Search

Polymeric assemblies have emerged as a kind of promising platform in biomedical fields. The strong potency of polyphenols to form versatile interactions with other small or polymeric molecules via covalent and noncovalent linkages enables polyphenols to serve as molecular glues, offering a magic driving force to assemble multiple functional molecules into a diversity of polyphenol‐based systems, such as nanoparticles and hydrogels. Due to the unique merits of anti‐tumor, anti‐bacterial, antioxidant, anti‐inflammatory, and cardioprotective properties of polyphenols, polyphenol‐based systems hold great promise to deal with a wide spectrum of diseases. This review comprehensively overviews the components, intermolecular interactions, and preparation methods implicated in the assembly of polyphenol‐based systems. In addition, their medical applications are introduced, particularly the treatments of various diseases, such as tumors, bacterial infections, inflammatory bowel disease (IBD), cardiovascular diseases (CVDs), chronic periodontitis, acute lung injury, osteoarthritis, and renal fibrosis.

Radiotherapy is widely applied for multiple malignant tumors ablation in the clinic. However, redundant doses of X-rays might destroy normal tissue in the periphery of tumor sites. Here, we developed an integrated nanosystem (Bac@BNP) composed of engineered bacteria (Bac) and Bi2S3nanoparticles (BNPs) for sensitizing radiotherapy. Bac could target and colonize in tumor sites alternatively, which overexpressed cytolysin A (ClyA) protein to regulate the cell cycle from a radioresistant phase to a radiosensitive phase. Simultaneously, peptide-modified BNPs, as a radiosensitizer with a high-Z element, was released from the surface of Bac owing to the matrix metalloproteinase-2 (MMP-2) response in the tumor microenvironment. Under X-ray irradiation, BNPs could enhance the radiotherapy sensitivity by triggering the intracellular generation of reactive oxygen species (ROS), coupled with DNA damage. In this constructed nanosystem, the combination of Bac@BNP and X-ray irradiation led to significant suppression of breast carcinoma in murine models with reduced side effects.

Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivostudy on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.

Two copper(I)‐based frameworks of complexes {[Cu(L)2(ClO4)]⋅CH3CN}(2) and {[Cu(L)(ClO4)]⋅ 2CH3CN} (3) (L = 1,3,5‐tris(4‐pyridylethynyl) benzene) were produced by reacting [Cu(MeCN)4(ClO4)] with different amounts of a ligand (L) using a hydrothermal method at temperatures of up to 130°C. The nitrogen atoms in the pyridine moieties of the ligand coordinate to the Cu(I) ion. The charge on the Cu(I) ion can be stabilized by extending the degree of conjugation in the system and by taking advantage of its highly symmetrical structure. The large degree of conjugation also supports numerous π–π interactions in the framework. The 3‐folded ligand compose interpenetrating structure caused by ππ interaction.

The development of nanomedicines that combine photothermal therapy (PTT) with photodynamic therapy (PDT) is considered promising for cancer treatment, but still faces the challenge of enhancing tumoricidal efficiency. Fortunately, apart from the well‐acknowledged effect on direct tumor cell‐killing, nitric oxide (NO) is also considered to be effective for the enhancement of both PTT and PDT. However, both the low loading efficiency of NO precursor and the short half‐life time and diffusion distance of NO hamper the synergistic therapeutic efficacy of NO. Taking the aforementioned factors into account, a mitochondria‐targeted nitric oxide nanogenerator, EArgFe@Ce6, is constructed to achieve high loading of the NO donor l‐Arginine (l‐Arg) for synergistic photodynamic/gas/photothermal therapy upon single 660 nm light irradiation. The coordination of epigallocatechin gallate (EGCG) and ferric ions (Fe3+) provides EArgFe@Ce6 supreme photothermal capability to perform low‐temperature PTT (mPTT). EGCG endows EArgFe@Ce6 with mitochondria‐targeting capability and meanwhile favors hypoxia alleviation for enhanced PDT. The PDT‐produced massive reactive oxygen species (ROS) further catalyzes l‐Arg to generate a considerable amount of NO to perform gas therapy and sensitize both mPTT and PDT. In vitro and in vivo studies demonstrate that the synergistic photodynamic/gas/photothermal therapy triggered by single 660 nm light irradiation is highly effective for tumor treatments. A nanomedicine EArgFe@Ce6 with high loading content of l‐arginine is constructed as a light‐triggered nitric oxide (NO) nanogenerator. A single 660 nm light irradiation can simultaneously realize photodynamic therapy (PDT) and photothermal therapy (PTT). PDT can propel l‐Arginine to generate NO, which achieves gas therapy and sensitizes both PDT and PTT. This synergistic photodynamic/gas/photothermal therapy achieves excellent therapeutic outcomes.

