Publications by authors named "Ying Shao"

324 Publications

The emerging roles of circular RNAs in vessel co-option and vasculogenic mimicry: clinical insights for anti-angiogenic therapy in cancers.

Cancer Metastasis Rev 2021 Oct 18. Epub 2021 Oct 18.

Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Unexpected resistance to anti-angiogenic treatment prompted the investigation of non-angiogenic tumor processes. Vessel co-option (VC) and vasculogenic mimicry (VM) are recognized as primary non-angiogenic mechanisms. In VC, cancer cells utilize pre-existing blood vessels for support, whereas in VM, cancer cells channel and provide blood flow to rapidly growing tumors. Both processes have been implicated in the development of tumor and resistance to anti-angiogenic drugs in many tumor types. The morphology, but rare molecular alterations have been investigated in VC and VM. There is a pressing need to better understand the underlying cellular and molecular mechanisms. Here, we review the emerging circular RNA (circRNA)-mediated regulation of non-angiogenic processes, VC and VM.
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http://dx.doi.org/10.1007/s10555-021-10000-8DOI Listing
October 2021

Enzymatic recombinase amplification coupled with CRISPR-Cas12a for ultrasensitive, rapid, and specific Porcine circovirus 3 detection.

Mol Cell Probes 2021 Oct 5:101772. Epub 2021 Oct 5.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Shushan District West Yangtze River Road 130#, Hefei, 230036, Anhui Province, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.mcp.2021.101772DOI Listing
October 2021

IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.

JCI Insight 2021 Oct 8;6(19). Epub 2021 Oct 8.

Centers for Cardiovascular Research.

Tregs play vital roles in suppressing atherogenesis. Pathological conditions reshape Tregs and increase Treg-weakening plasticity. It remains unclear how Tregs preserve their function and how Tregs switch into alternative phenotypes in the environment of atherosclerosis. In this study, we observed a great induction of CD4+Foxp3+ Tregs in the spleen and aorta of ApoE-/- mice, accompanied by a significant increase of plasma IL-35 levels. To determine if IL-35 devotes its role in the rise of Tregs, we generated IL-35 subunit P35-deficient (IL-35P35-deficient) mice on an ApoE-/- background and found Treg reduction in the spleen and aorta compared with ApoE-/- controls. In addition, our RNA sequencing data show the elevation of a set of chemokine receptor transcripts in the ApoE-/- Tregs, and we have validated higher CCR5 expression in ApoE-/- Tregs in the presence of IL-35 than in the absence of IL-35. Furthermore, we observed that CCR5+ Tregs in ApoE-/- have lower Treg-weakening AKT-mTOR signaling, higher expression of inhibitory checkpoint receptors TIGIT and PD-1, and higher expression of IL-10 compared with WT CCR5+ Tregs. In conclusion, IL-35 counteracts hyperlipidemia in maintaining Treg-suppressive function by increasing 3 CCR5-amplified mechanisms, including Treg migration, inhibition of Treg weakening AKT-mTOR signaling, and promotion of TIGIT and PD-1 signaling.
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http://dx.doi.org/10.1172/jci.insight.152511DOI Listing
October 2021

Iridium-catalyzed regio- and enantioselective allylic esterification of secondary allylic alcohols with carboxylic acids.

Chem Commun (Camb) 2021 Oct 21;57(84):11080-11083. Epub 2021 Oct 21.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.

We report herein an iridium-catalyzed asymmetric allylic esterification of racemic secondary allylic alcohols using free carboxylic acids as nucleophiles under mild conditions with broad functional group tolerance, exhibiting excellent regio- and enantioselectivity .
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http://dx.doi.org/10.1039/d1cc04861aDOI Listing
October 2021

Procaspase-1 patrolled to the nucleus of proatherogenic lipid LPC-activated human aortic endothelial cells induces ROS promoter CYP1B1 and strong inflammation.

Redox Biol 2021 Sep 27;47:102142. Epub 2021 Sep 27.

Centers of Cardiovascular Research, Inflammation Lung Research, USA; Metabolic Disease Research, Thrombosis Research, Departments of Cardiovascular Sciences, USA. Electronic address:

