Publications by authors named "Kaixuan Wang"

70 Publications

Positive Crosstalk Between Hedgehog and NF-κB Pathways Is Dependent on KRAS Mutation in Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 11;11:652283. Epub 2021 May 11.

Department of Gastroenterology, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Suzhou, China.

It has been shown that aberrant activation of the Hedgehog (Hh) and nuclear factor-kappa B (NF-κB) signaling pathways plays an important role in the pancreatic carcinogenesis, and KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDAC). Until now, the role of KRAS mutation in the context of crosstalk between Hh and NF-κB signaling pathways in PDAC has not been investigated. This study was to determine whether the crosstalk between the Hh and NF-κB pathways is dependent on KRAS mutation in PDAC. The correlation between Gli1, Shh, NF-κB p65 expression and KRAS mutation in PDAC tissues was firstly examined by immunohistochemistry. Next, Western blotting, qPCR, and immunofluorescence were conducted to examine the biological effects of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) as NF-κB signaling agonists, Shh as an Hh ligand alone or in combination with KRAS small interfering RNA (si-KRAS) in KRAS-mutant PDAC cells (MT-KRAS; SW1990 and Panc-1), wild-type KRAS PDAC cells (WT-KRAS; BxPC-3) and mutant KRAS knock-in BxPC-3 cells as well as tumor growth . KRAS mutation-dependent crosstalk between Hh and NF-κB in PDAC cells was further assessed by Ras activity and luciferase reporter assays. The aberrant Hh and NF-κB pathway activation was found in PDAC tissues with KRAS mutation. The same findings were confirmed in MT-KRAS PDAC cells and MT-KRAS knock-in BxPC-3 cells, whereas this activation was not observed in WT-KRAS PDAC cells. However, the activation was significantly down-regulated by KRAS silencing in MT-KRAS PDAC cells. Furthermore, MT-KRAS cancer cell proliferation and survival and tumor growth after inoculation with MT-KRAS cells were promoted by NF-κB and Hh signaling activation. The pivotal factor for co-activation of NF-κB and Hh signaling is MT-KRAS protein upregulation, showing that positive crosstalk between Hh and NF-κB pathways is dependent upon KRAS mutation in PDAC.
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http://dx.doi.org/10.3389/fonc.2021.652283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144522PMC
May 2021

Effect of High Strain Rate on Adiabatic Shearing of α+β Dual-Phase Ti Alloy.

Materials (Basel) 2021 Apr 19;14(8). Epub 2021 Apr 19.

State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi'an 710072, China.

In the present work, the localized features of adiabatic shear bands (ASBs) of our recently designed damage tolerance α+β dual-phase Ti alloy are investigated by the integration of electron backscattering diffraction and experimental and theoretical Schmid factor analysis. At the strain rate of 1.8 × 10 s induced by a split Hopkinson pressure bar, the shear stress reaches a maximum of 1951 MPa with the shear strain of 1.27. It is found that the α+β dual-phase colony structures mediate the extensive plastic deformations along α/β phase boundaries, contributing to the formations of ASBs, microvoids, and cracks, and resulting in stable and unstable softening behaviors. Moreover, the dynamic recrystallization yields the dispersion of a great amount of fine α grains along the shearing paths and in the ASBs, promoting the softening and shear localization. On the contrary, low-angle grain boundaries present good resistance to the formation of cracks and the thermal softening, while the non-basal slipping dramatically contributes to the strain hardening, supporting the promising approaches to fabricate the advanced damage tolerance dual-phase Ti alloy.
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http://dx.doi.org/10.3390/ma14082044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073931PMC
April 2021

KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.

Int J Mol Med 2021 06 13;47(6). Epub 2021 Apr 13.

Department of Urology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

Bladder cancer (BC) is among the most common urinary system tumors with a high morbidity and mortality worldwide. Despite advancements being made in the diagnosis and treatment of bladder cancer, targeted therapy remains the most promising treatment, and novel therapeutic targets are urgently required in to improve the outcomes of patients with BC. Kinesin family member 4A (KIF4A) is a plus‑end directed motor protein involved in the regulation of multiple cellular processes, such as mitosis and axon growth. Notably, KIF4A plays important roles in tumor growth and progression, and its expression is associated with the prognosis of several types of cancer. However, the potential role and molecular mechanisms of KIF4A in bladder cancer development remain unclear. The present study demonstrated that KIF4A was highly expressed in human BC tissues, and its expression was associated with patient clinicopathological characteristics, such as tumor stage (P=0.012) and with the prognosis of patients with BC. It was further found that KIF4A promoted the cell proliferation of bladder cancer both and . On the whole, the data presented herein provide evidence that KIF4A promotes the development of BC through the transcriptional activation of the expression of CDCA3. The present study indicates the involvement of KIF4A in the progression of BC and suggests that KIF4A may be a promising therapeutic target for the treatment of BC.
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http://dx.doi.org/10.3892/ijmm.2021.4932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041479PMC
June 2021

Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease.

Drug Deliv 2021 Dec;28(1):580-593

Department of Pharmacy, Affiliated Hospital of Guilin Medical University, Guilin, China.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-β (Aβ) protein by GO. Both and models were induced using Aβ, and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels ; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Aβ-induced AD. This proved that GO loaded with Dau could protect against Aβ-induced oxidative damage and apoptosis in both and AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD.
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http://dx.doi.org/10.1080/10717544.2021.1895909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971267PMC
December 2021

Soft gold nanowire sponge antenna for battery-free wireless pressure sensors.

