Cysteine-Specific Multifaceted Bioconjugation of Peptides and Proteins Using 5-Substituted 1,2,3-Triazines.

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine-specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5-substituted 1,2,3-triazine derivatives to achieve multifaceted bioconjugation targeting cysteine-containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3-triazine in biomolecular-specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one-pot dual-orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3-Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi-triazines enable peptide cyclization and dimerization. The examination of the stability of bi-triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine-selective modifications, providing new avenues for peptide-based drug development, protein bioconjugation, and chemical biology research.

Cellular and molecular mechanisms of oroxylin A in cancer therapy: Recent advances.

Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.

Traditional Chinese medicine combined with Moxibustion in the treatment of "long-COVID": A protocol for systematic review and meta-analysis.

BACKGROUND: From the end of 2019 to now, COVID-19 is still prevalent, which poses a great threat to international public health. With the increasing number of people infected, the number of patients with COVID-19 sequelae is also increasing, but there is no specific drug for COVID-19 sequelae. In China, traditional Chinese medicine combined with acupuncture has been widely used in COVID-19 sequelae, but there is still a lack of evidence-based medicine evaluation. The purpose of this study was to evaluate the efficacy and safety of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. METHODS: According to the retrieval strategy, the "long COVID" randomized controlled trial of traditional Chinese medicine combined with moxibustion will be search in eight databases composed of PubMed, Embase, Web of Science, China National knowledge Infrastructure Database, China Biomedical Database and China Science and Technology Journal Database, regardless of publication date or language. The study was screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the study. Meta-analysis was carried out using RevMan5.3 and STATA12.0 software. Finally, the level of evidence of the results will be evaluated. RESULTS: This study will evaluate whether traditional Chinese medicine combined with moxibustion can effectively treat the symptoms of COVID-19 sequelae. CONCLUSION: This study will provide evidence whether there is benefit of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. At the same time, our research results will provide a reference for clinical decision-making and guiding development in the future.

Semirigid Ureteroscopy Therapy against Childhood Kidney Stones.

Objective: The purpose of the current study was to assess the effectiveness of semirigid ureterorenoscopy (URS) as first-line therapy for early childhood patients with <20 mm stones in the pelvic, middle, or upper calices. Methods: In all, 61 pediatric kidney stone patients who had flexible ureteroscopy (fURS) between January 1, 2010, and December 31, 2019, were included in this study. Before fURS, semirigid URS employed the UreTron or holmium: YAG (Ho : YAG) laser was conducted. When semirigid URS was unsuccessful, fURS was used for retrograde intrarenal surgery (RIRS). All participants were monitored clinically for a minimum of three months after each procedure. Results: The patient's mean age was 4.52 ± 1.53 years, and 52 (83.61%) participants underwent semirigid URS successfully. Mean procedural duration of semirigid URS was 36.49 ± 7.72 min. The stone-free rate after semirigid URS was 92.16% (47/51). During the postprocedural medical observation, there were no serious adverse effects. Conclusions: Based on the present study's findings, semirigid URS is a low-risk, effective therapy for kidney stones in selected pediatric patients.

Mid-Infrared Emissivity Retrieval from Nighttime Sentinel-3 SLSTR Images Combining Split-Window Algorithms and the Radiance Transfer Method.

Land surface emissivity is a key parameter that affects energy exchange and represents the spectral characteristics of land cover. Large-scale mid-infrared (MIR) emissivity can be efficiently obtained using remote sensing technology, but current methods mainly rely on prior knowledge and multi-temporal or multi-angle remote sensing images, and additional errors may be introduced due to the uncertainty of external data such as atmospheric profiles and the inconsistency of multiple source data in spatial resolution, observation time, and other information. In this paper, a new practical method was proposed which can retrieve MIR emissivity with only a single image input by combining the radiance properties of TIR and MIR channels and the spatial information of remote sensing images based on the Sentinel-3 Sea and land surface temperature radiometer (SLSTR) data. Two split-window (SW) algorithms that use TIR channels only and MIR and TIR channels to retrieve land surface temperature (LST) were developed separately, and the initial values of MIR emissivity were obtained from the known LST and TIR emissivity. Under the assumption that the atmospheric conditions in the local area are constant, the radiance transfer equations for adjacent pixels are iterated to optimize the initial values to obtain stable estimation results. The experimental results based on the simulation dataset and real SLSTR images showed that the proposed method can achieve accurate MIR emissivity results. In future work, factors such as angular effects, solar radiance, and the influence of atmospheric water vapor will be further considered to improve performance.

