Publications by authors named "Tao Sheng"

79 Publications

Strategies for Browning Agent Delivery.

Pharm Res 2021 Aug 16;38(8):1327-1334. Epub 2021 Aug 16.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Obesity expands as a global climbing epidemic that is often correlated to cardiovascular diseases and endocrine disorders. Converting white adipocytes to brown adipocytes for enhanced energy expenditure has recently emerged as a promising anti-obesity treatment. However, the conventional approaches to apply browning agents systematically suffer from off-target effects, multiple dosage requirements, and poor patient compliance. To date, various delivery strategies have been reported to deliver browning agents for obesity treatment in a safer and more controllable manner. This review will discuss the latest designs in browning agent delivery systems with a focus on nanomedicines and transdermal patches.
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http://dx.doi.org/10.1007/s11095-021-03081-1DOI Listing
August 2021

Microneedle-Mediated Vaccination: Innovation and Translation.

Adv Drug Deliv Rev 2021 Aug 8:113919. Epub 2021 Aug 8.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Zhejiang Laboratory of Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311121, China; MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address:

Vaccine administration by subcutaneous or intramuscular injection is the most commonly prescribed route for inoculation, however, it is often associated with some deficiencies such as low compliance, high professionalism, and risk of infection. Therefore, the application of microneedles for vaccine delivery has gained widespread interests in the past few years due to its high compliance, minimal invasiveness, and convenience. This review focuses on recent advances in the development and application of microneedles for vaccination based on different delivery strategies, and introduces the current status of microneedle-mediated vaccination in clinical translation. The prospects for its application including opportunities and challenges are further discussed.
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http://dx.doi.org/10.1016/j.addr.2021.113919DOI Listing
August 2021

Melatonin and Its Homologs Induce Immune Responses Receptors trP47363-trP13076 in .

Front Plant Sci 2021 30;12:691835. Epub 2021 Jun 30.

Key Laboratory of Monitoring and Management of Crop Diseases and Pest Insects, Department of Plant Pathology, College of Plant Protection, Ministry of Education, Nanjing Agricultural University, Nanjing, China.

Melatonin (N-acetyl-5-methoxytryptamine), a naturally occurring small molecule, can protect plants against abiotic stress after exogenous treatmenting with it. It is not known if melatonin homologs, such as 5-methoxytryptamine and 5-methoxyindole, that are easy and more cost-effective to synthesize can stimulate the plant immune system in the same manner as melatonin. In the present study, we assessed the biological activity of the melatonin homologs, 5-methoxytryptamin and 5-methoxyindole. The results showed that melatonin and its homologs all induced disease resistance against in plants. The application of all three compounds also induced stomatal closure and the production of reactive oxygen species. Gene expression analysis indicated that the expression of genes involved in hydrogen peroxide (HO), nitric oxide (NO) production, and salicylic acid (SA) biosynthesis was significantly upregulated by all three compounds. Four homologs of the melatonin receptors were identified by blasting search with the phytomelatonin receptor in . Molecular docking studies were also used to identify four putative melatonin receptors in . Further experimentation revealed that silencing of the melatonin receptors trP47363 and trP13076 in compromised the induction of stomatal closure, gene expression and SA accumulation by all three compounds. Collectively, our data indicate that the induction of defense responses in by melatonin, 5-methoxytryptamine, and 5-methoxyindole involves the melatonin receptors trP47363 and trP13076.
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http://dx.doi.org/10.3389/fpls.2021.691835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278317PMC
June 2021

A novel 3D-printed multi-driven system for large-scale neurophysiological recordings in multiple brain regions.

J Neurosci Methods 2021 09 7;361:109286. Epub 2021 Jul 7.

Department of Neurology, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Science Center for Brain Science, Shanghai Medical School of Fudan University, Shanghai 200032, China; MOE Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu Province 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China. Electronic address:

Background: Electrical probes have been widely used for recording single-unit spike activity and local field potentials (LFPs) in brain regions. However, setting up an easily-assembled large-scale recording in multiple brain regions for long-term and stable neural activity monitoring is still a hard task.

New Method: We established a novel 3D-printed multi-drive system with high-density (up to 256 channels) tetrodes/grid electrodes that enables us to record cortical and subcortical brain regions in freely behaving animals.

Results: In this paper, we described the design and fabrication of this system in detail. By using this system, we obtained successful recording on both spikes and LFPs from seven distinct brain regions that are related to memory function.

Comparision With Existing Methods: The low cost, large-scale electrodes with small size and flexible 3D-printed design of the system allow us to implant assembled tetrodes or grid electrodes into multiple target brain areas.

Conclusions: The 3D-printed large-scale multi-drive platform we described here may serve as a powerful new tool for future studies of brain circuitry functions.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109286DOI Listing
September 2021

Discovery and preliminary mechanism of 1-carbamoyl β-carbolines as new antifungal candidates.

Eur J Med Chem 2021 Oct 2;222:113563. Epub 2021 Jun 2.

