl vinylsilanes with arylsulfonyl azides for delivering naphthyl-fused benzosiloles under visible-light photoredox conditions. The combination of experiments and density functional theory (DFT) energy profiles reveals the reaction mechanism involving α-silyl radical Smiles rearrangement.
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http://dx.doi.org/10.1038/s41467-021-23326-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175346PMC
June 2021

Synergistic Strategy of Manipulating the Number of Selenophene Units and Asymmetric Central Core of Small Molecular Acceptors Enables Polymer Solar Cells with 17.5% Efficiency.

Angew Chem Int Ed Engl 2021 May 29. Epub 2021 May 29.

Korea University, Chemistry, KOREA, REPUBLIC OF.

Recently, despite the great achievement made in non-fullerene small molecular acceptors (NF-SMAs)-based polymer solar cells (PSCs), the favourable trade-off among device parameters is still quite difficult to obtain for further development. Herein, a novel synergistic strategy of the asymmetric backbone and selenophene substitution on the central core was applied for the first time and a new family of symmetric or asymmetric A-DA'D-A type NF-SMAs ( S-YSS-Cl , A-WSSe-Cl , and S-WSeSe-Cl ) with different numbers of selenophene were successfully synthesized. From S-YSS-Cl to A-WSSe-Cl and to S-WSeSe-Cl , a gradually red-shifted absorption and a gradually larger electron mobility and crystallinity in neat thin film was observed. Moreover, single crystals results indicate that A-WSSe-Cl and S-WSeSe-Cl exhibit stronger and tighter intermolecular π-π stacking interactions, extra S∙∙∙N non-covalent intermolecular interactions from central benzothiadiazole, better ordered 3D interpenetrating charge-transfer networks in comparison with thiophene-based S-YSS-Cl . Furthermore, PM6 :A-WSSe-Cl blend film exhibits the most favourable morphology with the best face-on intermolecular packing, and the most efficient charge separation, transport and collection. The asymmetric A- WSSe-C l -based device presents an impressive PCE of 17.51%, which is obvious higher than that of symmetric S-WSeSe-Cl- based (16.01%) and is the highest value for selenophene-based NF-SMAs in binary PSCs. These results demonstrate that the combination of the subtle asymmetric core and precise replacement of selenophene on the central core is an effective approach to improve J sc and FF without over sacrificing of V oc for efficient NF-SMAs.
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http://dx.doi.org/10.1002/anie.202104766DOI Listing
May 2021

Syntheses, structure and properties of a new series of organic-inorganic Hg-based halides: adjusting halogens resulted in huge performance mutations.

Dalton Trans 2021 Jun;50(22):7563-7570

Institute of Materials Science, TU Darmstadt, 64287 Darmstadt, Germany.

Three new organic-inorganic hybrid perovskite (OIHP) halides, [N(CH3)4]HgCl0.63Br2.37 (I), [N(CH3)4]HgBrI2 (II) and [N(CH3)4]HgCl0.45I2.55 (III), were synthesized by a hydrothermal reaction. They feature different crystal structures, in which both II and III are isomorphic and contain a one-dimensional chain with organic cation [N(CH3)4]+ interspersed in the space, whereas II has a similar one-dimensional chain but significantly different spatial arrangement due to the enhanced hydrogen bond interaction. The experimental results show that the divergent second-order nonlinear optical (NLO) effect from Br(Cl) to I and the arrangement of anion groups change dramatically from the presence of hydrogen bonds to the absence of hydrogen bonds, leading to a sharply increased NLO response of II and III (18 and 25 times that of I) compared with that of I. Moreover, the phase matching ability disappeared and the band gap decreased significantly. Meanwhile, a high temperature phase transition was observed in II and III, which is rare in common OIHPs. All these results indicate that the regulation of halogen bonds plays a crucial role in the structural and property mutations of OIHP halides.
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http://dx.doi.org/10.1039/d1dt01085aDOI Listing
June 2021

Construction and Validation of Novel Nomograms for Predicting Prognosis of Pancreatic Ductal Adenocarcinoma After Surgery According to Different Primary Cancer Locations.

Front Oncol 2021 23;11:646082. Epub 2021 Apr 23.

Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.

Background/aims: Pancreatic ductal adenocarcinoma (PDAC) can occur in different parts of the pancreas. This study aimed to identify clinicopathological characteristics independently correlated with the prognosis of PDAC of the pancreatic head/uncinate (PHC) or body-tail (PBTC), and to develop novel nomograms for predicting cancer-specific survival (CSS) according to different primary cancer locations.

Methods: 1160 PDAC patients were retrospectively enrolled and assigned to training and test sets with each set divided into PHC and PBTC groups. Comparative analysis of clinicopathologic characteristics, survival analysis, and multivariate analysis were performed. Independent factors were identified and used for constructing nomograms. The performance of the nomograms was validated in the test set.