A universal strategy was reported that enables functional group-capped nanostructures with various morphologies and compositions to be coated by porphyrin metal–organic framework (MOF). Based on the nanostructure-induced heterogeneous nucleation, the controlled growth of MOF shell on the surface of nanostructures can be realized. It was demonstrated that this modification strategy can realize controlled growth of porphyrin MOF on a series of organic and inorganic nanostructures, such as polydopamine (PDA) nanoparticles, PDA@Ptnanoparticles, graphene oxide sheets, and Au nanorods. The as-prepared composites exhibit excellent catalytic and optical properties that originate from the nanostructure as well as the coated porphyrin MOF. We further explored the potential applications of PDA@MOFand PDA@Pt@MOFin nanomedicine and photocatalysis.

To overcome the limitations of doxorubicin (DOX) chemotherapy, nanomedicines that integrate additional photothermal therapy (PTT) and chemodynamic therapy (CDT) strategies are highlighted as promising alternatives for the treatment of malignant tumors. However, time‐consuming preparation processes, biosafety concerns, and the bottlenecks of individual therapeutic modalities often limit the practical applications of this strategy. To address these issues, this work designs an oxygen economizer that additionally serves as a Fenton reaction amplifier through the simple assembly of epigallocatechin gallate (EGCG), pluronic F‐127 (PF127), iron (III) ions, and doxorubicin (DOX) for the enhancement of synergistic PTT/CDT/chemotherapy. The resulting nanoformulation, EFPD, can target mitochondria and inhibit cell respiration to reduce O2consumption, thus boosting DOX‐mediated H2O2generation for enhanced CDT and simultaneously improving hypoxia‐limited DOX chemotherapy efficacy. Moreover, the coordination between EGCG and Fe3+provides EFPD with excellent photothermal conversion efficiencies (η= 34.7%) for PTT and photothermal‐accelerated drug release. Experimental results indicate that EFPD‐mediated synergistic enhancement of PTT/CDT/chemotherapy can achieve excellent therapeutic outcomes, including enhanced ablation of solid tumors, reduced metastasis and cardiotoxicity, and extended life spans. A metal‐polyphenol‐based nanomedicine, EFPD, is constructed to achieve self‐enhanced ternary synergistic therapy based on a simple hybrid assembly. By targeting mitochondria for cell respiration inhibition, hypoxia is alleviated and doxorubicin‐mediated H2O2generation is increased, thus leading to the enhancement of chemotherapy and chemodynamic therapy, respectively. Providing excellent photothermal capability, EFPD achieves self‐enhanced synergistic photothermal/chemodynamic/chemotherapy of tumors.

Due to the complexity and heterogeneity in the tumor microenvironment, the efficacy of breast cancer treatment has been significantly impeded. Here, we established a living system using an engineered M13 bacteriophage through chemical cross-linking and biomineralization to remodel the tumor microenvironment. Chemically cross-linking of the engineered bacteriophage gel (M13 Gel) could in situ synthesize photothermal palladium nanoparticles (PdNPs) on the pVIII capsid protein to obtain M13@Pd Gel. In addition, NLG919 was further loaded into a gel to form (M13@Pd/NLG gel) for down-regulating the expression of tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Both in vitro and in vivo studies showed that the M13 bacteriophage served not only as a cargo-loaded device but also as a self-immune adjuvant, which induced the immunogenic death of tumor cells effectively and down-regulated IDO1 expression. Such a bioactive gel system constructed by natural living materials could reverse immunosuppression and significantly improve the anti-breast cancer response.

We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2–100 μM carvedilol was incubated for 30 min at 37 °C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance (Vmax/Km) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased Kmand/or decreased Vmaxvalues. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins.

