Publications by authors named "Ao Zhang"

275 Publications

Exploratory Study: A Modification Training Method of Attentional Bias Toward Safety.

Saf Health Work 2021 Sep 18;12(3):346-350. Epub 2021 May 18.

School of Engineering and Technology, China University of Geosciences (Beijing), Beijing, 100083, China.

Background: The high sensitivity of individuals toward safety information in production activities, that is, attentional bias toward safety (ABS), can positively predict safe behaviors. It has become a hot topic in current organizational safety behavior research. However, there is no literature on its modification method.

Methods: Based on the modified dot-probe task, we designed a modification training method of ABS. The training method required subjects to respond to the location of detection points that presented after safety stimulus and neutral stimulus pictures. Subjects' attentional bias values of safety and neutral pictures were measured during the experiment. Twenty-one students were selected and divided into a control group and training group to gain comparable results.

Results: A novel training method was developed in this study to promote the efficacy of safety stimulus by activating ABS of the subjects. Moreover, repeated trainings and preacquired relative knowledge can enhance this effect.

Conclusion: This study develops an experimental approach to evaluate the effectiveness of safety education and safety training, and also provides a new research idea for accident prevention.
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http://dx.doi.org/10.1016/j.shaw.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430441PMC
September 2021

Overview of protein phosphorylation in bacteria with a main focus on unusual protein kinases in Bacillus subtilis.

Res Microbiol 2021 Sep 6:103871. Epub 2021 Sep 6.

Laboratoire de Chimie Bactérienne, UMR 7283, CNRS/Aix-Marseille Univ, Institut de Microbiologie de La Méditerranée, 31, Chemin Joseph Aiguier, Marseille, France. Electronic address:

Protein phosphorylation is a post-translational modification that affects protein activity through the addition of a phosphate moiety by protein kinases or phosphotransferases. It occurs in all life forms. In addition to Hanks kinases found also in eukaryotes, bacteria encode membrane histidine kinases that, with their cognate response regulator, constitute two-component systems and phosphotransferases that phosphorylate proteins involved in sugar utilization on histidine and cysteine residues. In addition, they encode BY-kinases and arginine kinases that phosphorylate protein specifically on tyrosine and arginine residues respectively. They also possess unusual bacterial protein kinases illustrated here by examples from Bacillus subtilis.
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http://dx.doi.org/10.1016/j.resmic.2021.103871DOI Listing
September 2021

Genomic Prediction of Resistance to Tar Spot Complex of Maize in Multiple Populations Using Genotyping-by-Sequencing SNPs.

Front Plant Sci 2021 16;12:672525. Epub 2021 Jul 16.

International Maize and Wheat Improvement Center (CIMMYT), El Batan, Mexico.

Tar spot complex (TSC) is one of the most important foliar diseases in tropical maize. TSC resistance could be furtherly improved by implementing marker-assisted selection (MAS) and genomic selection (GS) individually, or by implementing them stepwise. Implementation of GS requires a profound understanding of factors affecting genomic prediction accuracy. In the present study, an association-mapping panel and three doubled haploid populations, genotyped with genotyping-by-sequencing, were used to estimate the effectiveness of GS for improving TSC resistance. When the training and prediction sets were independent, moderate-to-high prediction accuracies were achieved across populations by using the training sets with broader genetic diversity, or in pairwise populations having closer genetic relationships. A collection of inbred lines with broader genetic diversity could be used as a permanent training set for TSC improvement, which can be updated by adding more phenotyped lines having closer genetic relationships with the prediction set. The prediction accuracies estimated with a few significantly associated SNPs were moderate-to-high, and continuously increased as more significantly associated SNPs were included. It confirmed that TSC resistance could be furtherly improved by implementing GS for selecting multiple stable genomic regions simultaneously, or by implementing MAS and GS stepwise. The factors of marker density, marker quality, and heterozygosity rate of samples had minor effects on the estimation of the genomic prediction accuracy. The training set size, the genetic relationship between training and prediction sets, phenotypic and genotypic diversity of the training sets, and incorporating known trait-marker associations played more important roles in improving prediction accuracy. The result of the present study provides insight into less complex trait improvement via GS in maize.
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http://dx.doi.org/10.3389/fpls.2021.672525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322742PMC
July 2021

Genetic Dissection of Quantitative Resistance to Common Rust () in Tropical Maize ( L.) by Combined Genome-Wide Association Study, Linkage Mapping, and Genomic Prediction.

Front Plant Sci 2021 2;12:692205. Epub 2021 Jul 2.

International Maize and Wheat Improvement Center (CIMMYT), Texcoco, Mexico.

