An atom‐economic and highly efficient vinylogous umpolung strategy is developed for deconjugated carbonyl compounds, which generate electron‐deficient π‐allylpalladium complexes with Pd(OAc)2 under ligand‐free conditions. In cooperation with a chiral‐phosphonium‐based phase‐transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3‐substituted oxindoles are furnished under O2 atmosphere. The γ‐ or even remote ϵ‐regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures effectively. The Mukaiyama dienol silyl ether can be utilized similarly, indicating that the current active π‐allylpalladium species results from tautomerization of the PdII‐dienolate intermediate.
High-efficiency treatment for tumor is not easy to achieve owing to the existence of metastasis, which remains the arch-criminal of most tumor deaths. Conventional chemotherapy exhibits insufficient inhibitory efficiency on tumor metastasis and more powerful strategies to conquer metastatic tumors are urgently needed. In this study, a rational chemoimmunotherapy strategy was adopted to treat highly aggressive melanoma based on a newly developed multifunctional nanoplatform. Firstly, immunoadjuvant cytosine-phosphate-guanine oligonucleotides (CpG ODNs) were used to boost the doxorubicin (DOX)-elicited immune responses, which synergistically suppressed tumor growth and metastasis. And the anti-metastatic low molecular weight heparin (LMWH) was also integrated, thus multiple anti-metastatic effects to against tumor metastasis were achieved.
Methods:
G4 PAMAM was serving as the main support to conjugate DOX by pH-sensitive hydrazone bond (PPD) and the synthesized conjugates were confirmed by
1
H-NMR spectra, IR spectra and HRMS. Immunoadjuvant CpG ODNs were loaded by electrostatic adsorption to formulate PPD/CpG. After the coating of anti-metastatic LMWH, the designed LMWH/PPD/CpG was fabricated and characterized. The platelets-related and platelets-unrelated anti-metastatic mechanisms were investigated on B16F10 melanoma cells. The capacity of DOX to elicit immunogenic cell death (ICD) on B16F10 melanoma cells was examined by flow cytometry, laser scanning confocal microscope and immumohistochemical staining. Then the immune activation effects, anti-tumor and anti-metastatic efficacy of LMWH/PPD/CpG were evaluated on a B16F10 melanoma xenograft model.
Results:
DOX elicited tumor-specific immune responses by ICD, and the immunological effects could be further promoted by CpG ODNs, exhibiting enhanced maturation of dendritic cells (DCs) and increased level of cytolytic T lymphocytes (CTLs)
in vivo
. Owing to the coating of LMWH, the platelets-induced epithelial-mesenchymal-like transition of tumor cells was hindered and the actin cytoskeletal arrangement of tumor cells was affected, thus the migration ability of tumor cells was further inhibited. This multifunctional nanoplatform showed enhanced treatment efficiency on melanoma primary tumor and pulmonary metastasis.
Conclusion:
The immune activation and multiple anti-metastatic effects of LMWH/PPD/CpG establish a novel therapeutic strategy for melanoma. This anti-metastatic nanoplatform could be broadly applied for the co-delivery of other nucleic acids and chemotherapeutic drugs to treat highly aggressive tumors.
Disclosing the composition of meat products in detail is essential to consumers' rights. In this study, we developed a rapid method based on loop-mediated isothermal amplification to visibly identify pork DNA in meat products. Four pig specific primers were designed according to the mitochondrial DN1 gene sequence. The analytical sensitivity of the LAMP assay for pork DNA detection is 0.5 pg in our experiment, and the results were not affected by processing temperature. We used the LAMP assay and the industry standard for Chinese entry-exit inspections and quarantines to analyze commercial halal products, and the results were comparable. In conclusion, the LAMP assay has excellent sensitivity and specificity and is a convenient method for pork DNA detection.
An asymmetric α-regioselective
allenylation reaction of activated ketimines with 3-butynoates is
disclosed under Cu(I) catalysis, probably via the generation of nucleophilic
γ-allenylcopper species in the presence of diisopropylethylamine.
A broad range of imines, derived from diverse ketones such as isatins,
pyrazolediones, isoquinoline-1,3,4-triones, and even trifluoromethyl
alkynyl ketones, can be utilized, generally affording the corresponding
α-allenyl amine derivatives in high yields (≤97%) with
excellent enantioselectivities (≤99% ee).
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