Our previous study detected totally 35 CYP2C9allelic variants in 2127 Chinese subjects, of whom 21 novel alleles were reported for the first time in Chinese populations. The aim of the present study was to characterize the 13 CYP2C9allelic variants both in vitro and in vivo. Different types of CYP2C9variants were highly expressed in COS-7 cells, and 50 μM tolbutamide was added as the probing substrate to evaluate their metabolic abilities in vitro. Subsequently, the concentrations of tolbutamide and its metabolite in the plasma and urine within individuals with different types of genotypes were determined by HPLC to evaluate the catalytic activity of the 13 mutant CYP2C9 proteins in vivo. Our results showed that compared with *1/*1wild-type subjects, subjects with *1/*40genotype showed increased oral clearance (CL/F), whereas individuals with *1/*3, *1/*13, *3/*3, *3/*13, *1/*16, *1/*19, *1/*34, *1/*42, *1/*45, *1/*46, and *1/*48genotype exhibited significantly decreased CL/F, and those with *1/*27, *1/*29, *1/*40,and *1/*41genotype presented similar CL/F value. When expressed in COS-7 cells, the CYP2C9variants showed similar pattern to the results in clinical study. The study suggests that, besides two typical defective alleles, *3and *13, seven CYP2C9allelic variants (*16, *19, *34, *42, *45, *46, and *48) cause defective effects on the enzymatic activities both in vitro and in vivo. In clinic, patients with these defective alleles should be paid close attention to.

Analysis the important significance of transformer short-circuit current calculation for the stable operation of power system. Lead to three different types of transformer short-circuit current calculation methods, this literature uses a simplified example to compare the characters among three methods. Meanwhile, calculation by using the theory to get a quantitative range of simplified method. The calculation results and theory support each other, finally, summarizing the application range of the three methods, and offering a reference for reasonable selection of short-circuit current methods.

The energy dissipation design method has received more attention by engineering circle. Nowadays, the buckling restrained braces (BRBs) are used in higher structures being dissipation energy components. So, it is very necessary to determine the damage quantity of BRBs under earthquake. Firstly, the meaning of the damage quantity of BRBs is clarified based on the energy theory. Secondly, a single degree of freedom analyses model which is suitable to the frame structure is proposed. The nonlinear dynamic time-history analysis of BRBs system is carried out by using FEMS software of ANSYS 11.0 and seismic response of BRBs is obtained. Finally, a practical calculation model of the Damage quantity of BRBs is established. Using MATLAB software, the Damage quantity of BRBs is obtained.

Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review.

This mechanical processing waste emulsion for the study, handled by pulse electrolysis. Arrangements by orthogonal testing, experimental study on plate distance (d), current density (i), the pH value and the pulse width (tP) impact on COD removal efficiency, very poor analysis of test data to determine various factors affecting the COD removal efficiency of primary and secondary sort: pH value > current density > pulse width > plate distance, optimal operating conditions. Orthogonal experimental data derived from regression analysis, determination of cross of quadratic polynomial regression equations, mathematical model. Tests confirmed that pulse electrochemical method for treatment of waste emulsion with low energy consumption, short response time, and other advantages, strong applicability of wastewater, building mathematical models, providing theoretical basis for subsequent design.

Bioassay-guided fractionation of the roots of Litsea hypophaealed to the isolation of seven new butanolides, namely, litseakolides H−N (1−7), all with the 3R,4Sconfiguration, as well as three new biarylpropanoids, hypophaone (8), hypophaol (9), and hypophane (10), and 15 known compounds. The structures of 1−10were determined by means of spectroscopic analysis. Litseakolide L (5) and N-trans-feruloylmethoxytyramine (11) showed antitubercular activity against Mycobacterium tuberculosisstrain H37Rv, with MIC values of 25 and 1.6 μg/mL, respectively.

Ligand-targeting drug delivery systems have made significant strides for disease treatments with numerous clinical approvals in this era of precision medicine. Herein, we report a class of small molecule-based immune checkpoint-targeting maytansinoid conjugates. From the ligand targeting ability, pharmacokinetics profiling, in vivoanti-pancreatic cancer, triple-negative breast cancer, and sorafenib-resistant liver cancer efficacies with quantitative mRNA analysis of treated-tumor tissues, we demonstrated that conjugate 40anot only induced lasting regression of tumor growth, but it also rejuvenated the once immunosuppressive tumor microenvironment to an “inflamed hot tumor” with significant elevation of gene expressions that were not accessible in the vehicle-treated tumor. In turn, the immune checkpoint-targeting small molecule drug conjugate from this work represents a new pharmacodelivery strategy that can be expanded with combination therapy with existing immune-oncology treatment options.

Background: Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods: H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results: In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion: Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO–), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide-co-glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO–in tumor. The generated ONOO–could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly viaONOO–-mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO–as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy.