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Prodrug‐based self‐assembled nanoparticles (PSNs) with tailored responses to tumor microenvironments show a significant promise for chemodynamic therapy (CDT) by generating highly toxic reactive oxygen species (ROS). However, the insufficient level of intracellular ROS and the limited drug accumulation remain major challenges for further clinical transformation. In this study, the PSNs for the delivery of artesunate (ARS) are demonstrated by designing the pH‐responsive ARS‐4‐hydroxybenzoyl hydrazide (HBZ)‐5‐amino levulinic acid (ALA) nanoparticles (AHA NPs) with self‐supplied ROS for excellent chemotherapy and CDT. The PSNs greatly improved the loading capacity of artesunate and the ROS generation from endoperoxide bridge using the electron withdrawing group attached directly to C10 site of artesunate. The ALA and ARS‐HBZ could be released from AHA NPs under the cleavage of hydrazone bonds triggered by the acidic surroundings. Besides, the ALA increased the intracellular level of heme in mitochondria, further promoting the ROS generation and lipid peroxidation with ARS‐HBZ for excellent anti‐tumor effects. Our study improved the chemotherapy of ARS through the chemical modification, pointing out the potential applications in the clinical fields. To overcome the pharmacological limitations of artemisinin in cancer therapy, the novel pH‐responsive artesunate (ARS)‐4‐hydroxybenzoyl hydrazide (HBZ)‐5‐amino levulinic acid (ALA) nanoparticles (AHA NPs) with self‐supplied capacity of reactive oxygen species (ROS) were reported to realize excellent chemotherapy and chemodynamic therapy (CDT).

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system and remains universally lethal due to lack of effective treatment options and their inefficient delivery to the brain. Here the development of multifunctional polymeric nanoparticles (NPs) for effective treatment of GBM is reported. The NPs are synthesized using a novel glutathione (GSH)‐reactive poly (2,2″‐thiodiethylene 3,3″‐dithiodipropionate) (PTD) polymer and engineered for brain penetration through neutrophil elastase‐triggered shrinkability, iRGD‐mediated targeted delivery, and lexiscan‐induced autocatalysis. It is found that the resulting lexiscan‐loaded, iRGD‐conjugated, shrinkable PTD NPs, or LiPTD NPs, efficiently penetrate brain tumors with high specificity after intravenous administration. Furthermore, it is demonstrated that LiPTD NPs are capable of efficient encapsulation and delivery of chemotherapy doxorubicin and sonosensitizer chlorin e6 to achieve combined chemotherapy and sonodynamic therapy (SDT). It is demonstrated that the capability of GSH depletion of LiPTD NPs further augments the tumor cell killing effect triggered by SDT. As a result, treatment with LiPTD NPs effectively inhibits tumor growth and prolongs the survival of tumor‐bearing mice. This study may suggest a potential new approach for effective GBM treatment. Glutathione (GSH)‐reactive polymer‐based nanoparticles (NPs), which can target drug delivery to the brain tumor through the integration of neutrophil elastase‐triggered shrinkability, ligand‐mediated interaction, and lexiscan‐induced blood–brain barrier modulation. The resulting NPs with excellent penetration capability can efficiently deliver chemotherapy drug doxorubicin and sonosensitizer chlorin e6 to tumors in the brain for effective chemo‐sonodynamic combination therapy.

Considered as the rotation axis of the northern celestial hemisphere, north pole star was called altun qazŋuq “gold stake” in OT (Old Turkic). The article finds that Turkic north pole star tradition exerted its influence on Chinese culture twice. At the first time, the Chinese transcribed OT qazŋuq into gōzhèn (勾陳) in the Warring States period. And at the second time, the transmission took place in the Qing dynasty, when the government tried to confirm that the huge rock called altan γadasu in Mongolian was the origin of the Yellow River, the Mongolian translation of OT altun qazŋuq was translated into “gold north pole star” (黃金北極星).

Breast cancer brain metastases (BCBM) is a devastating disease with dismal prognosis. Although chemotherapy is widely used for clinical management of most tumors, it is often ineffective for BCBM. Therefore, alternative approaches for improved treatment of BCBM are in great demand. Here, an innovative gene therapy regimen is reported that is designed for effective treatment of BCBM. First, poly(lactone‐co‐β‐amino ester) nanoparticles that are capable of efficient gene delivery are synthesized and are engineered for targeted delivery to BCBM through surface conjugation of AMD3100, which interacts with CXCR4 enriched in the tumor microenvironment. Next, an artificial gene, proMel, is designed for the expression of secretory promelittin protein, which has limited toxicity on its own but releases cytolytic melittin after activation by MMP‐2 accumulated in tumors. It is demonstrated that delivery of the proMel via the AMD3100‐conjugated nanoparticles effectively inhibits tumor progression in a BCBM mouse model. This study suggests a new direction to treat BCBM through targeted delivery of promelittin‐mediated gene therapy. Herein, a new generation of poly(lactone‐co‐β‐amino ester) is synthesized for gene delivery and an artificial gene, proMel, is designed for effective cancer gene therapy. The targeted delivery of proMel effective treatment of breast cancer brain metastases is demonstrated.