Common rust is one of the major foliar diseases in maize, leading to significant grain yield losses and poor grain quality. To dissect the genetic architecture of common rust resistance, a genome-wide association study (GWAS) panel and a bi-parental doubled haploid (DH) population, DH1, were used to perform GWAS and linkage mapping analyses. The GWAS results revealed six single-nucleotide polymorphisms (SNPs) significantly associated with quantitative resistance of common rust at a very stringent threshold of value 3.70 × 10 at bins 1.05, 1.10, 3.04, 3.05, 4.08, and 10.04. Linkage mapping identified five quantitative trait loci (QTL) at bins 1.03, 2.06, 4.08, 7.03, and 9.00. The phenotypic variation explained (PVE) value of each QTL ranged from 5.40 to 12.45%, accounting for the total PVE value of 40.67%. Joint GWAS and linkage mapping analyses identified a stable genomic region located at bin 4.08. Five significant SNPs were only identified by GWAS, and four QTL were only detected by linkage mapping. The significantly associated SNP of S10_95231291 detected in the GWAS analysis was first reported. The linkage mapping analysis detected two new QTL on chromosomes 7 and 10. The major QTL on chromosome 7 in the region between 144,567,253 and 149,717,562 bp had the largest PVE value of 12.45%. Four candidate genes of , , , and were identified, which played important roles in the response of stress resilience and the regulation of plant growth and development. Genomic prediction (GP) accuracies observed in the GWAS panel and DH1 population were 0.61 and 0.51, respectively. This study provided new insight into the genetic architecture of quantitative resistance of common rust. In tropical maize, common rust could be improved by pyramiding the new sources of quantitative resistance through marker-assisted selection (MAS) or genomic selection (GS), rather than the implementation of MAS for the single dominant race-specific resistance gene.
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http://dx.doi.org/10.3389/fpls.2021.692205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284423PMC
July 2021

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma.

Cancer Cell Int 2021 Jul 7;21(1):356. Epub 2021 Jul 7.

Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Background: In view of the fact that peripheral blood parameters have been reported as predictors of immunotherapy to various cancers, this study aimed to determine the predictors of response to anti-programmed death-1 (anti-PD-1) therapy in patients with esophageal squamous cell carcinoma (ESCC) from peripheral blood parameters.

Methods: A retrospective analysis was conducted to investigate the predictive value of peripheral blood parameters including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) in the response to anti-PD-1 antibody treatment. 119 ESCC patients receiving combined treatment including anti-PD-1 antibody were enrolled in this study.

Results: The median progression-free survival (PFS) of all ESCC patients was 3.73 months. PFS rate in ESCC patients with low NLR at 6 weeks post treatment was higher than patients with high NLR (HR = 2.097, 95% CI 0.996-4.417, P = 0.027). However, PFS rate in ESCC patients with low NLR at baseline (HR = 1.060, 95% CI 0.524-2.146, P = 0.869) or 3 weeks post treatment (HR = 1.293, 95% CI 0.628-2.663, P = 0.459) was comparable with high NLR. And no statistically different was found in PFS rate between low PLR and high PLR at baseline (HR = 0.786, 95% CI 0.389-1.589, P = 0.469), 3 weeks post treatment (HR = 0.767, 95% CI 0.379-1.552, P = 0.452) or 6 weeks post treatment (HR = 1.272, 95% CI 0.624-2.594, P = 0.488) in ESCC patients. PFS rate was also comparable between low MLR and high MLR at baseline (HR = 0.826, 95% CI 0.408-1.670, P = 0.587), 3 weeks post treatment (HR = 1.209, 95% CI 0.590-2.475, P = 0.580) or 6 weeks post treatment (HR = 1.199, 95% CI 0.586-2.454, P = 0.596). PFS rate was similar between patients with low SII and high SII at baseline (HR = 1.120, 95% CI 0.554-2.264, P = 0.749), 3 weeks post treatment (HR = 1.022, 95% CI 0.500-2.089, P = 0.951) and 6 weeks post treatment (HR = 1.759, 95% CI 0.851-3.635, P = 0.097).

Conclusions: NLR at 6 weeks post treatment is a predictor of the response to anti-PD-1 treatment in patients with ESCC.
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http://dx.doi.org/10.1186/s12935-021-02072-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262036PMC
July 2021

Nutrient consumption patterns of Lactobacillus plantarum and their application in suancai.

Int J Food Microbiol 2021 Sep 29;354:109317. Epub 2021 Jun 29.

Key Laboratory of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, 600 Changjiang Road, Harbin 150030, Heilongjiang, China. Electronic address:

The purpose of the present study was to control the fermentation time and nitrite content of suancai prepared with Lactobacillus plantarum. According to analyses of the consumption amount and rate of nutrients, growth-stimulating nutrients, essential nutrients and nutrients accelerating the fermentation process of suancai, Asp, Thr, Glu, Cys, Tyr, Mg, Mn and inosine were selected as additions to suancai prepared with L. plantarum. The fermentation time and nitrite content of suancai supplemented with nutrients and prepared with L. plantarum were shortened by 2 days and 5 days and reduced by approximately 0.1-fold and 0.7-fold, respectively, compared with unsupplemented suancai prepared with L. plantarum at 25 °C and 10 °C. The fermentation time and nitrite content of suancai supplemented with nutrients and prepared with L. plantarum were shortened by 6 days and 15 days and reduced by approximately 0.17-fold and 0.8-fold, respectively, compared with suancai undergoing spontaneous fermentation at 25 °C and 10 °C. Furthermore, no significant differences were observed in sensory properties in suancai. The results of this study indicated that certain nutrients accelerated the growth of L. plantarum and reduced the fermentation time and nitrite content of suancai prepared with L. plantarum. These findings help to establish a foundation for the practical use of nutrients to control the fermentation of suancai.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109317DOI Listing
September 2021

Associations of genetic risk and smoking with incident chronic obstructive pulmonary disease.

Eur Respir J 2021 Jun 25. Epub 2021 Jun 25.

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China

Background: Genetic and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on the smoking remains unclear. We aimed to investigate the association of PRS with COPD and explore whether smoking behaviors could modify such association.

Methods: Multivariable Cox proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of the PRS and smoking with COPD.