Nanoscale 2021 Feb;13(7):3957-3966

Department of Chemical Engineering, Monash University Clayton, Victoria 3800, Australia.

The past decade has witnessed growing interest in developing soft wearable pressure sensors with the ultimate goal of transforming today's hospital-centered diagnosis to tomorrow's patient-centered bio-diagnosis. In this context, battery-free wireless antenna-based pressure sensors will be highly advantageous for ubiquitous real-time health monitoring. However, current wireless antennas are largely based on thin films from traditional bulk metallic films or novel nanomaterials with an air-cavity design, which can only be operated in a limited pressure range due to the rigidity of active films and/or inherent cavity dimensions. Herein we report a soft battery-free wireless pressure sensor that is based on a three-dimensional (3D) porous gold nanowire foam-elastomer composite and is fabricated by solution-based conformal electroless plating technology, followed by elastomer encapsulation. We observe a transducer trade-off point for our foam antenna, below which the inductive effect and capacitive effect function together and above which the capacitive effect dominates. When an external pressure is applied, initially the inductance and capacitance increase simultaneously but the capacitance decreases afterwards. This can be transformed into a variable resonant frequency that first decreases linearly and then increases (in the capacitance domination pressure range). Importantly, the linear detection range of the sensor can be tuned simply by adjusting the thickness of the sponge or the rigidity of the elastomer (PDMS). We can achieve a wide pressure range of 0-248 kPa, which is the largest linear detection range reported in the literature (typically from 0 to 30 kPa) to the best of our knowledge. As a proof of concept, we further demonstrated that our gold nanowire foam sensor can be used to weigh people under both static and dynamic conditions.
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http://dx.doi.org/10.1039/d0nr07621jDOI Listing
February 2021

Efficient electrocatalysis for denitrification by using TiO nanotube arrays cathode and adding chloride ions.

Chemosphere 2021 Jul 23;274:129706. Epub 2021 Jan 23.

School of Mechanical Engineering and Birck Nanotechnology Center, Purdue University, West Lafayette, IN, 47907, USA.

Electrocatalysis is emerging as a promising alternative to bacterial denitrification for removing nitrate and ammonia from sewage. The technology is highly efficient and robust in actual wastewater treatment scenarios; however, there may be the generation of harmful intermediates (such as nitrite) on the traditional cathode material. In this study, we demonstrated that TiO nanotube arrays can be used as an effective cathode to reduce nitrate to ammonia without generation of nitrite. Alongside this, the addition of chloride ions in the solution can further oxidize ammonia to N. We looked into the key factors influencing the electrocatalytic denitrification, including the current density (2-10 mA/cm), initial pH values (3-11), and types of anions (HCO, Cl, SO). The results showed that 90.8% of nitrate and 59.4% of total nitrogen could be removed in 1.5 h under optimal conditions, with degradation kinetic constants of 1.61 h and 0.79 h, respectively. Furthermore, we investigated the formation of intermediate products and explored the electrocatalytic denitrification mechanism: (a) the surface oxygen vacancies and high specific surface area of TiO nanotube arrays electrode promote the reduction of nitrate to ammonia and N; (b) the active chlorine generated at the anode surface can effectively oxidize ammonium to N.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129706DOI Listing
July 2021

Controlling of two destructive zooplanktonic predators in Chlorella mass culture with surfactants.

Biotechnol Biofuels 2021 Jan 14;14(1):21. Epub 2021 Jan 14.

Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, 430074, China.

Background: Predatory flagellates and ciliates are two common bio-contaminants which frequently cause biomass losses in Chlorella mass culture. Efficient and targeted ways are required to control these contaminations in Chlorella mass cultivation aiming for biofuel production especially.

Results: Five surfactants were tested for its ability to control bio-contaminations in Chlorella culture. All five surfactants were able to eliminate the contaminants at a proper concentration. Particularly the minimal effective concentrations of sodium dodecyl benzene sulfonate (SDBS) to completely eliminate Poterioochromonas sp. and Hemiurosomoida sp. were 8 and 10 mg L, respectively, yet the photosynthesis and viability of Chlorella was not significantly affected. These results were further validated in Chlorella mass cultures in 5, 20, and 200 m raceway ponds.

Conclusions: A chemical method using 10 mg L SDBS as pesticide to control predatory flagellate or ciliate contamination in Chlorella mass culture was proposed. The method helps for a sustained microalgae biomass production and utilization, especially for biofuel production.
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http://dx.doi.org/10.1186/s13068-021-01873-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809840PMC
January 2021

Orientation-Dependent Soft Plasmonics of Gold Nanobipyramid Plasmene Nanosheets.

Nano Lett 2021 01 18;21(1):389-396. Epub 2020 Dec 18.

Department of Chemical Engineering, Faculty of Engineering, Monash University, Clayton 3800, Victoria Australia.