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. Electronic address:

Natural β-carboline alkaloids are ideal models for the discovery of pharmaceutically important entities. Various 1-substituted β-carbolines were synthesized from commercially inexpensive tryptophan and demonstrated significant in vitro antifungal activity against G. graminis. Significantly, compound 4m (EC = 0.45 μM) with carboxamide at 1-position displayed the best efficacy and nearly 20 folds enhancement in antifungal potential compared to Silthiopham (EC = 8.95 μM). Moreover, compounds 6, 7, and 4i exhibited excellent in vitro antifungal activities and in vivo protective and curative activities against B. cinerea and F. graminearum. Preliminary mechanism studies revealed that compound 4m caused reactive oxygen species accumulation, cell membrane destruction, and deregulation of histone acetylation. These findings indicated that 1-carbamoyl β-carboline can be selected as a promising model for the discovery of novel and broad-spectrum fungicide candidates.
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http://dx.doi.org/10.1016/j.ejmech.2021.113563DOI Listing
October 2021

Serotonin 2 Receptors, Agomelatine, and Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease.

Behav Neurol 2021 31;2021:5533827. Epub 2021 Mar 31.

Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong Province, China.

There are nearly 50 million Alzheimer's disease (AD) patients worldwide, 90% of whom develop behavioral and psychological symptoms of dementia (BPSD), which increase the mortality rate of patients, and impose an economic and care burden on families and society. As a neurotransmitter and neuromodulator, serotonin is involved in the regulation of psychoemotional, sleep, and feeding functions. Accumulating data support the importance of serotonin in the occurrence and development of BPSD. Studies have shown that reduction of serotonin receptors can increase depression and mental symptoms in AD patients. At present, there is no drug treatment for AD approved by the US Food and Drug Administration. Among them, agomelatine, as a new type of antidepressant, can act on serotonin 2 receptors to improve symptoms such as depression and anxiety. At present, research on BPSD is still in the preliminary exploratory stage, and there are still a lot of unknowns. This review summarizes the relationship between serotonin 2 receptors, agomelatine, and BPSD. It provides a new idea for the study of the pathogenesis and treatment of BPSD.
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http://dx.doi.org/10.1155/2021/5533827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026319PMC
August 2021

An innovative role for luteolin as a natural quorum sensing inhibitor in Pseudomonas aeruginosa.

Life Sci 2021 Jun 10;274:119325. Epub 2021 Mar 10.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China. Electronic address:

Aims: The emergence of antibiotic tolerance was a tricky problem in the treatment of chronic Pseudomonas aeruginosa-infected cystic fibrosis and burn victims. The quorum sensing (QS) inhibitor may serve as a new tactic for the bacterial resistance by inhibiting the biofilm formation and the production of virulence factors. This study explored the potential of luteolin as a QS inhibitor against P. aeruginosa and the molecular mechanism involved.

Main Methods: Crystal violet staining, CLSM observation, and SEM analysis were carried out to assess the effect of luteolin on biofilm formation. The motility assays and the production of virulence factors were determined to evaluate the QS-inhibitory activity of luteolin. Acyl-homoserine lactone, RT-PCR, and molecular docking assays were conducted to explain its anti-QS mechanisms.

Key Findings: The biofilm formation, the production of virulence factors, and the motility of P. aeruginosa could be efficiently inhibited by luteolin. Luteolin could also attenuate the accumulation of the QS-signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) (P < 0.01) and downregulate the transcription levels of QS genes (lasR, lasI, rhlR, and rhlI) (P < 0.01). Molecular docking analysis indicated that luteolin had a greater docking affinity with LasR regulator protein compared with OdDHL.

Significance: This study is important as it reports the molecular mechanisms involved in the anti-biofilm formation activity of luteolin against P. aeruginosa. This study also indicated that luteolin could be helpful when used for the treatment of clinical drug-resistant infections of P. aeruginosa.
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http://dx.doi.org/10.1016/j.lfs.2021.119325DOI Listing
June 2021

Discovery of Acyl-sulfonamide Na1.7 Inhibitors GDC-0276 and GDC-0310.

J Med Chem 2021 03 8;64(6):2953-2966. Epub 2021 Mar 8.

Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

Na1.7 is an extensively investigated target for pain with a strong genetic link in humans, yet in spite of this effort, it remains challenging to identify efficacious, selective, and safe inhibitors. Here, we disclose the discovery and preclinical profile of GDC-0276 () and GDC-0310 (), selective Na1.7 inhibitors that have completed Phase 1 trials. Our initial search focused on close-in analogues to early compound . This resulted in the discovery of GDC-0276 (), which possessed improved metabolic stability and an acceptable overall pharmacokinetics profile. To further derisk the predicted human pharmacokinetics and enable QD dosing, additional optimization of the scaffold was conducted, resulting in the discovery of a novel series of N-benzyl piperidine Na1.7 inhibitors. Improvement of the metabolic stability by blocking the labile benzylic position led to the discovery of GDC-0310 (), which possesses improved Na selectivity and pharmacokinetic profile over .
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http://dx.doi.org/10.1021/acs.jmedchem.1c00049DOI Listing
March 2021

Manganese Catalyzed Direct Amidation of Esters with Amines.

J Org Chem 2021 02 7;86(3):2339-2358. Epub 2021 Jan 7.

School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, North Fourth Road, Shihezi, Xinjiang 832003, People's Republic of China.

