Synthesis of Furans via Rhodium(III)-Catalyzed Cyclization of Acrylic Acids with α-Diazocarbonyl Compounds.

An efficient protocol for the synthesis of furans through Rh(III)-catalyzed vinyl C-H activation from acrylic acids and α-diazocarbonyl compounds has been developed. The reaction features broad functional group tolerance and affords a series of furans in moderate to good yields. Moreover, no additives such as copper or silver salts are required. Some control experiments are performed to give insight into the mechanism of this cascade transformation and the decarbonylation process is involved in the formation of the furan product.

Multiple fluorescence immunoassay for the simultaneous detection of Zearalenone and Ochratoxin A.

A sensitive and accurate multiple fluorescence immunoassay for the simultaneous quantitative detection of Zearalenone (ZEN) and Ochratoxin A (OTA) in single spot based on multicolor quantum dots (QDs) labeling was developed for the first time. Two kinds of ZnCdSe/ZnS (core/shell) QDs with maximum emission wavelengths at 520 nm (green) and 610 nm (orange-red) were selected as marking materials, respectively. The anti-ZEN-mAb-QDs and anti-OTA-mAb-QDs were designed as the immune fluorescent probes. Fluorescence was measured at the same excitation wavelength and two different emission wavelengths to determine each target. The procedure for QDs-based multiple fluorescence labeled immunosorbent assay (M-FLISA) was developed. The 50% inhibition concentrations (IC50) of ZEN and OTA were 0.034 and 1.175 ng/mL. Moreover, the limits of detection (LOD) for the simultaneous determination were 0.0239 and 2.339 ng/g for ZEN and OTA in maize, respectively. In addition, the recoveries ranged from 93.15 to 101.90% for ZEN and from 95.29 to 102.43% for OTA, with the coefficient variation (CV) of 2.70-8.86% and 3.51-6.22% respectively. There was good consistency between the M-FLISA and high performance liquid chromatography (HPLC) results, which confirmed that the M-FLISA was suitable for the simultaneous quantitative detection of various mycotoxins.

Detection of ochratoxin A by quantum dots-based fluorescent immunochromatographic assay.

Ochratoxin A (OTA) is a toxic metabolite produced mainly by Aspergillus and Penicillium species. A quantitative method was developed for the rapid, simple, and sensitive detection of OTA in corn by quantum dots-based fluorescent immunochromatographic assay (QDs-ICA). The CdSe/ZnS QDs-labelled anti-OTA monoclonal antibody (mAb) conjugates were designed as the fluorescent signal probe. The QDs-ICA included the designation of test line (T line) and control line (C line), which were sprayed with optimal concentrations of the OTA-OVA and staphylococcal protein-A (SPA), respectively. Under the optimal experimental conditions, the QDs-ICA exhibited excellent specificity and good accuracy and precision. For qualitative detection, the cut-off value for the T line of the visual detection method was 2.5 ng/mL. For quantitative detection, the linear regression equation of the standard curve was y = 0.366x + 0.514 with a reliable correlation coefficient (R2 = 0.992). Moreover, the 50% inhibition value (IC50) of the QDs-ICA was 0.91 ng/mL, the limit of detection (LOD) was 0.07 ng/mL, and the detection range was 0.05 to 10 ng/mL. In addition, the recovery rates ranged from 91.82 to 100.35% with a coefficient of variation (CV) below 3% for intra-assay, whereas the recovery rates for inter-assay changed from 94.29 to 104.62% with a CV below 10%. These results indicate that the QDs-ICA can serve as a potential large-scale preliminary device for rapid determination of OTA. Using CdSe/ZnS QDs as the fluorescent signal for quantum dots-based fluorescent immunochromatographic assay, the QDs-ICA provided a novel method for the rapid simultaneous qualitative and quantitative determination of OTA.

Redox-Neutral Rhodium(III)-Catalyzed Annulation of Arylhydrazines with Sulfoxonium Ylides To Synthesize 2-Arylindoles.

A rhodium-catalyzed redox-neutral reaction of arylhydrazines with sulfoxonium ylides to construct 2-arylindole derivatives in one pot has been developed. The transformation proceeds efficiently under mild conditions and involves tandem C-H activation and an intramolecular dehydration annulation sequence, providing a straightforward pathway to access pharmaceutically and biologically valuable 1-aminoindole derivatives.