In parallel to the burgeoning field of soft electronics, soft plasmonics focuses on the design and fabrication of plasmonic structures supported on elastomers and to understand how their properties respond to mechanical deformations. Here, we report on a partial ligand-stripping strategy to fabricate elastomer-supported gold nanobipyramid (NBP) plasmene nanosheets. Unlike spherelike building blocks, NBP-building blocks display complex orientation-dependent plasmonic responses to external strains. By collecting polarized plasmonic resonance spectra in conjunction with electrostatic eigenmode modeling, we reveal simultaneous changes in interparticle spacing and spatial orientations of NBP building blocks under mechanical strains. Such changes are directly related to initial NBP packing orders. Further analysis of strain sensitivities for various NBP plasmenes indicated that plasmonic spectra of ∼45° oriented samples are mostly susceptible to strain at acute polarized angles. The results presented may enable novel applications in future soft optoelectronic devices in sensing, encryption, and data storage.
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http://dx.doi.org/10.1021/acs.nanolett.0c03779DOI Listing
January 2021

A retrospective multicenter study comparing bupivacaine and ropivacaine in endoscopic ultrasound guided celiac plexus neurolysis.

Ann Palliat Med 2021 Feb 2;10(2):1755-1762. Epub 2020 Dec 2.

Department of Gastroenterology and Hepatology, Changhai Hospital, The Secondary Military Medical University, Shanghai, China.

Background: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) is widely practiced to palliate cancer pain in patients with inoperable abdominal malignancy. During CPN, the dehydrated alcohol is injected to ablate neural tissue and local anesthetics is to minimize the discomfort from alcohol injection. This study aims to compare the efficacy and safety of bupivacaine and ropivacaine in EUS-CPN.

Methods: We retrospectively pooled and analyzed two large EUS centers' 150 consecutive patients underwent EUS-CPN from January 2012 to March 2019. Patients were divided into 3 groups based on the selection of anesthetics: 0.5% ropivacaine (ROPI, n=23), 0.375% bupivacaine (0.375% BUPI, n=21), 0.75% bupivacaine (0.75% BUPI, n=106). Visual analogue scale (VAS) was used to measure pre/post-operative pain at 11 observation points. Additional data were collected from medical records.

Results: The incidence of procedure-related pain within 12 hours after CPN was significantly different among the three groups, 10.38% in 0.75% BUPI [OR =0.26 (95% CI: 0.07-0.94); P=0.04], 26.09% in ROPI and 23.81% in 0.375% BUPI group, respectively. The risk of post-procedural arrhythmia was similar between the 0.375% and 0.75% BUPI groups (19.05% versus 18.87%), while relatively lower in ROPI group (13.04%). No patients in any group developed symptoms of CNS toxicity related to anesthetics.

Conclusions: Compared with 0.375% bupivacaine and 0.5% ropivacaine, 0.75% bupivacaine in CPN can reduce post-procedural pain. Ropivacaine shows a tendency of less arrhythmogenic effect in CPN.
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http://dx.doi.org/10.21037/apm-20-1158DOI Listing
February 2021

A novel lncRNA PTTG3P/miR-132/212-3p/FoxM1 feedback loop facilitates tumorigenesis and metastasis of pancreatic cancer.

Cell Death Discov 2020 Nov 30;6(1):136. Epub 2020 Nov 30.

Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

Pseudogene pituitary tumor-transforming 3 (PTTG3P) is emerging as a key player in the development and progression of cancer. However, the biological role and clinical significance of PTTG3P in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we found that PTTG3P was significantly upregulated in PDAC tissues. Elevated PTTG3P expression correlated with larger tumor size and worse differentiation, and reduced overall survival. Bioinformatics and experimental evidence revealed that PTTG3P promoted malignant phenotypes and FoxM1 signaling pathway in PDAC cells. Mechanistically, PTTG3P functions as a microRNA sponge to positively regulate the expression of FoxM1 through sponging miR-132/212-3p. Moreover, it showed that FoxM1 transcriptionally activated PTTG3P expression, thus forming a feedback loop to promote the aggressiveness of PDAC cells. Taken together, our findings suggest that PTTG3P promotes PDAC progression through PTTG3P/miR-132/212-3p/FoxM1 feedforward circuitry and it may serve as a promising diagnostic marker or target for treatment in PDAC patients.
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http://dx.doi.org/10.1038/s41420-020-00360-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705684PMC
November 2020

Raney nickel coupled nascent hydrogen as a novel strategy for enhanced reduction of nitrate and nitrite.

Chemosphere 2021 Jan 6;263:128187. Epub 2020 Sep 6.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, 100875, People's Republic of China; Research Center for Eco-Environmental Engineering, Dongguan University of Technology, Dongguan, 523808, People's Republic of China. Electronic address:

Raney nickel (R-Ni) is a cost-effective hydrogenation catalyst, and nascent hydrogen (Nas-H) generated in situ on the cathode trends to more reactive than commercial hydrogen (Com-H). In the present work, nitrate and nitrite (NO) reduction via R-Ni/Nas-H catalytic system was investigated. The results show that hydrogenation of NO (C = 3.0 mM) follows pseudo-first-order reaction kinetics with kinetic constants of 5.18 × 10 min (NO) and 6.46 × 10 min (NO). The saturation demand for Nas-H is only 0.8 mL min at a fixed R-Ni dosage of 1.0 g L. The experiments reveal that both Nas-H and hydrogen adatoms (H∗) can drive the reduction of NO. The improved reduction ratios of NO are attributed to two aspects: (1) the micro/nano-sized Nas-H bubbles exhibits increased reactivity due to the fine dispersion of the hydrogen molecules; (2) the alkaline environment formed by the cathode positively maintain R-Ni activity, thus, Nas-H bubbles were more readily activated to generate powerful H∗. The results give insight into NO hydrogenation via introducing fine hydrogen resource, and can develop an efficient catalytic hydrogenation technique without noble metals.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128187DOI Listing
January 2021

Enhanced decomposition of long-chain perfluorocarboxylic acids (C9-C10) by electrochemical activation of peroxymonosulfate in aqueous solution.