Results: Primary tumor location was an independent risk factor for prognosis of PDAC after surgery. Specially, gender, fasting blood glucose, and preoperative cancer antigen 19-9 were significantly associated with prognosis of PHC, whereas age, body mass index, and lymph nodes were significantly correlated with the prognosis of PBTC. A significant difference in prognosis was found between PHC and PBTC in stage Ia and stage III. Three nomograms were established for predicting the prognosis for PDAC, PHC, and PBTC. Notably, these nomograms were calibrated modestly (c-indexes of 0.690 for PDAC, 0.669 for PHC, and 0.704 for PBTC), presented better accuracy and reliability than the 8 AJCC staging system, and achieved clinical validity.

Conclusions: PHC and PBTC share the differential clinical-pathological characteristics and survival. The nomograms show good performance for predicting prognosis in PHC and PBTC. Therefore, these nomograms hold potential as novel approaches for predicting survival of PHC and PBTC patients after surgery.
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http://dx.doi.org/10.3389/fonc.2021.646082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103839PMC
April 2021

Rh(III)-Catalyzed Csp-Csp σ-Bond Enolation of α-Indolyl Alcohols.

Org Lett 2021 May 6;23(10):3965-3969. Epub 2021 May 6.

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.

A Rh(III)-catalyzed Csp-Csp σ-bond carbenoid functionalization of α-(2-indolyl)alcohols with acceptor/acceptor diazo compounds has been developed. This transformation provides an efficient strategy to assemble stable C2-enolated indole skeletons via Csp-Csp σ-bond cleavage.
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http://dx.doi.org/10.1021/acs.orglett.1c01132DOI Listing
May 2021

Acentric Organic-Inorganic Hybrid Halide [N(CH)]HgBrI Featuring an Isolated [HgBrI] Tetrahedron and Second-Order Nonlinearity.

Inorg Chem 2021 May 22;60(9):6829-6835. Epub 2021 Apr 22.

State Key Laboratory of Crystal Materials and Institute of Crystal Materials, Shandong University, Jinan 250100, P. R. China.

A new hybrid compound [N(CH)]HgBrI, obtained by a hydrothermal reaction, crystallized in the noncentrosymmetric space group 222. Its structure contains an isolated asymmetric [HgBrI] tetrahedron with net polarization, connected by hydrogen bonds to form pseudo-one-dimensional chain structures. Moreover, its optical band gap, nonlinear optical (NLO) property, fluorescence property, and thermal property were characterized in detail. A rare high-temperature phase transition was observed in the compound. In addition, theoretical calculations were performed to elaborate the relation between electronic state, band structure, and their nonlinear optical response. These results indicate that [N(CH)]HgBrI is a new potential candidate for future photoelectronic applications in fluorescence and nonlinear optics.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00756DOI Listing
May 2021

CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer.

J Hematol Oncol 2021 Apr 13;14(1):60. Epub 2021 Apr 13.

Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, Fujian Province, People's Republic of China.

Background: Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear.

Methods: RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5 (SRSF5) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14 (METTL14) and Cyclin L2 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14 and Cyclin L2 skipping were surveyed.

Results: CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5, which inhibited METTL14 skipping while promoted Cyclin L2 skipping. In addition, aberrant METTL14 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2 promoted proliferation of PDAC cells.

Conclusions: The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.
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http://dx.doi.org/10.1186/s13045-021-01072-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045197PMC
April 2021

miR-214 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice.

Front Neurosci 2021 26;15:649982. Epub 2021 Mar 26.

The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Background: Ischemic stroke induces neuronal cell death and causes brain dysfunction. Preventing neuronal cell death after stroke is key to protecting the brain from stroke damage. Nevertheless, preventative measures and treatment strategies for stroke damage are scarce. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathogenesis of central nervous system (CNS) disorders and may serve as potential therapeutic targets.

Methods: A photochemically induced thrombosis (PIT) mouse model was used as an ischemic stroke model. qRT-PCR was employed to assess changes in miRNAs in ischemic lesions of PIT-stroke mice and primary cultured neurons subjected to oxygen-glucose deprivation (OGD). 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate brain infarction tissues . TUNEL staining was employed to assess neuronal death . Neurological scores and motor coordination were investigated to evaluate stroke damage, including neurological deficits and motor function.

Results: and results demonstrated that levels of miR-124 were significantly decreased following stroke, whereas changes in death-associated protein kinase 1 (DAPK1) levels exhibited the converse pattern. DAPK1 was identified as a direct target of miR-124. N-methyl-D-aspartate (NMDA) and OGD-induced neuronal death was rescued by miR-124 overexpression. Upregulation of miR-124 levels significantly improved PIT-stroke damage, including the overall neurological function in mice.

Conclusion: We demonstrate the involvement of the miR-124/DAPK1 pathway in ischemic neuronal death. Our results highlight the therapeutic potential of targeting this pathway for ischemic stroke.
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http://dx.doi.org/10.3389/fnins.2021.649982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032895PMC
March 2021

A unified framework for cross-population trait prediction by leveraging the genetic correlation of polygenic traits.

Am J Hum Genet 2021 04 25;108(4):632-655. Epub 2021 Mar 25.

