Publications by authors named "Weiwei Gao"

221 Publications

ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater.

J Am Chem Soc 2021 Jul 22. Epub 2021 Jul 22.

Department of NanoEngineering and Chemical Engineering Program, University of California San Diego, La Jolla, California 92093, United States.

The coronavirus SARS-CoV-2 can survive in wastewater for several days with a potential risk of waterborne human transmission, hence posing challenges in containing the virus and reducing its spread. Herein, we report on an active biohybrid microrobot system that offers highly efficient capture and removal of target virus from various aquatic media. The algae-based microrobot is fabricated by using click chemistry to functionalize microalgae with angiotensin-converting enzyme 2 (ACE2) receptor against the SARS-CoV-2 spike protein. The resulting ACE2-algae-robot displays fast (>100 μm/s) and long-lasting (>24 h) self-propulsion in diverse aquatic media including drinking water and river water, obviating the need for external fuels. Such movement of the ACE2-algae-robot offers effective "on-the-fly" removal of SARS-CoV-2 spike proteins and SARS-CoV-2 pseudovirus. Specifically, the active biohybrid microrobot results in 95% removal of viral spike protein and 89% removal of pseudovirus, significantly exceeding the control groups such as static ACE2-algae and bare algae. These results suggest considerable promise of biologically functionalized algae toward the removal of viruses and other environmental threats from wastewater.
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http://dx.doi.org/10.1021/jacs.1c04933DOI Listing
July 2021

Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis.

Nat Commun 2021 07 6;12(1):4136. Epub 2021 Jul 6.

Department of Nanoengineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

Acute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in 'lure and kill' mechanism (denoted 'MΦ-NP(L&K)') for the treatment of acute pancreatitis. MΦ-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MΦ-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders.
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http://dx.doi.org/10.1038/s41467-021-24447-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260623PMC
July 2021

Iridium-catalyzed regioselective hydrosilylation of internal alkynes facilitated by directing and steric effects.

Org Biomol Chem 2021 Jul;19(28):6216-6220

State Key Laboratory of Organic-Inorganic Composites, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.

Here we reported the iridium-catalyzed hydrosilylation of internal alkynes under simple and mild conditions. The intrinsic functional groups of alkyne substrates were disclosed to be crucial in facilitating both the hydrosilylation process and related regioselectivity owing to their coordination capability towards the iridium catalyst. Utilization of the steric trimethylsilyl-protected trihydroxysilane proved to be another critical factor in ensuring the efficient proceeding of this process.
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http://dx.doi.org/10.1039/d1ob00910aDOI Listing
July 2021

Genetically engineered cell membrane-coated nanoparticles for targeted delivery of dexamethasone to inflamed lungs.

Sci Adv 2021 Jun 16;7(25). Epub 2021 Jun 16.

Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.

As numerous diseases are associated with increased local inflammation, directing drugs to the inflamed sites can be a powerful therapeutic strategy. One of the common characteristics of inflamed endothelial cells is the up-regulation of vascular cell adhesion molecule-1 (VCAM-1). Here, the specific affinity between very late antigen-4 (VLA-4) and VCAM-1 is exploited to produce a biomimetic nanoparticle formulation capable of targeting inflammation. The plasma membrane from cells genetically modified to constitutively express VLA-4 is coated onto polymeric nanoparticle cores, and the resulting cell membrane-coated nanoparticles exhibit enhanced affinity to target cells that overexpress VCAM-1 in vitro. A model anti-inflammatory drug, dexamethasone, is encapsulated into the nanoformulation, enabling improved delivery of the payload to inflamed lungs and significant therapeutic efficacy in vivo. Overall, this work leverages the unique advantages of biological membrane coatings to engineer additional targeting specificities using naturally occurring target-ligand interactions.
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http://dx.doi.org/10.1126/sciadv.abf7820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208717PMC
June 2021

Atomic Force Microscopy Study of Non-DLVO Interactions between Drops and Bubbles.

Langmuir 2021 Jun 27;37(22):6830-6837. Epub 2021 May 27.

Beijing Key Laboratory of Urban Oil and Gas Distribution Technology, State Key Laboratory of Natural Gas Hydrates, MOE Key Laboratory of Petroleum Engineering, China University of Petroleum, Beijing, No. 18 Fuxue Road, Changping District, 102249 Beijing, P. R. China.