To determine the roles of nuclear localization of pro-caspase-1 in human aortic endothelial cells (HAECs) activated by proatherogenic lipid lysophosphatidylcholine (LPC), we examined cytosolic and nuclear localization of pro-caspase-1, identified nuclear export signal (NES) in pro-caspase-1 and sequenced RNAs. We made the following findings: 1) LPC increases nuclear localization of procaspase-1 in HAECs. 2) Nuclear pro-caspase-1 exports back to the cytosol, which is facilitated by a leptomycin B-inhibited mechanism. 3) Increased nuclear localization of pro-caspase-1 by a new NES peptide inhibitor upregulates inflammatory genes in oxidative stress and Th17 pathways; and SUMO activator N106 enhances nuclear localization of pro-caspase-1 and caspase-1 activation (p20) in the nucleus. 4) LPC plus caspase-1 enzymatic inhibitor upregulates inflammatory genes with hypercytokinemia/hyperchemokinemia and interferon pathways, suggesting a novel capsase-1 enzyme-independent inflammatory mechanism. 5) LPC in combination with NES inhibitor and caspase-1 inhibitor upregulate inflammatory gene expression that regulate Th17 activation, endotheli-1 signaling, p38-, and ERK- MAPK pathways. To examine two hallmarks of endothelial activation such as secretomes and membrane protein signaling, LPC plus NES inhibitor upregulate 57 canonical secretomic genes and 76 exosome secretomic genes, respectively, promoting four pathways including Th17, IL-17 promoted cytokines, interferon signaling and cholesterol biosynthesis. LPC with NES inhibitor also promote inflammation via upregulating ROS promoter CYP1B1 and 11 clusters of differentiation (CD) membrane protein pathways. Mechanistically, all the LPC plus NES inhibitor-induced genes are significantly downregulated in CYP1B1-deficient microarray, suggesting that nuclear caspase-1-induced CYP1B1 promotes strong inflammation. These transcriptomic results provide novel insights on the roles of nuclear caspase-1 in sensing DAMPs, inducing ROS promoter CYP1B1 and in regulating a large number of genes that mediate HAEC activation and inflammation. These findings will lead to future development of novel therapeutics for cardiovascular diseases (CVD), inflammations, infections, transplantation, autoimmune disease and cancers. (total words: 284).
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http://dx.doi.org/10.1016/j.redox.2021.102142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487079PMC
September 2021

Construction of C-C Axial Chirality via Asymmetric Carbene Insertion into Arene C-H Bonds.

Angew Chem Int Ed Engl 2021 Oct 1. Epub 2021 Oct 1.

Changzhou University, School of Pharmaceutical Engineering and Life Science, NO. 1 Gehu Road, 213164, Changzhou, CHINA.

By using diazonaphthoquinones and anilines as key reagents and through a point-to-axis chiral transfer strategy, the atroposelective synthesis via asymmetric C(sp 2 )-H bond insertion reaction of arenes has been realized under rhodium catalysis, providing the resulting biaryl atropisomers in moderate to excellent yields with good enantiomeric ratios (up to 99:1). Further elaboration indicates this type of axially biaryl scaffold may have promising potentials in developing novel chiral ligands.
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http://dx.doi.org/10.1002/anie.202110430DOI Listing
October 2021

Application of combined cyanide sources in cyanation reactions.

Org Biomol Chem 2021 Oct 20;19(40):8646-8655. Epub 2021 Oct 20.

School of Petrochemical Engineering and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou 213164, P. R. China.

The cyanation reaction is a key transformation due to the wide-ranging applications of nitrile compounds in organic chemistry. Traditionally, the cyanation reaction employs metal cyanides as cyanide sources, which are toxic and environmentally unfriendly. Very recently, many excellent examples of using combined cyanide sources as cyanating agents have been reported. This review summarizes the applications of combined cyano-group sources in a variety of cyanation reactions.
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http://dx.doi.org/10.1039/d1ob01520fDOI Listing
October 2021

The role of Escherichia coli type III secretion system 2 chaperone protein ygeG in pathogenesis of avian pathogenic Escherichia coli.

Res Vet Sci 2021 Nov 10;140:203-211. Epub 2021 Sep 10.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, PR China. Electronic address:

The Escherichia coli type III secretion system 2 (ETT2) is present in most E. coli strains, carries a 29.9-kb ETT2 pathogenicity island (PAI) and is involved in the virulence of avian pathogenic Escherichia coli (APEC). A chaperone protein is essential for the bacterial secretion system, but the function of the ETT2 chaperone protein has not been determined. This study showed that ygeG had sequence homology with the identified bacterial chaperone protein and it possessed tetratri-copeptide repeats (TPR) containing protein. To investigate the role of ygeG in the ETT2 of APEC, ygeG mutant and complemented strains were constructed and characterized. Inactivation of ygeG had no effect on APEC growth, but significantly promoted biofilm formation, and the adherence to and invasion of DF-1 cells, especially the survival abilities in specific-pathogen-free (SPF) chicken sera serum. Analysis of the role of ygeG in chicken infection models revealed that the deletion of ygeG increased bacterial virulence. RNA Sequencing (RNA-Seq) analyses comparing the APEC wild type and the ygeG mutant indicated that multiple genes encoding biofilm formation, outer membrane proteins, fimbrial genes and virulence effector protein genes were regulated by ygeG. These results revealed the role of ygeG as a chaperone protein that affected the virulence and pathogenicity of APEC.
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http://dx.doi.org/10.1016/j.rvsc.2021.09.011DOI Listing
November 2021

Enzymatic recombinase amplification coupled with CRISPR-Cas12a for ultrasensitive, rapid, and specific Porcine circovirus 3 detection.