Results: The study included 439 255 participants (mean age 56.5; 53.9% female), with a median follow-up of 9.0 years. The PRS containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than the PRS containing 279 genome-wide significance variants. Compared with the low genetic risk, the HRs of the medium and high genetic risk were 1.39 (95% CI, 1.31-1.48) and 2.40 (95% CI, 2.24-2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI, 10.31-13.10) times of low genetic risk and never smoking. There were significant interactions between the PRS and smoking status for incident COPD (p for interaction<0.001). From low genetic risk to high genetic risk, the HRs of current smoking increased from 4.32 (95% CI, 3.69-5.06) to 6.89 (95% CI, 6.21-7.64), and the population-attributable risks of smoking increased from 42.7% to 61.1%.

Conclusion: PRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.
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http://dx.doi.org/10.1183/13993003.01320-2021DOI Listing
June 2021

A C-Type Lectin Highly Expressed in Intestine Functions in AMP Regulation and Prophenoloxidase Activation.

Antibiotics (Basel) 2021 May 7;10(5). Epub 2021 May 7.

School of Marine Science, Ningbo University, Ningbo 315211, China.

A C-type lectin (PtCLec2) from was identified for characterization of its role in defense and innate immunity. PtCLec2 contains a single carbohydrate-recognition domain (CRD) with a conserved QPD motif, which was predicted to have galactose specificity. The mRNA expression of PtCLec2 was predominantly detected in intestine and increased rapidly and significantly upon pathogen challenge. The recombinant PtCLec2 (rPtCLec2) could bind various microorganisms and PAMPs with weak binding ability to yeast and PGN. It agglutinated the tested Gram-negative bacteria ( and ), Gram-positive bacteria ( and ), and rabbit erythrocytes in the presence of exogenous Ca, and these agglutination activities were suppressed by LPS, d-galactose, and d-mannose. Further, rPtCLec2 enhanced phagocytosis and clearance of , and displayed inhibitory activities against the tested bacteria. Knockdown of PtCLec2 decreased the transcription of two phagocytosis genes (PtArp and PtMyosin), three prophenoloxidase (proPO) system-related genes (PtPPAF, PtcSP1, and PtproPO), six antimicrobial peptides (AMPs) (PtALF4-7, PtCrustin1, and PtCrustin3), and PtRelish but upregulated the expression levels of PtJNK, PtPelle, and PtTLR. These results collectively indicate that PtCLec2 might perform its immune recognition function via binding and agglutination, and mediate pathogen elimination via regulating hemocyte phagocytosis, AMP synthesis, and proPO activation.
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http://dx.doi.org/10.3390/antibiotics10050541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151143PMC
May 2021

Peters plus syndrome mutations affect the function and stability of human β1,3-glucosyltransferase.

J Biol Chem 2021 07 28;297(1):100843. Epub 2021 May 28.

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA. Electronic address:

Peters Plus Syndrome (PTRPLS OMIM #261540) is a severe congenital disorder of glycosylation where patients have multiple structural anomalies, including Peters anomaly of the eye (anterior segment dysgenesis), disproportionate short stature, brachydactyly, dysmorphic facial features, developmental delay, and variable additional abnormalities. PTRPLS patients and some Peters Plus-like (PTRPLS-like) patients (who only have a subset of PTRPLS phenotypes) have mutations in the gene encoding β1,3-glucosyltransferase (B3GLCT). B3GLCT catalyzes the transfer of glucose to O-linked fucose on thrombospondin type-1 repeats. Most B3GLCT substrate proteins belong to the ADAMTS superfamily and play critical roles in extracellular matrix. We sought to determine whether the PTRPLS or PTRPLS-like mutations abrogated B3GLCT activity. B3GLCT has two putative active sites, one in the N-terminal region and the other in the C-terminal glycosyltransferase domain. Using sequence analysis and in vitro activity assays, we demonstrated that the C-terminal domain catalyzes transfer of glucose to O-linked fucose. We also generated a homology model of B3GLCT and identified D421 as the catalytic base. PTRPLS and PTRPLS-like mutations were individually introduced into B3GLCT, and the mutated enzymes were evaluated using in vitro enzyme assays and cell-based functional assays. Our results demonstrated that PTRPLS mutations caused loss of B3GLCT enzymatic activity and/or significantly reduced protein stability. In contrast, B3GLCT with PTRPLS-like mutations retained enzymatic activity, although some showed a minor destabilizing effect. Overall, our data supports the hypothesis that loss of glucose from B3GLCT substrate proteins is responsible for the defects observed in PTRPLS patients, but not for those observed in PTRPLS-like patients.
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http://dx.doi.org/10.1016/j.jbc.2021.100843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233153PMC
July 2021

Ablation Therapy Combined with EGFR TKIs in the Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med 2021 7;2021:6624429. Epub 2021 May 7.

Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine, Zhongshan 528400, China.

Objective: Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC).

Methods: We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3.

Results: A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, 0.01), partial response rate (PRR) (RR: -2.25, 95% CI: 1.41 to 3.59, 0.01), and disease control rate (DCR) (RR: -2.80, 95% CI: 1.64 to 4.80, < 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, 0.01), partial response rate (PRR) (RR: -1.66, 95% CI: 1.20 to 2.31, < 0.01), and disease control rate (DCR) (RR: -2.68, 95% CI: 1.41 to 5.06, < 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone.

Conclusion: Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.
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http://dx.doi.org/10.1155/2021/6624429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123993PMC
May 2021

Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase.

