Publications by authors named "Wei Yin"

584 Publications

Untangling Microbiota Diversity and Assembly Patterns in the World's Largest Water Diversion Canal.

Water Res 2021 Aug 28;204:117617. Epub 2021 Aug 28.

Key Laboratory of Coastal Environment and Resources of Zhejiang Province, School of Engineering, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China; Institute of Advanced Technology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China. Electronic address:

Large water diversion projects are important constructions for reallocation of human-essential water resources. Deciphering microbiota dynamics and assembly mechanisms underlying canal water ecosystem services especially during long-distance diversion is a prerequisite for water quality monitoring, biohazard warning and sustainable management. Using a 1432-km canal of the South-to-North Water Diversion Projects as a model system, we answer three central questions: how bacterial and micro-eukaryotic communities spatio-temporally develop, how much ecological stochasticity contributes to microbiota assembly, and which immigrating populations better survive and navigate across the canal. We applied quantitative ribosomal RNA gene sequence analyses to investigate canal water microbial communities sampled over a year, as well as null model- and neutral model-based approaches to disentangle the microbiota assembly processes. Our results showed clear microbiota dynamics in community composition driven by seasonality more than geographic location, and seasonally dependent influence of environmental parameters. Overall, bacterial community was largely shaped by deterministic processes, whereas stochasticity dominated micro-eukaryotic community assembly. We defined a local growth factor (LGF) and demonstrated its innovative use to quantitatively infer microbial proliferation, unraveling taxonomically dependent population response to local environmental selection across canal sections. Using LGF as a quantitative indicator of immigrating capacities, we also found that most micro-eukaryotic populations (82%) from the source water sustained growth in the canal and better acclimated to the hydrodynamical water environment than bacteria (67%). Taxa inferred to largely propagate include Limnohabitans sp. and Cryptophyceae, potentially contributing to water auto-purification. Combined, our work poses first and unique insights into the microbiota assembly patterns and dynamics in the world's largest water diversion canal, providing important ecological knowledge for long-term sustainable water quality maintenance in such a giant engineered system.
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http://dx.doi.org/10.1016/j.watres.2021.117617DOI Listing
August 2021

Immune Dysregulation in IgG-Related Disease.

Front Immunol 2021 1;12:738540. Epub 2021 Sep 1.

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

Immunoglobin G-related disease (IgG-RD) is one of the newly discovered autoimmune diseases characterized by elevated serum IgG concentrations and multi-organ fibrosis. Despite considerable research and recent advances in the identification of underlying immunological processes, the etiology of this disease is still not clear. Adaptive immune cells, including different types of T and B cells, and cytokines secreted by these cells play a vital role in the pathogenesis of IgG-RD. Antigen-presenting cells are stimulated by pathogens and, thus, contribute to the activation of naïve T cells and differentiation of different T cell subtypes, including helper T cells (Th1 and Th2), regulatory T cells, and T follicular helper cells. B cells are activated and transformed to plasma cells by T cell-secreted cytokines. Moreover, macrophages, and some important factors (TGF-β, etc.) promote target organ fibrosis. Understanding the role of these cells and cytokines implicated in the pathogenesis of IgG-RD will aid in developing strategies for future disease treatment and drug development. Here, we review the most recent insights on IgG-RD, focusing on immune dysregulation involved in the pathogenesis of this autoimmune condition.
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http://dx.doi.org/10.3389/fimmu.2021.738540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440903PMC
September 2021

Signaling networks in B cell development and related therapeutic strategies.

J Leukoc Biol 2021 Sep 16. Epub 2021 Sep 16.

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

B cells are essential for Ab production during humoral immune responses. From decades of B cell research, there is now a detailed understanding of B cell subsets, development, functions, and most importantly, signaling pathways. The complicated pathways in B cells and their interactions with each other are stage-dependent, varying with surface marker expression during B cell development. With the increasing understanding of B cell development and signaling pathways, the mechanisms underlying B cell related diseases are being unraveled as well, making it possible to provide more precise and effective treatments. In this review, we describe several essential and recently discovered signaling pathways in B cell development and take a look at newly developed therapeutic strategies targeted at B cell signaling.
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http://dx.doi.org/10.1002/JLB.2RU0221-088RRRDOI Listing
September 2021

Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity.

Front Immunol 2021 27;12:725587. Epub 2021 Aug 27.

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

With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment. In recent years, the wide application of whole-exome sequencing/whole-genome sequencing has tremendously promoted the discovery and further studies of new IEI. The number of discovered IEI is growing rapidly, followed by numerous studies of their pathogenesis and therapy. In this review, we focus on novel discovered primary immune dysregulation diseases, including deficiency of SLC7A7, CD122, DEF6, FERMT1, TGFB1, RIPK1, CD137, TET2 and SOCS1. We discuss their genetic mutation, symptoms and current therapeutic methods, and point out the gaps in this field.
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http://dx.doi.org/10.3389/fimmu.2021.725587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429820PMC
August 2021

gC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema.

Inflammation 2021 Sep 7. Epub 2021 Sep 7.

Department of Biomedical Engineering, Stony Brook University, NY, Stony Brook, USA.

Angioedema is characterized by swelling of the skin or mucous membranes. Overproduction of the vasodilator bradykinin (BK) is an important contributor to the disease pathology, which causes rapid increase in vascular permeability. BK formation on endothelial cells results from high molecular weight kininogen (HK) interacting with gC1qR, the receptor for the globular heads of C1q, the first component of the classical pathway of complement. Endothelial cells are sensitive to blood-flow-induced shear stress and it has been shown that shear stress can modulate gC1qR expression. This study aimed to determine the following: (1) how BK or angioedema patients' (HAE) plasma affected endothelial cell permeability and gC1qR expression under shear stress, and (2) if monoclonal antibody (mAb) 74.5.2, which recognizes the HK binding site on gC1qR, had an inhibitory effect in HK binding to endothelial cells. Human dermal microvascular endothelial cells (HDMECs) grown on Transwell inserts were exposed to shear stress in the presence of HAE patients' plasma. Endothelial cell permeability was measured using FITC-conjugated bovine serum albumin. gC1qR expression and HK binding to endothelial cell surface was measured using solid-phase ELISA. Cell morphology was quantified using immunofluorescence microscopy. The results demonstrated that BK at 1 µg/mL, but not HAE patients' plasma and/or shear stress, caused significant increases in HDMEC permeability. The mAb 74.5.2 could effectively inhibit HK binding to recombinant gC1qR, and reduce HAE patients' plasma-induced HDMEC permeability change. These results suggested that monoclonal antibody to gC1qR, i.e., 74.5.2, could be potentially used as an effective therapeutic reagent to prevent angioedema.
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http://dx.doi.org/10.1007/s10753-021-01532-wDOI Listing
September 2021

Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study.

Ren Fail 2021 Dec;43(1):1266-1275

Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University/The Second Clinical Medicine School of Guangzhou Medical University, Guangzhou, China.

Background: Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated.

Methods: From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment.

Results: At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77,  = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20,  = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed.

Conclusion: Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. : MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor.
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http://dx.doi.org/10.1080/0886022X.2021.1968432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425735PMC
December 2021

SARS-CoV-2 Structural Proteins Exposure Alter Thrombotic and Inflammatory Responses in Human Endothelial Cells.

Cell Mol Bioeng 2021 Aug 31:1-11. Epub 2021 Aug 31.

Department of Biomedical Engineering, Stony Brook University, 101 Bioengineering, Stony Brook, NY 11794-5281 USA.

Introduction: We have experienced a pandemic induced by the interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) structural proteins with innate structures. These interactions are especially prevalent for patients with underlying pathologies, such as cardiovascular diseases. However, there has been limited work to uncover the range of responses induced by SARS-CoV-2 structural proteins. Thus, our objective was to investigate how endothelial cell pro-thrombotic and pro-inflammatory responses are altered after exposure to SARS-CoV-2 spike, nucleocapsid, and membrane-envelope proteins. We hypothesized that after a short duration exposure, endothelial cells would have a heightened thrombotic and inflammatory potential. With longer exposures, this may lead to altered disease progression and the observed increased mortality and morbidity rates in patients with underlying vascular pathologies.

Methods: To test this hypothesis, human endothelial cells were exposed to SARS-CoV-2 structural proteins. After the exposure, the expression of thrombomodulin, PECAM-1, connexin-43, and gC1qR were assessed. In parallel, standard cell culture readouts were assessed to determine if these incubations altered cell growth and metabolism.

Results And Conclusions: We observed significant increases in thrombotic and inflammatory marker expression, with no change to the cell culture parameters (with the exception of a reduction in cell density in response to one SARS-CoV-2 structural protein). Importantly, these observations were dependent on the viral structural protein the cells were exposed to, suggesting that the interactions of SARS-CoV-2 with innate cells is complex and must be uncovered. Combined, this suggests that SARS-CoV-2 structural proteins can regulate inflammatory and thrombotic responses that underlie common pathologies observed during COVID-19.
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http://dx.doi.org/10.1007/s12195-021-00696-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407404PMC
August 2021

Carbon-Based Composites as Anodes for Microbial Fuel Cells: Recent Advances and Challenges.

Chempluschem 2021 Sep 7;86(9):1322-1341. Epub 2021 Aug 7.

MOE of the Key Laboratory of Bioinorganic and Synthetic Chemistry, The Key Lab of Low-carbon Chem &, Energy Conservation of Guangdong Province, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.

Owing to the low price, chemical stability and good conductivity, carbon-based materials have been extensively applied as the anode in microbial fuel cells (MFCs). In this review, apart from the charge storage mechanism and anode requirements, the major work focuses on five categories of carbon-based anode materials (traditional carbon, porous carbon, nano-carbon, metal/carbon composite and polymer/carbon composite). The relationship is demonstrated in depth between the physicochemical properties of the anode surface/interface/bulk (porosity, surface area, hydrophilicity, partical size, charge, roughness, etc.) and the bioelectrochemical performances (electron transfer, electrolyte diffusion, capacitance, toxicity, start-up time, current, power density, voltage, etc.). An outlook for future work is also proposed.
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http://dx.doi.org/10.1002/cplu.202100292DOI Listing
September 2021

Association between plasma neurofilament light chain levels and cognitive function in patients with Parkinson's disease.

