Publications by authors named "Shuo Yuan"

46 Publications

Design and synthesis of new indole containing biaryl derivatives as potent antiproliferative agents.

Bioorg Chem 2021 Mar 10;110:104821. Epub 2021 Mar 10.

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address:

A new series of indole containing biaryl derivatives were designed and synthesized, and further biological evaluations of their antiproliferative activity against cancer cell lines (MGC-803 and TE-1 cells) were also conducted. Of these synthesized biaryls, compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) performed as the most potent antiproliferative agent that inhibited cell viability of MGC-803 cells with an IC value of 8.28 µM. In addition, investigation of mechanism exhibited that the compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) could inhibit the expression of c-Myc and glycolysis related proteins, decrease the ATP and lactate production, and further induce apoptosis by activating the AMP-activated protein kinase (AMPK) and p53 signaling pathways.
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http://dx.doi.org/10.1016/j.bioorg.2021.104821DOI Listing
March 2021

Biomechanical characteristics of tibio-femoral joint after partial medial meniscectomy in different flexion angles: a finite element analysis.

BMC Musculoskelet Disord 2021 Apr 2;22(1):322. Epub 2021 Apr 2.

Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou, 510405, Guangdong Province, China.

Background: Recent studies have pointed out that arthroscopy, the commonly-used surgical procedure for meniscal tears, may lead to an elevated risk of knee osteoarthritis (KOA). The biomechanical factors of KOA can be clarified by the biomechanical analysis after arthroscopic partial meniscectomy (APM). This study aimed to elucidate the cartilage stress and meniscus displacement of the tibiofemoral joint under flexion and rotation loads after APM.

Methods: A detailed finite element model of the knee bone, cartilage, meniscus, and major ligaments was established by combining computed tomography and magnetic resonance images. Vertical load and front load were applied to simulate different knee buckling angles. At the same time, by simulating flexion of different degrees and internal and external rotations, the stresses on tibiofemoral articular cartilage and meniscus displacement were evaluated.

Results: Generally, the contact stress on both the femoral tibial articular cartilage and the meniscus increased with the increased flexion degree. Moreover, the maximum stress on the tibial plateau gradually moved backward. The maximum position shift value of the lateral meniscus was larger than that of the medial meniscus.

Conclusion: Our finite element model provides a realistic three-dimensional model to evaluate the influence of different joint range of motion and rotating tibiofemoral joint stress distribution. The decreased displacement of the medial meniscus may explain the higher pressure on the knee components. These characteristics of the medial tibiofemoral joint indicate the potential biomechanical risk of knee degeneration.
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http://dx.doi.org/10.1186/s12891-021-04187-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017646PMC
April 2021

New drug approvals for 2020: Synthesis and clinical applications.

Eur J Med Chem 2021 Apr 12;215:113284. Epub 2021 Feb 12.

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Military of Education, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

53 New drugs including 38 chemical entities and 15 biologics were approved by the U.S. Food and Drug Administration during 2020. Among the marketed drugs, 34 new small molecule drugs and 4 new diagnostic agents with privileged structures and novel clinical applications represent as promising leads for the development of new drugs with the similar indications and improved therapeutic efficacy. This review is mainly focused on the clinical applications and synthetic methods of 34 small-molecule drugs newly approved by the FDA in 2020.
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http://dx.doi.org/10.1016/j.ejmech.2021.113284DOI Listing
April 2021

Cu(OTf)-Catalyzed Intramolecular Radical Cascade Reactions for the Diversity-Oriented Synthesis of Quinoline-Annulated Polyheterocyclic Frameworks.

Org Lett 2021 Feb 9;23(4):1445-1450. Epub 2021 Feb 9.

School of Pharmaceutical Sciences, Zhengzhou University, Science Road 100, Zhengzhou 450001, China.

Compound libraries with high levels of structural diversity and novelty could cover underexploited chemical space and thus have been highly pursued in drug discovery. Herein, we report the first Cu(OTf)-catalyzed intramolecular radical cascade reactions that enable the diversity-oriented synthesis of quinoline-annulated polyheterocyclic compounds (7 unique scaffolds, 66 examples) in an efficient manner. This work demonstrates an alternative route to access the natural product- and druglike compound collection with high levels of structural diversity and novelty.
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http://dx.doi.org/10.1021/acs.orglett.1c00129DOI Listing
February 2021

What is the impact of knee morphology on posterior cruciate ligament avulsion fracture in men and women: a case control study.