Sci Total Environ 2021 Mar 20;758:143666. Epub 2020 Nov 20.

Research Center for Eco-environmental Engineering, Dongguan University of Technology, Dongguan, Guangdong 523808, PR China. Electronic address:

The decomposition of long-chain perfluorocarboxylic acids (PFCAs), including perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were investigated by electrochemical activation of peroxymonosulfate (PMS) on porous Ti/SnO-Sb membrane anode. The results indicated that PMS activation could efficiently promote PFNA/PFDA decomposition, with pseudo-first-order rate constants about 3.12/2.06 times as compared with that of direct electro-oxidations. The energy consumptions of PFNA and PFDA decomposition were 36.31 and 37.46 kWh·m·order, respectively. The quantitative detection results of •OH with electron paramagnetic resonance (EPR) demonstrated that PMS activation promoted •OH formation. The inhibited performance in radical scavengers indicated both •OH and SO might be mainly involved in PFNA decomposition, while SO might be mainly involved in PFDA decomposition during PMS activation process. The mineralization mechanism for long-chain PFCAs decomposition which was mainly by repeating CF-unzipping cycle via radical reaction based on the intermediates verification and mass balance of C and F, was proposed. These results suggested that electrochemical activation of PMS on porous Ti/SnO-Sb membrane anode exhibited high efficiency in mineralizing PFNA and PFDA under mild conditions. This work might provide an efficient way for persistent organic pollutants, including, but not limited to long-chain PFCAs elimination from wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143666DOI Listing
March 2021

Correction: FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer.

Oncogene 2020 Oct;39(42):6619-6620

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai, 200030, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41388-020-01441-6DOI Listing
October 2020

Application of surfactants for controlling destructive fungus contamination in mass cultivation of Haematococcus pluvialis.

Bioresour Technol 2020 Dec 15;317:124025. Epub 2020 Aug 15.

CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, PR China; Center of Economic Botany, Core Botanical Gardens, Chinese Academy of Sciences, Wuhan 430074, PR China. Electronic address:

Large-scale cultivation of Haematococcus pluvialis is frequently contaminated by the destructive fungus Paraphysoderma sedebokerense, which can cause huge losses in astaxanthin production. Here, we propose the use of four commercial surfactants to control P. sedebokerense contamination in H. pluvialis cultures. In laboratory experiments, sodium dodecylbenzene sulfonate, sodium dodecyl sulfate and primary alcohol ethoxylate treatments showed inhibitory effects on fungal contamination. Moreover, sodium dodecylbenzene sulfonate was the most promising because treatment at 7 mg L was effective against fungal infection without negatively affecting the growth or astaxanthin contents of H. pluvialis. This could be ascribed to their different cell coverings and structures. Additionally, applying sodium dodecylbenzene sulfonate to open raceway ponds prevented fungal contamination, and astaxanthin production reached 1.82 g m. Therefore, sodium dodecylbenzene sulfonate can be used as an effective and economical control agent for commercial production of astaxanthin fromH. pluvialis.
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http://dx.doi.org/10.1016/j.biortech.2020.124025DOI Listing
December 2020

Visible light-enabled selective depolymerization of oxidized lignin by an organic photocatalyst.

Chem Commun (Camb) 2020 Sep 21;56(76):11243-11246. Epub 2020 Aug 21.

Department of Chemistry, Shanghai Normal University, 100 Guilin Rd., Shanghai, 200234, China.

The development of an economic, environmental-friendly and energy-saving process for the selective depolymerization of lignin is an outstanding challenge. Herein, a novel and efficient visible-light-induced photocatalytic process for the selective depolymerization of lignin model compounds and organosolv lignin was first developed by using perylene diimide (PDI) as a metal-free organocatalyst. Interestingly, it can completely decompose the oxidized lignin models to phenolic and ketone fragmentation molecules with very high selectivity at room temperature under visible light illumination. Furthermore, the use of a home-made photocatalytic continuous-flow reactor efficiently shortened the reaction time within an hour. Even for organosolv lignin, nearly 86% mass ratio of lignin was degraded to low-molecular-mass monoaromatic or diaromatic products. We found that superior performances were realized by single-electron transfer (SET) from the photoexcited strongly reducing PDI˙ anion to the ketone groups of the β-O-4 linkage in the lignin.
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http://dx.doi.org/10.1039/d0cc01127dDOI Listing
September 2020

Amorphous Pd-Loaded TiO Electrode for Direct Anodic Destruction of Perfluorooctanoic Acid.

Environ Sci Technol 2020 09 17;54(17):10954-10963. Epub 2020 Aug 17.

Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut 06520, United States.

We here present a novel TiO-based electrode loaded with amorphous Pd clusters that achieve efficient anodic destruction of perfluorooctanoic acid (PFOA), a persistent water pollutant with significant environmental and human health concerns. These amorphous Pd clusters were characterized by the disordered, noncrystalline arrangement of Pd single atoms in close proximity, in contrast to crystalline Pd nanoparticles that have been often employed to tailor the electronic properties of an electrode. We found that the TiO electrode loaded with amorphous Pd clusters significantly outperformed the TiO electrode loaded with crystalline Pd particles due to enhanced electron transfer through dominant Pd-O bonds. Combined with the efficient binding of PFOA and its degradation intermediates to the fluorinated electrode surface, this electrode was capable of mineralizing PFOA and releasing fluoride as F. The reaction pathway was found to proceed without involving reactive oxygen species and therefore was not quenched by common anions in complex natural water systems such as chloride ions.
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http://dx.doi.org/10.1021/acs.est.0c03800DOI Listing
September 2020

PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.

Exp Cell Res 2020 10 25;395(2):112187. Epub 2020 Jul 25.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, 20030, Shanghai, China. Electronic address:

Growing evidences suggest that the overexpression of p21-activated kinase 5 (PAK5) plays an important role in various tumor progression. However, the role of PAK5 and its downstream target gene(s) in lung squamous cell carcinomas (LUSC) are waiting to be elucidated. TCGA data were utilized to evaluate the expression levels of PAK5 in LUSC. We then explored the role of PAK5 in maintaining the stem-like phenotype of lung squamous cancer cells through RT-PCR, flow cytometry, oncosphere-forming assay. In addition, co-immunoprecipitation, western blotting and immunofluorescence assays were used to determine SOX2 as a novel effector of PAK5. Xenograft models in nude mice were established to explore the roles of PAK5 in lung cancer growth. In this study, we have shown that PAK5 is overexpressed in LUSC tissues. The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. In xenograft models, knockdown or pharmacological inhibition of PAK5 suppressed the tumor growth and metastasis of lung squamous cancer cells in vivo. Taken together, our findings suggest that the PAK5-mediated SOX2 phosphorylation promoted the cancer stem cell-like phenotype of LUSC cells. PAK5 inhibition may be a promising target in the treatment of SOX2 positive lung squamous cell cancer.
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http://dx.doi.org/10.1016/j.yexcr.2020.112187DOI Listing
October 2020

Validation of a novel swine model for training in EUS-FNA (with videos).

Endosc Ultrasound 2020 Jul-Aug;9(4):232-237

Department of Gastroenterology, Changhai Hospital, Navy Medical University, Shanghai, China.

Background And Objectives: EUS-FNA is applied widely in clinical practice, but there remains a lack of authentic training models. The present study aimed to develop a novel swine training model and to perform a preliminary assessment of its feasibility and efficacy.

Materials And Methods: To create an internal lesion-like target, empty shells of iodine-125 seeds were implanted into the caudate lobe of the liver in Bama minipigs. A training program involving 10 trainees was subsequently carried out, in which a total of 60 needlings were performed, composed of 6 for each trainee obtained during two training steps. Comparisons of procedure-related variables were conducted between the two. Trainees completed a questionnaire to assess their basic endoscopic experiences and reasonability of the model.

Results: A target region of 2.0 cm × 2.0 cm in diameter was successfully established on the caudate lobe in all implanted pigs. In the training program, the average procedure time decreased from the first to the second step and the average time for the total 30 needlings' obtainment was significantly shorter for the second training step (23.8 ± 4.5 min vs. 40.9 ± 9.0 min, P < 0.001). For the second step, there was also a significant improvement in total success rate (86.7% vs. 56.7%, P = 0.020) and accuracy rate (76.7% vs. 43.3%, P = 0.017). All trainees scored the effectiveness of the model highly and all reported improved confidence after the training.

Conclusion: This novel swine training model could authentically mimic clinical EUS-FNA, providing an effective in vivo practice tool for novices before clinical practice.
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http://dx.doi.org/10.4103/eus.eus_13_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529007PMC
July 2020

In Situ One-Step Synthesis of Platinum Nanoparticles Supported on Metal-Organic Frameworks as an Effective and Stable Catalyst for Selective Hydrogenation of 5-Hydroxymethylfurfural.

ACS Omega 2020 Jul 25;5(26):16183-16188. Epub 2020 Jun 25.

The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.

A facile in situ one-step route for the preparation of platinum nanoparticles supported on metal-organic frameworks (MOFs) without adding stabilizing agents was developed. The obtained 10% [email protected] material possessed a large surface area and high crystallinity. Meanwhile, uniform and well-dispersed platinum nanoparticles were formed inside the cavities of MOFs, which could be attributed to the efficient complexation and stabilization effect derived from the dipyridyl groups. The as-synthesized 10% [email protected] sample showed high activity and selectivity in the hydrogenation of 5-hydroxymethylfurfural (HMF). This excellent catalytic performance could be attributed to the synergistic effects of well-dispersed platinum nanoparticles and electron donation offered by MOFs. Meanwhile, the presence of bipyridine ligands in the MOF framework avoided the irreversible adsorption of the hydrocarbon compounds, leading to the enhanced catalytic efficiency. Besides, it was easily recycled and reused at least five times, showing good recyclability.
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http://dx.doi.org/10.1021/acsomega.0c01759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346239PMC
July 2020

Effects of a trace amine-associated receptor 1 agonist RO 5263397 on ethanol-induced behavioral sensitization.