The heterointeraction between liquid drops and air bubbles dispersed in another immiscible liquid is studied with the application of the atomic force microscopy (AFM) probe techniques. The tetradecane drops and air bubbles readily coalescence to form a lens-like structure in 100 mM sodium chloride aqueous solution, demonstrating strong hydrophobic (HB) attraction. The interaction range and strength of this hydrophobic attraction between oil drops and air bubbles is investigated by fine control of electrical double layer thicknesses related to specific electrolyte concentrations, and a midrange term in combination with a short-range term is found to present a proper characterization of this hydrophobic attraction. A further step is taken by introducing a triblock copolymer (Pluronic F68) into the aqueous solution, with results indicating that a relatively long-range steric hindrance (SH) furnished by a polymer "brush" surmounts the hydrophobic attraction. Finally, the interaction between a water drop and an air bubble in tetradecane is also measured as a comparison. The repelling action between a hydrophobic body (air bubble) and water drop indicates a strong repulsion. The present results show an interesting understanding of hydrophobic interactions between drops and bubbles, which is of potential application in controlling dispersion stability.
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http://dx.doi.org/10.1021/acs.langmuir.1c00937DOI Listing
June 2021

Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway.

J Neuroinflammation 2021 May 22;18(1):119. Epub 2021 May 22.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Background: Cerebral ischemia-reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated.

Methods: We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen-glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization.

Results: The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2-3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood-brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments.

Conclusions: Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.
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http://dx.doi.org/10.1186/s12974-021-02174-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140477PMC
May 2021

Reversible fusion and fission of graphene oxide-based fibers.

Science 2021 05;372(6542):614-617

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Key Laboratory of Adsorption and Separation Materials and Technologies of Zhejiang Province, Zhejiang University, Hangzhou 310027, China.

Stimuli-responsive fusion and fission are widely observed in both bio-organizations and artificial molecular assemblies. However, the design of a system with structure and property persistence during repeated fusion and fission remains challenging. We show reversible fusion and fission of wet-spun graphene oxide (GO) fibers, in which a number of macroscopic fibers can fuse into a thicker one and can also separate into original individual fibers under stimulation of solvents. The dynamic geometrical deformation of GO fiber shells, caused by solvent evaporation and infiltration, is the key to the reversible fusion-fission cycles. This principle is extended to implement flexible transitions between complex fiber assemblies and the inclusion or expulsion of guest compounds.
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http://dx.doi.org/10.1126/science.abb6640DOI Listing
May 2021

A novel rat model of chronic subdural hematoma: Induction of inflammation and angiogenesis in the subdural space mimicking human-like features of progressively expanding hematoma.

Brain Res Bull 2021 Jul 28;172:108-119. Epub 2021 Apr 28.

Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin, 300052, China. Electronic address:

Pathophysiological mechanisms of chronic subdural hematoma (CSDH) involve localized inflammation, angiogenesis, and dysregulated coagulation and fibrinolysis. The scarcity of reproducible and clinically relevant animal models of CSDH hinders further understanding the underlying pathophysiology and improving new treatment strategies. Here, we developed a novel rat model of CSDH using extracellular matrices (Matrigel) and brain microvascular endothelial cell line (bEnd.3 cells). One hundred-microliter of Matrigel-bEnd.3 cell (10 cells per milliliter) mixtures were injected into the virtual subdural space of elderly male Sprague-Dawley rats. This approach for the first time led to a spontaneous and expanding subdural hematoma, encapsulated by internal and external neomembranes, formed as early as 3 d, reached its peak at 7 d, and lasted for more than 14 d, mimicking the progressive hemorrhage observed in patients with CSDH. The external neomembrane and hematoma fluid involved numerous inflammatory cells, fibroblasts, and highly fragile neovessels. Furthermore, a localized pathophysiological process was validated as evidenced by the increased expressions of inflammatory and angiogenic mediators in external neomembrane and hematoma fluid rather than in peripheral blood. Notably, the specific expression profiles of these mediators were closely associated with the dynamic changes in hematoma volume and neurological outcome. In summary, the CSDH model described here replicated the characteristics of human CSDH, and might serve as an ideal translational platform for preclinical studies. Meanwhile, the crucial roles of angiogenesis and inflammation in CSDH formation were reaffirmed.
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http://dx.doi.org/10.1016/j.brainresbull.2021.04.024DOI Listing
July 2021

Drug Targeting Platelet Membrane-Coated Nanoparticles.

Small Struct 2020 Oct 9;1(1). Epub 2020 Sep 9.

Departments of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.