BMC Musculoskelet Disord 2021 Jan 21;22(1):100. Epub 2021 Jan 21.

Department of Orthopedics, Beijing Shunyi District Hospital, Beijing, China.

Background: Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture.

Methods: 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture.

Results: Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05).

Conclusions: Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.
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http://dx.doi.org/10.1186/s12891-021-03984-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819342PMC
January 2021

Dual-terminal decentralized event-triggered control for switched systems with cyber attacks and quantization.

ISA Trans 2021 Apr 1;110:15-27. Epub 2020 Nov 1.

School of Automation, Shenyang Aerospace University, Shenyang 110136, China. Electronic address:

This article concerns dual-terminal event-triggered communication and decentralized control of switched systems that are the target of cyber attacks. Due to different properties of physical system, this system uses decentralized communication channels to transmit feedback data. In order to make efficient use of communication resources in each channel, the information sent by the sub-system needs to meet the given event-triggering conditions before it can be released. Moreover, the quantization is employed in both sides of the controller to further improve the data transmission efficiency. Then, considering that the triggered and quantified data are affected by dual-terminal cyber attacks, the event-triggered closed-loop switched (CLS) systems under attacks are derived. Furthermore, by utilizing average dwell time (ADT) technique and piecewise Lyapunov function (LF) method, sufficient conditions are given to ensure that the event-triggered CLS systems subject to dual-terminal cyber attacks are globally exponentially stable (GES). Accordingly, the design conditions for the gains of event-triggered dynamic output feedback (DOF) controllers and the parameters of decentralized event-triggering mechanisms (DETMs) are presented. Finally, simulations for verifying the system stability with and without cyber attacks are given.
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http://dx.doi.org/10.1016/j.isatra.2020.10.050DOI Listing
April 2021

Ganoderma lucidum Rhodiola compound preparation prevent D-galactose-induced immune impairment and oxidative stress in aging rat model.

Sci Rep 2020 11 6;10(1):19244. Epub 2020 Nov 6.

Chronic Diseases Research Center, Dalian University College of Medicine, Dalian, 116622, Liaoning, China.

Aging is an irreversible process. This research aims to study the anti-aging effects of GRCP, a compound preparation made by Ganoderma lucidum and Rhodiola rosen, in aging rats. Rats were subcutaneously injected with 400 mg/kg of D-galactose daily, and aging could be induced after 8 weeks. The aging rats were treated with GRCP. This experiment was divided into 6 groups. Rats were randomly divided into the model group, positive control group, low-dose GRCP group (25 mg/kg body weight), medium-dose GRCP group (50 mg/kg body weight), and high-dose GRCP group (100 mg/kg body weight), healthy and normal rats were used as blank controls. After the end, the results show that the use of GRCP at a dose of 100 mg/kg is the best treatment for improving aging rats. Rats gained weight, spleen and thymus indexes, and splenocyte proliferation improved, and inflammatory cytokine levels decreased. Besides, biochemical indicators show that GRCP can improve the antioxidant enzyme activity and reduce the content of lipofuscin and TGF-β in aging rats (P < 0.05). GRCP can also inhibit the activation of the MyD88/NF-κB pathway in rat hippocampus. These results seem to suggest that GRCP can be used as a potential natural supplement or functional food to prevent aging.
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http://dx.doi.org/10.1038/s41598-020-76249-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648061PMC
November 2020

Adaptive behaviors of planktonic Pseudomonas aeruginosa in response to the surface-deposited dead siblings.

Colloids Surf B Biointerfaces 2021 Jan 15;197:111408. Epub 2020 Oct 15.

Faculty of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, PR China.

In this study, the 3D motion behaviors and the underlying adaptation mechanism of planktonic Pseudomonas aeruginosa (PAO1) in response to the deposited dead siblings nearby were explored. Utilizing a real-time 3D tracking technique, digital holographic microscopy (DHM), we demonstrate that planktonic cells near the surface covered with dead siblings have a lower density and a reduced 3D velocity compared with those upon viable ones. As a sign of chemosensory responses, bacteria swimming near the dead siblings exhibit increase in frequency of the 'flick' motion. Transcriptomic analysis by RNA-seq reveals an upregulated expression of dgcM and dgcE inhibited the movement of PAO1, accompanied by increased transcriptional levels of the virulence factor-related genes hcp1, clpV1, and vgrG1. Moreover, the decrease in l-glutamate and the increase in succinic acid in the metabolites of the dead bacteria layer promote the dispersion of planktonic bacteria. As a result, the dead siblings on a surface inhibit the bacterial accumulation and activate the adaptive defensive responses of planktonic PAO1 in the vicinity.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111408DOI Listing
January 2021

Design of a robot-assisted system for transforaminal percutaneous endoscopic lumbar surgeries: study protocol.