The transition metal catalyzed amide bond forming reaction of esters with amines has been developed as an advanced approach for overcoming the shortcomings of traditional methods. The broad scope of substrates in transition metal catalyzed amidations remains a challenge. Here, a manganese(I)-catalyzed method for the direct synthesis of amides from a various number of esters and amines is reported with unprecedented substrate scope using a low catalyst loading. A wide range of aromatic, aliphatic, and heterocyclic esters, even in fatty acid esters, reacted with a diverse range of primary aryl amines, primary alkyl amines, and secondary alkyl amines to form amides. It is noteworthy that this approach provides the first example of the transition metal catalyzed amide bond forming reaction from fatty acid esters and amines. The acid-base mechanism for the manganese(I)-catalyzed direct amidation of esters with amines was elucidated by DFT calculations.
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http://dx.doi.org/10.1021/acs.joc.0c02478DOI Listing
February 2021

Achieving Universal Wearing of Face Masks During the COVID-19 Pandemic: A Practical Solution from Shanghai, China.

Risk Manag Healthc Policy 2020 21;13:3067-3077. Epub 2020 Dec 21.

School of Public Health, Fudan University, Shanghai 200032, People's Republic of China.

Background: Face masks are basic protective equipment for preventing respiratory infectious diseases. The measures to properly dispose of and allocate face masks during the early stage of an epidemic caused by respiratory infectious diseases deserve worldwide attention.

Methods: A qualitative research approach was used to document the practice of a citywide face mask-wearing strategy of the Shanghai Municipal Government (called the "Shanghai solution" in this article). Based on data from government work documents, an online face mask-allocation and sales system was built to offer real-time updates of face-mask appointments and sales information in all designated pharmacies and neighborhood committees in Shanghai.

Results: In the Shanghai solution, a total of 24.8 million residents in 6,031 committees were covered, in order to achieve universal wearing of face masks during the COVID-19 crisis. Up to 110 million face masks were dispensed to residents in six rounds of face-mask allocation during February to April. This practical experience in Shanghai solved two key problems (insufficient face-mask capacity, protection of vulnerable population) with the supply of face masks by addressing four essential characteristics: overall coordination, on-demand distribution, efficient distribution, and technical support.

Conclusion: The practice of the citywide face mask-supply strategy of Shanghai could provide several pointers for management of a shortage of emergency materials, dispatch, and transport to other countries during the pandemic.
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http://dx.doi.org/10.2147/RMHP.S280672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762766PMC
December 2020

CaMKKβ regulates proliferation, apoptosis, and glycolysis of hepatocellular carcinoma via PI3K/AKT pathway.

Ann Palliat Med 2020 Nov 17;9(6):3857-3869. Epub 2020 Nov 17.

Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background: Hepatocellular carcinoma (HCC) is the most common malignancy of liver cancer. Calcium ions/calmodulins stimulate protein kinase kinases β (CaMKKβ) is a multifunctional protein kinase that is overexpressed in many types of cancer. This study aims to investigate the effect of CaMKKβ interference on HCC in HepG2 cells and transplanted tumor mice.

Methods: CaMKKβ gene was knocked out in HepG2 cells as an experimental group, empty vector lentivirus as a negative control (NC) group, and untreated HepG2 cells as a control group. Cell proliferation, cell cycle, apoptosis, invasion, and glycolysis potential assays were conducted, respectively. In addition, the expression of PI3K, p-PI3K, AKT, and p-AKT was quantified by Western blot. Finally, the effect of CaMKKβ in vivo was investigated using a xenograft model.

Results: CaMKKβ knockdown significantly suppressed HepG2 cell proliferation, cell cycle, invasion, EMT, and glycolysis, promoted cell apoptosis, and reduced the expression of hexokinase 2 (HK2), pyruvate kinase M (PKM2), and lactate dehydrogenase A (LDHA), p-PI3K, and p-AKT. Post the addition of AKT highly expression plasmid, glucose uptake, lactic acid production, and cell proliferation decreased, accompanied by an increase in apoptosis, which were substantially reversed. Notably, xenograft model experiments in vivo also confirmed that CaMKKβ knockdown inhibited HCC growth.

Conclusions: CaMKKβ knockdown inhibited cell proliferation, invasion, and glycolysis through the PI3K/AKT pathway, heightened apoptosis, thus promoting the development of HCC. This might be a potential target for the diagnosis and treatment of HCC.
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http://dx.doi.org/10.21037/apm-20-1789DOI Listing
November 2020

Glycine attenuates cerebrovascular remodeling via glycine receptor alpha 2 and vascular endothelial growth factor receptor 2 after stroke.

Am J Transl Res 2020 15;12(10):6895-6907. Epub 2020 Oct 15.

Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University Guilin, PR China.

As a dual-acting neurotransmitter, glycine plays critical roles in cerebral ischemia by activating both glycine receptors (GlyRs) and N-methyl-D-aspartate acid receptors (NMDARs). However, the involvement of glycine receptor alpha 2 (GlyRa2) in cerebral ischemia has not been explored. The objective of this study was to determine the mechanism of action of GlyRa2 in cerebrovascular remodeling. After induction of rat tMCAO, levels of the gene and GlyRa2 protein were examined using q-PCR, western blot, and immunohistochemical analyses. Blood-brain barrier permeability, and the presence of hemorrhage and arteriosclerosis were also analyzed. The underlying mechanism of vascular remodeling was examined using immunohistochemical and immunofluorescence analyses. Both the gene and GlyRa2 protein were altered sharply after stroke. GlyRa2 of vascular origin appears to play a protective role after glycine treatment for ischemia. Blockade of GlyRa2 by the addition of cyclothiazide was found to abolish previous improvements in cerebrovascular survival after glycine treatment for tMCAO in rats. GlyRa2-dependent neurovascular remodeling was found to be correlated with the vascular endothelial growth factor receptor 2 (VEGFR2) pathways. These results suggest that vascular-derived GlyRa2 protects against post-ischemic injury. Vascular protection via GlyRa2 is due to VEGFR2/pSTAT3 signaling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653569PMC
October 2020

Binuclear Tridentate Hemilabile Copper(I) Catalysts for Utilization of CO into Oxazolidinones from Propargylic Amines.