Platelets possess distinct surface moieties responsible for modulating their adhesion to various disease-relevant substrates involving vascular damage, immune evasion, and pathogen interactions. Such broad biointerfacing capabilities of platelets have inspired the development of platelet-mimicking drug carriers that preferentially target drug payloads to disease sites for enhanced therapeutic efficacy. Among these carriers, platelet membrane-coated nanoparticles (denoted 'PNPs') made by cloaking synthetic substrates with the plasma membrane of platelets have emerged recently. Their 'top-down' design combines the functionalities of natural platelet membrane and the engineering flexibility of synthetic nanomaterials, which together create synergy for effective drug delivery and novel therapeutics. Herein, we review the recent progress of engineering PNPs with different structures for targeted drug delivery, focusing on three areas, including targeting injured blood vessels to treat vascular diseases, targeting cancer cells for cancer treatment and detection, and targeting drug-resistant bacteria to treat infectious diseases. Overall, current studies have established PNPs as versatile nanotherapeutics for drug targeting with strong potentials to improve the treatment of various diseases.
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http://dx.doi.org/10.1002/sstr.202000018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011559PMC
October 2020

Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors.

Nat Commun 2021 03 31;12(1):1999. Epub 2021 Mar 31.

Cello Therapeutics, Inc., San Diego, CA, 92121, USA.

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.
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http://dx.doi.org/10.1038/s41467-021-22311-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012593PMC
March 2021

Nanomaterial Biointerfacing via Mitochondrial Membrane Coating for Targeted Detoxification and Molecular Detection.

Nano Lett 2021 03 9;21(6):2603-2609. Epub 2021 Mar 9.

Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, California 92093, United States.

Natural cell membranes derived from various cell sources have been successfully utilized to coat nanomaterials for functionalization. However, intracellular membranes from the organelles of eukaryotes remain unexplored. Herein, we choose mitochondrion as a representative cell organelle and coat outer mitochondrial membrane (OMM) from mouse livers onto nanoparticles and field-effect transistors (FETs) through a membrane vesicle-substrate fusion process. Polymeric nanoparticles coated with OMM (OMM-NPs) can bind with ABT-263, a B-cell lymphoma protein 2 (Bcl-2) inhibitor that targets the OMM. As a result, OMM-NPs effectively protect the cells from ABT-263 induced cell death and apoptosis and attenuated ABT-263-induced thrombocytopenia . Meanwhile, FET sensors coated with OMM (OMM-FETs) can detect and distinguish anti-Bcl-2 antibody and small molecule agonists. Overall, these results show that OMM can be coated onto the surfaces of both nanoparticles and functional devices, suggesting that intracellular membranes can be used as coating materials for novel biointerfacing.
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http://dx.doi.org/10.1021/acs.nanolett.1c00238DOI Listing
March 2021

Synthesis of an isomer of lycoplanine A cascade cyclization to construct the spiro-N,O-acetal moiety.

Org Biomol Chem 2021 03;19(8):1748-1751

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China. and School of Pharmacy, Lanzhou University, No. 199 West Donggang Road, Lanzhou 730000, China.

An isomer of lycoplanine A with a 6/10/5/5 tetracyclic skeleton was synthesized using D-A reaction and cascasde reaction to respectively construct the [9.2.2] pentadecane skeleton and the challenging 1-oxa-6-azaspiro[4.4]nonane spirocenter. Morever, detailed DFT calculations were conducted to explain the selectivity in the D-A reaction. This study may provide sufficient experience for the total synthesis of lycoplanine A and other alkaloids with similar spiro-N,O-acetal cores.
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http://dx.doi.org/10.1039/d0ob02399jDOI Listing
March 2021

Cartilage-targeting ultrasmall lipid-polymer hybrid nanoparticles for the prevention of cartilage degradation.

Bioeng Transl Med 2021 Jan 10;6(1):e10187. Epub 2020 Sep 10.

Department of NanoEngineering Chemical Engineering Program, and Moores Cancer Center, University of California San Diego La Jolla California USA.

Current drug delivery approaches for the treatment of cartilage disorders such as osteoarthritis (OA) remain inadequate to achieve sufficient drug penetration and retention in the dense cartilage matrix. Herein, we synthesize sub-30 nm lipid-polymer hybrid nanoparticles functionalized with collagen-targeting peptides for targeted drug delivery to the cartilage. The nanoparticles consist of a polymeric core for drug encapsulation and a lipid shell modified with a collagen-binding peptide. By combining these design features, the nanoparticles can penetrate deep and accumulate preferentially in the cartilage. Using MK-8722, an activator of 5'-adenosine monophosphate-activated protein kinase (AMPK), as a model drug, the nanoparticles can encapsulate the drug molecules in high capacity and release them in a sustained and controllable manner. When injected into the knee joints of the mice with collagenase-induced OA, the drug-loaded nanoparticles can effectively reduce cartilage damage and alleviate the disease severity. Overall, the ultrasmall targeted nanoparticles represent a promising delivery platform to overcome barriers of dense tissues for the treatment of various indications, including cartilage disorders.
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http://dx.doi.org/10.1002/btm2.10187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823131PMC
January 2021

Morphology-Invariant Metallic Nanoparticles with Tunable Plasmonic Properties.