J Orthop Surg Res 2020 Oct 19;15(1):479. Epub 2020 Oct 19.

Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: Transforaminal percutaneous endoscopic lumbar surgeries (PELS) for lumbar disc herniation and spinal stenosis are growing in popularity. However, there are some problems in the establishment of the working channel and foraminoplasty such as nerve and blood vessel injuries, more radiation exposure, and steeper learning curve. Rapid technological advancements have allowed robotic technology to assist surgeons in improving the accuracy and safety of surgeries. Therefore, the purpose of this study is to develop a robot-assisted system for transforaminal PELS, which can provide navigation and foraminoplasty.

Methods: The robot-assisted system consists of three systems: preoperative planning system, navigation system, and foraminoplasty system. In the preoperative planning system, 3D visualization of the surgical segment and surrounding tissues are realized using the multimodal image fusion technique of computed tomography and magnetic resonance imaging, and the working channel planning is carried out to reduce the risk for injury to vital blood vessels and nerves. In the navigation system, the robot can obtain visual perception ability from a visual receptor and automatically adjust the robotic platform and robot arm to the appropriate positions according to the patient's position and preoperative plan. In addition, the robot can automatically register the surgical levels through intraoperative fluoroscopy. After that, the robot will provide navigation using the 6 degree-of-freedom (DOF) robot arm according to the preoperative planning system and guide the surgeon to complete the establishment of the working channel. In the foraminoplasty system, according to the foraminoplasty planning in the preoperative planning system, the robot performs foraminoplasty automatically using the high speed burr at the end of the robot arm. The system can provide real-time feedback on the working status of the bur through multi-mode sensors such as multidimensional force, position, and acceleration. Finally, a prototype of the system is constructed and performance tests are conducted.

Discussion: Our study will develop a robot-assisted system to perform transforaminal PELS, and this robot-assisted system can also be used for other percutaneous endoscopic spinal surgeries such as interlaminar PELS and percutaneous endoscopic cervical and thoracic surgeries through further research. The development of this robot-assisted system can be of great significance. First, the robot can improve the accuracy and efficiency of endoscopic spinal surgeries. In addition, it can avoid multiple intraoperative fluoroscopies, minimize exposure to both patients and the surgical staff, shorten the operative time, and improve the learning curve of beginners, which is beneficial to the popularization of percutaneous endoscopic spinal surgeries.
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http://dx.doi.org/10.1186/s13018-020-02003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569762PMC
October 2020

New drug approvals for 2019: Synthesis and clinical applications.

Eur J Med Chem 2020 Nov 29;205:112667. Epub 2020 Jul 29.

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Military of Education, Zhengzhou University, Zhengzhou, 450001, China.

48 new drugs including 38 chemical entities (33 new chemical entities, 3 new diagnostic agents, and 2 payloads of antibody drug conjugates) and 10 biologics were approved by the U.S. Food and Drug Administration (FDA) during 2019. These marketed new drugs represent privileged structures and novel action of mechanism, and thus can be served as leads to discover new drugs with the similar biological targets and improved therapeutic efficacy. This review aims to provide an overview regarding the synthetic approaches of 33 new chemical entities approved by the FDA in 2019 and their clinical applications.
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http://dx.doi.org/10.1016/j.ejmech.2020.112667DOI Listing
November 2020

Synthesis of new tetracyclic benzodiazepine-fused isoindolinones using recyclable mesoporous silica nanoparticles.

Chem Commun (Camb) 2020 Sep;56(77):11461-11464

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, China.

Pseudo natural products (NPs) feature structural novelty and diversity and thus are a new source of lead compounds for drug discovery. We first report the mesoporous silica nanoparticles (MSNs)-catalyzed de novo combination of benzodiazepine and isoindolinone, giving tetracyclic benzodiazepine-fused isoindolinone pseudo natural products (21 examples, 55-91% yields). The work also demonstrates that MSNs are efficient acidic catalysts for multi-component reactions.
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http://dx.doi.org/10.1039/d0cc04875eDOI Listing
September 2020

Preparation and Characterization of Nano-CL-20/TNT Cocrystal Explosives by Mechanical Ball-Milling Method.

ACS Omega 2020 Jul 7;5(28):17761-17766. Epub 2020 Jul 7.

National Special Superfine Powder Engineering Research Center of China, School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China.