J Org Chem 2020 Dec 9;85(23):15197-15212. Epub 2020 Nov 9.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Four binuclear tridentate copper(I) complexes were synthesized based on the trans effect of the hybrid ligands. The catalytic performance and behavior of the prepared copper(I) complexes were evaluated in the carboxylative cyclization of propargylic amines with CO. The combined use of copper(I) complexes and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) provided a catalytic system for the synthesis of a wide range of oxazolidinones from various propargylic amines and CO under mild reaction conditions (room temperature-40 °C and 1 bar CO). The key factor for the success of the protocol is the use of copper complexes possessing the quality of hemilabile properties between N-heterocyclic carbenes and nitrogen donors. NMR measurements, density functional theory (DFT) calculations, and previous reports for the coordination behavior of the nickel complexes support the existence of the trans effect between N-heterocyclic carbenes and nitrogen donors.
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http://dx.doi.org/10.1021/acs.joc.0c02065DOI Listing
December 2020

Electrochemical Decarboxylative -Alkylation of Heterocycles.

Org Lett 2020 10 17;22(19):7594-7598. Epub 2020 Sep 17.

Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

An operationally simple method to employ nonactivated carboxylic acids as alkylating agents in the -alkylation of heterocycles is reported through an electrochemically driven anodic decarboxylative process. A wide substrate scope across a range of heterocycles is demonstrated along with a series of applications that significantly reduce the step count required to access such medicinally relevant structures.
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http://dx.doi.org/10.1021/acs.orglett.0c02799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350983PMC
October 2020

Experimental study of expression profile and specific role of human microRNAs in regulating atrophic bone nonunion.

Medicine (Baltimore) 2020 Sep;99(36):e21653

Department of Orthopedics, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya.

The expression profile and specific roles of microRNAs (miRNAs) in regulation of atrophic bone nonunion are not fully understood. Here, we present evidence that miRNAs are involved in regulation of several osteogenic genes and may contribute to the development of atrophic bone nonunion.The miRNA expression profile of repairing tissues in atrophic bone nonunion patients (group A) and in callus tissues from patients with healed fractures (group B) were quantitatively measured. microRNA microarrays were used to identify differentially expressed miRNAs, and the bioinformatics methods were used to predict the potential target genes. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase reporter assay were performed in human bone marrow stromal cells (hBMSCs) to validate the microarray results.Nine miRNAs in group A were up-regulated 1.5 times compared to group B, while the other 9 miRNAs in group A were down-regulated 1.5 times. Several target regions of these miRNAs were identified in the osteogenic genes, as well as in the other genes in their families or related regulatory factors. Four miRNAs (hsa-miR-149, hsa-miR-221, hsa-miR-628-3p, and hsa-miR-654-5p) could play important roles in regulating bone nonunion development. hBMSCs transfected with these miRNAs significantly decreased mRNA levels of alkaline phosphatase, liver/bone/kidney (ALPL), platelet derived growth factor subunit A (PDGFA), and bone morphogenetic protein 2 (BMP2). Lower protein expression levels were observed using western blotting, confirming that ALPL, PDGFA, and BMP2 were directly targeted by hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p, respectively.In summary, hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p may play important biological roles by repressing osteogenic target genes ALPL, PDGFA, and BMP2, and, therefore, contributing to progression of atrophic bone nonunion.
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http://dx.doi.org/10.1097/MD.0000000000021653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478398PMC
September 2020

[Expression of miRNA let-7a and HMGA2 and Diagnostic Value of Serum miRNA let-7a Level in Pancreatic Cancer].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 Jul;51(4):540-545

The First Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.

Objective: To investigate the diagnostic value of miRNA let-7a, high mobility group A2 (HMGA2) expression and serum miRNA let-7a level in pancreatic cancer.

Methods: From January 2014 to January 2019, 60 patients with pancreatic cancer were collected for fresh pancreatic ductal adenocarcinoma tissue and normal pancreatic tissue adjacent to the cancer after the operation. Serum samples before and after operation were also collected, while 60 healthy people were enrolled as the control group. The expression of miRNA let-7a (qRT-PCR) and HMGA2 (qRT-PCR and Western blot) in cancer and adjacent normal tissues were measured. The serum level of miRNA let-7a was detected by qRT-PCR. The relationship between miRNA let-7a and HMGA2 expression and the clinicopathological features of pancreatic cancer was analyzed. The diagnostic value of serum miRNA let-7a pre-operation in patients with pancreatic cancer was also analyzed with ROC curve.

Results: Compared with normal tissues adjacent to the cancer, the expression level of miRNA let-7a in pancreatic cancer tissues decreased ( =20.291, <0.01), and the expression of 2 mRNA increased ( =46.681, <0.01). The expression of HMGA2 protein in cancer tissues was higher than that in normal tissues adjacent to the cancer ( =22.973, <0.01). The serum level of miRNA let-7a in pancreatic cancer patients was significantly lower than that in healthy controls ( =24.854, <0.01). The relative level of serum miRNA let-7a at 1 week after surgery was significantly lower than that before surgery in pancreatic cancer patients ( =6.885, <0.01). There was a positive correlation between cancer tissue and serum miRNA let-7a expression 1 week after surgery ( =0.411, =0.000). The relative expression levels of miRNA let-7a and HMGA2 in pancreatic cancer tissues were significantly different in different TNM stages and lymph node metastasis ( <0.05). The area under curve of pre-operation serum miRNA let-7a for the diagnosis of pancreatic cancer was 0.823 ( 95% confidence interval: 0.665-0.917); when the optimal cut-off value of miRNA let-7a was 0.614, the sensitivity was 82.3%, the specificity was 74.1%.