ACS Nano 2021 02 29;15(2):2428-2438. Epub 2021 Jan 29.

Department of Chemistry, University of Central Florida, Orlando, Florida 32816, United States.

Current methods for tuning the plasmonic properties of metallic nanoparticles typically rely on alternating the morphology (i.e., size and/or shape) of nanoparticles. The variation of morphology of plasmonic nanoparticles oftentimes impairs their performance in certain applications. In this study, we report an effective approach based on the control of internal structure to engineer morphology-invariant nanoparticles with tunable plasmonic properties. Specifically, these nanoparticles were prepared through selective growth of Ag on the inner surfaces of preformed Ag-Au alloyed nanocages as the seeds to form [email protected](Ag-Au) [email protected] nanocages. Plasmonic properties of the [email protected](Ag-Au) nanocages can be conveniently and effectively tuned by varying the amount of Ag deposited on the inner surfaces, during which the overall morphology of the nanocages remains unchanged. To demonstrate the potential applications of the [email protected](Ag-Au) nanocages, they were applied to colorimetric sensing of human carcinoembryonic antigen (CEA) that achieved low detection limits. This work provides a meaningful concept to design and craft plasmonic nanoparticles.
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http://dx.doi.org/10.1021/acsnano.0c06123DOI Listing
February 2021

Pd(II)-Catalyzed Annulation Reactions of Epoxides with Benzamides to Synthesize Isoquinolones.

Org Lett 2021 Feb 19;23(3):863-868. Epub 2021 Jan 19.

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China.

Epoxides as alkylating reagents are unprecedentedly applied in Pd(II)-catalyzed C-H alkylation and oxidative annulation of substituted benzamides to synthesize isoquinolones rather than isochromans, which is accomplished through alerting the previously reported reaction mechanism by the addition of oxidant and TEA. Under these conditions, various isoquinolones have been prepared with yields up to 92%. In addition, this methodology has been successfully employed in the total syntheses of rupreschstyril, siamine, and cassiarin A in an expedient fashion.
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http://dx.doi.org/10.1021/acs.orglett.0c04097DOI Listing
February 2021

Facile Method for Surface-Grafted Chitooligosaccharide on Medical Segmented Poly(ester-urethane) Film to Improve Surface Biocompatibility.

Membranes (Basel) 2021 Jan 4;11(1). Epub 2021 Jan 4.

Shandong Tianming Pharmaceutical Co., Ltd., Jinan 250100, China.

In the paper, the chitooligosaccharide (CHO) was surface-grafted on the medical segmented poly(ester-urethane) (SPU) film by a facile two-step procedure to improve the surface biocompatibility. By chemical treatment of SPU film with hexamethylene diisocyanate under mild reaction condition, free -NCO groups were first introduced on the surface with high grafting density, which were then coupled with -NH groups of CHO to immobilize CHO on the SPU surface (SPU-CHO). The CHO-covered surface was characterized by FT-IR and water contact angle test. Due to the hydrophilicity of CHO, the SPU-CHO possessed higher surface hydrophilicity and faster hydrolytic degradation rate than blank SPU. The almost overlapping stress-strain curves of SPU and SPU-CHO films demonstrated that the chemical treatments had little destruction on the intrinsic properties of the substrate. In addition, the significant inhibition of platelet adhesion and protein adsorption on CHO-covered surface endowed SPU-CHO an outstanding surface biocompatibility (especially blood compatibility). These results indicated that the CHO-grafted SPU was a promising candidate as blood-contacting biomaterial for biomedical applications.
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http://dx.doi.org/10.3390/membranes11010037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824666PMC
January 2021

Bidirectional mid-infrared communications between two identical macroscopic graphene fibres.

Nat Commun 2020 Dec 11;11(1):6368. Epub 2020 Dec 11.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38 Zheda Road, 310027, Hangzhou, People's Republic of China.

Among light-based free-space communication platforms, mid-infrared (MIR) light pertains to important applications in biomedical engineering, environmental monitoring, and remote sensing systems. Integrating MIR generation and reception in a network using two identical devices is vital for the miniaturization and simplification of MIR communications. However, conventional MIR emitters and receivers are not bidirectional due to intrinsic limitations of low performance and often require cryogenic cooling. Here, we demonstrate that macroscopic graphene fibres (GFs) assembled from weakly-coupled graphene layers allow room-temperature MIR detection and emission with megahertz modulation frequencies due to the persistence of photo-thermoelectric effect in millimeter-length and the ability to rapidly modulate gray-body radiation. Based on the dual-functionality of GFs, we set up a system that conducts bidirectional data transmission by switching modes between two identical GFs. The room-temperature operation of our systems and the potential to produce GFs on industrial textile-scale offer opportunities for simplified and wearable optical communications.
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http://dx.doi.org/10.1038/s41467-020-20033-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733474PMC
December 2020

First report of root rot caused by Fusarium armeniacum on American ginseng in China.