Dearomatization-rearomatization strategy of tyrosine for peptide/protein modification through thiol-addition reactions.

We have developed a dearomatization-rearomatization strategy for the modification of peptides/proteins through a thiol-Michael addition to the electrophilic cyclohexadienone intermediate that is generated in situ via the oxidation of tyrosine. This strategy enriches the conjugation toolbox and has great potential for applications in medicinal chemistry and chemical biology.

Tyrosine-Specific Modification via a Dearomatization-Rearomatization Strategy: Access to Azobenzene Functionalized Peptides.

Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides. This method enriches the postsynthetic modification toolbox of peptides and has great potential to be applied in medicinal chemistry and chemical biology.

Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy.

Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

Direct Synthesis of a Dioxabenzobicyclo[3.2.1]octane Core from Salicylaldehydes.

A copper(II) trifluoromethanesulfonate via Prins reaction between salicylaldehydes and allyl alcohols is realized under mild conditions. A series of compounds containing dioxabenzobicyclo[3.2.1]octane motifs are obtained in moderate to good yields. The current method can efficiently construct the valuable structural motif from easily accessed starting materials, providing a smooth method to build benzobicyclo skeletons.

The Important Role of the Byproduct Triphenylphosphine Oxide in the Magnesium(II)-Catalyzed Enantioselective Reaction of Hemiacetals and Phosphorus Ylides.

By employing a simple in situ generated magnesium catalyst, a direct asymmetric reaction between hemiacetals and phosphorus ylides was achieved through a tandem Wittig-oxa-Michael reaction sequence. Enantioenriched chromans, isochromans, and tetrahydropyrans were obtained in good chemical yields, and (-)-erythrococcamide B was synthesized in enantioenriched form. The byproduct triphenylphosphine oxide was identified as a necessary additive for this process.

Nickel-Mediated Asymmetric Allylic Alkylation between Nitroallylic Acetates and Acyl Imidazoles.

A nickel-mediated asymmetric allylic alkylation reaction between imidazole-modified ketones and nitroallylic acetates is presented. This reaction is catalyzed by a simple chiral diamine-nickel catalyst under mild conditions and leads to a series of novel enantioenriched α-allylic adducts in moderate to good yields with excellent enantioselectivities. Furthermore, transformation of the allylic adducts could smoothly lead to chiral γ-nitro-esters containing three continuous stereocenters in good yields.

Development of Biligands Magnesium Catalysis in Asymmetric Conjugate Reactions of C3-Pyrrolyl-Oxindoles.

A magnesium catalyzed asymmetric conjugate reaction of C3-pyrrolyl-oxindoles with terminal alkynones is presented. The current asymmetric conjugate reaction relies on the development of novel combinational magnesium catalysis involving two chiral ligands. The current protocol proceeds smoothly and gives the corresponding enantioenriched 3,3-disubstituted oxindole skeletons with good enantioselectivities. Furthermore, the conjugate adducts could be transferred to spiro oxindole structures containing an eight-membered ring in high ee values.

Magnesium Catalysis Mediated Tetrazoles in Desymmetrization Reaction of Aziridines.

A magnesium-catalyzed asymmetric ring-opening reaction of aziridines with substituted tetrazoles is reported. The current protocol proceeds smoothly and gives the corresponding desymmetrization products in high yields and good enantioselectivities. A new chiral ligand was synthesized from azetidine and (R)-BINOL and was employed in the current in situ generated magnesium catalyst. The Mg(II)-mediated desymmetrization reaction could be performed on gram scale under mild conditions and was transformed to chiral alkyl amines by a deprotection process.

An Efficient Nickel-Catalyzed Asymmetric Oxazole-Forming Ugi-Type Reaction for the Synthesis of Chiral Aryl-Substituted THIQ Rings.