Conclusion: The expression of HMGA2 may be involved in the invasion and metastasis of pancreatic cancer. The level of serum miRNA let-7a may provide a reference for the diagnosis and postoperative monitoring of pancreatic cancer.
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http://dx.doi.org/10.12182/20200760107DOI Listing
July 2020

[Simultaneous determination of 16 flavonoids and ferulic acid in honey by solid phase extraction and high performance liquid chromatography-tandem mass spectrometry].

Se Pu 2020 May;38(5):529-537

College of Bee Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Flavonoids are polyphenol compounds that are widely distributed in honey; they play an important role in its antioxidant activity and aid in distinguishing various species of honey. An analytical method based on solid phase extraction and high performance liquid chromatography with tandem mass spectrometry (SPE-HPLC-MS/MS) for the simultaneous determination of rutin, myricetin, morin, quercetin, naringenin, hesperetin, luteolin, genistein, kaempferol, isorhamnetin, apigenin, pinocembrin, wogonin, chrysin, galangin, genkwanin, and ferulic acid in honey was developed and validated. The honey samples were diluted with HCl solution (pH 2) and cleaned up on a C column by solid phase extraction; the methanol eluent was filtered through a nylon membrane and analyzed by LC-MS/MS on an ODS-3 column (150 mm×4.6 mm, 3 μm). Quantitative detection was performed by LC-MS/MS in the multiple reaction monitoring (MRM) mode under negative electrospray ionization (ESI) conditions. The external standard method was used for quantitation. The method validation data were obtained. The calibration standard curve solutions were prepared by honey matrix-matching; the linear range was 0-200 μg/kg, with correlation coefficients of the calibration standard curves greater than 0.997. The limits of quantification (LOQs) of this method were 20 μg/kg. The recoveries were in the range of 64.5%-113%, and the relative standard deviations were 1.4%-14.5% at three spiked levels (20, 40, and 100 μg/kg). The developed method is convenient, rapid, and effective, and it is suitable for the determination and confirmation of flavonoids in honey samples.
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http://dx.doi.org/10.3724/SP.J.1123.2019.06030DOI Listing
May 2020

TVT-O vs TVT-S for female stress urinary incontinence: A systematic review and meta-analysis.

Int J Clin Pract 2020 Sep 2;74(9):e13506. Epub 2020 Aug 2.

Department of Urology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China.

Background: Tension-free vaginal tape obturator (TVT-O) and tension-free vaginal tape secur (TVT-S) are common surgeries for the treatment of stress urinary incontinence (SUI), several randomised controlled trials (RCTs) have compared the effects of TVT-O and TVT-S, yet the results remained inconsistent. Therefore, we attempted to conduct this systematic review and meta-analysis to analyse the role of TVT-O and TVT-S in patients with SUI.

Methods: We searched PubMed databases from inception date to Jan 15, 2020 for RCTs that compared TVT-O and TVT-S in SUI patients. Two authors independently screened and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated for each outcome by fixed- or random-effects model.

Results: Seven RCTs with a total of 755 patients were identified, with 373 patients for TVT-O and 382 patients for TVT-S. TVT-O preceded TVT-S in the objective cure at 12 months (OR = 1.72, 95% CI 1.21-2.45), subjective cure (OR = 1.98, 95% CI 1.08-3.62); but TVT-S have more advantage in the incidence of postoperative thigh pain (OR = 18.94, 95% CI 7.01-51.15); no significant differences on the duration of operative procedure (OR = -1.09, 95% CI -2.37-0.18), urinary retention (OR = 0.77, 95% CI 0.36-1.62) and urinary infection (OR = 1.80, 95% CI 0.63-5.13) were found.

Conclusions: TVT-O should be preferred for patients with SUI even though with higher risks of postoperative thigh pain when compared with TVT-S, more related studies are needed to identify the role of TVT-O and TVT-S for the treatment of SUI.
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http://dx.doi.org/10.1111/ijcp.13506DOI Listing
September 2020

Synthesis of Benzodiazepines Through Ring Opening/Ring Closure of Benzimidazole Salts.

Chemistry 2020 Mar 25;26(15):3252-3258. Epub 2020 Feb 25.

School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, 832003, Shihezi, P. R. China.

Pyrido-benzodiazepine derivatives are undoubtedly one of the most important structural motifs in the marketed drugs and the drug candidates. Commonly synthetic methods for construction of the benzodiazepine ring derivatives are based on the condensation reactions of two highly functionalized synthons. The development of synthesis for these compounds, however, is hampered by the regioselectivity and atom economy. In this work, a one-step synthesis of pyrido-benzodiazepine backbones and its analogues is achieved through continuous ring-opening hydrolysis of benzimidazole salts and intramolecular C-H bond activation. The reaction mechanism is explored by control experiments and density functional theory (DFT) calculations.
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http://dx.doi.org/10.1002/chem.201905828DOI Listing
March 2020

Continuous hydrogen and methane production from the treatment of herbal medicines wastewater in the two-phase 'UASB-IC' system.