Plant Dis 2020 Nov 19. Epub 2020 Nov 19.

Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Medicinal Plant Development, 198148, Malianwa North Road 151, Haidian District, Beijing, P. R. China, Haidian District, China, 100193;

American ginseng (Panax quinquefolius) is an important medicinal plant cultivated in China since the 1980s. Its dried roots are used for food, health care products, and medicine in China (Yuan et al. 2010). Root rot caused by Fusarium spp. was a major disease, with 33 to 41% incidence surveyed in main production areas of Wendeng County (121.80 °E, 37.09 °N) in Shandong Province, China in 2016 to 2019. Symptoms included soft, water-soaked, dark brown to black lesions on the roots. Lesions progressed and the inner parts gradually disintegrated. One-year-old diseased roots were collected in September 2016. Symptomatic tissues were surface-sterilized in 75% ethanol for 30 s and 0.8% NaOCl for 3 min, rinsed in sterile water, plated on potato dextrose agar (PDA), and incubated at 25°C in darkness. Single colonies were then obtained and transferred to carnation leaf agar (CLA) (Burgess et al. 1993) for growth at 25°C with a 12-h photoperiod. Colonies cultured on PDA for 7 days were white to light pink, turning to apricot pigmentation in color. After 30 days on CLA, the colonies produced elongate, falcate macroconidia having 3 to 5 septa, with a long, tapering and curved apical cell, and having the size ranging from 31.1 to 45.6 μm long x 4 to 4.6 μm wide. Microconidia were zero to 1septate, ellipsoid to ovoid and varied in size from 9.5 to 16.8 μm long x 3 to 3.2 μm wide. Chlamydospores formed abundantly, in chains or clusters. This fungus was identified as F. armeniacum (Burgess et al. 1993). Identification was confirmed by sequencing three DNA regions including the internal spacer ribosomal DNA (ITS), elongation factor 1α and β-tubulin genes (Lu et al. 2019). The three DNA regions (MN417271, MG457199, and MN427653) had 100% homology to the sequences of F. armeniacum (KJ737378, HM744664 and HQ141640) (Wang et al. 2015, Yli-Mattila et al. 2011). Pathogenicity tests were conducted on 1- to 2-year-old bare roots and 2-year-old whole plants. For root inoculation, 14 healthy roots were inoculated with two mycelial PDA plugs/root. After 3 to 10 days at 25°C, all the inoculated roots showed water-soaked and root rot symptoms while no lesions were observed in the control roots. For plant inoculation, eight seedlings planted in pots filled with sterilized soil were inoculated by pouring a conidial suspension of 1×105 conidia/ml at 30 ml/pot. Eight seedlings inoculated with sterilized water served as the controls. After 90 days, only 37.5% of the roots survived with typical root rot symptoms whereas the control plants remained symptomless. F. armeniacum was re-isolated from symptomatic roots but not from the control roots. Besides F. armeniacum, F. solani and F. oxysporum that have been reported to be associated with American ginseng root rot in China and Canada (Reeleder et al. 2002; Punja et al. 2008) were also obtained from the diseased root samples in this study. However, the development of root rot caused by F. armeniacum was much more rapid and its symptoms were more severe. Moreover, F. armeniacum could directly infect American ginseng with no wound requirement. F. armeniacum was previously reported on Glycine max (Leguminosae) (Ellis et al. 2012), Platycodon grandiflorus (Campanulaceae) (Wang et al. 2015) and natural grasses (Poaceae) (Nichea et al. 2015). This is the first report of F. armeniacum causing root rot on American ginseng in China. As this species is more virulent to American ginseng, more research is needed to work on this disease.
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http://dx.doi.org/10.1094/PDIS-12-19-2554-PDNDOI Listing
November 2020

Prediction of Intrinsic Ferroelectricity and Large Piezoelectricity in Monolayer Arsenic Chalcogenides.

Nano Lett 2020 Nov 2;20(11):8346-8352. Epub 2020 Nov 2.

Center for Computational Materials, Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, Texas 78712, United States.