J Med Chem 2021 06 27;64(11):7667-7690. Epub 2021 May 27.

Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyperinflammatory and autoimmune diseases, and the cGAS-targeting small molecule has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound (G140), we conducted a structural optimization on both its side chain and the central tricyclic core, leading to several subseries of compounds, including those unexpectedly cyclized complex ones. Compound bearing an -glycylglycinoyl side chain was identified as the most potent one with cellular IC values of 1.38 and 11.4 μM for h- and m-cGAS, respectively. Mechanistic studies confirmed its direct targeting of cGAS. Further, compound showed superior in vivo anti-inflammatory effects in the lipopolysaccharide-induced mouse model. The encouraging result of compound provides solid evidence for further pursuit of cGAS-targeting inhibitors as a new anti-inflammatory treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00398DOI Listing
June 2021

From colloidal particles to photonic crystals: advances in self-assembly and their emerging applications.

Chem Soc Rev 2021 May;50(10):5898-5951

Research Institute for Frontier Science, Beijing Advanced Innovation Center for Biomedical Engineering, School of Space and Environment, Beihang University, Beijing 100191, China.

Over the last three decades, photonic crystals (PhCs) have attracted intense interests thanks to their broad potential applications in optics and photonics. Generally, these structures can be fabricated via either "top-down" lithographic or "bottom-up" self-assembly approaches. The self-assembly approaches have attracted particular attention due to their low cost, simple fabrication processes, relative convenience of scaling up, and the ease of creating complex structures with nanometer precision. The self-assembled colloidal crystals (CCs), which are good candidates for PhCs, have offered unprecedented opportunities for photonics, optics, optoelectronics, sensing, energy harvesting, environmental remediation, pigments, and many other applications. The creation of high-quality CCs and their mass fabrication over large areas are the critical limiting factors for real-world applications. This paper reviews the state-of-the-art techniques in the self-assembly of colloidal particles for the fabrication of large-area high-quality CCs and CCs with unique symmetries. The first part of this review summarizes the types of defects commonly encountered in the fabrication process and their effects on the optical properties of the resultant CCs. Next, the mechanisms of the formation of cracks/defects are discussed, and a range of versatile fabrication methods to create large-area crack/defect-free two-dimensional and three-dimensional CCs are described. Meanwhile, we also shed light on both the advantages and limitations of these advanced approaches developed to fabricate high-quality CCs. The self-assembly routes and achievements in the fabrication of CCs with the ability to open a complete photonic bandgap, such as cubic diamond and pyrochlore structure CCs, are discussed as well. Then emerging applications of large-area high-quality CCs and unique photonic structures enabled by the advanced self-assembly methods are illustrated. At the end of this review, we outlook the future approaches in the fabrication of perfect CCs and highlight their novel real-world applications.
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http://dx.doi.org/10.1039/d0cs00706dDOI Listing
May 2021

Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells.

Nat Commun 2021 05 11;12(1):2681. Epub 2021 May 11.

Department of Surgery and Immunobiology and Transplant Science Center, Houston Methodist, Houston, TX, USA.

Innate immune cells are critical in protective immunity against viral infections, involved in sensing foreign viral nucleic acids. Here we report that the poly(ADP-ribose) polymerase 9 (PARP9), a member of PARP family, serves as a non-canonical sensor for RNA virus to initiate and amplify type I interferon (IFN) production. We find knockdown or deletion of PARP9 in human or mouse dendritic cells and macrophages inhibits type I IFN production in response to double strand RNA stimulation or RNA virus infection. Furthermore, mice deficient for PARP9 show enhanced susceptibility to infections with RNA viruses because of the impaired type I IFN production. Mechanistically, we show that PARP9 recognizes and binds viral RNA, with resultant recruitment and activation of the phosphoinositide 3-kinase (PI3K) and AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS). PI3K/AKT3 then activates the IRF3 and IRF7 by phosphorylating IRF3 at Ser385 and IRF7 at Ser437/438 mediating type I IFN production. Together, we reveal a critical role for PARP9 as a non-canonical RNA sensor that depends on the PI3K/AKT3 pathway to produce type I IFN. These findings may have important clinical implications in controlling viral infections and viral-induced diseases by targeting PARP9.
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http://dx.doi.org/10.1038/s41467-021-23003-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113569PMC
May 2021

A graphene oxide coated tapered microfiber acting as a super-sensor for rapid detection of SARS-CoV-2.

Lab Chip 2021 06;21(12):2398-2406

Shanghai Key Laboratory of Modern Optical System, Engineering Research Center of Optical Instrument and System (Ministry of Education), School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

COVID-19 is a new strain of highly contagious coronavirus, and at present, more than 221.4 million people have been infected with this virus, and the death toll exceeds 2793398. Early and fast detection of COVID-19 from infected individuals is critical to limit its spreading. Here, we report an innovative approach to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein by combining DNA/RNA oligomers as aptamers and a graphene oxide (GO) coated optical microfiber as a sensor system. The DNA/RNA aptamers can effectively capture the SARS-CoV-2 N protein in vitro, with the GO coated optical microfiber aptasensor for real-time monitoring of the SARS-CoV-2 N protein. Due to the extremely high surface-to-volume ratio and excellent optical and biochemical properties of the GO surface layer, the fixing effect of the microfiber surface is significantly improved and the lowest limit of detection (LOD) is 6.25 × 10-19 M. Furthermore, in order to prove the feasibility of this sensing method in clinical applications, we use this sensor to detect the N protein mixed in fetal bovine serum (FBS) samples. The experimental results show that the biosensor can quickly and effectively detect the N protein (1 × 10-9 M) in a complex sample matrix within 3 minutes. These findings suggest that this approach can be utilized for quantitative monitoring of coronavirus particles due to its high sensitivity, which can help to quickly exclude patients who do not have the infection. Collectively, the optical microfiber sensor system could be expected to become an important platform for the diagnosis of coronavirus due to its simple detection scheme and easy miniaturization.
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http://dx.doi.org/10.1039/d0lc01231aDOI Listing
June 2021

Analyses of production capacity of Sr and Sr in the 2 MW molten salt reactor.