Mol Cell Probes 2021 Oct 9;59:101763. Epub 2021 Sep 9.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Shushan District West Yangtze River Road 130#, Hefei, 230036, Anhui Province, People's Republic of China. Electronic address:

Porcine circovirus type 3 (PCV3) is a disease associated with porcine dermatitis and nephrotic syndrome (PDNS) that has caused significant economic losses to swine herds since its discovery in 2016. To develop a simple, on-site, rapid, and sensitive assay to combat the spread of PCV3, we optimized the CRISPR/Cas12a (also known as Cpf1) system combined with enzymatic recombinase amplification (ERA) nucleic acid amplification to diagnose PCV3. The results showed that the ERA-CRISPR/Cas12a reaction could detect PCV3 within 1 h in genomic DNA harboring a minimum of seven copies. Additionally, we confirmed no cross-reactivity with PCV2, PCV4, or other porcine viruses, revealing the good specificity of this technique. These results demonstrated the ability of ERA-CRISPR/Cas12a to detect DNA at the single-molecule level and provide a rapid, simple, ultrasensitive, one-pot point-of-care test for PCV3 and suggest its potential for a variety of nucleic acid detection applications.
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http://dx.doi.org/10.1016/j.mcp.2021.101763DOI Listing
October 2021

Demonstration of an aggregated biomarker response approach to assess the impact of point and diffuse contaminant sources in feral fish in a small river case study.

Sci Total Environ 2021 Sep 1;804:150020. Epub 2021 Sep 1.

Department for Evolutionary Ecology and Environmental Toxicology, Goethe University, Max-von-Laue Straße 13, 60438 Frankfurt am Main, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), 60325 Frankfurt am Main, Germany. Electronic address:

The assessment of the exposure of aquatic wildlife to complex environmental mixtures of chemicals originating from both point and diffuse sources and evaluating the potential impact thereof constitutes a significant step towards mitigating toxic pressure and the improvement of ecological status. In the current proof-of-concept study, we demonstrate the potential of a novel Aggregated Biomarker Response (ABR) approach involving a comprehensive set of biomarkers to identify complex exposure and impacts on wild brown trout (Salmo trutta fario). Our scenario used a small lowland river in Germany (Holtemme river in the Elbe river catchment) impacted by two wastewater treatment plants (WWTP) and diffuse agricultural runoff as a case study. The trout were collected along a pollution gradient (characterised in a parallel study) in the river. Compared to fish from the reference site upstream of the first WWTP, the trout collected downstream of the WWTPs showed a significant increase in micronucleus formation, phase I and II enzyme activities, and oxidative stress parameters in agreement with increasing exposure to various chemicals. By integrating single biomarker responses into an aggregated biomarker response, the two WWTPs' contribution to the observed toxicity could be clearly differentiated. The ABR results were supported by chemical analyses and whole transcriptome data, which revealed alterations of steroid biosynthesis and associated pathways, including an anti-androgenic effect, as some of the key drivers of the observed toxicity. Overall, this combined approach of in situ biomarker responses complemented with molecular pathway analysis allowed for a comprehensive ecotoxicological assessment of fish along the river. This study provides evidence for specific hazard potentials caused by mixtures of agricultural and WWTP derived chemicals at sublethal concentrations. Using aggregated biomarker responses combined with chemical analyses enabled an evidence-based ranking of sites with different degrees of pollution according to toxic stress and observed effects.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150020DOI Listing
September 2021

Acute depletion of CTCF rewires genome-wide chromatin accessibility.

Genome Biol 2021 08 24;22(1):244. Epub 2021 Aug 24.

Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.

Background: The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription.

Results: Here, we systematically integrate multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, and CRISPR-Cas9 survival dropout screens, and time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewires genome-wide chromatin accessibility. Increased accessible chromatin regions are frequently located adjacent to CTCF-binding sites at promoter regions and insulator sites associated with enhanced transcription of nearby genes. In addition, we use CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners. We successfully identify 40 candidates, including multiple established partners. Interestingly, many CTCF co-regulators that have alterations of their respective downstream gene expression do not show changes of their own expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription.

Conclusions: This study highlights that CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation.
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http://dx.doi.org/10.1186/s13059-021-02466-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386078PMC
August 2021

Sublethal effects of organophosphorus insecticide phoxim on patch time allocation and oviposition behavior in a parasitoid wasp .

Bull Entomol Res 2021 Aug 24:1-10. Epub 2021 Aug 24.

Jiangsu Key Laboratory of Sericultural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang212018, PR China.

Parasitoid wasps are key agents for controlling insect pests in integrated pest management programs. Although many studies have revealed that the behavior of parasitic wasps can be influenced by insecticides, the strategies of patch time allocation and oviposition have received less attention. In the present study, we forced the endoparasitoid Meteorus pulchricornis to phoxim exposure at the LC30 and tested the foraging behavior within patches with different densities of the host, the larvae of the tobacco cutworm Spodoptera litura. The results showed that phoxim treatment can significantly increase the patch-leaving tendency of female wasps, while host density had no impact. The number of oviposition and the number of previous patch visits also significantly influenced the patch time allocation decisions. The occurrence of oviposition behavior was negatively affected by phoxim exposure; however, progeny production was similar among patches with different host densities. Phoxim exposure shaped the offspring fitness correlates, including longer durations from cocoon to adult wasps, smaller body size, and shorter longevity. The findings of the present study highlight the sublethal effects that reduce the patch residence time and the fitness of parasitoid offspring, suggesting that the application of phoxim in association with M. pulchricornis should be carefully schemed in agroecosystems.
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http://dx.doi.org/10.1017/S0007485321000614DOI Listing
August 2021

Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators.