Two-dimensional materials that exhibit spontaneous electric polarization are of notable interest for functional materials. However, despite the prediction of many two-dimensional polar materials, the number of experimentally confirmed two-dimensional ferroelectrics is far less than bulk ferroelectrics. We provide strong evidence that the 2 phase of arsenic chalcogenides AsX (X = S, Se, and Te), which include the recently isolated monolayer orpiment, are intrinsic ferroelectrics and demonstrate strong in-plane piezoelectricity. We found the calculated energy barriers for collectively reversing the electric polarization or moving a 180° domain wall are reasonable compared to previously reported ferroelectrics. We propose a high-symmetry structure (with space group) that transforms into the ferroelectric 2 phase by a soft B phonon mode. By studying other soft modes of the high-symmetry structure, we identify several undiscovered metastable polymorphs, including a polar phase (with a 2 space group) with sizable piezoelectricity.
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http://dx.doi.org/10.1021/acs.nanolett.0c03511DOI Listing
November 2020

Nanomaterials arising amid antibiotic resistance.

Nat Rev Microbiol 2021 01;19(1):5-6

Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

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http://dx.doi.org/10.1038/s41579-020-00469-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538279PMC
January 2021

CD4 T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy.

mBio 2020 09 15;11(5). Epub 2020 Sep 15.

Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USA

Therapeutic strategies that provide effective and broad-spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4 T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outstanding neutralizing breadth and potency; they neutralized all 125 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, and transmitted/founder viruses, with a geometric mean 80% inhibitory concentration (IC) of 819μg ml (range, 72 to 8,570 μg ml). TNP also selectively bound to and induced autophagy in HIV-1-infected CD4 T cells and macrophages, while having no effect on uninfected cells. This TNP-mediated autophagy inhibited viral release and reduced cell-associated HIV-1 in a dose- and phospholipase D1-dependent manner. Genetic or pharmacological inhibition of autophagy ablated this effect. Thus, we can use TNP as therapeutic agents to neutralize cell-free HIV-1 and to target HIV-1 gp120-expressing cells to decrease the HIV-1 reservoir. HIV-1 is a major global health challenge. The development of an effective vaccine and/or a therapeutic cure is a top priority. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 hinders this progress. Here we developed an approach using nanoengineered CD4 T cell membrane-coated nanoparticles (TNP). Not only do TNP effectively neutralize all strains of HIV-1, but they also selectively bind to infected cells and decrease the release of HIV-1 particles through an autophagy-dependent mechanism with no drug-induced off-target or cytotoxic effects on bystander cells.
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http://dx.doi.org/10.1128/mBio.00903-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492730PMC
September 2020

FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer.

Respir Res 2020 Aug 10;21(1):210. Epub 2020 Aug 10.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.

Background: This study investigated the role of fibrinogen-like protein 1 (FGL1) in regulating gefitinib resistance of PC9/GR non-small cell lung cancer (NSCLC).

Methods: The effect of different concentrations of gefitinib on cell proliferation were evaluated using the CCK-8 assay. FGL1 expression in the normal human bronchial epithelial cell line Beas-2B, as well as four lung tumor cell lines, H1975, A549, PC9, and PC9/GR, was investigated by using western blotting and qRT-PCR. FGL1 was knocked down using small interfering RNA to evaluate the effects of FGL1 on PC9 and PC9/GR. The correlation between FGL1 expression and gefitinib resistance was determined in vitro via CCK-8 and colony formation assays, and flow cytometry and in vivo via flow cytometry and immunohistochemistry.

Results: FGL1 expression was significantly upregulated in non-small cell lung cancer cells with EGFR mutation and higher in the gefitinib-resistant NSCLC cell line PC9/GR than in the gefitinib-sensitive NSCLC cell line PC9. Further, FGL1 expression in PC9 and PC9/GR cells increased in response to gefitinib treatment in a dose-dependent manner. Knockdown of FGL1 suppressed cell viability, reduced the gefitinib IC50 value, and enhanced apoptosis in PC9 and PC9/GR cells upon gefitinib treatment. Mouse xenograft experiments showed that FGL1 knockdown in PC9/GR tumor cells enhanced the inhibitory and apoptosis-inducing actions of gefitinib. The potential mechanism of gefitinib in inducing apoptosis of PC9/GR cells involves inhibition of PARP1 and caspase 3 expression via suppression of FGL1.

Conclusions: FGL1 confers gefitinib resistance in the NSCLC cell line PC9/GR by regulating the PARP1/caspase 3 pathway. Hence, FGL1 is a potential therapeutic target to improve the treatment response of NSCLC patients with acquired resistance to gefitinib.
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http://dx.doi.org/10.1186/s12931-020-01477-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418324PMC
August 2020

A Transparent, Skin-Inspired Composite Film with Outstanding Tear Resistance Based on Flat Silk Cocoon.