Nano-CL-20/TNT cocrystal explosive was successfully prepared by mechanical ball milling with 0.38 mm grinding beads. The micromorphology and particle size of cocrystal explosive were characterized by scanning electron microscopy. The average particle size of nano-CL-20/TNT cocrystal explosive was 119.5 nm and showed a spherical-like micromorphology. The crystal structure of cocrystal explosive was characterized by powder X-ray diffraction, infrared spectroscopy, and Raman spectroscopy. The results show that mechanical ball milling does not change the molecular structure of the raw material, but the sample after ball milling has a new crystal phase, rather than a simple mixing of raw materials. Differential scanning calorimetry tests show that nano-CL-20/TNT cocrystal explosive has a higher decomposition temperature; impact sensitivity tests show that the properties of cocrystal explosive are 26 and 21.7 cm higher than those of CL-20 and CL-20/TNT mixture, respectively, which indicates that nano-CL-20/TNT cocrystal explosive has better thermal stability and safety.
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http://dx.doi.org/10.1021/acsomega.0c02426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379102PMC
July 2020

Lumbar decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jul;99(27):e20323

Department of Orthopedics, Beijing Chao-Yang Hospital, Beijing, China.

Background: The goal of this study was to review relevant randomized controlled trials in order to determine the efficacy of decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis.

Method: Using appropriate keywords, we identified relevant studies in PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through July 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval to assess and synthesize outcomes.

Result: Twenty-one randomized controlled trials were eligible for this meta-analysis with a total of 3636 patients. Compared with decompression, decompression and fusion significantly increased length of hospital stay, operative time and estimated blood loss. Compared with fusion, decompression significantly decreased operative time, estimated blood loss and overall visual analogue scale (VAS) scores. Compared with endoscopic decompression, microscopic decompression significantly increased length of hospital stay, and operative time. Compared with traditional surgery, endoscopic discectomy significantly decreased length of hospital stay, operative time, estimated blood loss, and overall VAS scores and increased Japanese Orthopeadic Association score. Compared with TLIF, MIS-TLIF significantly decreased length of hospital stay, and increased operative time and SF-36 physical component summary score. Compared with multi-level decompression and single level fusion, multi-level decompression and multi-level fusion significantly increased operative time, estimated blood loss and SF-36 mental component summary score and decreased Oswestry disability index score. Compared with decompression, decompression with interlaminar stabilization significantly decreased operative time and the score of Zurich claudication questionnaire symptom severity, and increased VAS score.

Conclusion: Considering the limited number of included studies, we still need larger-sample, high-quality, long-term studies to explore the optimal therapy for lumbar spinal stenosis.
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http://dx.doi.org/10.1097/MD.0000000000020323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337434PMC
July 2020

The essential role of intraflagellar transport protein IFT81 in male mice spermiogenesis and fertility.

Am J Physiol Cell Physiol 2020 06 1;318(6):C1092-C1106. Epub 2020 Apr 1.

Department of Physiology, Wayne State University, Detroit, Michigan.

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that is indispensable for the formation and maintenance of cilia and flagella; however, the implications and functions of IFT81 remain unknown. In this study, we disrupted IFT81 expression in male germ cells starting from the spermatocyte stage. As a result, homozygous mutant males were completely infertile and displayed abnormal sperm parameters. In addition to oligozoospermia, spermatozoa presented dysmorphic and nonfunctional flagella. Histological examination of testes from homozygous mutant mice revealed abnormal spermiogenesis associated with sloughing of germ cells and the presence of numerous multinucleated giant germ cells (symblasts) in the lumen of seminiferous tubules and epididymis. Moreover, only few elongated spermatids and spermatozoa were seen in analyzed cross sections. Transmission electron microscopy showed a complete disorganization of the axoneme and para-axonemal structures such as the mitochondrial sheath, fibrous sheath, and outer dense fibers. In addition, numerous vesicles that contain unassembled microtubules were observed within developing spermatids. Acrosome structure analysis showed normal appearance, thus excluding a crucial role of IFT81 in acrosome biogenesis. These observations showed that IFT81 is an important member of the IFT process during spermatogenesis and that its absence is associated with abnormal flagellum formation leading to male infertility. The expression levels of several IFT components in testes, including IFT20, IFT25, IFT27, IFT57, IFT74, and IFT88, but not IFT140, were significantly reduced in homozygous mutant mice. Overall, our study demonstrates that IFT81 plays an essential role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.
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http://dx.doi.org/10.1152/ajpcell.00450.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311741PMC
June 2020

A novel EDA1 missense mutation in X-linked hypohidrotic ectodermal dysplasia.