Ruthenium-Catalyzed Ring-Opening Addition of Anilides to 7-Azabenzonorbornadienes: A Diastereoselective Route to Hydronaphthylamines.

The ruthenium(II)-catalyzed direct ring-opening reaction of 7-azabenzonorbornadienes with anilides via C-H activation to access hydronaphthylamines has been developed. The transformation proceeds with a high stereoselectivity to give cis-configuration products under redox-neutral conditions.

Cobalt-Catalyzed Cyclization of Aliphatic Amides and Terminal Alkynes with Silver-Cocatalyst.

A new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes was discovered through a C-H bond functionalization process on unactivated sp(3) carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp(3))-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. The reaction tolerates a wide variety of functional groups including -F, -Cl, -Br, -CF3, ether, cyclopropane, and thiophene. Both pyridine ligand and aromatic solvent play the important role for the promotion of reactivity. This cobalt-catalyzed cyclization reaction can be successfully extended to a variety of aromatic amides to afford a variety of isoindolinones. Attractive features of this catalytic system include its low cost, easy operation, and convenient access to a wide range of pyrrolidinones and isoindolinones.

Metal-free C-N- and N-N-bond formation: synthesis of 1,2,3-triazoles from ketones, N-tosylhydrazines, and amines in one pot.

A novel synthetic approach toward 1,4-disubstituted 1,2,3-triazoles by C-N- and N-N-bond formation has been established under transition-metal-free conditions. Complete control of the regioselectivity was successfully achieved. Commercially available anilines, ketones, and N-tosylhydrazine were treated with molecular iodine in one pot to allow the regioselective generation of 1,4-disubstituted 1,2,3-triazoles in high yields without the use of azides.

Efficient synthesis of 1,2,3-triazoles by copper-mediated C-N and N-N bond formation starting from N-tosylhydrazones and amines.

An effective copper-mediated synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30 mol % amino acid is added into the reaction mixture. This methodology exhibits many notable features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and N-N bond formation process.

Synthesis of 2,3-dihydro-1H-indazoles by Rh(III)-catalyzed C-H cleavage of arylhydrazines.

A rhodium-catalyzed efficient method for the synthesis of 2,3-dihydro-1H-indazoles is described. The reaction of arylhydrazines with olefins results in the corresponding 2,3-dihydro 1H-indazoles with exclusive regioselectivity via C-H bond activation. The utility of the methodology is illustrated by a rapid synthesis of 1H-indazoles under mild reaction conditions in half an hour.

Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.

Introduction: Patients with relapsed/refractory (r/r) acute T-lymphoblastic leukemia (T-ALL) have a poor prognosis. We developed donor CD7 chimeric antigen receptor T (CAR-T) cells to salvage r/r T-ALL patients and obtained encouraging results. Patients who had not received allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) before CAR-T therapy would develop pancytopenia and immunodeficiency for a long period after CD7 CAR-T therapy; therefore, allo-HSCT is needed in these patients. Here, we report two pediatric r/r T-ALL patients who received donor CD7 CAR-T bridging to allo-HSCT with leukemia-free survival (LFS) and sustained negative minimal residual disease for >2 years. Case presentation: Patient 1 was a 10-year-old boy who visited our hospital because of a T-ALL relapse with multiple lymphadenopathies without discomfort. The patient did not achieve remission after one course of induction chemotherapy. The patient then received donor (his father) CD7 CAR-T cells and achieved complete remission (CR). Thirty days after the first CAR-T cell infusion, he received allo-HSCT, and his father was also the donor. His LFS was >3 years. Patient 2 was an 8-year-old boy who was admitted to our hospital with relapsed T-ALL with fever, cough, and mild dyspnea. He did not achieve remission after one course of induction chemotherapy; therefore, he received donor (his father) CD7 CAR-T cells and achieved CR. Twenty-six days after CAR-T cell infusion, the patient received allo-HSCT, with his father as the donor. He has survived for >2 years free of leukemia. At the last follow up, both patients were alive and presented a good quality of life. Conclusion: The long-term survival of these two patients supports the use of CD7 CAR-T therapy bridging to allo-HSCT as an effective and safe treatment with the capacity to make r/r T-ALL a curable disease, similar to r/r acute B-lymphoblastic leukemia.