Many synthetic polycationic vectors for non-viral gene delivery show high efficiency in vitro , but their usually excessive charge density makes them toxic for in vivo applications. Here we describe the synthesis of a series of high molecular weight terpolymers with low charge density, and show that they exhibit efficient gene delivery, some surpassing the efficiency of the commercial transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl diester and amino diol, and their hydrophobicity adjusted by varying the lactone content and by selecting a lactone comonomer of specific ring size. Targeted delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the terpolymers results in significant inhibition of tumour growth, with minimal toxicity both in vitro and in vivo . Our findings suggest that the gene delivery ability of the terpolymers stems from their high molecular weight and increased hydrophobicity, which compensates for their low charge density. Many synthetic polymer nanoparticles used for non-viral gene delivery contain excess cations on their surface, which makes the particles cytotoxic and the delivery of genes inefficient. Terpolymers with a low charge density, high molecular weight and increased hydrophobicity are now shown to have minimal toxicity, and to efficiently deliver the apoptosis-inducing TRAIL gene to transplanted tumours in mice.

With natural limonite as the precursor and an ammonium tungstate hydrate as modification, the W/limonite composite catalysts were synthesized by the impregnation method. Their structures and properties were systematically characterized and analyzed; the denitrification activity and resistance to water and sulfur on catalysts were investigated. The results indicated that the W/limonite composite with W/Fe mass ratio of 9% and calcination temperature of 300 °C had highly catalytic activity, enhanced resistance to sulfur and water. The NO conversion efficiency was maintained over 85% with NO initial concentration of 500 ppm, the gas hourly space velocity (GHSV) of 36,000 h −1 , and reaction temperature of 100 °C, while it was greater than 98% with addition of 200 ppm SO 2 and 3 vol. % H 2 O at the reaction temperature of 250 °C. The superior performance was mainly ascribed to the formation of W-OH species and W = O species with wide dispersion on the surface of goethite or in Fe 2 O 3 lattice defects, to generate more acidic hydroxyl groups and more oxygen defects and strong acidity Brønsted for the SCR reaction.

With natural limonite as the precursor and an ammonium tungstate hydrate as modification, the W/limonite composite catalysts were synthesized by the impregnation method. Their structures and properties were systematically characterized and analyzed; the denitrification activity and resistance to water and sulfur on catalysts were investigated. The results indicated that the W/limonite composite with W/Fe mass ratio of 9% and calcination temperature of 300 °C had highly catalytic activity, enhanced resistance to sulfur and water. The NO conversion efficiency was maintained over 85% with NO initial concentration of 500 ppm, the gas hourly space velocity (GHSV) of 36,000 h , and reaction temperature of 100 °C, while it was greater than 98% with addition of 200 ppm SO and 3 vol. % H O at the reaction temperature of 250 °C. The superior performance was mainly ascribed to the formation of W-OH species and W = O species with wide dispersion on the surface of goethite or in Fe O lattice defects, to generate more acidic hydroxyl groups and more oxygen defects and strong acidity Brønsted for the SCR reaction.

Alternating ethylene-carbon monoxide copolymer (E-CO copolymer) was prepared by direct polymerization of carbon monoxide with ethylene, using (Pd(CH $\\sb3$ CN) $\\sb2$ (PPh $\\sb3)\\sb2$ ) (BF $\\sb4)\\sb2$as the catalyst. Reaction of the E-CO copolymer with primary amines has resulted in formation of a new type of functionalized polymer derivatives, N-substituted poly(ethylenepyrrole). The nonconjugated poly(ethylenepyrrole) derivatives exhibited high electrical conductivity after doping with iodine. Furthermore, dehydrogenation of the derivatized poly(ethylenepyrrole) has led to the synthesis of a new conjugated polymer system, poly(ethynepyrrole). Palladium complexes--Pd(2,6- $\\sp{\\rm t}$ Bu $\\sb2$ -pyridine) $\\sb2$ (CH $\\sb3$ NO $\\sb2)\\sb2$ (BF $\\sb4)\\sb2$ ,1; Pd(PPh $\\sb3)\\sb2$ (BF $\\sb4)\\sb2$2; Pd(Ph $\\sb2$ PCH $\\sb2$ CH $\\sb2$ PPh $\\sb2$ )(BF $\\sb4)\\sb2$ , 3--were prepared through either ligand substitution reaction using (Pd(CH $\\sb3$ CN) $\\sb4$ ) (BF $\\sb4)\\sb2$as starting reagent or reaction of PdL $\\sb2$ Cl $\\sb2$(L: corresponding ancillary ligand) with two equivalents of AgBF $\\sb4$in nitromethane. Compounds 1-3 were found to selectively catalyze the dimerization or oligomerization/polymerization of a variety of olefins while the compound (Pd(CH $\\sb3$ CN) $\\sb4$ ) (BF $\\sb4)\\sb2$ , polymerized olefins nonselectively. The initiation mechanism of the cationic dimerization and polymerization of olefins is proposed. One of these highly selective catalysts, Pd(PPh $\\sb3)\\sb2$ (BF $\\sb4)\\sb2$(2), was also used for the synthesis of linear poly(p-divinylbenzene). Catalyzed by 2, p-divinylbenzene (p-DVB) polymerized gradually through a stepwise intermolecular vinyl coupling process to form a linear unsaturated poly(p-DVB). In addition, terminally functionalized poly(p-DVB) was prepared through cross vinyl coupling between terminal vinyl groups of the poly(p-DVB) and the vinyl group of functional group substituted styrene, using the same catalyst. The kinetics of the p-DVB polymerization catalyzed by 2 and the styrene dimerization and$\\alpha$ -methylstyrene oligomerization reaction catalyzed by 1 were studied. The reaction rate equations were determined, in general, as follows: Rate = k (Olefin)$\\sp1$(Pd(II))$\\sp{\\rm m}$Olefin: styrene,$\\alpha$ -methylstyrene or p-DVB Pd(II): 1 or 2, total Pd(II) species in solution m: 0.6-0.7 in the styrene dimerization and p-DVB polymerization reaction, 2.2 in the$\\alpha$ -methylstyrene oligomerization reaction Quantitative analysis shows that m is dependent on the equilibria involving the interactions between the cationic metal species and its counteranion. Fractional order m varies with the change in the dissociation constants of BF $\\sb4\\sp-$from the metal cation. The solvent, whose polarity affects the dissociation equilibria, could also change the value of the order m.

Background Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. Results We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k -mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28–34%, genus level). PHP also outperformed these two alignment-free methods much (24–38% vs 18–20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. Conclusions The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

Background The comorbidity between polycystic ovary syndrome (PCOS) and obesity has long been observed in clinical settings, but their shared genetic basis remains unclear. Methods Leveraging summary statistics of large-scale GWAS(s) conducted in European-ancestry populations on body mass index (adult BMI, N female =434,794; childhood BMI, N =39,620), waist-to-hip ratio (WHR, N female =381,152), WHR adjusted for BMI (WHR adj BMI, N female =379,501), and PCOS ( N case =10,074, N control =103,164), we performed a large-scale genome-wide cross-trait analysis to quantify overall and local genetic correlation, to identify shared loci, and to infer causal relationship. Results We found positive genetic correlations between PCOS and adult BMI ( r g =0.47, P =2.19×10 −16 ), childhood BMI ( r g =0.31, P =6.72×10 −5 ), and WHR ( r g =0.32, P =1.34×10 −10 ), all withstanding Bonferroni correction. A suggestive significant genetic correlation was found between PCOS and WHR adj BMI ( r g =0.09, P =0.04). Partitioning the whole genome into 1703 nearly independent regions, we observed a significant local genetic correlation for adult BMI and PCOS at chromosome 18: 57630483–59020751. We identified 16 shared loci underlying PCOS and obesity-related traits via cross-trait meta-analysis including 9 loci shared between BMI and PCOS (adult BMI and PCOS: 5 loci; childhood BMI and PCOS: 4 loci), 6 loci shared between WHR and PCOS, and 5 loci shared between WHR adj BMI and PCOS. Mendelian randomization (MR) supported the causal roles of both adult BMI (OR=2.92, 95% CI=2.33–3.67) and childhood BMI (OR=2.76, 95% CI=2.09–3.66) in PCOS, but not WHR (OR=1.19, 95% CI=0.93–1.52) or WHR adj BMI (OR=1.03, 95% CI=0.87–1.22). Genetic predisposition to PCOS did not seem to influence the risk of obesity-related traits. Conclusions Our cross-trait analysis suggests a shared genetic basis underlying obesity and PCOS and provides novel insights into the biological mechanisms underlying these complex traits. Our work informs public health intervention by confirming the important role of weight management in PCOS prevention.