Behav Brain Res 2020 07 12;390:112641. Epub 2020 May 12.

Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, United States. Electronic address:

Background: Alcohol dependence is a chronic and severe health problem which puts a heavy burden on society. Alcohol activates mesolimbic dopamine circuity to achieve its reinforcing effect. While TAAR1 is critically involved in the modulation of dopamine, there is little evidence indicating that TAAR1 could play a role in behavioral effects of ethanol.

Methods: By using the animal model of behavioral sensitization induced by ethanol in mice, the present study was performed to investigate whether the activation of TAAR1 would affect the behavioral plasticity of ethanol.

Results: Repeated administration with ethanol induced a significant increased locomotion in WT mice with females showing higher level of sensitization to ethanol than male mice. The TAAR1 agonist RO5263397 significantly decreased the expression of ethanol-induced behavioral sensitization both in male and female WT mice (0.1 and 0.32 mg/kg). Repeated RO5263397 exposure also prevented the development of behavioral sensitization to ethanol both in male and female WT mice. Moreover, while TAAR1-KO mice developed normal levels of ethanol-induced behavioral sensitization, RO5263397 did not affect this behavior in TAAR1-KO mice.

Conclusions: These results indicated that the TAAR1 agonist RO5263397 negatively regulated the expression and development of ethanol-elicited behavioral sensitization in WT but not in TAAR1-KO mice. The present study suggests that TAAR1 is probably involved in certain addiction-like effects of alcohol and could be a useful drug target for the development of new medications to treat alcohol dependence.
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http://dx.doi.org/10.1016/j.bbr.2020.112641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286772PMC
July 2020

Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage.

J Nanobiotechnology 2020 Apr 19;18(1):61. Epub 2020 Apr 19.

Clinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China.

Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1β, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis.
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http://dx.doi.org/10.1186/s12951-020-00616-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168846PMC
April 2020

miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer.

J Cancer 2020 5;11(11):3199-3206. Epub 2020 Mar 5.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an JiaoTong University, 277 Yanta West Road, Xi'an, Shaanxi, China.

Gastric cancer (GC) exhibits a poor prognosis due to extensive invasion and lymphatic metastasis in the advanced stage. In this study, we firstly found that the expression of miR-204-5p markedly decreased in GC patients' tissue and serum, especially in GC with lymphatic metastasis. And ROC analysis showed miR-204-5p also served as a predicted factor for the lymphatic metastasis of GC. CXCL12 and CXCR4 were predicted and confirmed as the functional targets of miR-204-5p by Targetscan analysis, dual luciferase assay and western blotting analysis. In addition, we further determined that miR-204-5p suppresses migration and invasion in GC. This finding elucidates new functions and mechanisms for miR-204-5p in GC development and provides a new potential diagnostic marker and therapeutic targets for GC.
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http://dx.doi.org/10.7150/jca.33273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097947PMC
March 2020

Insights into electrochemical decomposition mechanism of lipopolysaccharide using TiO nanotubes arrays electrode.

J Hazard Mater 2020 06 8;391:122259. Epub 2020 Feb 8.

Research Center for Eco-environmental Engineering, Dongguan University of Technology, Dongguan, Guangdong 523808, PR China. Electronic address:

Electrochemical decomposition of lipopolysaccharide (LPS) was firstly investigated over titania nanotubes (TNTs) arrays electrode. The TNTs layer of this electrode consisted of numerous tubular structures which arranged tightly, and the average diameter of each nanotube is 100 ± 5 nm. The degradation of LPS and polysaccharides followed pseudo-first-order kinetics. The optimal LPS removal ratio was nearly 80 %. The endotoxin toxicity of LPS steadily decreased during the electrolysis process. The acute toxicity of the intermediates increased suddenly at the beginning of electrochemical degradation process (< 5 min), then maintained high inhibition ratio (> 95 %) for about 150 min, and decreased significantly (< 10 %) after electrolysis for 240 min. After 20 min of electrolysis, LPS with molecular weight of 116,854 Da was transformed into small molecular compounds with molecular weights of 59,312 - 12,209 Da. Possible degradation and detoxification mechanisms of LPS including electric-field-force-driving accumulation, adsorption and direct electron transfer on TNTs arrays electrode, and •OH oxidation were proposed. This study underscores that electrochemical technique can be applied to eliminate and decrease the toxicity of LPS from contaminated water.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122259DOI Listing
June 2020

Enhanced perfluorooctanoic acid degradation by electrochemical activation of peroxymonosulfate in aqueous solution.

Environ Int 2020 04 18;137:105562. Epub 2020 Feb 18.