Guangzhou HKUST Fok Ying Tung Research Institute, Guangzhou 511458, China; Department of Mathematics, The Hong Kong University of Science and Technology, Hong Kong SAR, China. Electronic address:

The development of polygenic risk scores (PRSs) has proved useful to stratify the general European population into different risk groups. However, PRSs are less accurate in non-European populations due to genetic differences across different populations. To improve the prediction accuracy in non-European populations, we propose a cross-population analysis framework for PRS construction with both individual-level (XPA) and summary-level (XPASS) GWAS data. By leveraging trans-ancestry genetic correlation, our methods can borrow information from the Biobank-scale European population data to improve risk prediction in the non-European populations. Our framework can also incorporate population-specific effects to further improve construction of PRS. With innovations in data structure and algorithm design, our methods provide a substantial saving in computational time and memory usage. Through comprehensive simulation studies, we show that our framework provides accurate, efficient, and robust PRS construction across a range of genetic architectures. In a Chinese cohort, our methods achieved 7.3%-198.0% accuracy gain for height and 19.5%-313.3% accuracy gain for body mass index (BMI) in terms of predictive R compared to existing PRS approaches. We also show that XPA and XPASS can achieve substantial improvement for construction of height PRSs in the African population, suggesting the generality of our framework across global populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059341PMC
April 2021

Using Collaborative Mixed Models to Account for Imputation Uncertainty in Transcriptome-Wide Association Studies.

Methods Mol Biol 2021 ;2212:93-103

Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore.

Transcriptome-wide association studies (TWASs) integrate expression quantitative trait loci (eQTLs) studies with genome-wide association studies (GWASs) to prioritize candidate target genes for complex traits. TWASs have become increasingly popular. They have been used to analyze many complex traits with expression profiles from different tissues, successfully enhancing the discovery of genetic risk loci for complex traits. Though conceptually straightforward, some steps are required to perform the TWAS properly. Here we provide a step-by-step guide to integrate eQTL data with both GWAS individual-level data and GWAS summary statistics from complex traits.
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http://dx.doi.org/10.1007/978-1-0716-0947-7_7DOI Listing
April 2021

Interfacial superstructures and chemical bonding transitions at metal-ceramic interfaces.

Sci Adv 2021 Mar 12;7(11). Epub 2021 Mar 12.

Department of NanoEngineering, Program of Materials Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.

Metal-ceramic interfaces are scientifically interesting and technologically important. However, the transition of chemical bonding character from a metal to a nonoxide ceramic is not well understood. The effects of solute segregation and interfacial structural transitions are even more elusive. In this study, aberration-corrected electron microscopy is combined with atomic-resolution energy-dispersive x-ray and electron energy loss spectroscopy to investigate Ti-, V-, and Cr-segregated WC-Co interfaces as model systems. The experiments reveal the general anisotropic formation of reconstructed trilayer-like superstructures with segregant-specific compositional profiles that facilitate the transition from covalent to metallic electronic structures. Density functional theory calculations confirm the gradual increasing metallicity from WC to Co in the interfacial trilayers via increasing metallic solute concentration. This study uncovers unprecedented details of the sophisticated interfacial superstructures at metal-ceramic interfaces. It sheds light on how a metal transits to a ceramic at a "general" interface with strong segregation.
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http://dx.doi.org/10.1126/sciadv.abf6667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954454PMC
March 2021

Evaluation of the Bioequivalence of Acarbose in Healthy Chinese People.

Clin Pharmacol Drug Dev 2021 Feb 19. Epub 2021 Feb 19.

Clinical Pharmacology Institute, Nanchang University, Nanchang, P. R. China.

The purpose of this study was to determine whether the reference formulation and test formulation of acarbose are bioequivalent among healthy Chinese subjects based on evaluation of the pharmacodynamic end point. Two clinical trials with acarbose were conducted: study A, a pilot study (n = 12; 50 and 100 mg), and study B, a pivotal study (n = 60; 50 mg). In study A, there was a dose-dependent relationship between 50 mg acarbose and 100 mg acarbose and a significant difference compared with sucrose alone. In study B, after logarithmic conversion, a linear mixed-effects model was used to analyze the maximum serum glucose value and area under the serum glucose-time curve from 0 to 2 hours. The geometric mean ratios (test formulation/reference formulation) were 92.68% and 95.70%, with 90% confidence intervals of 84.08%-102.17% and 84.21%-108.76%, respectively, falling between 80.00% and 125.00%. According to the geometric least-squares mean, the test formulation (or reference formulation) was statistically significantly different as a single sucrose (P < .001). The effective dose of acarbose in healthy Chinese volunteers was 50 mg. The reference and test formulations were bioequivalent.
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http://dx.doi.org/10.1002/cpdd.921DOI Listing
February 2021

MR-LDP: a two-sample Mendelian randomization for GWAS summary statistics accounting for linkage disequilibrium and horizontal pleiotropy.

NAR Genom Bioinform 2020 Jun 4;2(2):lqaa028. Epub 2020 May 4.

Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore 169857, Singapore.