Cu(II)-promoted palladium-catalyzed C-H ortho-arylation of N,N-dimethylbenzylamines.

A novel protocol for palladium-catalyzed arylation of the C(sp(2))-H bond directed by a N,N-dimethylaminomethyl group in the presence of AgOAc and Cu(OAc)2·H2O is described. Various aryl iodides proved to be efficient coupling partners, furnishing the corresponding ortho monoarylated or diarylated arenes in moderate to good yields. Cu(OAc)2·H2O is found to be the important additive to improve the yields in this transformation.

Palladium-catalyzed oxidative acetoxylation of benzylic C-H bond using bidentate auxiliary.

Pd(OAc)2-catalyzed oxidative acetoxylation of benzylic C-H bonds utilizing a bidentate system has been explored. A variety of picolinoyl- or quinoline-2-carbonyl-protected toluidine derivatives react with PhI(OAc)2 in the presence of Pd(OAc)2 to afford the acetoxylated products in synthetically useful yields. A broad of functionalities, such as CH3, F, Cl, Br, I, COCH3, CO2Et, SO2CH3, and NO2, were tolerated. This transformation provides easy access to 2-hydroxymethylaniline derivatives.

Capacitor-parallel-amplified decoupled photoelectrochemical/electrochromic dual-mode bioassay for sensitive detection of microRNA with high reliability.

To achieve sensitive detection of low-content microRNA, photoelectrochemical/electrochromic dual-mode sensor with intrinsically low background signal has been developed, but the two detection modules are usually designed with a series-connected structure, which may cause signal interference and thus affect the detection reliability. To solve the above problems, a decoupled dual-mode bioassay for sensitive miRNA-21 detection with high reliability is constructed in this work, by selecting two capacitors to realize parallel amplification for the two detection modules, supplemented with a 3D DNA nanoring photoelectrode signal amplification strategy. The complete decoupling of the two detection modes, photoelectrochemical and electrochromic, as well as the use of digital multimeter, improves the reliability and accuracy of the sensor, and also frees it from dependence on electrochemical workstation, making detection more intuitive and faster. With simple structure, low cost, good reproducibility, high sensitivity, and easy operation, the capacitor-parallel-amplified decoupled photoelectrochemical/electrochromic dual-mode bioassay has broad application prospect in on-site point-of-care detection of diseases and low-cost clinical diagnosis. The design idea of decoupled dual-mode detector can also be extended to the construction of other dual-mode methods.

Cryptococcus neoformans, a global threat to human health.

BACKGROUND: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. METHODS: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. RESULTS: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. CONCLUSION: The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

Rh-Catalyzed Coupling of Acrylic/Benzoic Acids with α-Diazocarbonyl Compounds: An Alternative Route for α-Pyrones and Isocoumarins.

A coupling of acrylic acids/benzoic acids with α-diazocarbonyl compounds has been realized by a combined catalytic system of rhodium catalyst and Zn(OAc)2 additive. The presence of Zn(OAc)2 obviously accelerates the C(sp2)-H activation and destructed the formation of carboxylic ester that is formed via a nucleophilic O-H insertion to metal carbenoid. The procedure featured mild reaction conditions and broad substrate scope, providing a straightforward approach to the synthesis of α-pyrones and isocoumarins without the transformation of carboxylic acids to the corresponding amides.

Synthesis of Pyranones: Ru-Catalyzed Cascade Reaction via Vinylic C-H Addition to Glyoxylate.

The efficient synthesis of pyranones is presented by a three-component cascade reaction from readily available acrylic acids, ethyl glyoxylate, and p-toluenesulfonamide under ruthenium catalysis. For the first time, the nucleophilic addition of the vinylic C-H bond of acrylic acids across aldehyde is achieved, and the intramolecular cyclization as well as subsequent second insertion to aldehyde form the substituted butenolides. The elimination of sulfonamides occurs at higher temperature to give the pyranones.

Catalytic wet air oxidation of toxic containments over highly dispersed Cu(II)/Cu(I)-N species in the framework of g-C3N4.