Front Cardiovasc Med 2021 22;8:713170. Epub 2021 Jul 22.

Centers for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.

To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum-MT, MT fusion, autophagosome-lysosome fusion, and autophagosome/endosome-lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome-lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)-MT contact, ER- plasma membrane (PM) junction, autophagosome/endosome-lysosome fusion, sarcoplasmic reticulum-MT, autophagosome-endosome/lysosome fusion, and ER-Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4CD25 T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.
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http://dx.doi.org/10.3389/fcvm.2021.713170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339352PMC
July 2021

Ovarian Metastasis by Gastric-type Endocervical Adenocarcinoma: A Clinicopathologic Description of 12 Cases.

Int J Gynecol Pathol 2021 Aug 4. Epub 2021 Aug 4.

Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province (B.L.) Departments of Surgical Pathology (B.L., H.S., Y.S.) Gynecologic Oncology (J.X.), Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Cervical gastric-type adenocarcinoma has a propensity for ovarian metastasis, but the clinicopathologic findings and possible routes of tumor spread have not been well characterized to date. To address these points, we reported 12 cervical gastric-type adenocarcinomas with ovarian metastases from a single institution. Seven patients with gastric-type adenocarcinoma had concurrent endometrial fallopian tube involvement, 5 of which showed tumors confined to the fallopian tube mucosa. Two of these 5 patients died of disease at 2 and 16 mo, and 1 recurred at 18 mo. In the remaining 5 patients, 3 had wide pelvic/peritoneal spread while the other 2 showed no evidence of uterine or tubal involvement. Among them, 1 died of disease at 94 mo, and another relapsed at 20 mo. Morphologically, ovarian tumors frequently had surface involvement consistent with metastasis, but also mimicked a primary tumor with a mixture of benign/borderline/intraepithelial carcinoma-like areas, as well as carcinoma with expansile or destructive stromal invasion. The tubal lesions were predominantly in the form of mucosal colonization without invasion of the underlying structures. Block p16 and high-risk human papillomavirus mRNA signals were not detected in cervical gastric-type adenocarcinomas and ovarian metastatic tumors. We conclude that fallopian tube spread may be associated with ovarian metastasis of cervical gastric-type adenocarcinomas that have bad clinical outcomes. Ovarian involvement may be a part of the aggressive nature of these tumors.
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http://dx.doi.org/10.1097/PGP.0000000000000815DOI Listing
August 2021

miR-148a-3p silences the CANX/MHC-I pathway and impairs CD8 T cell-mediated immune attack in colorectal cancer.

FASEB J 2021 08;35(8):e21776

Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China.

Nonresponse, or acquired resistance to immune checkpoint inhibitors in colorectal cancer (CRC) highlight the importance of finding potential tolerance mechanisms. Low expression of major histocompatibility complex, class I (MHC-I) on the cell surface of the tumor is one of the main mechanisms of tumor escape from T-cell recognition and destruction. In this study, we demonstrated that a high level of calnexin (CANX) in the tumors is positively correlated with the overall survival in colorectal cancer patients. CANX is a chaperone protein involved in the folding and assembly of MHC-I molecules. Using miRNA target prediction databases and luciferase assays, we identified miR-148a-3p as a potential regulator of CANX. Inhibition of miR-148a-3p restores surface levels of MHC-I and significantly enhanced the effects of CD8 T-cell-mediated immune attack in vitro and in vivo by promoting CANX expression. These results reveal that miR-148a-3p can function as a tumor promotor in CRC by targeting the CANX/MHC-I axis, which provides a rationale for immunotherapy through targeting the miR-148a-3p/CANX/MHC-I pathway in patients with CRC.
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http://dx.doi.org/10.1096/fj.202100235RDOI Listing
August 2021

Particle-bound PAHs induced glucose metabolism disorders through HIF-1 pathway.

Sci Total Environ 2021 Nov 20;797:149132. Epub 2021 Jul 20.

Key Laboratory of the Three Gorges Reservoir Eco-environment, Ministry of Education, Chongqing University, 174 Shazheng Road Shapingba, 400045 Chongqing, China. Electronic address:

Vehicle exhaust, as one of the most important compositions of air pollution, induced various adverse health effects, especially diabetes, on human beings. Even though monitoring and epidemiological data indicates that particle-bound polycyclic aromatic hydrocarbons (PAHs) is an inducing factor of diabetes, the specific causative mechanisms are still unclear. In the current study, the concentration of particulate matters (PMs, including PM, PM and PM) and PAHs was investigated at rush hour of weekday in three urban underground parking garages (UPGs). To evaluate the impacts of particle-bound PAHs on human beings, analysis of non-target metabolomics and unmetabolized PAHs were conducted for UPG and non-UPG worker urine samples. The results showed that the highest concentrations of PMs and total PAHs were found at the UPG entrance. The concentrations of unmetabolized 5-6 rings PAHs in the UPG worker urine were significantly higher than that in non-UPG worker urine samples, which induced glucose metabolism disorders through hypoxia-inducible factor 1 (HIF-1) signaling pathway. This could be a reason for particle-bound PAHs induced-diabetes on road workers, drivers and garage staff. These findings can serve as a step towards air pollution management and the pathological mechanism analysis of environmental factor induced-diseases.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149132DOI Listing
November 2021

Transcriptional response of detoxifying enzyme genes in Bombyx mori under chlorfenapyr exposure.