The proliferation of genome-wide association studies (GWAS) has prompted the use of two-sample Mendelian randomization (MR) with genetic variants as instrumental variables (IVs) for drawing reliable causal relationships between health risk factors and disease outcomes. However, the unique features of GWAS demand that MR methods account for both linkage disequilibrium (LD) and ubiquitously existing horizontal pleiotropy among complex traits, which is the phenomenon wherein a variant affects the outcome through mechanisms other than exclusively through the exposure. Therefore, statistical methods that fail to consider LD and horizontal pleiotropy can lead to biased estimates and false-positive causal relationships. To overcome these limitations, we proposed a probabilistic model for MR analysis in identifying the causal effects between risk factors and disease outcomes using GWAS summary statistics in the presence of LD and to properly account for horizontal pleiotropy among genetic variants (MR-LDP) and develop a computationally efficient algorithm to make the causal inference. We then conducted comprehensive simulation studies to demonstrate the advantages of MR-LDP over the existing methods. Moreover, we used two real exposure-outcome pairs to validate the results from MR-LDP compared with alternative methods, showing that our method is more efficient in using all-instrumental variants in LD. By further applying MR-LDP to lipid traits and body mass index (BMI) as risk factors for complex diseases, we identified multiple pairs of significant causal relationships, including a protective effect of high-density lipoprotein cholesterol on peripheral vascular disease and a positive causal effect of BMI on hemorrhoids.
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http://dx.doi.org/10.1093/nargab/lqaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671398PMC
June 2020

SHCBP1 interacting with EOGT enhances O-GlcNAcylation of NOTCH1 and promotes the development of pancreatic cancer.

Genomics 2021 Mar 28;113(2):827-842. Epub 2021 Jan 28.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, PR China; Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, PR China. Electronic address:

O-GlcNAcylation is important in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The glycosyltransferase EGF domain-specific O-linked GlcNAc transferase (EOGT) acts as a key participant in glycosylating NOTCH1. High-throughput sequencing of specimens from 30 advanced PDAC patients identified SHCBP1 and EOGT as factors of poor prognosis. We hypothesized that they could mediate PDAC progression by influencing NOTCH1 O-GlcNAcylation. Thus, 186 PDAC tissue specimens were immunostained for EOGT and SHCBP1. Pancreatic cancer cell lines and nude mouse models were used for in vitro and in vivo experiments. Respectively, The protein expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation, migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice, whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. We further clarified the molecular mechanisms by which EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, Subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.
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http://dx.doi.org/10.1016/j.ygeno.2021.01.010DOI Listing
March 2021

A highly sensitive and selective method for the determination of ceftiofur sodium in milk and animal-origin food based on molecularly imprinted solid-phase extraction coupled with HPLC-UV.

Food Chem 2021 Jun 8;347:129013. Epub 2021 Jan 8.

School of Environment, Henan Key Laboratory for Environmental Pollution Control, Key Laboratory for Yellow River and Huai River Water Environmental Pollution Control, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, PR China. Electronic address:

The effective analysis of cephalosporin antibiotics in food animals has attracted considerable attention. Herein, a high-performance liquid chromatograph equipped with a UV method based on molecularly imprinted-solid phase extraction (MISPE-HPLC-UV) was developed for preconcentration, cleanup and determination of ceftiofur sodium (CTFS) in food samples. In this method, an eco-friendly molecularly imprinted polymer (MIP) was synthesized and employed as an adsorbent, which exhibited excellent selectivity towards CTFS in water, and adsorption equilibrium could be reached within 1 h. Under the optimized conditions, good linearity was obtained for CTFS in the range of 0.005-1.0 mg L with a lower LOD of 0.0015 mg L, and the average recoveries were higher than 91.9% (RSD less than 8.5%) at three spiked levels in milk, chicken, pork and beef samples. After 20 cycles, the recovery of the MISPE cartridge for CTFS was still higher than 95%, which proved that the MISPE-HPLC-UV method was highly sensitive and selective for the analysis of CTFS in food samples.
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http://dx.doi.org/10.1016/j.foodchem.2021.129013DOI Listing
June 2021

Exploring the Relationship Between Psychiatric Traits and the Risk of Mouth Ulcers Using Bi-Directional Mendelian Randomization.

Front Genet 2020 16;11:608630. Epub 2020 Dec 16.

Key Laboratory for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Although the association between mouth ulcers and psychiatric traits has been reported by observational studies, their causal relationship remains unclear. Mendelian randomization (MR), powered by large-scale genome-wide association studies (GWAS), provides an opportunity to clarify the causality between mouth ulcers and psychiatric traits.

Methods: We collected summary statistics of mouth ulcers (sample size = 461,106) and 10 psychiatric traits from the largest publicly available GWAS on Europeans, including anxiety disorder ( = 83,566), attention deficit/hyperactivity disorder ( = 53,293), autism spectrum disorder ( = 46,350), bipolar disorder ( = 51,710), insomnia ( = 1,331,010), major depressive disorder ( = 480,359), mood instability ( = 363,705), neuroticism ( = 168,105), schizophrenia ( = 105,318), and subjective wellbeing ( = 388,538). We applied three two-sample bi-directional MR analysis methods, namely the Inverse Variance Weighted (IVW) method, the MR pleiotropy residual sum and outlier (MR-PRESSO) method, and the weighted median method, to assess the causal relationship between each psychiatric trait and mouth ulcers.