Water Sci Technol 2019 Sep;80(6):1134-1144

College of Environmental and Chemical Engineering, Heilongjiang University of Science and Technology, Harbin 150022, China E-mail:

A two-phase anaerobic system comprised of upflow anaerobic sludge bed (UASB) reactor for hydrogen production and internal circulation reactor (IC) for methane production was proposed and investigated at laboratory scale and mesophilic temperature (35 °C). Hydrogen was efficiently produced from the UASB with the highest production rate of 3.00 ± 0.04 L · L · d at optimum hydraulic retention time (HRT) of 6 h and in the IC, methane was also produced from residual organic matter and soluble metabolite products (SMP) with a production rate of 2.54 ± 0.04 L · L · d at optimum HRT of 15 h. Finally, system HRT of 21 h was determined to be the optimum HRT at which energy conversion efficiency increased from 9.6 ± 0.1% (hydrogen only production) to 72.4 ± 2.5% (hydrogen and methane coproduction) and system chemical oxygen demand (COD) removal reached up to the high level of 90.1 ± 2.1%.
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http://dx.doi.org/10.2166/wst.2019.352DOI Listing
September 2019

Emission characteristics of fine particulate matter from ultra-low emission power plants.

Environ Pollut 2019 Dec 6;255(Pt 1):113157. Epub 2019 Sep 6.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

As one of the highest energy consuming and polluting industries, the power generation industry is an important source of particulate matter emissions. Recently, implementation of ultra-low emission technology has changed the emission characteristic of fine particulate matter (PM). In this study, PM emitted from four typical power plants in China was sampled using a dilution channel sampling system, and analyzed for elements, water-soluble ions and carbonaceous fractions. The results showed that PM concentrations emitted from the four power plants were 0.78 ± 0.16, 0.63 ± 0.09, 0.29 ± 0.07 and 0.28 ± 0.01 mg m, respectively. Emission factors were 0.004-0.005 g/kg coal, nearly 1-2 orders of magnitude lower than those reported in previous studies. The highest proportions of PM consisted of organic carbon (OC), SO, elemental carbon (EC), NH, Al and Cl. Coefficients of divergence (CDs) were in the ranges 0.22-0.41 (for an individual plant), 0.43-0.69 (among different plants), and 0.60-0.99 (in previous studies). The results indicated that the source profiles of each tested power plant were relatively similar, but differed from those in previous studies. Enrichment factors showed elevated Se and Hg, in accordance with the source markers Se and As. Comparing source profiles with previous studies, the proportion of OC, EC and NH were higher, while the proportion of Al in PM were relatively lower. The OC/EC ratio became concentrated at ∼5. Results from this study can be used for source apportionment and emission inventory calculations after implementation of ultra-low emission technologies.
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http://dx.doi.org/10.1016/j.envpol.2019.113157DOI Listing
December 2019

A high temporal-spatial emission inventory and updated emission factors for coal-fired power plants in Shanghai, China.

Sci Total Environ 2019 Oct 14;688:94-102. Epub 2019 Jun 14.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

With the implementation of the ultra-low emission policy in China, emission factors (EFs) of power plant pollutants are constantly changing. Emission inventories developed using the recommended EFs contain high levels of uncertainty and it is difficult to achieve a high temporal resolution. Detailed sulfur dioxide (SO), nitrogen oxides (NOx), and particulate matter (PM) emission data based on a continuous emission monitoring system (CEMS) were obtained from 33 units at 13 power plants in Shanghai in 2017. The data were used to develop an hourly unit-based emission inventory and to devise updated EFs for coal-fired power plants. Emissions of SO, NOx, and PM typically met the ultra-low emission limit, with total emissions of SO, NOx, and PM of 2895.0, 5348.3, and 503.8 tons, respectively. Emission proportions of SO and NOx for 300-600, 600-1000, and above 1000 MW units were similar, while the emission proportion of PM decreased with an increase in unit capacity. Emissions of SO, NOx, and PM displayed similar monthly variations, peaking in winter and summer. Diurnal hourly variations of SO, NOx, and PM emissions displayed a bimodal trend, with higher emissions at night on weekends than on weekdays. EFs based on CEMS (EF) of SO, NOx, and PM were 0.10, 0.36, and 0.04 g kg of coal, respectively, which were one or two orders of magnitude lower than the widely-used EFs and 4-30 times lower than EFs based on the mass balance approach. After replacing the recommended fixed decontamination efficiencies with individually fitted values, the calculated EFs were consistent with the corresponding EF and discrepancies were further reduced. The new inventory and updated EFs will enable a better understanding of the temporal variations of power plant emissions and reduce the uncertainty caused by the overestimation of EFs after the implementation of ultra-low emissions technology.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.201DOI Listing
October 2019

Investigation of rice straw and kitchen waste degradation through vermicomposting.

J Environ Manage 2019 Aug 15;243:269-272. Epub 2019 May 15.

College of Environmental and Chemical Engineering, Heilongjiang University of Science and Technology, Harbin, China.