Appl Radiat Isot 2021 Jul 3;173:109714. Epub 2021 Apr 3.

Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China; CAS Innovative Academies in TMSR Energy System, Chinese Academy of Sciences, Shanghai, 201800, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The production capacity of Sr and Sr in the 2 MW MSR are evaluated. The gaseous Kr and Kr are extracted from the core through the helium bubbling system, and then decay to Sr and Sr, respectively. In order to improve purity of Sr product, two cooling devices are adopted in the Sr and Sr production system. The annual yields of Sr and Sr are about 9000 Ci and 32 Ci, respectively, and the impurity of Sr product is less than 2 ppm which can meet the medical requirement.
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http://dx.doi.org/10.1016/j.apradiso.2021.109714DOI Listing
July 2021

Creativity and Leadership in the Creative Industry: A Study From the Perspective of Social Norms.

Front Psychol 2021 6;12:651817. Epub 2021 Apr 6.

School of Business, Dalian University of Technology, Dalian, China.

Individual creativity has been the focus of long-term research in creative industries. However, few studies have explored the impact on individual creativity from social factors. At the same time, the influence of individual creativity on the existence of subsequent factors in the creative industry is also worthy of further investigation. From a social standpoint, this research aims to explore how social norms affect individual creativity, and how individual creativity affects subsequent leadership. The present research takes creative entrepreneurs in creative enterprises as the research objects, and the structural equation model is used to analyze the data obtained from 202 valid questionnaires. Besides, the mediating effect of individual creativity between social norms and individual leadership is verified. The results show that social norms can effectively promote the generation of individual creativity that has a positive impact on both transactional or transformational leadership. It is revealed that social norms are effective tools for enhancing creativity, answering the question of how creative ideas are transformed into creative work and leadership. Individual creativity plays a mediating role between social norms and individual leadership.
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http://dx.doi.org/10.3389/fpsyg.2021.651817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057347PMC
April 2021

Intercalated architecture of MAZ family layered van der Waals materials with emerging topological, magnetic and superconducting properties.

Nat Commun 2021 Apr 21;12(1):2361. Epub 2021 Apr 21.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 110016, Shenyang, People's Republic of China.

The search for new two-dimensional monolayers with diverse electronic properties has attracted growing interest in recent years. Here, we present an approach to construct MAZ monolayers with a septuple-atomic-layer structure, that is, intercalating a MoS-type monolayer MZ into an InSe-type monolayer AZ. We illustrate this unique strategy by means of first-principles calculations, which not only reproduce the structures of MoSiN and MnBiTe that were already experimentally synthesized, but also predict 72 compounds that are thermodynamically and dynamically stable. Such an intercalated architecture significantly reconstructs the band structures of the constituents MZ and AZ, leading to diverse electronic properties for MAZ, which can be classified according to the total number of valence electrons. The systems with 32 and 34 valence electrons are mostly semiconductors. Whereas, those with 33 valence electrons can be nonmagnetic metals or ferromagnetic semiconductors. In particular, we find that, among the predicted compounds, (Ca,Sr)GaTe are topologically nontrivial by both the standard density functional theory and hybrid functional calculations. While VSiP is a ferromagnetic semiconductor and TaSiN is a type-I Ising superconductor. Moreover, WSiP is a direct gap semiconductor with peculiar spin-valley properties, which are robust against interlayer interactions. Our study thus provides an effective way of designing septuple-atomic-layer MAZ with unusual electronic properties to draw immediate experimental interest.
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http://dx.doi.org/10.1038/s41467-021-22324-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060390PMC
April 2021

Development of Potent NEDD8-Activating Enzyme Inhibitors Bearing a Pyrimidotriazole Scaffold.

J Med Chem 2021 05 15;64(9):6161-6178. Epub 2021 Apr 15.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The ubiquitin-like protein NEDD8 is a critical signaling molecule implicated in the functional maintenance and homeostasis of cells. Dysregulation of this process is involved in a variety of human diseases, including cancer. Therefore, NEDD8-activating enzyme E1 (NAE), the only activation enzyme of the neddylation pathway, has been an emergent anticancer target. In view of the single-agent modest response of the clinical NAE inhibitor, pevonedistat (compound , MLN4924), efforts on development of new inhibitors with both high potency and better safety profiles are urgently needed. Here, we report a structural hopping strategy by optimizing the central deazapurine framework and the solvent interaction region of compound , leading to compound bearing a pyrimidotriazole scaffold. Compound not only has compatible potency in the biochemical and cell assays but also possesses improved pharmacokinetic (PK) properties than compound . In vivo, compound showed significant antitumor efficacy and good safety in xenograft models.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00242DOI Listing
May 2021

The ups, downs and new trends of IDO1 inhibitors.