Results: We found significant effects of autism spectrum disorder, insomnia, major depressive disorder, and subjective wellbeing on mouth ulcers, with the corresponding odds ratio () from the IVW method being 1.160 [95% confidence interval (): 1.066-1.261, = 5.39 × 10], 1.092 (1.062-1.122, = 3.37 × 10), 1.234 (1.134-1.342, = 1.03 × 10), and 0.703 (0.571-0.865, = 8.97 × 10), respectively. We also observed suggestive evidence for mood instability to cause mouth ulcers [IVW, OR = 1.662 (1.059-2.609), = 0.027]. These results were robust to weak instrument bias and heterogeneity. We found no evidence on causal effects between other psychiatric traits and mouth ulcers, in either direction.

Conclusion: Our findings suggest a protective effect of subjective wellbeing and risk effects of autism spectrum disorder, insomnia, major depressive disorder, and mood instability on mouth ulcers. These results clarify the causal relationship between psychiatric traits and the development of mouth ulcers.
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http://dx.doi.org/10.3389/fgene.2020.608630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793678PMC
December 2020

Accurate genetic and environmental covariance estimation with composite likelihood in genome-wide association studies.

PLoS Genet 2021 01 4;17(1):e1009293. Epub 2021 Jan 4.

Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States of America.

Genetic and environmental covariances between pairs of complex traits are important quantitative measurements that characterize their shared genetic and environmental architectures. Accurate estimation of genetic and environmental covariances in genome-wide association studies (GWASs) can help us identify common genetic and environmental factors associated with both traits and facilitate the investigation of their causal relationship. Genetic and environmental covariances are often modeled through multivariate linear mixed models. Existing algorithms for covariance estimation include the traditional restricted maximum likelihood (REML) method and the recent method of moments (MoM). Compared to REML, MoM approaches are computationally efficient and require only GWAS summary statistics. However, MoM approaches can be statistically inefficient, often yielding inaccurate covariance estimates. In addition, existing MoM approaches have so far focused on estimating genetic covariance and have largely ignored environmental covariance estimation. Here we introduce a new computational method, GECKO, for estimating both genetic and environmental covariances, that improves the estimation accuracy of MoM while keeping computation in check. GECKO is based on composite likelihood, relies on only summary statistics for scalable computation, provides accurate genetic and environmental covariance estimates across a range of scenarios, and can accommodate SNP annotation stratified covariance estimation. We illustrate the benefits of GECKO through simulations and applications on analyzing 22 traits from five large-scale GWASs. In the real data applications, GECKO identified 50 significant genetic covariances among analyzed trait pairs, resulting in a twofold power gain compared to the previous MoM method LDSC. In addition, GECKO identified 20 significant environmental covariances. The ability of GECKO to estimate environmental covariance in addition to genetic covariance helps us reveal strong positive correlation between the genetic and environmental covariance estimates across trait pairs, suggesting that common pathways may underlie the shared genetic and environmental architectures between traits.
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http://dx.doi.org/10.1371/journal.pgen.1009293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808654PMC
January 2021

Green synthesis of boron and nitrogen co-doped TiO with rich B-N motifs as Lewis acid-base couples for the effective artificial CO photoreduction under simulated sunlight.

J Colloid Interface Sci 2021 Mar 25;585:95-107. Epub 2020 Nov 25.

School of Environment, Henan Normal University, Xinxiang, Henan 453007, PR China; Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China. Electronic address:

Boron and nitrogen co-doped Titanium dioxide (TiO) nanosheets (BNT) with high surface area of 136.5 m g were synthesized using ammonia borane as the green and triple-functional regent, which avoids the harmful and explosive reducing regents commonly used to create surface defects on TiO. The decomposition of ammonia borane could incorporate reactive Lewis acid-base (B, N) pairs, together with the as-generated H to create mesoporous structure and rich oxygen vacancies in pristine TiO. The BNTs prepared from various ammonia borane loading are evaluated in photoreduction of carbon dioxide (CO) with steam under simulated sunlight, achieving about 3.5 times higher carbon monoxide (CO) production than pristine TiO under the same conditions. Steady state and transient optical measurements indicated BNT with reduced band gap, rich defect states and elevated conduction band position could enhance the light harvesting efficiency and promote the charge transfer at the catalyst/CO interface. Density functional theory simulation and in situ FTIR suggest that the Lewis acid-base (B, N) pairs on BNT may very substantially increase the activation of inert CO which facilitates their photoreduction with the hydrogen from the water splitting at the surface defects on TiO. Finally, a reaction mechanism of Lewis acid-base assisted CO photoreduction leading to substantially improved performance is proposed.
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http://dx.doi.org/10.1016/j.jcis.2020.11.075DOI Listing
March 2021

One-step synthesis of functional metal organic framework composite for the highly efficient adsorption of tylosin from water.

J Colloid Interface Sci 2021 Mar 26;586:269-278. Epub 2020 Oct 26.