Catalytic wet air oxidation (CWAO) is a harmless, cheap and effective technology for the degradation of toxic containments directly to CO2 and H2O. In this work, highly dispersed Cu(II)/Cu(I)-N that embedded in the framework of g-C3N4 (Cux-g-C3N4) were synthesized in a facile thermal polymerization method and used in the CWAO of phenols, antibiotics and vitamins. Characterization results confirmed that g-C3N4 formed in the prepared catalyst and copper was chemically coordinated with N in g-C3N4, which inhibited the aggregation of copper. Meanwhile, Cu(II) or Cu(I) in the framework of g-C3N4 was more effective for the degradation of phenol than Cu(0) and CuO, and more than 23 toxic containments could be degraded under mild conditions. The prominent performance of Cu0.1-g-C3N4 for CWAO reaction was discussed on the base of these experiments and it was disclosed that in-situ formed H2O2 might be contributed to the highly activity.

Using extracellular vesicles derived from human umbilical cord mesenchymal stem cells for a topical coating promotes oral mucositis healing in rats.

Background: Oral mucositis (OM) affects the quality of life and therapeutic outcomes of cancer patients. More effective drugs and methods for treating OM are urgently required for clinical application. Extracellular vesicles can play important roles in cutaneous wound healing. However, their role in OM remains unclear. Our aim was to investigate the function and mechanisms of topical coatings of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) in OM. Methods: HUC-MSC-EVs were isolated by differential ultracentrifugation. We used glacial acetic acid to induce the formation of OM in rats. HUC-MSC-EVs were covered on the OM topically once a day. Rats' body weights were measured on alternative days. The healing degree of OM was evaluated with macroscopic observations and histological examinations. We also analyzed the mechanisms of hUC-MSC-EVs when promoting the healing of OM. The expression levels of NF-κB, IL-6, TNF-α, and IL-1ß in mucosal tissue were evaluated using immunohistochemistry. Results: The median healing time of OM in the blank control, rhaFGF, 0.25 µg/µL EVs, 0.75 µg/µL EVs, and 1.50 µg/µL EVs groups was 14, 11, 10, 7, and 11 days, respectively. The most significant effect of hUC-MSC-EVs in promoting healing was at the concentration of 0.75 µg/µL. The median healing scores in the 0.75 µg/µL EVs group were 4 on day 5 and 3 on day 8 (*P<0.05 vs. the blank control group). After modeling, the body weight of rats started to recover from day 8 in the blank control group and day 4 in the 0.75 µg/µL EVs group. The 0.75 µg/µL EVs group showed lower immunostaining intensity of NF-κB, IL-6, and TNF-α on day 5 and 8 (*P<0.05 vs. the blank control group). However, there was no significant difference between the blank control group and the 0.75 µg/µL EVs group in IL-1ß. Conclusions: Our results showed for the first time that coating hUC-MSC-EVs topically can promote healing of OM because it may inhibit the activation of the NF-κB signaling pathway.

Cobalt-Catalyzed Vinylic C-H Addition to Formaldehyde: Synthesis of Butenolides from Acrylic Acids and HCHO.

A carboxyl-assisted C-H functionalization of acrylic acids with formaldehyde to give butenolides is described. It is the first time that the addition of an inert vinylic C-H bond to formaldehyde has been achieved via cobalt-catalyzed C-H activation. The unique reactivity of the cobalt species was observed when compared with related Rh or Ir catalysts. γ-Hydroxymethylated butenolides were produced by the treatment of Na2CO3 after the catalytic reaction in one pot.

Synthesis of Cyclopentenones through Rhodium-Catalyzed C-H Annulation of Acrylic Acids with Formaldehyde and Malonates.

An efficient rhodium-catalyzed protocol for the synthesis of cyclopentenones based on a three-component reaction of acrylic acids, formaldehyde, and malonates via vinylic C-H activation is reported. Exploratory studies showed that 5-alkylation of as-prepared cyclopentenones could be realized smoothly by the treatment of a variety of alkyl halides with a Na2CO3/MeOH solution. Excess formaldehyde and malonate led to a multicomponent reaction that afforded the multisubstituted cyclopentenones through a Michael addition.