Adv Mater 2020 Aug 19;32(34):e2002695. Epub 2020 Jul 19.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

Flexible and transparent substrates play a fundamental role as a mechanical support in advanced electronic devices. However, commonly used polymer films, such as polydimethylsiloxane, show low tear resistance because of their crack sensitivity. Herein, inspired by the excellent mechanical robustness of the skin and its fibrous structure, an epoxy-resin-based composite with a flat silk cocoon as a reinforcing fiber network is fabricated. With only 1 wt% of silk fiber, the tensile strength and modulus of the as-prepared composite film are considerably increased by 300% and 612% compared to those of pure resin, while still maintaining flexibility and transparency. More importantly, the composite shows remarkable tear resistance: without fracture after ≈30 000 tensile cycles. The potential application of such transparent composite films as mechanically robust substrates for flexible electronics is also demonstrated. In addition, this study represents a bioinspired strategy to construct high-performance functional composite materials.
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http://dx.doi.org/10.1002/adma.202002695DOI Listing
August 2020

The Comparison of HHHFNC and NCPAP in Extremely Low-Birth-Weight Preterm Infants After Extubation: A Single-Center Randomized Controlled Trial.

Front Pediatr 2020 26;8:250. Epub 2020 Jun 26.

Neonatal Department, Guangdong Women and Children Hospital, Guangzhou, China.

To compare the clinical efficacy of heated, humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) in extremely low-birth-weight preterm infants (ELBWI) after extubation. This trial included 94 extremely low-birth-weight infants (ELBWI), within 7 days after birth, and prepared for tracheal extubation and a change to non-invasive ventilation in the neonatal intensive care unit (NICU) admitted to our hospital from January 2015 to December 2018, with 48 infants in the HHHFNC group and 46 infants in the NCPAP group. Reintubation rate within 72 h after initial extubation, total ventilation time, non-invasive ventilation time, total oxygen inhalation time, and the time to reach full enteral feeding were the primary outcome measures. Total intestinal feeding time, average weight gain rate, days of hospitalization, costs of hospitalization, and complication rates, including nasal injury, IVH, BPD, NEC, ROP, and PDA, were used as secondary outcomes. Data were analyzed using Student's -test or the Mann-Whitney -test with a Chi-square test or Fisher's exact test, as appropriate, in SPSS (25.0). HHHFNC not only shortened the oxygen exposure time but also effectively reduced the incidence of nasal injury (6.25 vs. 36.96%) and NEC (10.42 vs. 28.26%) ( < 0.05). Additionally, HHHFNC achieved a significant advance in the time to reach full enteral feeding (31.24 ± 11.35 vs. 34.21 ± 14.09 days); increased the average weight gain rate (16.07 ± 3.10 vs. 13.74 ± 4.21) and reduced the days of hospitalization (73.45 ± 18.84 vs. 79.24 ± 19.75), with a lower cost of hospitalization (16.04 ± 3.64 vs.18.79 ± 4.13) thousand dollars (all < 0.05). Compared with NCPAP, HHHFNC was effective in preventing extubation failure in mechanically ventilated preterm ELBWI. HHHFNC shortens oxygen consumption time and significantly reduces the incidence of nasal injury and necrotizing enterocolitis; moreover, it can also reduce the length of stay and the hospitalization costs.
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http://dx.doi.org/10.3389/fped.2020.00250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332541PMC
June 2020

High Preoperative Fibrinogen and Systemic Inflammation Response Index (F-SIRI) Predict Unfavorable Survival of Resectable Gastric Cancer Patients.

J Gastric Cancer 2020 Jun 6;20(2):202-211. Epub 2020 May 6.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Purpose: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer.

Materials And Methods: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis.

Results: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio [HR], 2.299; 95% confidence interval [CI], 1.482-3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584-3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273-3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480-3.705; P<0.001) in multivariate Cox regression analysis.

Conclusions: Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.
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http://dx.doi.org/10.5230/jgc.2020.20.e18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311210PMC
June 2020

Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity.

Nano Lett 2020 07 17;20(7):5570-5574. Epub 2020 Jun 17.

Department of NanoEngineering, Chemical Engineering Program and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, United States.

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.
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http://dx.doi.org/10.1021/acs.nanolett.0c02278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301960PMC
July 2020

A review of multifunctional nacre-mimetic materials based on bidirectional freeze casting.