Medicine (Baltimore) 2020 Mar;99(11):e19244

Department of Prosthodontics, School and Hospital of Stomatology, Hebei Medical University and Hebei Key Laboratory of Stomatology, Shijiazhuang.

A mutation in the epithelial morphogen gene ectodysplasin-A1 (EDA1) is responsible for the disorder X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia. XLHED is characterized by impaired development of hair, eccrine sweat glands, and teeth. This study aimed to identify potentially pathogenic mutations in four Chinese XLHED families.Genomic DNA was extracted from the peripheral blood and sequenced. Sanger sequencing was used to carry out mutational analysis of the EDA1 gene, and the three-dimensional structure of the novel mutant residues in the EDA trimer was determined. Transcriptional activity of NF-κB was tested by Dual luciferin assay.We identified a novel EDA1 mutation (c.1046C>T) and detected 3 other previously-reported mutations (c.146T>A; c.457C>T; c.467G>A). Our findings demonstrated that novel mutation c.1046C>T (p.A349 V) resulted in XLHED. The novel mutation could cause volume repulsion in the protein due to enlargement of the amino acid side chain. Dual luciferase assay revealed that transcriptional NF-κB activation induced by XLHED EDA1 protein was significantly reduced compared with wild-type EDA1.These results extend the spectrum of EDA1 mutations in XLHED patients and suggest a functional role of the novel mutation in XLHED.
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http://dx.doi.org/10.1097/MD.0000000000019244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220389PMC
March 2020

Construction of Biologically Important Biaryl Scaffolds through Direct C-H Bond Activation: Advances and Prospects.

Top Curr Chem (Cham) 2020 Feb 17;378(2):23. Epub 2020 Feb 17.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Biaryl scaffolds are prevalent in natural products and drug molecules, and biaryl-containing compounds have been shown to exhibit diverse and interesting biological activities. To date, numerous synthetic methods, particularly direct C-H bond activation, have been developed for the construction of such scaffolds, due to their interesting structural features and biological profiles. We highlight herein recent advances in the construction of biologically important biaryl fragments through direct C-H bond activation and also demonstrate the application of direct C-H arylation in the total synthesis of biaryl-containing natural products and drug molecules. Selected biaryl-containing compounds.
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http://dx.doi.org/10.1007/s41061-020-0285-9DOI Listing
February 2020

Dissecting the SPAG6 domain that mediates interaction with Snapin.

Mol Reprod Dev 2020 02 21;87(2):260-261. Epub 2020 Jan 21.

Department of Occupational and Environmental Health, School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, China.

SPAG6 domain encompassing amino acids 199-280 mediates an interaction between SPAG6 and Snapin.
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http://dx.doi.org/10.1002/mrd.23318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187922PMC
February 2020

Murine germ cell-specific disruption of Ift172 causes defects in spermiogenesis and male fertility.

Reproduction 2020 04;159(4):409-421

Department of Physiology, Wayne State University, Detroit, Michigan, USA.

Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. IFT172 is a component of the IFT complex. Global disruption of mouse Ift172 gene caused typical phenotypes of ciliopathy. Mouse Ift172 gene appears to translate two major proteins; the full-length protein is highly expressed in the tissues enriched in cilia and the smaller 130 kDa one is only abundant in the testis. In male germ cells, IFT172 is highly expressed in the manchette of elongating spermatids. A germ cell-specific Ift172 mutant mice were generated, and the mutant mice did not show gross abnormalities. There was no difference in testis/body weight between the control and mutant mice, but more than half of the adult homozygous mutant males were infertile and associated with abnormally developed germ cells in the spermiogenesis phase. The cauda epididymides in mutant mice contained less developed sperm that showed significantly reduced motility, and these sperm had multiple defects in ultrastructure and bent tails. In the mutant mice, testicular expression levels of some IFT components, including IFT20, IFT27, IFT74, IFT81 and IFT140, and a central apparatus protein SPAG16L were not changed. However, expression levels of ODF2, a component of the outer dense fiber, and AKAP4, a component of fibrous sheath, and two IFT components IFT25 and IFT57 were dramatically reduced. Our findings demonstrate that IFT172 is essential for normal male fertility and spermiogenesis in mice, probably by modulating specific IFT proteins and transporting/assembling unique accessory structural proteins into spermatozoa.
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http://dx.doi.org/10.1530/REP-17-0789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187893PMC
April 2020

Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

BMC Cancer 2020 Jan 14;20(1):33. Epub 2020 Jan 14.

Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou, 350000, China.

Background: Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear.

Methods: The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model.

Results: We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo.

Conclusions: MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.
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http://dx.doi.org/10.1186/s12885-020-6521-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958600PMC
January 2020

Palladium-Catalyzed Ligand-Free Double Cyclization Reactions for the Synthesis of 3-(1'-Indolyl)-phthalides.

Org Lett 2020 02 14;22(3):814-817. Epub 2020 Jan 14.

School of Pharmaceutical Sciences , Zhengzhou University , Zhengzhou 450001 , China.

Indole and phthalide are privileged heterocyclic scaffolds in numerous natural products and bioactive molecules. The synthesis and biological evaluation of the compounds combining these two scaffolds have rarely been reported. Herein, we repot the first palladium-catalyzed ligand-free double cyclization reactions that enable efficient synthesis of 3-(1'-indolyl)-phthalides (42 examples, up to 96% yield) under mild conditions. Notably, only 1.0 mol % of catalyst loading is used, suggesting high efficiency. Late-stage elaborations give highly functionalized analogues.
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http://dx.doi.org/10.1021/acs.orglett.9b04241DOI Listing
February 2020

Enhanced Photoresponse of Indium-Doped Tin Disulfide Nanosheets.

ACS Appl Mater Interfaces 2020 Jan 6;12(2):2607-2614. Epub 2020 Jan 6.

Institute of Micro-Nano Photoelectron and Electromagnetic Technology Innovation, School of Electronics and Information Engineering, Hebei University of Technology , Tianjin 300401 , China.

Doping of tin disulfide (SnS) is an effective strategy to regulate its physical and chemical properties. In this work, In doping was used to manipulate the photoresponse behavior of SnS-based photodetectors. In-doped SnS nanosheets were synthesized via a facile hydrothermal method. It was found that the In doping concentration plays an important role in the size of the fabricated SnS nanosheets. With the increase in the In doping concentration, the lateral size of samples increased from ∼210 to ∼420 nm, but the crystallinity became poor at higher concentrations. Energy dispersive X-ray-mapping results show that the In was homogeneously distributed in the samples. In addition, a red shift was observed in the binding energy of Sn and S with increased In doping concentration, which may be due to the p-type doping of In in SnS. After In doping, the performance of SnS-based photodetectors was significantly improved. The photoresponse speed of In-doped SnS-based photodetectors was faster than that of pristine SnS-based devices under the illumination of 532 and 405 nm lasers. This work develops an effective approach of In doping to enhance the photoresponse characteristics of SnS-based photodetectors and proves that In-doped SnS has a vast potential in optoelectronic applications.
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http://dx.doi.org/10.1021/acsami.9b16321DOI Listing
January 2020

PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in .

Cell Discov 2019 10;5:44. Epub 2019 Sep 10.

1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Ptc is a gatekeeper to avoid abnormal Hh signaling activation, but the key regulators involved in Ptc-mediated inhibition remain largely unknown. Here, we identify PKAc as a key regulator required for Ptc inhibitory function. In the absence of Hh, PKAc physically interacts with Ptc and phosphorylates Ptc at Ser-1150 and -1183 residues. The presence of Hh unleashes PKAc from Ptc and activates Hh signaling. By combining both in vitro and in vivo functional assays, we demonstrate that such Ptc-PKAc interaction and Ptc phosphorylation are both important for Ptc inhibitory function. Interestingly, we further demonstrate that PKAc is subjected to palmitoylation, contributing to its kinase activity on plasma membrane. Based on those novel findings, we establish a working model on Ptc inhibitory function: In the absence of Hh, PKAc interacts with and phosphorylates Ptc to ensure its inhibitory function; and Hh presence releases PKAc from Ptc, resulting in Hh signaling activation.
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http://dx.doi.org/10.1038/s41421-019-0112-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796939PMC
September 2019

"On-Water" Palladium-Catalyzed Tandem Cyclization Reaction for the Synthesis of Biologically Relevant 4-Arylquinazolines.

Chemistry 2019 Oct 18;25(57):13109-13113. Epub 2019 Sep 18.

School of Pharmaceutical sciences, Zhengzhou University, Zhengzhou, 450001, P. R. China.