Pestic Biochem Physiol 2021 Aug 10;177:104899. Epub 2021 Jun 10.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, PR China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, PR China. Electronic address:

The silkworm, Bombyx mori (B. mori) is an important economic insect which ingests mulberry leaves and products the silk in industry. Chlorfenapyr is a new halogenated pyrrole insecticide which has been promoted for the control of mulberry insect pests in China. However, the detoxification mechanism of the silkworm to chlorfenapyr has not been investigated yet. In the present study, we first estimated the LC dose of chlorfenapyr for 3rd instar B. mori larvae, and then, in order to characterise the chlorfenapyr detoxification mechanism, the transcriptomes of chlorfenapyr-treated and untreated 3rd instar B. mori larvae were compared using RNA-sequencing. In total, 146, 533, 126 and 148, 957, 676 clean reads were obtained from insecticide-treated and control silkworm larvae, respectively, and these reads generated 10, 954 genes. The transcriptional profile of silkworm larvae was significantly influenced by chlorfenapyr treatment. A total of 1196 differentially expressed genes (DEGs) were identified in insecticide-treated and control B. mori larvae, in which 644 genes were upregulated and 552 genes were downregulated. Results showed that multiple DEGs were enriched in detoxication-related gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Eleven detoxifying enzyme genes which differentially expressed were screened, and their expression patterns were validated by qRT-PCR. Furthermore, we successfully knocked down all differentially upregulated detoxifying enzyme genes, and a bioassay showed that the mortality of chlorfenapyr-treated silkworm larvae was significantly higher after silencing these genes than in groups injected with dsGFP. The present study reveals the molecular basis of silkworm detoxification to chlorfenapyr exposure, and provides new insights into the management of insecticide damage in the silkworm.
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http://dx.doi.org/10.1016/j.pestbp.2021.104899DOI Listing
August 2021

Endothelial Immunity Trained by Coronavirus Infections, DAMP Stimulations and Regulated by Anti-Oxidant NRF2 May Contribute to Inflammations, Myelopoiesis, COVID-19 Cytokine Storms and Thromboembolism.

Front Immunol 2021 25;12:653110. Epub 2021 Jun 25.

Centers of Cardiovascular Research, Inflammation, Translational & Clinical Lung Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States.

To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19). The expressions of IGs are modulated in 21 human EC transcriptomic datasets by various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia and oxLDL. Upregulation of many IGs such as nucleic acid sensors are shared between ECs infected by MERS-CoV and those stimulated by PAMPs and DAMPs. Human heart EC and mouse aortic EC express all four types of coronavirus receptors such as ANPEP, CEACAM1, ACE2, DPP4 and virus entry facilitator TMPRSS2 (heart EC); most of coronavirus replication-transcription protein complexes are expressed in HMEC, which contribute to viremia, thromboembolism, and cardiovascular comorbidities of COVID-19. ECs have novel trained immunity (TI), in which subsequent inflammation is enhanced. Upregulated proinflammatory cytokines such as TNFα, IL6, CSF1 and CSF3 and TI marker IL-32 as well as TI metabolic enzymes and epigenetic enzymes indicate TI function in HMEC infected by MERS-CoV, which may drive cytokine storms. Upregulated CSF1 and CSF3 demonstrate a novel function of ECs in promoting myelopoiesis. Mechanistically, the ER stress and ROS, together with decreased mitochondrial OXPHOS complexes, facilitate a proinflammatory response and TI. Additionally, an increase of the regulators of mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis in ECs infected with MERS-CoV and the upregulation of pro-thrombogenic factors increase thromboembolism potential. Finally, NRF2-suppressed ROS regulate innate immune responses, TI, thrombosis, EC inflammation and death. These transcriptomic results provide novel insights on the roles of ECs in coronavirus infections such as COVID-19, cardiovascular diseases (CVD), inflammation, transplantation, autoimmune disease and cancers.
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http://dx.doi.org/10.3389/fimmu.2021.653110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269631PMC
August 2021

Copper-Catalyzed Tandem Cross-Coupling and Alkynylogous Aldol Reaction: Access to Chiral Exocyclic α-Allenols.

Org Lett 2021 07 17;23(13):5175-5179. Epub 2021 Jun 17.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China.

An enantioselective copper-catalyzed tandem cross-coupling/alkynylogous aldol reaction has been developed. The tetrasubstituted allenoates containing both central and axial chirality have been obtained in moderate to good yields and excellent enantio- and diastereoselectivity. Distinct from the previous use of Cu(I) salts, this protocol features the use of copper(II) salts as a catalytic precursor in this asymmetric cross-coupling reaction.
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http://dx.doi.org/10.1021/acs.orglett.1c01712DOI Listing
July 2021

[Retracted] Additive effects of eukaryotic co‑expression plasmid carrying GRIM‑19 and LKB1 genes on breast cancer and .