School of Environment, Henan Normal University, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Xinxiang 453007, China. Electronic address:

Functional metal organic framework composite can effectively remove antibiotics from environmental water samples. However, designing excellent adsorbents with multiple active sites via a rapid one-step method is still a challenging problem. A novel metal organic framework composite (UiO-66-NH-AMPS) was synthesized through one-step polymerization by adding functional monomer 2-acrylamide-2-methylpropanesulfonic acid (AMPS) during the preparation of UiO-66-NH. The microstructure and morphology of the UiO-66-NH-AMPS composite were characterized, and the adsorption performance towards tylosin (TYL) in water was explored by equilibrium adsorption experiment. The results illustrated that the adsorption equilibrium can be reached within 1 h, and the maximum binding amount of UiO-66-NH-AMPS for TYL was 161.60 mg g, which was approximately 2.1-329 times of that of the other adsorbents. The pseudo second-order kinetic and Liu isotherm model were suitable for the adsorption process, and thermodynamic study displayed that the adsorption of UiO-66-NH-AMPS composite for TYL is spontaneous and endothermal. The infrared and X-ray photoelectron spectra exhibited that hydrogen bond and electrostatic interaction were the primary recognition force for TYL. The UiO-66-NH-AMPS composite have been successfully applied to remove TYL from environmental water. After 5 cycles, the removal efficiency of UiO-66-NH-AMPS was still above 91.30%.
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http://dx.doi.org/10.1016/j.jcis.2020.10.090DOI Listing
March 2021

LncRNA STXBP5-AS1 suppresses stem cell-like properties of pancreatic cancer by epigenetically inhibiting neighboring androglobin gene expression.

Clin Epigenetics 2020 11 7;12(1):168. Epub 2020 Nov 7.

Department of Hepato-Biliary-Pancreatic Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, No. 134 East Street, Fuzhou, 350001, Fujian, China.

Previous studies suggest the tumor suppressor role of long non-coding RNA (lncRNA) STXBP5-AS1 in cervical and gastric cancer, but its expression pattern and functional mechanism are still elusive in pancreatic cancer (PC). Relative expression of STXBP5-AS1 in PC both in vivo and in vitro was analyzed by real-time PCR. IC of Gemcitabine was determined by the MTT assay. Cell proliferation in response to drug treatment was investigated by colony formation assay. Cell apoptosis was measured by both caspase-3 activity and Annexin V/PI staining. Cell invasion capacity was scored by the transwell assay in vitro, and lung metastasis was examined with the tail vein injection assay. Cell stemness was determined in vitro by sphere formation and marker profiling, respectively, and in vivo by limited dilution of xenograft tumor incidence. Subcellular localization of STXBP5-AS1 was analyzed with fractionation PCR. Association between STXBP5-AS1 and EZH2 was investigated by RNA-immunoprecipitation. The binding of EZH2 on ADGB promoter was analyzed by chromatin immunoprecipitation. The methylation was quantified by bisulfite sequencing. We showed downregulation of STXBP5-AS1 in PC associated with poor prognosis. Ectopic STXBP5-AS1 inhibited chemoresistance and metastasis of PC cells. In addition, STXBP5-AS1 compromised stemness of PC cells. Mechanistically, STXBP5-AS1 potently recruited EZH2 and epigenetically regulated neighboring ADGB transcription, which predominantly mediated the inhibitory effects of STXBP5-AS1 on stem cell-like properties of PC cells. Our study highlights the importance of the STXBP5-EZH2-ADGB axis in chemoresistance and stem cell-like properties of PC.
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http://dx.doi.org/10.1186/s13148-020-00961-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648265PMC
November 2020

Anterior gradient 2 is a novel pro-tumor factor in pancreatic cancer under NF-κB subunit RelA trans-regulation that can be suppressed by eugenic acid.

Biomed Pharmacother 2020 Dec 12;132:110830. Epub 2020 Oct 12.

The Second School of Clinical Medicine, Southern Medical University, No.1023 South Shatai Road, Baiyun District, Guangzhou, 510515 Guangdong, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080 Guangdong, China. Electronic address:

This study aimed to examine eugenic acid (EA) as an alternative therapeutic approach against pancreatic cancer. The pancreatic cancer xenograft mouse model was employed to determine the impacts of treatment with EA on the growth of tumors. Expressions of NF-κB subunit RelA as well as Anterior gradient 2 (AGR2) were quantified in pancreatic cells treated with EA. Chromatin immunoprecipitation and luciferase report assay were performed to examine the regulation of AGR2 by RelA. The function of AGR2 as a downstream effector EA treatment was further assessed through overexpression of AGR2 in pancreatic cells. EA suppressed the growth of xenograft pancreatic tumor, and promoted the overall survival of animals with xenograft tumors. Furthermore, EA downregulated the expression of AGR2 in pancreatic cancer cells via the RelA binding site. Ectopic AGR2 overexpression attenuated the EA-elicited inhibition on the growth of xenograft pancreatic tumor, and negated the EA-induced enhancement of mouse survival. EA ameliorates pancreatic cancer through suppression of AGR2 expression, and future studies in clinical settings are needed to further assess the anti-cancer efficacy of EA.
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http://dx.doi.org/10.1016/j.biopha.2020.110830DOI Listing
December 2020

Acute psychological effects of Coronavirus Disease 2019 outbreak among healthcare workers in China: a cross-sectional study.

Transl Psychiatry 2020 10 13;10(1):348. Epub 2020 Oct 13.

Department of Psychiatry, Renmin Hospital of Wuhan University, 430060, Wuhan, China.