Bioorg Chem 2021 05 10;110:104815. Epub 2021 Mar 10.

Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Cancer immunotherapy has become an emerging driving force in the development of innovative strategies to fight against cancer. Despite the significant clinical benefits that many cancer patients have gained, the generally average response rate of ~ 20% is far behind the expectation for immune checkpoint inhibitors (ICIs). Combination of ICIs with indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors is considered as an alternative solution and has proved effective in tremendous preclinical studies. However, the failure of phase III ECHO-301/KEYNOTE-252 trial seriously dampened the enthusiasm on the rationality of IDO1-targeting strategy. Fortunately, in spite of the ups and downs in the developmental journey of IDO1 inhibitors, multiple new approaches have been proposed to bridge the gap between lab to the clinic. Here, we review the recent advances in the development of small molecule inhibitors targeting IDO1 especially the new trend of IDO1 inhibitors after ECHO-301 clinical trials, including dual or pan-inhibitors targeting IDO1 and TDO or IDO2, apo-IDO1 inhibitors, IDO1 PROTACs, as well as other IDO1 inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2021.104815DOI Listing
May 2021

TMA/TMAO in Hypertension: Novel Horizons and Potential Therapies.

J Cardiovasc Transl Res 2021 Mar 11. Epub 2021 Mar 11.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Hypertension is the most prevalent chronic disease and a risk factor for various diseases. Although its mechanisms and therapies are constantly being updated and developed, they are still not fully clarified. In recent years, novel gut microbiota and its metabolites have attracted widespread attention. It is strongly linked with physiological and pathological systems, especially TMA and TMAO. TMA is formed by intestinal microbial metabolism of choline and L-carnitine and converted into TMAO by FMO3. This paper collected and collated the latest researches and mainly discussed the following four parts. It introduced gut microbiota; provided a focus on TMA, TMA-producing bacteria, and TMAO; summarized the alternations in hypertensive patients and animals; discussed the mechanisms of TMAO with two respects; and summarized the regulatory factors may be as new interventions and therapies of hypertension. And, more relevant studies are still prospected to be accomplished between hypertension and TMA/TMAO for further clinical services.
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http://dx.doi.org/10.1007/s12265-021-10115-xDOI Listing
March 2021

Development of hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of medulloblastoma.

Acta Pharm Sin B 2021 Feb 21;11(2):488-504. Epub 2020 Jul 21.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

Medulloblastoma (MB) is a common yet highly heterogeneous childhood malignant brain tumor, however, clinically effective molecular targeted therapy is lacking. Modulation of hedgehog (HH) signaling by epigenetically targeting the transcriptional factors GLI through bromodomain-containing protein 4 (BRD4) has recently spurred new interest as potential treatment of HH-driven MB. Through screening of current clinical BRD4 inhibitors for their inhibitory potency against glioma-associated oncogene homolog (GLI) protein, the BRD4 inhibitor was selected as the lead for further structural optimization, which led to the identification of compounds and as the high potency HH inhibitors. Mechanism profiling showed that both compounds suppressed HH signaling by interacting with the transcriptional factor GLI, and were equally potent against the clinical resistant mutants and the wild type of smoothened (SMO) receptor with IC values around 1 nmol/L. In the resistant MB allograft mice, compound was well tolerated and markedly suppressed tumor growth at both 5 mg/kg (TGI = 83.3%) and 10 mg/kg (TGI = 87.6%) doses. Although further modification is needed to improve the pharmacokinetic (PK) parameters, compound represents an efficacious lead compound of GLI inhibitors, possessing optimal safety and tolerance to fight against HH-driven MB.
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http://dx.doi.org/10.1016/j.apsb.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893122PMC
February 2021

N(6)-methyladenosine-binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay.

EMBO Rep 2021 04 19;22(4):e50128. Epub 2021 Feb 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

N -methyladenosine (m A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B-cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m A modification in human NPC biopsies, patient-derived xenograft tissues, and cells at different EBV infection stages. m A-modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m A-dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post-transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV-associated cancers.
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http://dx.doi.org/10.15252/embr.202050128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025027PMC
April 2021

Glycogen synthase kinase 3β inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer.

Cell Death Dis 2021 02 15;12(2):183. Epub 2021 Feb 15.

Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in a limited objective response rate (≤60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Here, we found that GSK3 inhibitors (GSK3i) exhibited a strong synergistic effect with PARPi in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. The combination of GSK3β and PARP inhibition causes replication stress and DNA double-strand breaks, resulting in increased anaphase bridges and abnormal spindles. Mechanistically, inhibition or genetic depletion of GSK3β was found to impair the HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity. Our results provide a mechanistic understanding of the combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients.
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http://dx.doi.org/10.1038/s41419-021-03475-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884722PMC
February 2021

Effects of autophagy inhibitor 3-Methyladenine on ischemic stroke: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(4):e23873

Nanjing University of Chinese Medicine, Nanjing, China.

Background: Ischemic stroke is a huge threat to human health globally. Rescuing neurons in the ischemic penumbra (IP) is pivotal after the onset of ischemic stroke, and autophagy is essential to the survival of IP neurons and the development of related pathological processes. As the most common autophagy inhibitor, 3-Methyladenine (3-MA) is widely used in studies related to the mechanism of neuronal autophagy in ischemic stroke; however, there is no consensus has been reached on its effects of neuroprotection or neurodamage, which hinders the development and clinical application of autophagy-targeted therapy strategies for the treatment of ischemic stroke.