Mol Med Rep 2021 Aug 16;24(2). Epub 2021 Jun 16.

Department of Cosmetology Plastic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data featured in Figs. 1C and 4C, and tumour images in Fig. 5A, were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 12: 7665‑7672, 2015; DOI: 10.3892/mmr.2015.4393].
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http://dx.doi.org/10.3892/mmr.2021.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222962PMC
August 2021

Canonical Secretomes, Innate Immune Caspase-1-, 4/11-Gasdermin D Non-Canonical Secretomes and Exosomes May Contribute to Maintain Treg-Ness for Treg Immunosuppression, Tissue Repair and Modulate Anti-Tumor Immunity ROS Pathways.

Front Immunol 2021 18;12:678201. Epub 2021 May 18.

Centers for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.

We performed a transcriptomic analyses using the strategies we pioneered and made the following findings: Normal lymphoid Tregs, diseased kidney Tregs, splenic Tregs from mice with injured muscle have 3, 17 and 3 specific (S-) pathways, respectively; Tumor splenic Tregs share 12 pathways with tumor Tregs; tumor splenic Tregs and tumor Tregs have 11 and 8 S-pathways, respectively; Normal and non-tumor disease Tregs upregulate some of novel 2641 canonical secretomic genes (SGs) with 24 pathways, and tumor Tregs upregulate canonical secretomes with 17 pathways; 4) Normal and non-tumor disease tissue Tregs upregulate some of novel 6560 exosome SGs with 56 exosome SG pathways (ESP), tumor Treg ESP are more focused than other Tregs; 5) Normal, non-tumor diseased Treg and tumor Tregs upregulate some of novel 961 innate immune caspase-1 SGs and 1223 innate immune caspase-4 SGs to fulfill their tissue/SG-specific and shared functions; Most tissue Treg transcriptomes are controlled by Foxp3; and Tumor Tregs had increased Foxp3 non-collaboration genes with ROS and 17 other pathways; Immune checkpoint receptor PD-1 does, but CTLA-4 does not, play significant roles in promoting Treg upregulated genes in normal and non-tumor disease tissue Tregs; and tumor splenic and tumor Tregs have certain CTLA-4-, and PD-1-, non-collaboration transcriptomic changes with innate immune dominant pathways; Tumor Tregs downregulate more immunometabolic and innate immune memory (trained immunity) genes than Tregs from other groups; and ROS significantly regulate Treg transcriptomes; and ROS-suppressed genes are downregulated more in tumor Tregs than Tregs from other groups. Our results have provided novel insights on the roles of Tregs in normal, injuries, regeneration, tumor conditions and some of canonical and innate immune non-canonical secretomes ROS-regulatory mechanisms and new therapeutic targets for immunosuppression, tissue repair, cardiovascular diseases, chronic kidney disease, autoimmune diseases, transplantation, and cancers.
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http://dx.doi.org/10.3389/fimmu.2021.678201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168470PMC
May 2021

Eugenol-chitosan nanoemulsion as an edible coating: Its impact on physicochemical, microbiological and sensorial properties of hairtail (Trichiurus haumela) during storage at 4 °C.

Int J Biol Macromol 2021 Jul 28;183:2199-2204. Epub 2021 May 28.

College of Food Science and Technology, Hainan Tropical Ocean University, Sanya 572022, China. Electronic address:

Effects of the eugenol-chitosan nanoemulsion as an edible coating on the quality of hairtail (Trichiurus haumela) during storage at 4 °C were evaluated. For all samples, such parameters as pH, thiobarbituric acid (TBA), total volatile basic nitrogen (TVB-N), water holding capacity (WHC), electrical conductivity (EC), total bacteria count (TVC) and sensory were examined periodically. The results demonstrated that eugenol-chitosan nanoemulsion coating showed better preservative effects than chitosan nanoemulsion alone. Therefore, a coating based on eugenol-chitosan nanoemulsion could be regarded as an effective food-grade biopreservative to maintain the quality of hairtail fish and prolong its shelf life during chilled storage.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.183DOI Listing
July 2021

Chemo- and Enantioselective Insertion of Furyl Carbene into the N-H Bond of 2-Pyridones.

Angew Chem Int Ed Engl 2021 Jul 29;60(31):16942-16946. Epub 2021 Jun 29.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, 1 Gehu Road, 213164, Changzhou, China.

Asymmetric carbene insertion reactions represent one of the most important protocols to construct carbon-heteroatom bonds. The use of donor-acceptor diazo compounds bearing an ester group is however a prerequisite for achieving high enantioselectivity. Herein, we report a chemo- and enantioselective formal N-H insertion of 2-pyridones that has been accomplished for the first time with enynones as the donor-donor carbene precursors. DFT calculations indicate an unprecedented enantioselective 1,4-proton transfer from O to C. The rhodium catalyst provides a chiral pocket in which the steric repulsion and the π-π interaction of the propeller ligand play a critical role in determining the selectivities.
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http://dx.doi.org/10.1002/anie.202104708DOI Listing
July 2021

Evidence of increased estrogenicity upon metabolism of Bisphenol F - Elucidation of the key metabolites.