A nickel-catalyzed asymmetric oxazole-forming Ugi reaction of C,N-cyclic azomethine imines and isonitriles is disclosed. The reported protocol proceeds smoothly, and gives the corresponding adducts, which contain two important pharmaceutically active ring-systems (tetrahydroquinoline and oxazole rings), in good yields and excellent enantioselectivities by employing an easily accessible chiral diamine as a ligand. This simple and efficient strategy provides easy access to a series of C1-substituted aryl tetrahydroisoquinolines.

Simple magnesium catalyst mediated γ-butyrolactams in desymmetrization of meso-aziridines.

The first α-sp(2)-carbon of carbonyl compounds attacked catalytic desymmetrization reaction of aziridines is disclosed. A simple in situ generated magnesium catalyst from 3,3'-bromine-8H-BINOL and dibutylmagnesium was employed. It is interesting that the bromine atom on the chiral ligand plays a key role in introducing a high level of enantioselectivities and high reaction efficiency. Both enantiomers of the ring-opening product could be smoothly obtained by using (R)- and (S)-L7.

Mg(II) -Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of ß-Naphthols with Dialkyl Acetylenedicarboxylates.

A Mg(II) -mediated catalytic asymmetric dearomatization (CADA) reaction of ß-naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated ß-naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway.

Catalytic Asymmetric Ring-Opening Reactions of Aziridines with 3-Aryl-Oxindoles.

A highly enantioselective ring-opening alkylation reaction between 3-aryl-oxindole and N-(2-picolinoyl) aziridine has been realized for the first time. The reaction is efficiently mediated by a simple in-situ-generated magnesium catalyst and 3,3'-fluorinated-BINOL (BINOL=1,1'-binaphthalene-2,2'-diol) has been identified as a powerful chiral ligand. Notably, the fluorine atom on the chiral ligand plays a key role in providing the desired chiral 3-alkyl-3-aryl oxindoles with excellent enantioselectivities.

[Study of building quantitative analysis model for chlorophyll in winter wheat with reflective spectrum using MSC-ANN algorithm].

Preprocess method of multiplicative scatter correction (MSC) was used to reject noises in the original spectra produced by the environmental physical factor effectively, then the principal components of near-infrared spectroscopy were calculated by nonlinear iterative partial least squares (NIPALS) before building the back propagation artificial neural networks method (BP-ANN), and the numbers of principal components were calculated by the method of cross validation. The calculated principal components were used as the inputs of the artificial neural networks model, and the artificial neural networks model was used to find the relation between chlorophyll in winter wheat and reflective spectrum, which can predict the content of chlorophyll in winter wheat. The correlation coefficient (r) of calibration set was 0.9604, while the standard deviation (SD) and relative standard deviation (RSD) was 0.187 and 5.18% respectively. The correlation coefficient (r) of predicted set was 0.9600, and the standard deviation (SD) and relative standard deviation (RSD) was 0.145 and 4.21% respectively. It means that the MSC-ANN algorithm can reject noises in the original spectra produced by the environmental physical factor effectively and set up an exact model to predict the contents of chlorophyll in living leaves veraciously to replace the classical method and meet the needs of fast analysis of agricultural products.

[Estimations of chlorophyll and water contents in live leaf of winter wheat with reflectance spectroscopy].

For estimating the yield of wheat, and for crop growth monitoring by using hyperspectral remote sensing, it is very important to quantitatively determine the chlorophyll and water contents in live leaf of winter wheat. In the range of 350-1650 nm, the reflectance spectrum of winter wheat's leaf in different growth periods were scanned by ASD FieldSpec Pro FR portable spectrometer and LI-COR 1800 integrating spheres. Partial least squares method was used to develop the quantitative analysis models for chlorophyll and water contents with reflectance spectroscopy. The model of chlorophyll content with reflectance spectroscopy was built in the range of 400-750 nm, and the results show that the correlation coefficient between the estimated values and the real values is 0.898, and relative standard deviation is 13.6%. The model of water content with reflectance spectroscopy was built in the range of 1400-1600 nm, and the results indicate that the correlation coefficient between the estimated values and the real values is 0.999, and relative standard deviation is 0.3%. These results are satisfying in agricultural production.