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Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect

A new orchid species, Bulbophyllum versicolor (Malaxideae, Epidendroideae, Orchidaceae), from Malipo, Yunnan, China, is described and illustrated here. Detailed morphological study indicates that B. versicolor is similar to B. japonicum, but it differs in the shape and size of leaf and flower and flower colour. Molecular analyses based on the nuclear ribosomal DNA (nrITS) and plastid DNA (matK, atpI-atpH and trnL-F) reveal that B. versicolor is a new species and genetically similar to B. japonicum.

A new orchid species, Bulbophyllum contortum (Malaxideae, Epidendroideae, Orchidaceae) from Zhenyuan, Yunnan, China, is described and illustrated here. Detailed morphological comparisons indicate that B. contortum is similar to B. lemnisactum and B. lemniscatoides, but it differs in the shape and size of pseudobulbs, inflorescence shape, flower colour and shape and size of the sepalar appendages.

Hydrogen auto-transfer (HAT) or borrowing hydrogen (BH) methodology which combines dehydrogenation, intermediate reaction and hydrogenation, is recognized as an excellent strategy for one-pot synthesis from an economic and environmental point of view. Although much effort has been made on the development of catalysts for HAT reactions, harsh conditions, external base or large amounts of noble metals are still required in most reported catalysis systems, and thus the exploration of a highly efficient and recyclable heterogeneous catalyst remains meaningful. In this work, a novel bimetallic catalyst, Fe10Pd1/NC500 derived from bimetallic MOF NH2-MIL-101(Fe10Pd1), has been prepared, and the catalyst exhibits superior catalytic performance for the N-alkylation of amines with alcohols via a hydrogen auto-transfer methodology. High yields of the desired products were achieved at 120 °C with an alcohol/amine molar ratio of 2 : 1 and required no external additive or solvent. A distinct enhancement in catalytic performance is observed when compared with monometallic catalysts, which can be ascribed to the “synergistic effects” inside the bimetallic alloys. The N-doped carbon support has been revealed to provide the necessary basicity which avoids the requirement of an external base. Moreover, a wide substrate range and remarkable reusability have been shown by Fe10Pd1/NC500, and this work highlights new possibilities for bimetallic catalysts applied in sustainable chemistry.

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel “core‒shell” co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and “green” method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment., Graphical abstract A carrier-free nanosystem was constructed based on natural sources of ursolic acid and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) treatment. The dual-drugs self-assembly nanosystem induced synergistic and efficient therapeutic effect by activating the innate and acquired immunity.Image 1

The iron-catalyzed α-C–H alkylation of N-methylanilines without any directing group by cross-dehydrogenative coupling between unactivated C(sp3)–H and C(sp3)–H bonds has been established for the fi...

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.

The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene-chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core-shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene-drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site in vivo and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene-drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.

An unprecedented acylation at the ortho C–H bond of chelating arenes via the Ni(II)-catalyzed cross dehydrogenative coupling strategy has been developed here. This new procedure exhibits excellent regioselectivity and good functional group tolerance. This discovery could be of great importance for the C–H acylation reactions of chelating arenes without any extraneous directing group and for the application of nickel-catalyzed C–H activation. Mechanistic investigations into the reaction process are also described.

A straightforward Ni(II)-catalyzed general strategy was developed for the ortho-halogenation of electron-deficient arenes with easily available halogenating reagents N-halosuccinimides (NXS; X = Br, Cl and I). The transformation was highly regioselective and a wide substrate scope and functional group tolerance were observed. This discovery could be of great significance for the selective halogenation of amides, benzoic esters and other substances with guiding groups. Mechanistic investigations were also described.

The first cobalt-catalyzed regioselective C–H methylation/acetoxylation reactions of anilides using peroxides and acetic acid respectively as attacking reagents have been developed herein. This new strategy features low cost, high selectivity, a broad range of functional groups, use of green and low toxic DTBP and HOAc, and avoidance of extraneous directing groups, thus offering a good complement to previous C–H methylation/acetoxylation reactions and expanding the application of cobalt-catalyzed C–H activations. Mechanistic explorations into the reaction process are also described in detail.

The nanocarrier-based delivery system has emerged as a promising candidate for cancer therapy; nevertheless, their quality problems, variation between batches, and carrier-related toxicity issues have restricted their clinical utilization. Compared with traditional carrier-based nanoparticles, carrier-free nanodrug delivery systems preferred to overcome all these drawbacks and will have a wide range of applications in biomedicine and nanotechnology. Herein, we developed a novel carrier-free nanodrug Asp-UA consisted of the classical drug aspirin and the natural plant drug UA via a green and simple approach. The Asp-UA NPs were investigated for shape, particle size, zeta potential, stability, and UV-vis spectroscopy absorption. Cellular uptake study showed that Asp-UA NPs could be easily internalized by HepG2 cells; cellular study demonstrated that Asp-UA NPs held better inhibitory efficiency on tumor metastasis with low toxicity in vitro and in vivo. Moreover, Asp-UA NPs could obviously suppress the progress of cancer metastasis by H22 cells in vivo. Overall, Asp-UA NPs possess a variety of advantages and hold promise to become an alternative to the treatment of cancer metastasis.

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H2O2-responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1β, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE-/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy.