Sci Total Environ 2021 Sep 11;787:147669. Epub 2021 May 11.

Department of Ecosystem Analysis, Institute for Environmental Research (Biology V), ABBt - Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; Ruhr District Institute of Hygiene, Rotthauser Str. 21, 45879 Gelsenkirchen, Germany. Electronic address:

The increasing concern over bisphenol A (BPA) has directed much attention toward bisphenol F (BPF) and bisphenol S (BPS) as BPA alternatives for the development of "BPA-free" products. Consequently, BPS and BPF were frequently detected in surface water, sediment, sewage effluent, indoor dust, and even in food and biological fluids in humans. Thus, environmental researches start to focus on the potential environmental risks of BPA alternatives. While the estrogenically active metabolites and the specific estrogenically active structure are still unknown. In this study, the MTT assay on acute cytotoxicity and the recombinant transactivation assay were carried out to determine whether BPF and BPS are suitable alternatives to BPA. Our results show that the cytotoxic and estrogenic activities of BPS and BPF are lower than those of BPA. However, after the addition of a rat liver homogenate to simulate mammal metabolism, BPF exhibited higher estrogenic activity than BPA. To identify the chemical structures and estrogen receptor binding affinities of active estrogenic metabolites, LC-MS, MetaPrint2D(-React), and VirtualToxLab were integrated. The observed results indicated that the para-hydroxylated BPF and BPF-OCH might have strong ER binding affinities. These results demonstrate that metabolization is important to consider upon investigating endocrine disruption of chemicals getting into contact with humans, such as in dental sealing or food packaging. Alternatives to potentially hazardous substances should be thoroughly tested prior to use.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147669DOI Listing
September 2021

HDAC6 suppresses microRNA-199a transcription and augments HPV-positive cervical cancer progression through Wnt5a upregulation.

Int J Biochem Cell Biol 2021 07 29;136:106000. Epub 2021 Apr 29.

Department of Oncology Radiotherapy, Huizhou Central People's Hospital, Huizhou, 516000, Guangdong, PR China.

High-risk human papillomavirus (HR-HPV) infection is a major risk factor for the initiation and progression of cervical cancer (CC). This study aimed to explore the role of histone deacetylase 6 (HDAC6) in HPV-positive CC and the molecules implicated. Differentially expressed genes between HPV-positive and HPV-negative tissues, and differentially expressed microRNAs (miRNAs) in cells after HDAC6 downregulation were identified using microarray analyses. The expression profiles of HDAC6 and miR-199a and their cellular functions were investigated via loss-of-function studies. Xenograft tumors were induced in mice for in vivo studies. HDAC6 and Wnt5a were highly expressed, whereas miR-199a was poorly expressed in HPV-positive CC tissues. Downregulation of HDAC6 reduced proliferation, migration, invasion, and resistance to apoptosis of HPV-positive CC cells. HDAC6 suppressed the transcription of miR-199a, and miR-199a targeted Wnt5a to inactivate the Wnt signaling pathway. Further downregulation of miR-199a blocked the inhibitory effect of HDAC6 silencing on CC cell growth both in vivo and in vitro, whereas further artificial inhibition of Wnt5a inactivated Wnt signaling and blocked the malignant behaviors of CC cells. This study showed that HDAC6 suppresses the transcription of miR-199a and enhances the progression of HPV-positive cervical cancer through upregulation of Wnt5a.
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http://dx.doi.org/10.1016/j.biocel.2021.106000DOI Listing
July 2021

Complete Genetic Analysis of Plasmids Carrying and Other Resistance Genes in Avian Pathogenic Escherichia coli Isolates from Diseased Chickens in Anhui Province in China.

mSphere 2021 04 14;6(2). Epub 2021 Apr 14.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control College of Animal Science and Technology, Anhui Agricultural University, Hefei, China

Antimicrobial resistance associated with colistin has emerged as a significant concern worldwide, threatening the use of one of the most important antimicrobials for treating human disease. This study aimed to investigate the prevalence of colistin-resistant avian-pathogenic (APEC) and shed light on the possibility of transmission of (mobilized colistin resistance)-positive APEC. A total of 72 APEC isolates from Anhui Province in China were collected between March 2017 and December 2018 and screened for the gene. Antimicrobial susceptibility testing was performed using the broth dilution method. Pulsed-field gel electrophoresis, Southern blot analysis, and conjugation assay were performed to determine the location and conjugative ability of the gene. Whole-genome sequencing and analysis were performed using Illumina MiSeq and Nanopore MinION platforms. Three APEC isolates (AH25, AH62, and AH65) were found to be positive for the gene and showed multidrug resistance. The genes were located on IncI2 plasmids, and conjugation assays revealed that these plasmids were transferrable. Notably, strains AH62 and AH65, both belonging to ST1788, were collected from different places but carried the same drug resistance genes and shared highly similar plasmids. This study highlights the potential for a possible epidemic of -positive APEC and the urgent need for continuous active monitoring. In this study, three plasmids carrying were isolated and characterized from APEC isolates from Anhui Province in China. The genes were located on IncI2 plasmids, and these plasmids were transferrable. These three IncI2 plasmids had high homology with the plasmids harbored by pathogenic bacteria isolated from other species. This finding showed that IncI2 plasmids poses a risk for the exchange of genetic material between different niches. Although colistin has been banned for use in food-producing animals in China, the coexistence of the broad-spectrum β-lactamase and genes on a plasmid can also lead to the stable existence of genes. The findings illustrated the need to improve the monitoring of drug resistance in poultry systems so as to curb the transmission or persistence of multidrug-resistant bacteria.
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http://dx.doi.org/10.1128/mSphere.01135-20DOI Listing
April 2021