Methods: We will search the following electronic bibliographic databases: PubMed, EMBASE, Scopus, Science Direct, and Web of Science. Participant intervention comparator outcomes of this study are as flowing: P, animal models of ischemic stroke; I, received 3-MA treatment merely; C, received only vehicle or sham treatment, or no treatment; O, Primary outcomes are infarct volume; neuro-behavioral scores. Secondary outcomes are cerebral blood flow, blood-brain barrier permeability, cerebral hemorrhage, brain water content. Review Manager 5.3 and Stata 15.1 will be used in data analysis. The characteristics of the studies, the experimental model, and the main results will be described, the quality assessment and the risk of bias assessment will be conducted. A narrative synthesis will be made for the included studies. Besides, if sufficient qualitative data is available, a meta-analysis will be conducted. I2 statistics will be used to assess heterogeneity.

Discussion: This systematic review and meta-analysis of the autophagy inhibitor 3-MAs effects on animal models of ischemic stroke can help us to understand whether inhibiting autophagy brings protection or damage to IP neurons; in addition, it also helps to clarify the specific role of autophagy in cerebral infarction. Therefore, this study can provide evidence for the future development of therapy strategies targeting autophagy and bring more hope to patients with ischemic stroke.

Prospero Registration Number: CRD42020194262.
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http://dx.doi.org/10.1097/MD.0000000000023873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850754PMC
January 2021

Genetic analysis of maize shank length by QTL mapping in three recombinant inbred line populations.

Plant Sci 2021 Feb 22;303:110767. Epub 2020 Nov 22.

College of Biological Science and Technology, Liaoning Province Research Center of Plant Genetic Engineering Technology, Shenyang Key Laboratory of Maize Genomic Selection Breeding, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address:

In maize, the shank is a unique tissue linking the stem to the ear. Shank length (SL) mainly affects the transport of photosynthetic products to the ear and the dehydration of kernels via regulated husk morphology. The limited studies on SL revealed it is a highly heritable quantitative trait controlled by significant additive and additive-dominance effects. However, the genetic basis of SL remains unclear. In this study, we analyzed three maize recombinant inbred line (RIL) populations to elucidate the molecular mechanism underlying the SL. The data indicated the SL varied among the three RIL populations and was highly heritable. Additionally, the SL was positively correlated with the husk length (HL), husk number (HN), ear length (EL), and ear weight (EW) in the BY815/K22 (BYK) and CI7/K22 (CIK) RIL populations, but was negatively correlated with the husk width (HW) in the BYK RIL population. Moreover, 10 quantitative trait loci (QTL) for SL were identified in the three RIL populations, five of which were large-effect QTL. The percentage of the total phenotypic variation explained by the QTL for SL was 13.67 %, 20.45 %, and 30.81 % in the BY815/DE3 (BYD), BYK, and CIK RIL populations, respectively. Further analyses uncovered some genetic overlap between SL and EL, SL and ear row number (ERN), SL and cob weight (CW), and SL and HN. Unlike the large-effect QTL qSL BYK-2-2, which spanned the centromere, the other four large-effect QTL were delimited to a single peak bin via bin map. Furthermore, 2, 5, 6, and 12 genes associated with SL were identified for qSL BYK-2-1, qSL CIK-2-1, qSL CIK-9-1, and qSL CIK-9-2, respectively. Five of the candidate genes for SL may contribute to the hormone metabolism and sphingolipid biosynthesis regulating cell elongation, division, differentiation, and expansion. These results may be relevant for future studies on the genetic basis of SL and for the molecular breeding of maize based on marker-assisted selection to develop new varieties with an ideal SL.
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http://dx.doi.org/10.1016/j.plantsci.2020.110767DOI Listing
February 2021

Structure-Activity Relationship Study of Amidobenzimidazole Analogues Leading to Potent and Systemically Administrable Stimulator of Interferon Gene (STING) Agonists.

J Med Chem 2021 02 20;64(3):1649-1669. Epub 2021 Jan 20.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

Activation of the stimulator of interferon gene (STING) has emerged as an exciting immuno-oncology therapeutic strategy; however, the first-generation STING agonists, cyclic dinucleotide (CDN) analogues, have suffered from many disadvantages and failed in clinical trials. Therefore, non-CDN small-molecule STING agonists are urgently needed. In view of the unique structure of the high potency of dimeric amidobenzimidazole STING agonist , a structural elaboration was conducted by modifying several structural hotspots of this scaffold. Triazole was identified as a new potent STING activator, possessing EC values of 0.24 and 39.51 μM for h- and m-STING, respectively. This compound has a slightly better pharmacokinetic profile and is >20-fold more aqueously soluble than . It activated the STING signaling dramatically by directly binding and stabilizing all h-STING isoforms and m-STING. In vivo, intermittent administration of was found to have significant antitumor efficacy with good tolerance in two mouse tumor models.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01900DOI Listing
February 2021

A novel tricyclic BTK inhibitor suppresses B cell responses and osteoclastic bone erosion in rheumatoid arthritis.

Acta Pharmacol Sin 2021 Jan 13. Epub 2021 Jan 13.

Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Rheumatoid arthritis (RA) is characterized by joint leukocyte infiltration, synovial inflammation and bone damage result from osteoclastogenesis. Bruton's tyrosine kinase (BTK) is a key regulator of B cell receptor (BCR) and Fc gamma receptor (FcγR) signaling involved in the pathobiology of RA and other autoimmune disorders. SOMCL-17-016 is a potent and selective tricyclic BTK inhibitor, structurally distinct from other known BTK inhibitors. In present study we investigated the therapeutic efficacy of SOMCL-17-016 in a mouse collagen-induced arthritis (CIA) model and underlying mechanisms. CIA mice were administered SOMCL-17-016 (6.25, 12.5, 25 mg·kg·d, ig), or ibrutinib (25 mg·kg·d, ig) or acalabrutinib (25 mg·kg·d, ig) for 15 days. We showed that oral administration of SOMCL-17-016 dose-dependently ameliorated arthritis severity and bone damage in CIA mice; it displayed a higher in vivo efficacy than ibrutinib and acalabrutinib at the corresponding dosage. We found that SOMCL-17-016 administration dose-dependently inhibited anti-IgM-induced proliferation and activation of B cells from CIA mice, and significantly decreased anti-IgM/anti-CD40-stimulated RANKL expression in memory B cells from RA patients. In RANKL/M-CSF-stimulated RAW264.7 cells, SOMCL-17-016 prevented osteoclast differentiation and abolished RANK-BTK-PLCγ2-NFATc1 signaling. In summary, this study demonstrates that SOMCL-17-016 presents distinguished therapeutic effects in the CIA model. SOMCL-17-016 exerts a dual inhibition of B cell function and osteoclastogenesis, suggesting that it to be a promising drug candidate for RA treatment.
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http://dx.doi.org/10.1038/s41401-020-00578-0DOI Listing
January 2021

Auxilin-like protein MoSwa2 promotes effector secretion and virulence as a clathrin uncoating factor in the rice blast fungus Magnaporthe oryzae.

New Phytol 2021 04 13;230(2):720-736. Epub 2021 Feb 13.

Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing, 210095, China.

Plant pathogens exploit the extracellular matrix (ECM) to inhibit host immunity during their interactions with the host. The formation of ECM involves a series of continuous steps of vesicular transport events. To understand how such vesicle trafficking impacts ECM and virulence in the rice blast fungus Magnaporthe oryzae, we characterised MoSwa2, a previously identified actin-regulating kinase MoArk1 interacting protein, as an orthologue of the auxilin-like clathrin uncoating factor Swa2 of the budding yeast Saccharomyces cerevisiae. We found that MoSwa2 functions as an uncoating factor of the coat protein complex II (COPII) via an interaction with the COPII subunit MoSec24-2. Loss of MoSwa2 led to a deficiency in the secretion of extracellular proteins, resulting in both restricted growth of invasive hyphae and reduced inhibition of host immunity. Additionally, extracellular fluid (ECF) proteome analysis revealed that MoSwa2-regulated extracellular proteins include many redox proteins such as the berberine bridge enzyme-like (BBE-like) protein MoSef1. We further found that MoSef1 functions as an apoplastic virulent factor that inhibits the host immune response. Our studies revealed a novel function of a COPII uncoating factor in vesicular transport that is critical in the suppression of host immunity and pathogenicity of M. oryzae.
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http://dx.doi.org/10.1111/nph.17181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048681PMC
April 2021

Synergistic Interplay between Asymmetric Backbone Conformation, Molecular Aggregation, and Charge-Carrier Dynamics in Fused-Ring Electron Acceptor-Based Bulk Heterojunction Solar Cells.

ACS Appl Mater Interfaces 2021 Jan 7;13(2):2961-2970. Epub 2021 Jan 7.

Physik-Department, Lehrstuhl für Funktionelle Materialien, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany.

Asymmetric fused-ring electron acceptors (a-FREAs) have proved to be a promising type of electron acceptor for high-performance organic solar cells (OSCs). However, the relationship among molecular structures of a-FREAs and their nanoscale morphology, charge-carrier dynamics, and device performance remains unclear. In this contribution, two FREAs differing in conjugated backbone geometry with an asymmetric conformation (IPT-2F) or symmetric one (INPIC-2F) are selected to systematically explore the superiorities of the asymmetric conformation. Despite the frailer extinction coefficient and weaker crystallinity, IPT-2F shows stronger dipole interactions in the asymmetrical backbone, which would induce a closer lamellar packing than that of the symmetrical counterpart. Using PBDB-T as the electron donor, the IPT-2F-based OSCs achieve the best power conversion efficiency of 14.0%, which is ca. 67% improvement compared to the INPIC-2F-based ones (8.37%), resulting from a simultaneously increased short-circuited current density () and fill factor. Systematical investigations on optoelectronic and morphological properties show that the asymmetric conformation-structured IPT-2F exhibits better miscibility with the polymer donor to induce a favorable blend ordering with small domain sizes and suitable phase separation compared to the INPIC-2F symmetric molecule. This facilitates an efficient charge generation and transport, inhibits charge-carrier recombination, and promotes valid charge extraction in IPT-2F-based devices.
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http://dx.doi.org/10.1021/acsami.0c19700DOI Listing
January 2021

Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway.

Acta Pharm Sin B 2020 Dec 13;10(12):2272-2298. Epub 2020 Mar 13.

Research Laboratory of Medicinal Chemical Biology & Frontiers on Drug Discovery (RLMCBFDD), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS‒STING‒TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS‒STING‒TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.
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http://dx.doi.org/10.1016/j.apsb.2020.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745059PMC
December 2020
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