Research Center for Eco-environmental Engineering, Dongguan University of Technology, Dongguan 523808, PR China. Electronic address:

Perfluorooctanoic acid (PFOA) was efficiently decomposed at Ti/SnO-Sb anode via peroxymonosulfate (PMS) activation. PFOA degradation followed both pseudo-zero-order (0-30 min) and pseudo-first-order (30-120 min) kinetics. The pseudo-first-order kinetics constant could increase to 0.0484 min (3.84 times higher than that without PMS) during 30-120 min electrolysis. The inhibited performance in radical scavengers implied both sulfate radical (SO) and hydroxyl radical (•OH) contributed to PFOA degradation. The •OH quantitative detection experiments demonstrated that SO formed from PMS activation could promote •OH generation (from 0.12 mM to 0.24 mM). Electron spin resonance (ESR) tests further proved that SO and •OH were generated during PFOA degradation. According to linear sweep voltammetry (LSV) analyses, the oxygen evolution potential (OEP) value of Ti/SnO-Sb electrode increased from 1.59 V to 1.72 V (vs SCE) via PMS addition, indicating the inhibited oxygen evolution which was beneficial for the reactive species formation (i.e. •OH, SO). On the basis of intermediates verification and mass balance of carbon and fluorine, PFOA was proposed to be oxidized into short-chain perfluorocarboxylic acids mainly by •OH and SO.
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http://dx.doi.org/10.1016/j.envint.2020.105562DOI Listing
April 2020

Antioxidative and antiapoptosis: Neuroprotective effects of dauricine in Alzheimer's disease models.

Life Sci 2020 Feb 27;243:117237. Epub 2019 Dec 27.

Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China. Electronic address:

Aims: Dauricine has been found that has significant neuroprotective effect on Alzheimer's disease (AD), but the mechanism is unclear, so we further investigated the possible mechanism of dauricine on AD.

Main Methods: Cell counting kit-8 (CCK8) was applied to measure the cytotoxicity of dauricine on SH-SY5Y cells that overexpress the Swedish mutant form of human β-amyloid precursor protein (APPsw) and control cells (Neo). We used the Cu to induce oxidative damage on APPsw cells, then tested the effect of dauricine on the damage and relative factors including reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) activity. The secretion level of amyloid beta 1-42(Aβ), protein expression of apoptosis-related factors and the components of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were determined by western blotting. Aβ-transgenic Caenorhabditis elegans GMC101, a model of AD, was applied to evaluate the neuroprotective effect of dauricine through the behavioral experiment and relative anti-oxidative tests.

Key Findings: In vitro, dauricine decreased the secretion level of Aβ, significantly reduced the level of Cu-induced ROS, and restored MMP and SOD activity in APPsw cells. Meanwhile, dauricine could suppress the activation of caspase-3 and to upregulate the expression of Bcl-2. Dauricine also regulated the proteins levels of Nrf2, and Kelch-like ECH-associated protein 1 (Keap1) that is necessary for the activation of Nrf2 in APPsw cell. As oxidative stress induced by Aβ or paraquat (PQ), dauricine showed protective effects in the survival experiment of GMC101 worms.

Significance: Those data revealed that dauricine has the pharmacological activity of anti-oxidative and anti-apoptosis, and shows the potential therapeutic value for AD.
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http://dx.doi.org/10.1016/j.lfs.2019.117237DOI Listing
February 2020

Stochastic Multi-Molecular Modeling Method of Organic-Modified Ceramics in Two-Photon Induced Photopolymerization.

Materials (Basel) 2019 Nov 24;12(23). Epub 2019 Nov 24.

Key Laboratory of Micro/Nano and Ultra-Precision Manufacturing, School of Mechatronic Engineering, Changchun University of Technology, Changchun 130012, China.

Organic-modified ceramics (Ormocer) are an outstanding class of hybrid materials due to the fact of their various excellent properties, and they have been successfully used in two-photon polymerization microfabrication fields. A series of functional devices has been fabricated and widely used in aerospace, information science, biomedicine, and other fields. However, quantization of intermolecular energy during the fabrication process is still a difficult problem. A stochastic multi-molecular modeling method is proposed in this paper. The detailed molecular-interaction energies during the photon polymerization of Ormocer were obtained by molecular dynamics analysis. The established molecular model was verified by comparing the simulated shrinkage results with commercial calibrated ones. This work is expected to provide a reference for optimizing the fabrication of organically modified ceramics and reducing photoresist shrinkage in two-photon polymerization.
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http://dx.doi.org/10.3390/ma12233876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926505PMC
November 2019

Aggregation kinetics and mechanisms of silver nanoparticles in simulated pollution water under UV light irradiation.

Water Environ Res 2020 Jun 5;92(6):840-849. Epub 2019 Dec 5.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, China.