J Mech Behav Biomed Mater 2020 09 25;109:103820. Epub 2020 Apr 25.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China. Electronic address:

Nacre has achieved an excellent combination of strength and toughness through its unique brick-and-mortar structure of layered aragonite platelets bonded with biopolymers. Mimicking nacre has been considered as a practical way for the development of high-performance structural composites. Over the past years, many techniques have been developed to fabricate multifunctional nacre-mimetic materials, including freeze casting, layer-by-layer assembly, vacuum filtration, 3D printing and so on. Among them, freeze casting, especially bidirectional freeze casting, as an environmentally friendly and scalable method, has attracted extensive attention recently. In this review, we begin with the introduction and discussion of various fabrication techniques comparing their advantages and disadvantages, focusing on the most recent advances of the bidirectional freeze casting technique. Then, we summarize representative examples of applying the bidirectional freeze casting technique to assemble various building blocks into multifunctional nacre-mimetic materials and their wide applications. At the end, we discuss the future direction of using bidirectional freeze casting to make nacre-mimetic materials.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103820DOI Listing
September 2020

Engineered Cell-Membrane-Coated Nanoparticles Directly Present Tumor Antigens to Promote Anticancer Immunity.

Adv Mater 2020 Jul 15;32(30):e2001808. Epub 2020 Jun 15.

Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.

The recent success of immunotherapies has highlighted the power of leveraging the immune system in the fight against cancer. In order for most immune-based therapies to succeed, T cell subsets with the correct tumor-targeting specificities must be mobilized. When such specificities are lacking, providing the immune system with tumor antigen material for processing and presentation is a common strategy for stimulating antigen-specific T cell populations. While straightforward in principle, experience has shown that manipulation of the antigen presentation process can be incredibly complex, necessitating sophisticated strategies that are difficult to translate. Herein, the design of a biomimetic nanoparticle platform is reported that can be used to directly stimulate T cells without the need for professional antigen-presenting cells. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells engineered to express a co-stimulatory marker. Combined with the peptide epitopes naturally presented on the membrane surface, the final formulation contains the necessary signals to promote tumor antigen-specific immune responses, priming T cells that can be used to control tumor growth. The reported approach represents an emerging strategy that can be used to develop multiantigenic, personalized cancer immunotherapies.
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http://dx.doi.org/10.1002/adma.202001808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669572PMC
July 2020

Multiple subcutaneous tuberculous abscesses in a dermatomyositis patient without pulmonary tuberculosis: a case report and literature review.

BMC Infect Dis 2020 Jun 12;20(1):409. Epub 2020 Jun 12.

Clinical Research Center, the second hospital of Nanjing, Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Gulou district, Nanjing, 210003, Jiangsu province, China.

Background: Even though remarkable progress for diagnostics of pulmonary TB has been made, it is still a challenge to establish a definitive diagnosis for extrapulmonary TB (EPTB) in clinical practice. Among all the presentations of EPTB, cold abscesses are unusual and deceptive, which are often reported in the chest wall and spine. Subcutaneous abscess in the connective tissue of limbs is extremely rare.

Case Presentation: A 48-year-old man with dermatomyositis was hospitalized because of multiple subcutaneous tuberculous abscesses in his limbs, but without pulmonary tuberculosis. Particularly, one insidious abscess appeared during anti-TB treatment due to "paradoxical reaction". After routine anti-TB therapy, local puncture drainage and surgical resection, the patient was cured and discharged.

Conclusions: Tuberculous infection should be kept in mind for the subcutaneous abscess of immunocompromised patients, even without previous TB history. Treatment strategy depends on the suppurating progress of abscess lesions. Meanwhile, complication of newly-developed insidious abscess during treatment should be vigilant.
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http://dx.doi.org/10.1186/s12879-020-05137-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291664PMC
June 2020

Recent Advances in Iodine-Promoted C-S/N-S Bonds Formation.

Chemistry 2020 Dec 5;26(72):17289-17317. Epub 2020 Oct 5.

School of Pharmacy, Lanzhou University, 199 West Donggang Road, Lanzhou, 730000, P. R. China.

Sulfur-containing scaffold, as a ubiquitous structural motif, has been frequently used in natural products, bioactive chemicals and pharmaceuticals, particularly C-S/N-S bonds are indispensable in many biological important compounds and pharmaceuticals. Development of mild and general methods for C-S/N-S bonds formation has great significance in modern research. Iodine and its derivatives have been recognized as inexpensive, environmentally benign and easy-handled catalysts or reagents to promote the construction of C-S/N-S bonds under mild reaction conditions, with good regioselectivities and broad substrate scope. Especially based on this, several new strategies, such as oxidation relay strategy, have been greatly developed and accelerated the advancement of this field. This review focuses on recent advances in iodine and its derivatives promoted hybridized C-S/N-S bonds formation. The features and mechanisms of corresponding reactions are summarized and the results of some cases are compared with those of previous reports. In addition, the future of this domain is discussed.
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http://dx.doi.org/10.1002/chem.202001414DOI Listing
December 2020