J Neuroimmunol 2021 Sep 13;358:577662. Epub 2021 Jul 13.

Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province 650032, PR China. Electronic address:

This study investigated the potential association between levels of plasma neurofilament light chain (NfL) and cognitive function in patients suffering from Parkinson's disease (PD) in P.R. China.We collected a total of 168 participants (130 PD patients and 38 healthy controls),and evaluated the relationship of plasma NfL levels with cognitive dysfunction in PD patients. Our results shown that plasma NfL levels increased with an increase in cognitive impairment across the three groups of PD patients: PD with normal cognition (PD-NC), 17.9 ± 8.9 pg/ml; PD with mild cognitive impairment (PD-MCI),21.9 ± 10.3 pg/ml; and PD dementia (PDD), 35.7 ± 21.7 pg/ml. Higher MMSE scores were associated with lower plasma NfL levels (r = -0.49, 95% CI -0.61 to -0.34, p < 0.0001). Our results associating plasma NfL levels with cognitive dysfunction in PD are consistent with previous studies carried out in several countries/district, based on our meta-analysis.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577662DOI Listing
September 2021

Physical and cognitive demands associated with police in-vehicle technology use: an on-road case study.

Ergonomics 2021 Aug 6:1-14. Epub 2021 Aug 6.

Industrial and Systems Engineering, Texas A&M University, College Station, TX, USA.

Motor vehicle crashes are a leading cause of police officers' deaths in line of duty. These crashes have been mainly attributed to officers' driving distraction caused by the use of in-vehicle technologies while driving. This paper presents a 3-h ride-along study of 20 police officers to assess the physical and cognitive demands associated with using in-vehicle technologies. The findings suggested that the mobile computer terminal (MCT) was the most frequently used in-vehicle system for the officers. In addition, officers perceived the MCT to significantly increase their visual, cognitive, and physical demands compared to other in-vehicle technologies. Evidence from electromyography and eye-tracking measures suggested that officers with more experience as a patrol officer and those who were working in more congested areas experienced higher cognitive workload. Furthermore, it was found that as the ride-along duration increased, there were indications of muscle fatigue in medial deltoid and triceps brachii muscles. This study assessed the impact of police in-vehicle technology use in an on-road case study. The findings provide new data and knowledge for police agencies and vehicle manufacturers to develop administrative measures and in-vehicle technology innovations to improve police officers' health and safety.
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http://dx.doi.org/10.1080/00140139.2021.1960429DOI Listing
August 2021

Design, Synthesis, and Biological Evaluation of Organic Nitrite (NO) Donors as Potential Anticerebral Ischemia Agents.

J Med Chem 2021 Aug 22;64(15):10919-10933. Epub 2021 Jul 22.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, P.R. China.

The treatment of ischemic stroke (IS) remains a big challenge in clinics, and it is urgently needed to develop novel, safe, and effective medicines against IS. Here, we report the design, synthesis, and biological evaluation of organic NO donors as potential agents for the treatment of IS. The representative compound was able to slowly generate low concentrations of NO by reaction with a thiol-containing nucleophile, and the NO was selectively converted into NO under ischemic/hypoxia conditions to protect primary rat neurons from oxygen-glucose deprivation and recovery (OGD/R)-induced cytotoxicity by enhancing the Nrf2 signaling and activating the NO/cGMP/PKG pathway. Treatment with at 2 h before or after ischemia mitigated the ischemia/reperfusion-induced brain injury in middle cerebral artery occlusion (MCAO) rats by producing NO and enhancing Nrf2 signaling. Furthermore, significantly promoted endothelial cell proliferation and angiogenesis within the ischemic penumbra. Our findings suggest that this type of NO donors, like , may be valuable to fight IS and other ischemic diseases.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00282DOI Listing
August 2021

Curculigoside Protects against Titanium Particle-Induced Osteolysis through the Enhancement of Osteoblast Differentiation and Reduction of Osteoclast Formation.

J Immunol Res 2021 4;2021:5707242. Epub 2021 Jul 4.

Department of Orthopaedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou, 311201 Zhejiang Province, China.

Wear particle-induced periprosthetic osteolysis is mainly responsible for joint replacement failure and revision surgery. Curculigoside is reported to have bone-protective potential, but whether curculigoside attenuates wear particle-induced osteolysis remains unclear. In this study, titanium particles (Ti) were used to stimulate osteoblastic MC3T3-E1 cells in the presence or absence of curculigoside, to determine their effect on osteoblast differentiation. Rat osteoclastic bone marrow stromal cells (BMSCs) were cocultured with Ti in the presence or absence of curculigoside, to evaluate its effect on osteoclast formation . Ti was also used to stimulate mouse calvaria to induce an osteolysis model, and curculigoside was administrated to evaluate its effect in the osteolysis model by micro-CT imaging and histopathological analyses. As the results indicated, in MC3T3-E1 cells, curculigoside treatment attenuated the Ti-induced inhibition on cell differentiation and apoptosis, increased alkaline phosphatase activity (ALP) and cell mineralization, and inhibited TNF-, IL-1, and IL-6 production and ROS generation. In BMSCs, curculigoside treatment suppressed the Ti-induced cell formation and suppressed the TNF-, IL-1, and IL-6 production and F-actin ring formation. , curculigoside attenuated Ti-induced bone loss and histological damage in murine calvaria. Curculigoside treatment also reversed the RANK/RANKL/OPG and NF-B signaling pathways, by suppressing the RANKL and NF-B expression, while activating the OPG expression. Our study demonstrated that curculigoside treatment was able to attenuate wear particle-induced periprosthetic osteolysis in and experiments, promoted osteoblastic MC3T3-E1 cell differentiation, and inhibited osteoclast BMSC formation. It suggests that curculigoside may be a potential pharmaceutical agent for wear particle-stimulated osteolysis therapy.
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http://dx.doi.org/10.1155/2021/5707242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275416PMC
July 2021

A visible-light mediated ring opening reaction of alkylidenecyclopropanes for the generation of homopropargyl radicals.