To study the acute psychological effects of Coronavirus Disease 2019 (COVID-19) outbreak among healthcare workers (HCWs) in China, a cross-sectional survey was conducted among HCWs during the early period of COVID-19 outbreak. The acute psychological effects including symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) were assessed using the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder (GAD-7) questionnaire, and the Impact of Event Scale-Revised (IES-R). The prevalence of depression, anxiety, and PTSD was estimated at 15.0%, 27.1%, and 9.8%, respectively. Having an intermediate technical title, working at the frontline, receiving insufficient training for protection, and lacking confidence in protection measures were significantly associated with increased risk for depression and anxiety. Being a nurse, having an intermediate technical title, working at the frontline, and lacking confidence in protection measures were risk factors for PTSD. Meanwhile, not worrying about infection was a protective factor for developing depression, anxiety, and PTSD. Psychological interventions should be implemented among HCWs during the COVID-19 outbreak to reduce acute psychological effects and prevent long-term psychological comorbidities. Meanwhile, HCWs should be well trained and well protected before their frontline exposure.
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http://dx.doi.org/10.1038/s41398-020-01031-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552583PMC
October 2020

A tissue-specific collaborative mixed model for jointly analyzing multiple tissues in transcriptome-wide association studies.

Nucleic Acids Res 2020 11;48(19):e109

Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore.

Transcriptome-wide association studies (TWASs) integrate expression quantitative trait loci (eQTLs) studies with genome-wide association studies (GWASs) to prioritize candidate target genes for complex traits. Several statistical methods have been recently proposed to improve the performance of TWASs in gene prioritization by integrating the expression regulatory information imputed from multiple tissues, and made significant achievements in improving the ability to detect gene-trait associations. Unfortunately, most existing multi-tissue methods focus on prioritization of candidate genes, and cannot directly infer the specific functional effects of candidate genes across different tissues. Here, we propose a tissue-specific collaborative mixed model (TisCoMM) for TWASs, leveraging the co-regulation of genetic variations across different tissues explicitly via a unified probabilistic model. TisCoMM not only performs hypothesis testing to prioritize gene-trait associations, but also detects the tissue-specific role of candidate target genes in complex traits. To make full use of widely available GWASs summary statistics, we extend TisCoMM to use summary-level data, namely, TisCoMM-S2. Using extensive simulation studies, we show that type I error is controlled at the nominal level, the statistical power of identifying associated genes is greatly improved, and the false-positive rate (FPR) for non-causal tissues is well controlled at decent levels. We further illustrate the benefits of our methods in applications to summary-level GWASs data of 33 complex traits. Notably, apart from better identifying potential trait-associated genes, we can elucidate the tissue-specific role of candidate target genes. The follow-up pathway analysis from tissue-specific genes for asthma shows that the immune system plays an essential function for asthma development in both thyroid and lung tissues.
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http://dx.doi.org/10.1093/nar/gkaa767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641735PMC
November 2020

Vinylene-Linked Covalent Organic Frameworks (COFs) with Symmetry-Tuned Polarity and Photocatalytic Activity.

Angew Chem Int Ed Engl 2020 Dec 26;59(52):23845-23853. Epub 2020 Oct 26.

School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China), .

The polarity of a semiconducting molecule affects its intrinsic photophysical properties, which can be tuned by varying the molecular geometry. Herein, we developed a D -symmetric tricyanomesitylene as a new monomer which could be reticulated into a vinylene-linked covalent organic framework (g-C N -COF) via Knoevenagel condensation with another D -symmetric monomer 2,4,6-tris(4'-formyl-biphenyl-4-yl)-1,3,5-triazine. Replacing tricyanomesitylene with a C -symmetric 3,5-dicyano-2,4,6-trimethylpyridine gave a less-symmetric vinylene-linked COF (g-C N -COF). The octupolar conjugated characters of g-C N -COF were reflected in its scarce solvatochromic effects either in ground or excited states, and endowed it with more promising semiconducting behavior as compared with g-C N -COF, such as enhanced light-harvesting and excellent photo-induced charge generation and separation. Along with the matched energy level, g-C N -COF enabled the two-half reactions of photocatalytic water splitting with an average O evolution rate of 51.0 μmol h  g and H evolution rate of 2518.9 μmol h  g . Such values are among the highest of state-of-the-art COF photocatalysts.
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http://dx.doi.org/10.1002/anie.202011852DOI Listing
December 2020

Psychological intervention in Fangcang shelter hospitals for COVID-19 in China.

Psychiatry Clin Neurosci 2020 11 25;74(11):618-619. Epub 2020 Sep 25.

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

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http://dx.doi.org/10.1111/pcn.13149DOI Listing
November 2020

N-Rich Carbon Catalysts with Economic Feasibility for the Selective Oxidation of Hydrogen Sulfide to Sulfur.

Environ Sci Technol 2020 10 8;54(19):12621-12630. Epub 2020 Sep 8.

State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350116, P. R. China.