This study investigated the effect of vermicomposting on the degradation of rice straw and kitchen waste. Different ratios of straw and kitchen waste mixtures were used as feedstocks. After vermicomposting the substrates for 45 days under 20-25 °C moisture 60%, the vermicomposting resulted in a significant increase in phosphorous (31.38-55.89%) and potassium (33.40-63.15%), whereas a decrease was seen in TOC (38.24-43.49%) as well as TN (9.01-32.52%). The growth rate of earthworm (Eisenia foetida) was obtained in all feedstocks, the optimal rice straw/kitchen waste ratio for the earthworm growth was 3/2, excessive kitchen waste as negative impacts on the growth of earthworms. The result indicated that vermicomposting rice straw and kitchen waste with Eisenia foetida promoted nutrition content in a short period of time.
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http://dx.doi.org/10.1016/j.jenvman.2019.04.126DOI Listing
August 2019

[Effect of ethanolic extract of Polygonum cuspidatum on acute gouty arthritis in mice through NLRP3/ASC/caspase-1 axis].

Zhongguo Zhong Yao Za Zhi 2019 Feb;44(3):546-552

College of Pharmaceutical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20180925.001DOI Listing
February 2019

Mechanical properties and degradation of drug eluted bioresorbable vascular scaffolds prepared by three-dimensional printing technology.

J Biomater Sci Polym Ed 2019 05 7;30(7):547-560. Epub 2019 Apr 7.

a Department of Vascular Surgery , Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School , Nanjing , People's Republic of China.

Bioresorbable vascular scaffolds are expected to replace the traditional metal stent, avoiding the long-term complications of metal stents. However, it is hard for the traditional scaffold manufacturing process to meet the requirements of individualized treatment for vascular lesions, which requires different morphologies. Here, we used a new method of scaffold manufacturing, three-dimensional printing technology, to prepare bioresorbable vascular scaffolds. The fabricated scaffold was loaded with sirolimus mixed with scaffold preparation material for slow drug release. The engineered, drug- loaded, bioresorbable vascular scaffold (BVS) was analyzed and tested in vivo. The scaffolds produced by three-dimensional printing technology exhibited good mechanical properties and in vitro degradation performance. The results also suggested that these scaffolds could maintain effective radial strength after long-term degradation and sustained release of the drug. As a new scaffold preparation method, it may provide a promising idea for developing bioresorbable vascular scaffold technology.
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http://dx.doi.org/10.1080/09205063.2019.1586303DOI Listing
May 2019

Use of a three-dimensional printed polylactide-coglycolide/tricalcium phosphate composite scaffold incorporating magnesium powder to enhance bone defect repair in rabbits.

J Orthop Translat 2019 Jan 16;16:62-70. Epub 2018 Aug 16.

Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518057, PR China.

Background: The repair of large bone defects remains challenging for orthopaedic surgeons. Bone grafting remains the method of choice; such grafts fill spaces and enhance bone repair. Therapeutic agents also aid bone healing. The objective of this study is to develop a composite bioactive scaffold composed of polylactide-coglycolide (PLGA) and tricalcium phosphate (TCP) (the basic carrier) incorporating osteogenic, bioactive magnesium metal powder (Mg).

Method: Porous PLGA/TCP scaffolds incorporating Mg were fabricated using a low-temperature rapid-prototyping process. We term the PLGA/TCP/Mg porous scaffold (hereafter, PPS). PLGA/TCP lacking Mg served as the control material when evaluating the efficacy of PPS. A total of 36 New Zealand white rabbits were randomly divided into blank, PLGA/TCP (P/T) and PPS group, with 12 rabbits in each group. We established bone defects 15 mm in length in rabbit radii to evaluate the osteogenic potential of the bioactive scaffold in terms of the direct controlled release of osteogenic Mg ion during scaffold degradation. Radiographs of the operated radii were taken immediately after implantation and then at 2, 4, 8 and 12 weeks. Micro-computed tomography of new bone formation and remaining scaffold and histological analysis were performed at 4, 8, 12 weeks after operation.

Results: X-ray imaging performed at weeks 4, 8 and 12 post-surgery revealed more newly formed bone within defects implanted with PPS and PLGA/TCP scaffolds than blank group (). And micro-computed tomography performed at weeks 4 and 8 after surgery revealed more newly formed bone within defects implanted with PPS scaffolds than PLGA/TCP scaffolds ( < 0.05). Histologically, the PPS group had more newly mineralized bone than controls ( < 0.05). The increases in new bone areas (total implant regions) in the PPS and PLGA/TCP groups were 19.42% and 5.67% at week 4 and 48.23% and 28.93% at week 8, respectively. The percentages of remaining scaffold material in total implant regions in the PPS and PLGA/TCP groups were 53.30% and 7.65% at week 8 and 20.52% and 2.70% at week 12, respectively.

Conclusion: Our new PPS composite scaffold may be an excellent orthopaedic substitute; it exhibits good biocompatibility and may potentially have clinical utility.

Translational Potential Of This Article: Magnesium and beta-tricalcium phosphate had osteoinduction. It is significant to print a novel bone composite scaffold with osteoinduction to repair segmental bone defects. This study evaluated efficacy of PPS in the rabbit radius segmental bone defect model. The results showed that the novel scaffold with good biocompatibility may be an excellent graft and potentially have clinical utility.
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http://dx.doi.org/10.1016/j.jot.2018.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350073PMC
January 2019

A smartphone-assisted microfluidic chemistry analyzer using image-based colorimetric assays for multi-index monitoring of diabetes and hyperlipidemia.

Anal Chim Acta 2019 Apr 15;1052:105-112. Epub 2018 Nov 15.

Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, China; National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China. Electronic address:

A smartphone-assisted microfluidic chemistry analyzer using an image-based colorimetric detection method was successfully developed for the simultaneous analysis of three diabetes- and hyperlipidemia-related indexes, glucose (GLU), triglyceride (TG), and total cholesterol (TC). A fan-shaped microfluidic chip was designed and optimized to reliably allocate a premixed serum sample into four reaction chambers by a simple pipetting. The color changes of the peroxidase-HO enzymatic reactions in the chambers were captured and analyzed using a smartphone-controlled analyzer with a LED light source and a CCD camera. The highly quantitative relationships between the analyte concentrations and the color characteristic values of the green channel of the captured images were successfully established, enabling accurate and reproducible detections of GLU, TG, and TC simultaneously at a low cost. The parallel analyses of 111 serum samples using our system and a conventional chemistry analyzer were conducted, yielding an excellent correlation and consistency between these two systems. This study proved the feasibility of performing the multi-index monitoring of diabetes, hyperlipidemia, and other chronic diseases on a point-of-care platform at a high fidelity, but a low cost.
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http://dx.doi.org/10.1016/j.aca.2018.11.025DOI Listing
April 2019

[Pollution Characteristics and Health Risk Assessment of VOCs in Areas Surrounding a Petrochemical Park in Shanghai].

Huan Jing Ke Xue 2018 Nov;39(11):4901-4908

National Environmental Protection Shanghai Dianshan Lake Science Observatory Research Station, Shanghai Environmental Monitoring Center, Shanghai 200235, China.

To investigate the pollution characteristics of volatile organic compounds (VOCs) in the vicinity of a petrochemical park, the composition and concentration of VOCs was successively monitored by application of a gas chromatography-flame ionization detector in the residential area surrounding a petrochemical park in Shanghai in October 2017. Moreover, the maximum incremental reactive method was employed to estimate the O-formation potential contributed by VOCs, and health risks were assessed. Results showed that during the observation period, TVOCs concentrations ranged from 16.4 μg·m to 1947.8 μg·m with an average concentration of 40.7 μg·m, whereas the average proportions of alkanes, alkene/alkynes, and aromatic hydrocarbons were 66.2%, 25.9%, and 7.9%, respectively. The diurnal variation of total VOCs concentration showed a monomodal change, with a peak concentration of 127.9 μg·m at 07:00, whereas the TVOCs had an average ozone formation potential (OFP) of 249.7 μg·m. Analysis of OFP indicated that trans-2-butene and ethylene were the most important species in ozone production with accountabilities for total OFP of 153.4 μg·m. Propylene, trans-2-butene, and ethylene were the key active species. Furthermore, health risk assessments revealed that no significant health risks had been caused by hexane, benzene, toluene, ethylbenzene, -xylene, and -xylene.
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http://dx.doi.org/10.13227/j.hjkx.201803186DOI Listing
November 2018

Feasibility of dry anaerobic digestion of beer lees for methane production and biochar enhanced performance at mesophilic and thermophilic temperature.

Bioresour Technol 2019 Mar 27;276:65-73. Epub 2018 Dec 27.

College of Environmental and Chemical Engineering, Heilongjiang University of Science and Technology, Harbin 150022, China. Electronic address:

This study investigated the feasibility of dry anaerobic digestion using beer lees as substrate and the effect of cow manure-derived biochar addition on dry anaerobic digestion performance at mesophilic and thermophilic temperature, respectively. With TS content of 25%, maximum cumulative methane production and yield were achieved to be 5230 ± 91 mL d and 220.1 ± 7.7 mL g VS at mesophilic condition and 7386 ± 134 mL d and 310.4 ± 9.2 mL g VS at thermophilic condition in the control cultures. The biochar addition has a positive effect in improving dry anaerobic digestion performance. The maximum cumulative methane production and yield in the cultures with 10 g L biochar were substantially improved by 82.9% and 82.6% at mesophilic condition and 47.2% and 46.8% at mesophilic condition when compared to the control.
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http://dx.doi.org/10.1016/j.biortech.2018.12.105DOI Listing
March 2019

Identification of Selective Acyl Sulfonamide-Cycloalkylether Inhibitors of the Voltage-Gated Sodium Channel (Na) 1.7 with Potent Analgesic Activity.

J Med Chem 2019 01 21;62(2):908-927. Epub 2018 Dec 21.

Xenon Pharmaceuticals Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada.

Herein, we report the discovery and optimization of a series of orally bioavailable acyl sulfonamide Na1.7 inhibitors that are selective for Na1.7 over Na1.5 and highly efficacious in in vivo models of pain and hNa1.7 target engagement. An analysis of the physicochemical properties of literature Na1.7 inhibitors suggested that acyl sulfonamides with high f could overcome some of the pharmacokinetic (PK) and efficacy challenges seen with existing series. Parallel library syntheses lead to the identification of analogue 7, which exhibited moderate potency against Na1.7 and an acceptable PK profile in rodents, but relatively poor stability in human liver microsomes. Further, design strategy then focused on the optimization of potency against hNa1.7 and improvement of human metabolic stability, utilizing induced fit docking in our previously disclosed X-ray cocrystal of the Na1.7 voltage sensing domain. These investigations culminated in the discovery of tool compound 33, one of the most potent and efficacious Na1.7 inhibitors reported to date.
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http://dx.doi.org/10.1021/acs.jmedchem.8b01621DOI Listing
January 2019
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