Chem Sci 2021 Jul 28;12(26):9088-9095. Epub 2021 May 28.

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry & Molecular Engineering, East China University of Science and Technology Meilong Road No. 130 Shanghai 200237 China.

Classical cyclopropylcarbinyl radical clock reactions have been widely applied to conduct mechanistic studies for probing radical processes for a long time; however, alkylidenecyclopropanes, which have a similar molecular structure to methylcyclopropanes, surprisingly have not yet attracted researcher's attention for similar ring opening radical clock processes. In recent years, photocatalytic NHPI ester activation chemistry has witnessed significant blooming developments and provided new synthetic routes for cross-coupling reactions. Herein, we wish to report a non-classical ring opening radical clock reaction using innovative NHPI esters bearing alkylidenecyclopropanes upon photoredox catalysis, providing a brand-new synthetic approach for the direct preparation of a variety of alkynyl derivatives. The potential synthetic utility of this protocol is demonstrated in the diverse transformations and facile synthesis of bioactive molecules or their derivatives and medicinal substances.
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http://dx.doi.org/10.1039/d1sc01889bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261759PMC
July 2021

Virtual Normal: Enforcing Geometric Constraints for Accurate and Robust Depth Prediction.

IEEE Trans Pattern Anal Mach Intell 2021 Jul 16;PP. Epub 2021 Jul 16.

Monocular depth prediction plays a crucial role in understanding 3D scene geometry. Although recent methods have achieved impressive progress in evaluation metrics such as the pixel-wise relative error, most methods neglect the geometric constraints in the 3D space. We show the importance of the high-order 3D geometric constraints for depth prediction. By designing a loss term that enforces a simple geometric constraint, virtual normal directions determined by randomly sampled three points in the reconstructed 3D space, we significantly improve the accuracy and robustness of monocular depth estimation. The virtual normal loss disentangles the scale information and enrich the model with better shape information. We show state-of-the-art results on NYU Depth-V2 and KITTI. Besides, we are now able to recover good 3D structures of the scene such as the point cloud and surface normal directly from the depth with better qualities, eliminating the necessity of training new sub-models as was previously done. Furthermore, when not having absolute metric depth training data, we can use virtual normal to learn a robust affine-invariant depth generated on diverse scenes. We construct a large-scale and diverse dataset for training affine-invariant depth, termed Diverse Scene Depth dataset (DiverseDepth), which consists of a broad range of scenes.
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http://dx.doi.org/10.1109/TPAMI.2021.3097396DOI Listing
July 2021

Safety, pharmacokinetics and quantitative EEG modulation of TAK-071, a novel muscarinic M1 receptor positive allosteric modulator, in healthy subjects.

Br J Clin Pharmacol 2021 Jul 8. Epub 2021 Jul 8.

Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.

Aims: TAK-071 is a muscarinic M receptor positive allosteric modulator designed to have low cooperativity with acetylcholine. This was a first-in-human study to evaluate the safety, pharmacokinetics, and pharmacodynamics of TAK-071.

Methods: TAK-071 was administered as single and multiple doses in a randomized, double-blind, placebo-controlled, parallel-group design in healthy volunteers alone and in combination with donepezil. Laboratory, electrocardiogram (ECG) and electroencephalogram (EEG) evaluations were performed. Cerebrospinal fluid and blood samples were taken to evaluate the pharmacokinetics (PK), relative bioavailability and food effect.

Results: TAK-071 was safe and well tolerated, and no deaths or serious adverse events occurred. TAK-071 demonstrated a long mean (% coefficient of variation) half-life of 46.3 (25.2%) to 60.5 (51.5%) hours and excellent brain penetration following oral dosing. Coadministration with donepezil had no impact on the PK of either drug. There was no food effect on systemic exposure. Quantitative EEG analysis revealed that TAK-071 40-80 mg increased power in the 7-9 Hz range in the posterior electrode group with eyes open and 120-160 mg doses increased power in the 16-18 Hz range and reduced power in the 2-4 Hz range in central-posterior areas with eyes open and eyes closed. Functional connectivity was significantly reduced after TAK-071 at high doses and was enhanced with coadministration of donepezil under the eyes-closed condition.

Conclusions: PK and safety profiles of TAK-071 were favorable, including those exceeding expected pharmacologically active doses based on preclinical data. When administered without donepezil TAK-071 was largely free of cholinergic adverse effects. Further clinical evaluation of TAK-071 is warranted.
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http://dx.doi.org/10.1111/bcp.14975DOI Listing
July 2021

Fruit Detection and Pose Estimation for Grape Cluster-Harvesting Robot Using Binocular Imagery Based on Deep Neural Networks.