The efficient removal of hydrogen sulfide (HS) from exhaust emissions is a great challenge to chemical industries. Selective catalytic oxidation of HS into elemental sulfur is regarded as one of the most promising approaches to alleviate environmental pollution, while recycling sulfur resources. It is therefore highly desirable to develop efficient catalysts for the conversion of HS to sulfur under mild reaction conditions. Here we present a nitrogen-rich carbon obtained by the direct thermal treatment of commercial polyaniline (PANI) for the selective oxidation of HS in a continuous way at relatively low temperature (180 °C). The efficient conversion of HS over the N-rich carbon catalysts was attributed to the in situ generation of pyridine-N on the carbon matrix, which served as the active sites to promote the absorption and dissociation of HS molecules, achieving a superior catalytic conversion rate of 99% and selectivity up to 95% at 180 °C.
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http://dx.doi.org/10.1021/acs.est.0c02967DOI Listing
October 2020

Testing and controlling for horizontal pleiotropy with probabilistic Mendelian randomization in transcriptome-wide association studies.

Nat Commun 2020 07 31;11(1):3861. Epub 2020 Jul 31.

Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.

Integrating results from genome-wide association studies (GWASs) and gene expression studies through transcriptome-wide association study (TWAS) has the potential to shed light on the causal molecular mechanisms underlying disease etiology. Here, we present a probabilistic Mendelian randomization (MR) method, PMR-Egger, for TWAS applications. PMR-Egger relies on a MR likelihood framework that unifies many existing TWAS and MR methods, accommodates multiple correlated instruments, tests the causal effect of gene on trait in the presence of horizontal pleiotropy, and is scalable to hundreds of thousands of individuals. In simulations, PMR-Egger provides calibrated type I error control for causal effect testing in the presence of horizontal pleiotropic effects, is reasonably robust under various types of model misspecifications, is more powerful than existing TWAS/MR approaches, and can directly test for horizontal pleiotropy. We illustrate the benefits of PMR-Egger in applications to 39 diseases and complex traits obtained from three GWASs including the UK Biobank.
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http://dx.doi.org/10.1038/s41467-020-17668-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395774PMC
July 2020

Heteroatom Dopants Promote Two-Electron O Reduction for Photocatalytic Production of H O on Polymeric Carbon Nitride.

Angew Chem Int Ed Engl 2020 Sep 29;59(37):16209-16217. Epub 2020 Jun 29.

Division of Environmental Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, South Korea.

Polymeric carbon nitride modified with selected heteroatom dopants was prepared and used as a model photocatalyst to identify and understand the key mechanisms required for efficient photoproduction of H O via selective oxygen reduction reaction (ORR). The photochemical production of H O was achieved at a millimolar level per hour under visible-light irradiation along with 100 % apparent quantum yield (in 360-450 nm region) and 96 % selectivity in an electrochemical system (0.1 V vs. RHE). Spectroscopic analysis in spatiotemporal resolution and theoretical calculations revealed that the synergistic association of alkali and sulfur dopants in the polymeric matrix promoted the interlayer charge separation and polarization of trapped electrons for preferable oxygen capture and reduction in ORR kinetics. This work highlights the key features that are responsible for controlling the photocatalytic activity and selectivity toward the two-electron ORR, which should be the basis of further development of solar H O production.
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http://dx.doi.org/10.1002/anie.202006747DOI Listing
September 2020

Electron-Deficient and Quinoid Central Unit Engineering for Unfused Ring-Based A -D-A -D-A -Type Acceptor Enables High Performance Nonfullerene Polymer Solar Cells with High V and PCE Simultaneously.

Small 2020 Jun 6;16(22):e1907681. Epub 2020 May 6.

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Beijing, 100081, China.

Here, a pair of A -D-A -D-A unfused ring core-based nonfullerene small molecule acceptors (NF-SMAs), BO2FIDT-4Cl and BT2FIDT-4Cl is synthesized, which possess the same terminals (A ) and indacenodithiophene unit (D), coupling with different fluorinated electron-deficient central unit (difluorobenzoxadiazole or difluorobenzothiadiazole) (A ). BT2FIDT-4Cl exhibits a slightly smaller optical bandgap of 1.56 eV, upshifted highest occupied molecular orbital energy levels, much higher electron mobility, and slightly enhanced molecular packing order in neat thin films than that of BO2FIDT-4Cl. The polymer solar cells (PSCs) based on BT2FIDT-4Cl:PM7 yield the best power conversion efficiency (PCE) of 12.5% with a V of 0.97 V, which is higher than that of BO2FIDT-4Cl-based devices (PCE of 10.4%). The results demonstrate that the subtle modification of A unit would result in lower trap-assisted recombination, more favorable morphology features, and more balanced electron and hole mobility in the PM7:BT2FIDT-4Cl blend films. It is worth mentioning that the PCE of 12.5% is the highest value in nonfused ring NF-SMA-based binary PSCs with high V over 0.90 V. These results suggest that appropriate modulation of the quinoid electron-deficient central unit is an effective approach to construct highly efficient unfused ring NF-SMAs to boost PCE and V simultaneously.
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http://dx.doi.org/10.1002/smll.201907681DOI Listing
June 2020

Protection of melatonin against acidosis-induced neuronal injuries.

J Cell Mol Med 2020 06 4;24(12):6928-6942. Epub 2020 May 4.

Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10  mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3β and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.
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http://dx.doi.org/10.1111/jcmm.15351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299701PMC
June 2020