The quinazoline scaffold is prevalent in pharmaceutically relevant molecules that show diverse biological activities. Herein, we report an efficient "on-water" palladium-catalyzed tandem cyclization reaction from commercially available arylboronic acids and benzonitriles that enable the rapid access to 4-arylquinazoline scaffolds in good to excellent yields (45 examples, up to 98 % yield). This protocol has shown good functional group tolerance and broad substrate scope. The reaction was also performed on a gram scale and successfully applied to the synthesis of the highly potent and selective PI3Kδ inhibitor N11, showing the practicability and synthetic utility of the protocol. In this reaction, the quinazoline scaffold is efficiently constructed with the simultaneous formation of one C-C bond and one C-N bond. Collectively, the protocol could serve as an alternative strategy to synthesize biologically important quinazoline scaffolds.
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http://dx.doi.org/10.1002/chem.201903464DOI Listing
October 2019

Glass stabilized ultra-stable dual-emitting Mn-doped cesium lead halide perovskite quantum dots for cryogenic temperature sensing.

Nanoscale 2019 Aug;11(32):15010-15016

College of Physics and Energy, Fujian Normal University, Fuzhou, 350117, China.

Mn-Doped CsPb(Cl/Br)3 quantum dots possess multi-functional optical, electronic and magnetic characteristics. However, they usually suffer from decomposition in air, and Mn2+ dopants will be gradually expelled from the perovskite host due to a radius mismatch between Pb2+ and Mn2+. To solve these crucial issues, the synthesis of glass stabilized Mn-doped quantum dots via an appropriate glass composition design and in situ glass crystallization is reported. Mn2+ dopants act as nucleating agents to promote the nucleation/growth of CsPb(Cl/Br)3 from B-P-Zn-Cs-Pb based oxyhalide glass and partition into the perovskite host to produce dual-color luminescence via efficient exciton-to-dopant energy transfer. Benefitting from the effective protection of robust glass, Mn-doped CsPb(Cl/Br)3 quantum dots exhibit superior water resistance and thermal stability. Particularly, almost 100% luminescence is retained after immersing the composite in water for 30 days. Interestingly, rapid thermal quenching for exciton recombination relative to Mn2+ d-d transition at cryogenic temperatures enables its promising applications as a ratiometric temperature sensing medium.
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http://dx.doi.org/10.1039/c9nr05831aDOI Listing
August 2019

Clerodane diterpenoids from Casearia kurzii and their cytotoxic activities.

J Nat Med 2019 Sep 10;73(4):826-833. Epub 2019 Jun 10.

State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University, Tianjin, 300350, People's Republic of China.

A search for bioactive natural products as anticancer lead compounds resulted in the isolation of one previously undescribed and three known clerodane diterpenoids (1-4) from Casearia kurzii. The structures of these compounds were established by analysis of their NMR, MS, and electronic circular dichroism data. The cytotoxic activities of four compounds against three human cancer cell lines were evaluated. Compound 2 was found to be the most active with an IC value of 4.1 μM against HeLa cells, and was selected to investigate the possible cytotoxic mechanism.
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http://dx.doi.org/10.1007/s11418-019-01324-5DOI Listing
September 2019

The sperm-associated antigen 6 interactome and its role in spermatogenesis.

Reproduction 2019 08;158(2):181-197

Department of Physiology, Wayne State University, Detroit, Michigan, USA.

Mammalian SPAG6, the orthologue of Chlamydomonas reinhardtii PF16, is a component of the central apparatus of the '9 + 2' axoneme that controls ciliary/flagellar motility, including sperm motility. Recent studies revealed that SPAG6 has functions beyond its role in the central apparatus. Hence, we reexamined the role of SPAG6 in male fertility. In wild-type mice, SPAG6 was present in cytoplasmic vesicles in spermatocytes, the acrosome of round and elongating spermatids and the manchette of elongating spermatids. Spag6-deficient testes showed abnormal spermatogenesis, with abnormalities in male germ cell morphology consistent with the multi-compartment pattern of SPAG6 localization. The armadillo repeat domain of mouse SPAG6 was used as a bait in a yeast two-hybrid screen, and several proteins with diverse functions appeared multiple times, including Snapin, SPINK2 and COPS5. Snapin has a similar localization to SPAG6 in male germ cells, and SPINK2, a key protein in acrosome biogenesis, was dramatically reduced in Spag6-deficient mice which have defective acrosomes. SPAG16L, another SPAG6-binding partner, lost its localization to the manchette in Spag6-deficient mice. Our findings demonstrate that SPAG6 is a multi-functional protein that not only regulates sperm motility, but also plays roles in spermatogenesis in multiple cellular compartments involving multiple protein partners.
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http://dx.doi.org/10.1530/REP-18-0522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368494PMC
August 2019

Minimally invasive spine surgery in the treatment of pyogenic spondylodiscitis: an initial retrospective series study.