A cascade and heterogeneous neural network for CT pulmonary nodule detection and its evaluation on both phantom and patient data.

Comput Med Imaging Graph 2021 06 4;90:101889. Epub 2021 Mar 4.

Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Screening of pulmonary nodules in computed tomography (CT) is crucial for early diagnosis and treatment of lung cancer. Although computer-aided diagnosis (CAD) systems have been designed to assist radiologists to detect nodules, fully automated detection is still challenging due to variations in nodule size, shape, and density. In this paper, we first propose a fully automated nodule detection method using a cascade and heterogeneous neural network trained on chest CT images of 12155 patients, then evaluate the performance by using phantom (828 CT images) and clinical datasets (2640 CT images) scanned with different imaging parameters. The nodule detection network employs two feature pyramid networks (FPNs) and a classification network (BasicNet). The first FPN is trained to achieve high sensitivity for nodule detection, and the second FPN refines the candidates for false positive reduction (FPR). Then, a BasicNet is combined with the second FPR to classify the candidates into either nodules or non-nodules for the final refinement. This study investigates the performance of nodule detection of solid and ground-glass nodules in phantom and patient data scanned with different imaging parameters. The results show that the detection of the solid nodules is robust to imaging parameters, and for GGO detection, reconstruction methods "iDose4-YA" and "STD-YA" achieve better performance. For thin-slice images, higher performance is achieved across different nodule sizes with reconstruction method "iDose4-STD". For 5 mm slice thickness, the best choice is the reconstruction method "iDose4-YA" for larger nodules (>5 mm). Overall, the reconstruction method "iDose4-YA" is suggested to achieve the best balanced results for both solid and GGO nodules.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101889DOI Listing
June 2021

The challenge of micropollutants in surface water of the Yangtze River.

Sci Total Environ 2021 Aug 18;780:146537. Epub 2021 Mar 18.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, College of Environment and Ecology, Chongqing University, Chongqing 400030, PR China. Electronic address:

The Yangtze River, the third largest river and supporting nearly one-third of Chinese population, has been severely polluted in recent decades. Among the numerous pollutants, organic micropollutants, as one kind of important emerging contaminants, are currently key contaminants of concern. However, few studies have focused on their mixture environmental impacts, especially for the complex environmental mixtures. In the current study, four categories of organic micropollutants, including 16 polycyclic aromatic hydrocarbons (PAHs), 32 polychlorinated biphenyls (PCBs), 27 organochlorine pesticides (OCPs) and 20 pharmaceutical and personal care products (PPCPs) are analyzed in 10 study sites on the Yangtze River. Subsequently, comprehensive risk assessment for micropollutant mixtures was conducted by risk quotient based on the sum of PEC/PNEC values (RQ) and risk quotient based on the toxic units (RQ). The mixture risk evaluation based on the detected environmental concentrations indicates that micropollutant mixtures in surface water of the Yangtze River exhibited relative high risks for aquatic organisms. The observed results revealed that mixture risk assessments have to consider the complexity of environmental samples; PCBs dominated main mixture risks in the upper stream; PAHs contributed major comprehensive risks in the middle stream; and OCPs were the key micropollutants in the downstream. The outcomes of the present study here can serve for pollution control in the Yangtze River, which provide the scientific underpinnings and regulatory reference for risk management and river protection.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146537DOI Listing
August 2021

Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.

Acta Pharmacol Sin 2021 Mar 25. Epub 2021 Mar 25.

Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.
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http://dx.doi.org/10.1038/s41401-021-00632-5DOI Listing
March 2021

An artificial-intelligence lung imaging analysis system (ALIAS) for population-based nodule computing in CT scans.

Comput Med Imaging Graph 2021 04 11;89:101899. Epub 2021 Mar 11.

Shanghai United Imaging Intelligence Co. Ltd, Shanghai, China. Electronic address:

Computed tomography (CT) screening is essential for early lung cancer detection. With the development of artificial intelligence techniques, it is particularly desirable to explore the ability of current state-of-the-art methods and to analyze nodule features in terms of a large population. In this paper, we present an artificial-intelligence lung image analysis system (ALIAS) for nodule detection and segmentation. And after segmenting the nodules, the locations, sizes, as well as imaging features are computed at the population level for studying the differences between benign and malignant nodules. The results provide better understanding of the underlying imaging features and their ability for early lung cancer diagnosis.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101899DOI Listing
April 2021
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