This paper investigated the effect mechanism of complex components (fulvic acid [FA], sodium dodecylbenzene sulfonate [SDBS], and sodium nitrate [NaNO ]) on the aggregation kinetics of polyvinylpyrrolidone-modified silver nanoparticles (PVP-AgNPs) under UV irradiation. The results showed that FA and NaNO alone did not cause aggregation due to the high steric hindrance and/or electrostatic repulsive forces. In high concentration of SDBS solution (20-50 mM), the stability of PVP-AgNPs was reduced by adsorbing SDBS on nanoparticle surface and replacing their PVP coatings. A mixed system of two pollutants had a synergistic effect on PVP-AgNPs aggregation. In the mixed system of SDBS and FA, the interaction of SDBS and PVP-AgNPs dominated the aggregation of PVP-AgNPs. NaNO significantly improved the aggregation rate of PVP-AgNPs in SDBS solution due to the charge neutralization effect of electrolyte. In 20 mg/L FA solution, the aggregation rate increased slightly with increasing NaNO concentration from 50 to 200 mM due to the charge neutralization effect, while the hydrodynamic diameters of PVP-AgNPs increased linearly and rapidly to micrometer size because the spatial conformation of adsorbed FA became compact in high-salinity solution. The calculation results of eDLVO theory were basically consistent with most of the experimental results. PRACTITIONER POINTS: PVP-AgNPs was uniformly dispersed in NaNO or FA solution under UV irradiation. PVP-AgNPs formed aggregates in SDBS solutions under UV irradiation. A system with two mixed pollutants had a synergistic effect on promoting aggregation of PVP-AgNPs. eDLVO theory could explain the aggregation results in different chemical conditions except in NaNO solution.
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http://dx.doi.org/10.1002/wer.1276DOI Listing
June 2020

A strategy for identifying species-specific peptide biomarkers in deer-hide gelatin using untargeted and targeted mass spectrometry approaches.

Anal Chim Acta 2019 Dec 26;1092:32-41. Epub 2019 Sep 26.

School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53705, USA. Electronic address:

Deer-hide gelatin (DHG) is an important animal-derived traditional Chinese medicine (TCM), which has been applied in TCM for over 400 years. However, it is extremely difficult to distinguish DHG with adulteration or made with other animal skins due to the highly processing procedure. Therefore, a simple strategy for identifying species-specific peptide biomarkers in deer-hide gelatin (DHG) is needed. In the present study, untargeted and targeted mass spectrometry approaches were implemented to analyze comprehensive peptidomic profiles of trypsin-digested animal gelatins. Mathematics set theory was then used to interrogate the relationship between different samples and peptides in the target species set, while the peptides were not considered as species-specific biomarkers in other sets. Two peptides were identified as DHG-specific peptides. Targeted mass spectrometry approach was then used to verify these two peptides. It showed that these two peptides could be used for distinguishing DHG from other animal hide gelatins. The present strategy provides a simple method for peptide biomarker discovery, which can be applied in the identification of specific peptides in some highly processed animal derived traditional Chinese medicines (TCMs). Thus, the present work provides an effective strategy for rapid, simple discovery and application of species-specific peptide biomarkers to ensure animal derived TCMs quality and make them authenticable and traceable.
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http://dx.doi.org/10.1016/j.aca.2019.09.064DOI Listing
December 2019

Characterization of an Amphiphilic Phosphonated Calixarene Carrier Loaded With Carboplatin and Paclitaxel: A Preliminary Study to Treat Colon Cancer and .

Front Bioeng Biotechnol 2019 1;7:238. Epub 2019 Oct 1.

Clinical Research Center for Neurological Diseases of Guangxi Province, Affiliated Hospital of Guilin Medical University, Guilin, China.

The inadequacy of available detection methods and a naturally aggressive progression have made colon cancer the third most common type of cancer, accounting for ~10% of all cancer cases. The heterogeneity and genomic instability of colon cancer tumors make current treatments unsatisfactory. This study evaluated a novel nanoscale delivery platform comprising phosphonated calixarenes (P4C6) co-loaded with paclitaxel (PTX) and carboplatin (CPT). The nanoparticles showed average hydrodynamic sizes of 84 ± 8 nm for empty P4C6 nanoparticle and 119 ± 13 nm for PTX-CPT-P4C6. The corresponding zeta potentials were -40.8 ± 8.8 and -35.4 ± 4.2 mV. The optimal CPT:PTX ratio was 5.22:1, and PTX-CPT-P4C6 with this ratio was more cytotoxic against HT-29 cells than against Caco-2 cells (IC, 0.4 ± 0.02 vs. 2.1 ± 0.3 μM), and it induced higher apoptosis in HT-29 cells (56.6 ± 4.5 vs. 44.9 ± 3.44%). PTX-CPT-P4C6 inhibited the invasion and migration of HT-29 cells more strongly than the free drugs. It also inhibited the growth of HT-29 tumors in mice to the greatest extent of all formulations, with negligible side effects. This research demonstrates the potential of P4C6 to deliver two chemotherapeutic agents to colon cancer tumors to provide synergistic efficacy than single drug administration.
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http://dx.doi.org/10.3389/fbioe.2019.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779836PMC
October 2019

Asymmetric Synthesis of Oxa-Bridged Oxazocines through a Catalytic Rh /Zn Relay [4+3] Cycloaddition Reaction.

Angew Chem Int Ed Engl 2019 Dec 6;58(51):18438-18442. Epub 2019 Nov 6.

Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China.

Oxa-bridged oxazocines bearing three chiral carbon centers were synthesized efficiently through a bimetallic catalytic asymmetric tandem reaction of β,γ-unsaturated α-ketoesters with diazoimides. The process contained a rhodium-promoted in situ generation of isomünchnone from diazoimide decomposition, and a [4+3]-cycloaddition of β,γ-unsaturated α-ketoester catalyzed by a chiral N,N'-dioxide-Zn complex. Ligand-accelerated catalysis was found, and a possible transition-state model was proposed to explain the origin of stereoselectivity.
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http://dx.doi.org/10.1002/anie.201910898DOI Listing
December 2019