The combination of chemotherapy and photothermal therapy displays improved anti-cancer effects and lower systematic toxicity of a free drug compared with monotherapy. In this study, we designed innovative, carrier-free nanodrugs (PTX/ICG NDs) composed of the chemotherapeutic agent paclitaxel (PTX) and the photosensitizer indocyanine green (ICG) via self-assembly. The nanodrugs not only incorporated two different modalities into one delivery system for combined chemo-photothermal therapy but also enhanced the solubility of PTX without the need for any carrier. The as-prepared PTX/ICG NDs exhibited the merits of a relatively uniform size of 140 ± 1.4 nm, surface charge of -36 ± 2.2 mV, and high drug loading content of PTX. The combination strategy exerted a synergistic effect on the cytotoxicity of cancer cells in vitro, which could be attributed to the high cellular uptake and sustained release of PTX. Furthermore, an in vivo study indicated that PTX/ICG NDs showed higher accumulation in the tumor site than free ICG and possessed strong synergistic chemo-photothermal therapy efficacy against tumors in H22 tumor-bearing mice. Taken together, our study demonstrates that PTX/ICG NDs hold promise to become an alternative chemo-photothermal therapy agent to treat cancers.

The iron-catalyzed α-C-H alkylation of N-methylanilines without any directing group by cross-dehydrogenative coupling between unactivated C(sp

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease system (CRISPR/Cas9) has become a powerful toolbox as a gene fixed-point knock-out method and hold the promising prospect for cancer therapy. However, the biological safety of the viral vectors and the instability of exogenous plasmid in blood circulation limits its application. Herein, we reported a lactobionic acid functionalized and stimuli-responsive chitosan based nanocomplex to co-deliver sgVEGFR2/Cas9 plasmid and paclitaxel for hepatoma carcinoma therapy. The genome editing efficiency of sgVEGFR2/Cas9 in the nanosystem achieved up to 38.6% of HepG2 cells in vitro and 33.4% of tumor tissues in vivo. The nanocomplex suppressed >60% VEGFR2 protein expression of HepG2 cells and inhibited hepatoma carcinoma (HCC) tumor progress by 70% on mice. In vivo study indicated the obvious tumor accumulation and the good biosafety of the nanosystem. Moreover, the gene-drug co-loaded nanoparticles stimulate anti-tumorigenic pathway of HCC by suppressing pro-inflammatory cytokines (IL-6/IL-8) and tumor angiogenesis-related protein (NF-κB p65) expression, which revealed the potential pathway inhibition of PTX when combined with the gene therapy for overexpression VEGFR2 on HCC cells. Overall, this strategy provided a versatile method for high efficiency CRISPR/Cas9 system delivery and showed tremendous application prospect for gene-chemo synergistic therapy.

Electromagnetic (EM) field is often referred to diffusion (quasi-static assumption) that displacement currents are neglected during data processing in geophysical application, while the ratio of conduct currents to displacement currents is higher than 10, that is ,we think EM field is diffusion dominated and wave dominate for the ratio less than 0.1. Our simulating with Horizontal Electric Dipole Field indicated that frequency range of wave dominated is that the ratio is less than 0.007, the magnitude curves of EM component and impedance referring to diffusion and wave are different from those of diffusion. And in transform zone () the curves are different from those of wave and diffusion.

Started from structure construction ,this paper carried out numerical analysis about the test members through computer simulation and studied the influence of cover thickness and stirrup spacing on the rust expansion crack by means of rapid electrifying for accelerating the corrosion of longitudinal reinforcement. Based on this, it established the correlativity between member surface stress and concrete cover thickness, stirrup spacing. And this paper found the influence law of cover thicknesses and stirrup spacing on rust expansion crack on specimen surface.

In our study, BrdU-labeled marrow stem cells (MSCs) were directly (group 1), by the coronary artery (group 2), or by the ear vein (group 3) transplanted into myocardium to observe their distribution and differentiation in acute myocardial infarction (AMI) rabbit models. BrdU-positive cells, and BrdU and α-sarcomeric actin double positive cells were visible in the infarcted zones and its peripheral region. Cell processes between BrdU-positive cells and between BrdU-positive cells and host cardiomyocytes linked together. Transverse striation and sarcomere were seen. In above zones, new blood capillaries composed of Brdu-positive endothelial cells were present. Density of new blood capillaries was greater in group 1-3 than in control group (p < 0.05) and was the greatest in group 2. Hear function in group 1-3 was improved and was the best in group 2 (p < 0.05). In group 2 and 3, BrdU-positive cells were found in the lungs, liver, and kidneys. In group 3, BrdU-positive cells were greater in the lungs than in the liver and kidneys. We can see that MSCs transplanted by the three ways all can induce the regeneration of cardiomyocytes and blood capillaries. The order from good to poor effectiveness is group 2, group 1, and group 3.

In our study, BrdU-labeled marrow stem cells (MSCs) were directly (group 1), by the coronary artery (group 2), or by the ear vein (group 3) transplanted into myocardium to observe their distribution and differentiation in acute myocardial infarction (AMI) rabbit models. BrdU-positive cells, and BrdU and α-sarcomeric actin double positive cells were visible in the infarcted zones and its peripheral region. Cell processes between BrdU-positive cells and between BrdU-positive cells and host cardiomyocytes linked together. Transverse striation and sarcomere were seen. In above zones, new blood capillaries composed of Brdu-positive endothelial cells were present. Density of new blood capillaries was greater in group 1-3 than in control group (p0.05) and was the greatest in group 2. Hear function in group 1-3 was improved and was the best in group 2 (p0.05). In group 2 and 3, BrdU-positive cells were found in the lungs, liver, and kidneys. In group 3, BrdU-positive cells were greater in the lungs than in the liver and kidneys. We can see that MSCs transplanted by the three ways all can induce the regeneration of cardiomyocytes and blood capillaries. The order from good to poor effectiveness is group 2, group 1, and group 3.