Front Robot AI 2021 22;8:626989. Epub 2021 Jun 22.

School of Mechatronics Engineering and Automation, Foshan University, Foshan, China.

Reliable and robust fruit-detection algorithms in nonstructural environments are essential for the efficient use of harvesting robots. The pose of fruits is crucial to guide robots to approach target fruits for collision-free picking. To achieve accurate picking, this study investigates an approach to detect fruit and estimate its pose. First, the state-of-the-art mask region convolutional neural network (Mask R-CNN) is deployed to segment binocular images to output the mask image of the target fruit. Next, a grape point cloud extracted from the images was filtered and denoised to obtain an accurate grape point cloud. Finally, the accurate grape point cloud was used with the RANSAC algorithm for grape cylinder model fitting, and the axis of the cylinder model was used to estimate the pose of the grape. A dataset was acquired in a vineyard to evaluate the performance of the proposed approach in a nonstructural environment. The fruit detection results of 210 test images show that the average precision, recall, and intersection over union () are 89.53, 95.33, and 82.00%, respectively. The detection and point cloud segmentation for each grape took approximately 1.7 s. The demonstrated performance of the developed method indicates that it can be applied to grape-harvesting robots.
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http://dx.doi.org/10.3389/frobt.2021.626989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259879PMC
June 2021

Occurrence, spatial distribution and risk assessment of high concern endocrine-disrupting chemicals in Jiangsu Province, China.

Chemosphere 2021 Jun 30;285:131396. Epub 2021 Jun 30.

Nanjing Institute of Environmental Science, Ministry of Ecology and Environment, Nanjing, 210042, China. Electronic address:

Endocrine-disrupting chemicals (EDCs) have attracted much concern because of the environmental and health risks they pose. Here we used liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry to quantify 10 types of EDCs at 118 sampling sites in Jiangsu Province, China, and then evaluated their respective environmental risk using a conservative risk quotient method. The results show that, in surface water, the targeted nonylphenol (NP), 4-tert-octylphenol (4-t-OP), and (2-ethylhexyl)phthalate (DEHP) were ranked highest, having mean concentrations above 300 ng/L. In comparison, both 4-t-OP and DEHP were also ranked highest, with mean concentrations above 100 ng/g, in the sediment samples. Moreover, the ∑EDCs concentration in the Huai River Basin was similar to that in the Yangtze River Basin. Notably, Huai'an city had the maximum mean concentration for EDCs in the Huai River Basin, followed by Xuzhou city and Suqian city, while Yangzhou city ranked highest in the Yangtze River Basin. Furthermore, the corresponding risk distribution revealed that (1) NP, bisphenol A (BPA), and 4-t-OP are of medium to high risk in 70%, 100% and 95% of the surface water samples, and likewise in 45%, 88% and 100% of the sediment samples, respectively; the maximum RQ value for NP in surface water samples reached 74.9; (2) DEHP belongs to the high-risk category in all samples (100%), whose maximum RQ reached 54.7. To our best knowledge, this is the first study to report on the occurrence, spatial distribution, and risk assessment of EDCs of high concern in Jiangsu Province, China.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131396DOI Listing
June 2021

Thermally-Induced Intramolecular [4+2] Cycloaddition of Allylamino- or Allyloxy-Tethered Alkylidenecyclopropanes.

Chem Asian J 2021 Sep 19;16(17):2463-2468. Epub 2021 Jul 19.

State Key Laboratory of Organometallic Chemistry, Center for Excellence Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032, P. R. China.

A thermally-induced intramolecular [4+2] cycloaddition reaction of allylamino- or allyloxy-tethered alkylidenecyclopropanes has been reported in this paper, giving a new protocol for the rapid construction of polycyclic skeleton molecules in moderate to excellent yields with a broad substrate scope. On the basis of control experiments and DFT calculations, we disclosed that the reaction proceeded through a [4+2] cycloaddition and trace of water assisted 1,3-H shift process to give the target product.
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http://dx.doi.org/10.1002/asia.202100635DOI Listing
September 2021

SARS-CoV-2 and Plasma Hypercoagulability.

Cell Mol Bioeng 2021 Jun 28:1-10. Epub 2021 Jun 28.

Department of Biomedical Engineering, Stony Brook University, Bioengineering Building, Room 109, Stony Brook, NY 11794 USA.

Hypercoagulability has emerged as a prominent consequence of COVID-19. This presents challenges not only in the clinic, but also in thrombosis research. Health and safety considerations, the status of the blood and plasma supply, the infection status of individual donors, and the mechanisms by which SARS-CoV-2 activates coagulation are all of concern. In this review, we discuss these topics from the basic research perspective. As in other respiratory illnesses, blood and plasma from COVID-19 positive patients carries minimal to no risk of infection to practitioners or researchers. There are currently no special regulatory mandates directing individual donors (for research purposes), blood centers/services or vendors (for blood products for research) to test blood/plasma for SARS-CoV-2 or antibodies. We discuss current theories about how SARS-CoV-2 leads to hyper-coagulant state in severe cases of COVID-19. Our current understanding of the mechanisms behind COVID-19 associated thromboembolic events have centered around three different pathways: (1) direct activation of platelets, enhancing coagulation; (2) direct infection and indirect activation (e.g. cytokine storm) of endothelial cells by SARS-CoV-2, shifting endothelium from an anti-thrombotic to a pro-thrombotic state; and (3) direct activation of complement pathways, promoting thrombin generation. Further investigation on how SARS-CoV-2 affects thrombosis in COVID-19 patients may bring novel anti-thrombotic therapies to combat the disease.
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http://dx.doi.org/10.1007/s12195-021-00685-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238024PMC
June 2021

Damage to intestinal barrier integrity in piglets caused by porcine reproductive and respiratory syndrome virus infection.

Vet Res 2021 Jun 23;52(1):93. Epub 2021 Jun 23.

College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.

Porcine reproductive and respiratory syndrome (PRRS) induces respiratory disease and reproductive failure accompanied by gastroenteritis-like symptoms. The mechanism of intestinal barrier injury caused by PRRSV infection in piglets has yet to be investigated. An in vivo PRRSV-induced model was established in 30-day-old piglets by the intramuscular injection of 2 mL of 10 TCID/mL PRRSV for 15 days. Observations of PRRSV replication and histology were conducted in the lungs and intestine, and goblet cell counts, relative MUC2 mRNA expression, and tight junction protein, proinflammatory cytokine, TLR4, MyD88, IκB and p-IκB expression were measured. PRRSV replicated in the lungs and small intestine, as demonstrated by absolute RT-qPCR quantification, and the PRRSV N protein was detected in the lung interstitium and jejunal mucosa. PRRSV infection induced both lung and gut injury, markedly decreased villus height and the villus to crypt ratio in the small intestine, and obviously increased the number of goblet cells and the relative expression of MUC2 mRNA in the jejunum. PRRSV infection aggravated the morphological depletion of tight junction proteins and increased IL-1β, IL-6, IL-8 and TNF-α expression by activating the NF-κB signalling pathway in the jejunum. PRRSV infection impaired intestinal integrity by damaging physical and immune barriers in the intestine by inducing inflammation, which may be related to the regulation of the gut-lung axis. This study also provides a new hypothesis regarding the pathogenesis of PRRSV-induced diarrhoea.
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http://dx.doi.org/10.1186/s13567-021-00965-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220790PMC
June 2021

Copper-Catalyzed Synthesis of Indolyl Benzo[]carbazoles and Their Photoluminescence Property.

Org Lett 2021 Jul 18;23(13):5133-5137. Epub 2021 Jun 18.

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Science, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.

A copper-catalyzed cascade cyclization of dihydroisobenzofurans with indoles for the rapid construction of indoly benzo[]carbazoles has been reported, providing the desired products in moderate to good yields under mild conditions along with a broad substrate scope and good functional group tolerance. The photoluminescence property of these indoly benzo[]carbazoles has also been investigated.
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http://dx.doi.org/10.1021/acs.orglett.1c01659DOI Listing
July 2021

Identification of Significant Predictors for the Need of Insulin Therapy and Onset of Postpartum Impaired Glucose Tolerance in Gestational Diabetes Mellitus Patients.

Diabetes Metab Syndr Obes 2021 10;14:2609-2617. Epub 2021 Jun 10.

Department of Reproductive Medicine Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Background: Gestational diabetes mellitus (GDM) during pregnancy can greatly increase the risk for a number of adverse prenatal and postpartum consequences, including postpartum impaired glucose tolerance (IGT). Determining the need for insulin therapy is critical for controlling the glycemic level in GDM patients. The study contains two major purposes: 1) to identify the potential predictors for the need of insulin therapy in GDM patients; 2) to identify the factors that are related to the onset of postpartum IGT.

Materials And Methods: Here, we performed a retrospective study on 112 GDM patients in China to identify the significant predictors for the need of insulin therapy and onset of postpartum IGT in patients with GDM.

Results: Age and gestational weeks at GDM diagnosis, pregestational BMI, family history of diabetes mellitus (DM), plasma glucose levels assessed by 75-g OGTT at both the 1-hour and 2-hour time points (PG-1h and PG-2h) and HbA1c level were all significantly different between the patients that received insulin therapy and those did not. During postpartum, family history of DM, PG-1h PG-2h and HbA1c level were found to be significantly different between the patients with normal glucose tolerance and those with IGT.

Conclusion: Our results reveal a number of factors that are closely associated with the need of insulin therapy and onset of postpartum IGT, especially the PG-1h and PG-2h levels. These findings will provide valuable indications on selection of treatment strategy for GDM and GDM-induced postpartum IGT.
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http://dx.doi.org/10.2147/DMSO.S309618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203192PMC
June 2021

Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe.

Chem Sci 2020 May 11;11(20):5238-5245. Epub 2020 May 11.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School Room 2301, Building 149, Charlestown Boston Massachusetts 021291 USA

Differentiating amyloid beta (Aβ) subspecies Aβ40 and Aβ42 has long been considered an impossible mission with small-molecule probes. In this report, based on recently published structures of Aβ fibrils, we designed iminocoumarin-thiazole (ICT) fluorescence probes to differentiate Aβ40 and Aβ42, among which Aβ42 has much higher neurotoxicity. We demonstrated that robustly responds to Aβ fibrils, evidenced by turn-on fluorescence intensity and red-shifting of emission peaks. Remarkably, showed different spectra towards Aβ40 and Aβ42 fibrils. results demonstrated that could be used to differentiate Aβ40/42 in solutions. Moreover, our data revealed that could be used to separate Aβ40/42 components in plaques of AD mouse brain slides. In addition, two-photon imaging suggested that was able to cross the BBB and label plaques . Interestingly, we observed that was specific toward plaques, but not cerebral amyloid angiopathy (CAA) on brain blood vessels. Given Aβ40 and Aβ42 species have significant differences of neurotoxicity, we believe that can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.
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http://dx.doi.org/10.1039/d0sc02060eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159352PMC
May 2020

CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More.

Front Cell Dev Biol 2021 20;9:674467. Epub 2021 May 20.

Department of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

In recent years, immunotherapy has showed fantastic promise in pioneering and accelerating the field of cancer therapy and embraces unprecedented breakthroughs in clinical practice. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as a versatile gene-editing technology, lays a robust foundation to efficiently innovate cancer research and cancer therapy. Here, we summarize recent approaches based on CRISPR/Cas9 system for construction of chimeric antigen receptor T (CAR-T) cells and T cell receptor T (TCR-T) cells. Besides, we review the applications of CRISPR/Cas9 in inhibiting immune checkpoint signaling pathways and highlight the feasibility of CRISPR/Cas9 based engineering strategies to screen novel cancer immunotherapy targets. Conclusively, we discuss the perspectives, potential challenges and possible solutions in this vivid growing field.
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http://dx.doi.org/10.3389/fcell.2021.674467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172808PMC
May 2021

Synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells.

Biochem Cell Biol 2021 06 26;99(3):322-329. Epub 2021 May 26.

Hangzhou Cancer Hospital, No. 34 Yanguanxiang, Hangzhou Zhejiang 310002, China.

This study explored the synergistic effects of autophagy inhibitors combined with cisplatin against cisplatin-resistant nasopharyngeal cancer cells by treating HNE-1 and cisplatin (diamminedichloroplatinum; DDP)-resistant HNE1/DDP nasopharyngeal cancer cell lines with DDP, autophagy inhibitors, or a combination of autophagy inhibitors and DDP. Cell viability was determined via MTT (colorimetric) and colony-forming assays, and the rate of apoptosis was determined using propidium iodide (PI) and annexin V double-staining. The expressions of proteins were determined by Western blotting. For our in-vivo studies, a murine xenograft model was established to evaluate the anti-tumor effects of the combination of autophagy inhibitor and DDP. The results showed that treatment with DDP increased the expressions of ATP-binding cassette sub-family B member 1 (ABCB1), ATP Binding Cassette Subfamily C Member 1 (ABCC1), and P-glycoprotein 1 (P-gp) in the HNE1/DDP cell lines. Treatment with chloroquine decreased the expression levels of ABCB1, ABCC1, and P-gp, and increased the formation of LC3-II and the expression levels of p62 in the HNE1/DDP cells. Additionally, the combination of autophagy inhibitors and DDP produced a synergistic effect on DDP-induced cell death and apoptosis. Furthermore, the combination of the autophagy inhibitor and DDP showed significant anti-tumor effects in the xenograft mouse model. In summary, autophagy inhibitors show synergistic anti-tumor effects with DDP in vitro against DDP-resistant nasopharyngeal cancer cells and in vivo in our xenograft murine model.
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http://dx.doi.org/10.1139/bcb-2020-0283DOI Listing
June 2021

Probing Biosensing Interfaces With Single Molecule Localization Microscopy (SMLM).

Front Chem 2021 29;9:655324. Epub 2021 Apr 29.

Core Facilities, School of Medicine, Zhejiang University, Hangzhou, China.

Far field single molecule localization microscopy (SMLM) has been established as a powerful tool to study biological structures with resolution far below the diffraction limit of conventional light microscopy. In recent years, the applications of SMLM have reached beyond traditional cellular imaging. Nanostructured interfaces are enriched with information that determines their function, playing key roles in applications such as chemical catalysis and biological sensing. SMLM enables detailed study of interfaces at an individual molecular level, allowing measurements of reaction kinetics, and detection of rare events not accessible to ensemble measurements. This paper provides an update to the progress made to the use of SMLM in characterizing nanostructured biointerfaces, focusing on practical aspects, recent advances, and emerging opportunities from an analytical chemistry perspective.
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http://dx.doi.org/10.3389/fchem.2021.655324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117217PMC
April 2021

Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A.

Br J Clin Pharmacol 2021 May 14. Epub 2021 May 14.

Takeda Pharmaceuticals USA, Ltd, Cambridge, MA, USA.

Aims: Dysregulation of histone methylation epigenetic marks may result in intellectual and developmental disability, as seen in Kabuki syndrome. Animal data suggest that increasing histone methylation by inhibiting lysine-specific demethylase 1A (LSD1) may improve cognitive outcomes in a model of Kabuki syndrome. TAK-418 is a novel LSD1 inhibitor, developed as a potential therapeutic agent for central nervous system disorders such as Kabuki syndrome. Here, we report safety, tolerability, pharmacokinetic and pharmacodynamic profiles of single and multiple doses of TAK-418 (ClinicalTrials.gov: NCT03228433, NCT03501069).

Methods: Two randomized, double-blind, placebo-controlled, phase 1 studies of oral TAK-418 were performed, a first-in-human single-rising-dose (SRD) study (5-60 mg) in healthy adult male and female volunteers (placebo, n = 10; TAK-418, n = 30), and an SRD (120-160 mg) and multiple-rising-dose (MRD) study (20-160 mg once daily for 10 days) in healthy female volunteers (placebo, n = 2 [SRD] and n = 6 [MRD]; TAK-418, n = 6 [SRD] and n = 18 [MRD]).

Results: TAK-418 was well tolerated. No clinically significant changes in laboratory test results or vital signs were observed and no serious adverse events were reported. TAK-418 had a nearly linear pharmacokinetic profile, with rapid absorption and short terminal half-life across the evaluated dose range. No obvious accumulation was observed after daily administration for 10 days. Administration with food delayed peak plasma concentrations but overall exposure was unaffected. TAK-418 rapidly crossed the blood-brain barrier and generally showed a dose-dependent response in the peripheral pharmacodynamic biomarker formyl-flavin adenine dinucleotide.

Conclusion: The brain-penetrant LSD1 inhibitor TAK-418 was well tolerated, with pharmacokinetic and pharmacodynamic effects that support further investigation.
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http://dx.doi.org/10.1111/bcp.14912DOI Listing
May 2021

A review on China's constructed wetlands in recent three decades: Application and practice.

J Environ Sci (China) 2021 Jun 11;104:53-68. Epub 2020 Dec 11.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Constructed wetlands (CWs) have been introduced to and developed in China for environmental engineering over the most prosperous three decades (1990-2020). To study the origin, development process, and future trend of CWs, this review summarized a wide range of literatures between 1990 and 2020 by Chinese authors. Firstly, the publication number over years, research highlights, and the author contributions with the most published papers in this field were conducted through bibliometric analysis. Secondly, the most principal components of CWs, substrates and macrophytes were summarized and analyzed. Thirdly, the typical application cases from traditional CWs, pond systems to combined pond-wetland systems were presented. In China, CWs were predominately distributed in the east of the so-called 'Hu Huanyong Line'. Therefore CWs were limited by the socio-economic level and climatic conditions. It is unquestionable that the overall level of China's CWs has improved significantly, and one of the most prominent features has started towards the plural pattern development. There has been a trend of large-scale or low-cost CW application in the recent years. However, lifecycle research and management are required for better strategies in the future.
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http://dx.doi.org/10.1016/j.jes.2020.11.032DOI Listing
June 2021

Single-shot 3D shape measurement using an end-to-end stereo matching network for speckle projection profilometry.

Opt Express 2021 Apr;29(9):13388-13407

Speckle projection profilometry (SPP), which establishes the global correspondences between stereo images by projecting only a single speckle pattern, has the advantage of single-shot 3D reconstruction. Nevertheless, SPP suffers from the low matching accuracy of traditional stereo matching algorithms, which fundamentally limits its 3D measurement accuracy. In this work, we propose a single-shot 3D shape measurement method using an end-to-end stereo matching network for SPP. To build a high-quality SPP dataset for training the network, by combining phase-shifting profilometry (PSP) and temporal phase unwrapping techniques, high-precision absolute phase maps can be obtained to generate accurate and dense disparity maps with high completeness as the ground truth by phase matching. For the architecture of the network, a multi-scale residual subnetwork is first leveraged to synchronously extract compact feature tensors with 1/4 resolution from speckle images for constructing the 4D cost volume. Considering that the cost filtering based on 3D convolution is computationally costly, a lightweight 3D U-net network is proposed to implement efficient 4D cost aggregation. In addition, because the disparity maps in the SPP dataset should have valid values only in the foreground, a simple and fast saliency detection network is integrated to avoid predicting the invalid pixels in the occlusions and background regions, thereby implicitly enhancing the matching accuracy for valid pixels. Experiment results demonstrated that the proposed method improves the matching accuracy by about 50% significantly compared with traditional stereo matching methods. Consequently, our method achieves fast and absolute 3D shape measurement with an accuracy of about 100µm through a single speckle pattern.
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http://dx.doi.org/10.1364/OE.418881DOI Listing
April 2021

Palladium catalyzed divergent cycloadditions of vinylidenecyclopropane-diesters with methyleneindolinones enabled by zwitterionic π-propargyl palladium species.

Chem Commun (Camb) 2021 May;57(39):4783-4786

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, People's Republic of China. and State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.

A palladium-catalyzed divergent synthesis of spirooxindoles fused with a five- or a six-membered ring by a cycloaddition reaction of vinylidenecyclopropane-diesters with methyleneindolinones was disclosed. This protocol features an in situ generated unprecedented zwitterionic π-propargyl palladium species in cycloaddition reactions and a switchable process between (3+2) and (4+2) cycloadditions by changing the phosphine ligand.
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http://dx.doi.org/10.1039/d1cc01453fDOI Listing
May 2021
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