Wideochir Inne Tech Maloinwazyjne 2019 Apr 11;14(2):333-339. Epub 2018 Oct 11.

Affiliated Hospital of Jining Medical University, Jining, China.

Introduction: Pyogenic spondylodiscitis is a bacterial infection affecting the intervertebral disc and its adjacent vertebrae. Although relatively rare, it is a challenging medical disease with a poor prognosis that requires immediate diagnosis and treatment with suitable antibiotics.

Aim: To evaluate the clinical outcome of minimally invasive spine surgery (MIS) for pyogenic spondylodiscitis.

Material And Methods: The retrospective study cohort consisted of 10 consecutive patients who had undergone MIS decompression and/or discectomy for thoracic or lumbar pyogenic spondylodiscitis in our hospital. Data including patient characteristics, symptoms, visual analog scale (VAS) score, surgical approach and postoperative outcomes were obtained for retrospective analysis.

Results: Between January 2005 and December 2013, 10 patients underwent MIS decompression in the Department of Orthopedics in our medical university. Seven of these patients had lumbar infections and 3 had thoracic infections. All 10 patients had improved VAS scores immediately after surgery and after discharge. The VAS score (respectively on postoperative day 1 and day 7) suggested that the patients in this study had significantly less pain than preoperatively (day 1: 5 vs. 9, p < 0.001; day 7: 2.9 vs. 9, p < 0.001). The organism was obtained in 10 (100%) patients by the operative cultures. All patients achieved an excellent clinical recovery without the need for further spine surgery. All patients underwent postoperative imaging during follow-up and showed complete resolution or dramatically improved magnetic resonance imaging changes.

Conclusions: Minimally invasive spine surgery is a safe and effective surgical approach for pyogenic spondylodiscitis.
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http://dx.doi.org/10.5114/wiitm.2018.78891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528123PMC
April 2019

Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Deletion.

Front Cell Neurosci 2019 26;13:111. Epub 2019 Mar 26.

Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Mutations within the gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11-21 of , leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of -deficient rats were impaired detected by biochemical and electrophysiological analyses. -depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in -deficient rats. It is worth to note that -deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for -related neurodevelopmental disorders.
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http://dx.doi.org/10.3389/fncel.2019.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444209PMC
March 2019

Bioactive Diterpenoids from the Stems of Euphorbia royleana.

J Nat Prod 2019 02 7;82(2):183-193. Epub 2019 Feb 7.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research , Nankai University , Tianjin 300350 , People's Republic of China.

Two ingenane- (1 and 2), two ent-atisane- (3 and 4), two ent-kaurane- (5 and 6), two ent-abietane- (7 and 8), and one ent-isopimarane-type (9) diterpenoid and 12 known analogues have been isolated from the methanolic extract of the stems of Euphorbia royleana. Their structures, including absolute configurations, were determined by extensive spectroscopic methods and ECD data analysis. The nitric oxide inhibitory activities of those diterpenoids were examined biologically in lipopolysaccharide-stimulated BV-2 cells, with compounds 1, 2, 5-7, 10, and 12 having IC values lower than 40 μM. Molecular docking was used to investigated the possible mechanism of compounds 1, 2, 5-7, 10, and 12.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00493DOI Listing
February 2019

Optimizing and adjusting the photoluminescence of Mn-doped fluoride phosphors via forming composite particles.

Dalton Trans 2019 Jan;48(2):711-717

College of Materials & Environmental Engineering, Hangzhou Dianzi University, Hangzhou, 310018, P. R. China.

Nowadays, Mn4+-doped red phosphors are widely used in white LEDs to improve the color rendering index and decrease the correlated color temperature. Great efforts have been made to enhance the luminous efficiency. In this work, new composite particles containing two fluorides with similar structures K2LiAlF6 and K2NaAlF6 were developed to improve the emission intensity. The composite particles contain K2LiAlF6 and K2NaAlF6 phases with an increase of Na content. The particle sizes of the products were in the nanoscale and the element distribution was investigated. Importantly, the as-prepared composite particles had higher emission intensity than simple mixtures. Structural and optical characterization studies were systematically carried out to understand the enhancement mechanism. Finally, a white LED device was fabricated by combining the synthesized red phosphor and YAG:Ce on a blue chip.
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http://dx.doi.org/10.1039/c8dt04335cDOI Listing
January 2019