Search

A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOXADH and D-DOXcar conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOXADH (D-DOXADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios, that had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

International audience; The synthesis of CdSe/CdS core/shell nanoparticles was revisited with the help of a causal inference machine learning framework. The tadpole morphology with 1–2 tails was experimentally discovered. The causal inference model revealed the causality between the oleic acid (OA), octadecylphosphonic acid (ODPA) ligands, and the detailed tail shape of the tadpole morphology. Further, with the identified causality, a neural network was provided to predict and directly lead to the original experimental discovery of new tadpole-shaped structures. An entropy-driven nucleation theory was developed to understand both the ligand and temperature dependent experimental data and the causal inference from the machine learning framework. This work provided a vivid example of how the artificial intelligence technology, including machine learning, could benefit the materials science research for the discovery.

Stereoselective glycosylation is challenging in carbohydrate chemistry. Herein, stereoselective thioglycosylation of glycals via palladium-catalyzed allylic rearrangement yields various substituents on α-isomer thioglycosides. Two comprehensive series of aryl and benzyl thioglycosides were obtained via a combination of thiosulfates with glycals derived from glucose, arabinose, galactose, and rhamnose. Furthermore, diosgenyl α-l-rhamnoside and isoquercitrin achieved selectivity via stereospecific [2,3]-sigma rearrangements of α-sulfoxide-rhamnoside and α-sulfoxide-glucoside, respectively.

Olivine-structured LiFePO4 is one of the most popular cathode materials in lithium-ion batteries (LIBs) for sustainable applications. Significant attention has been paid to investigating the dynamics of the lithiation/delithiation process in Li x FePO4 (0 ≤ x ≤ 1), which is crucial for the development of high-performance LiFePO4 material. Various macroscopic models based on experimental evidence have been proposed to explain the mechanism of phase transition from LiFePO4 to FePO4, such as the shrinking core (i.e., core-shell) model, Laffont's (i.e., new core-shell) model, domino-cascade model, phase transformation wave, solid solution model, many-particle models, etc. However, these models, unfortunately, contradict each other and their validity is still under debate. An atomistic model is urgently required to depict the lithiation/delithiation process in Li x FePO4. In this article, we reveal the lithiation/delithiation process in LiFePO4 simulated by a computational model using the generalized gradient approximation (GGA + U) method. We find that the clustered configuration is the most energetically favorable, leading to co-operative Jahn-Teller distortion among the inter-polyhedrons that can be observed clearly from the bond patterns. This atomistic model not only offers answers to experimental results obtained at moderate or high rates but also gives the direction to further improve the rate capability of LiFePO4 cathode material for high-power LIBs.

Hypertension has become a major public health challenge, and previous studies have observed associations between hypertension and sodium, potassium, and sodium to potassium ratio. However, little is known about how the whole continuum of blood pressure (BP) is related to dietary intake of sodium and potassium. This study aims to examine quantile-specific associations of blood pressure with dietary intake of sodium and potassium. It is based on national-level, cross sectional data for US adults aged ≥18 years from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. A total of 11,095 eligible subjects were included in this study. Quantile regression (QR) models were used to investigate distributional effects in the dietary intake of sodium and potassium on blood pressure by adjusting the confounding factors. We observed some evidence indicating distributional effects of dietary intake of sodium and potassium on systolic blood pressure (SBP) and diastolic blood pressure (DBP). QR showed that the consumption of sodium was positively associated with SBP (P10) and DBP (P10) in males, and positively associated with DBP (P80-P90) alone in females. Intake of potassium was, however, negatively associated with SBP (P20-P30, P70-P80) in males, and also negatively associated with SBP (P10-P80) and DBP(P20-P50) in females. Sodium to potassium ratio was positively associated with SBP (P10-P50, P80) and DBP (P70-P90) in males, and was positively associated with SBP(P10-P70, P90) in females. QR models provided a more detailed view on associations of SBP and DBP with the dietary intake of sodium and potassium and uncovered the quantile-related patterns.

A nickel-catalyzed coupling of N-sulfonyl-1,2,3-triazole with various H-phosphine oxides for the construction of C(sp2)–P bonds is established. This unexpected reaction proceeds through a formal nickel-bound ketenimine pathway, representing a previously unknown 1,2-reactivity type of an azavinyl carbene. The method provides an efficient approach to the stereoselective and site-selective synthesis of α-aminovinylphosphoryl derivatives with moderate to good yield. A plausible mechanism is proposed based on experimental and theoretical studies.

A new two-dimensional carbon allotrope, which consists of 18 atoms in a hexagonal cell, is theoretically investigated by performing first-principle method. The allotrope displays a P6/mmm symmetry (termed as hP-C18 carbon). The new 2D carbon phase has an sp2-sp3 network, consisting of hexagons and octagons formed by near-by atoms. The calculations demonstrate that hP-C18 carbon is a metastable 2D carbon phase compared to graphene, but it is more energetically stable than penta-graphene. The dynamical, thermal and mechanical stabilities are demonstrated by phonon dispersion, ab inito MD simulations and elastic constants, respectively. The analysis of electronic band structure shows that hP-C18 is an indirect semiconductor with a band gap of 2.93 eV (HSE06). Besides, its buckled 3D structure, hP-C18-3D carbon, is also predicted. The stability of the new 3D phase is discussed by phonon dispersion and elastic constants. It is found that hP-C18-3D carbon is a super-hard indirect semiconductor with an indirect band gap of 2.24 eV (HSE06). Thus, hP-C18 carbon and its buckled 3D structure may possess not only potential electronic applications but also mechanical applications.

Polyprodrugs, in which drug was used as the structural unit by linking with each other via the dynamic covalent bonds in the main chain, are expected to endow excellent drug delivery performance. Here, acid-triggered degradable diblock polyprodrug, poly(doxorubicin)-polyethylene glycol (PDOX-PEG), was designed with DOX as structural unit alternately linked with acid-labile hydrazone and maleic amide groups, by the polycondensation of DOX-based dimers (D-DOXADH or D-DOXMAH) with PEGylated dimer (DOX-ADH-DOX-PEG) as end capping agent. The optimized PDOX-PEG, which was synthesized with D-DOXADH and the PEGylated dimer at a feeding ratio of 10%, possessed a high Mn of 3.1 × 104 g/mol with a high DOX content of 75.42%. It could easily self-assemble into near spherical nanoparticles with average hydrodynamic diameter of 135 nm. They showed excellent pH-triggered sustained drug release owing to the acid-triggered degradation of the polyprodrug block in the tumor intracellular microenvironment, with low premature drug leakage of 4.39 % within 60 h. The MTT results indicated the enhanced antitumor efficacy of the proposed PDOX-PEG nanoparticles than free DOX. The results demonstrated the promising potential of the proposed acid-triggered degradable diblock PDOX-PEG polyprodrug for tumor treatment.

Microplastics have become an emerging concerned global environmental pollution problem. Their strong adsorption towards the coexisting organic pollutants can cause additional environmental risks. Therefore, the adsorption capacity and mechanisms are necessary information for the comprehensive environmental assessments of both microplastics and organic pollutants. To overcome the lack of adsorption information, five quantitative structure–property relationship (QSPR) models were developed for predicting the microplastic/water partition coefficients (log Kd) of organics between polyethylene/seawater, polyethylene/freshwater, polyethylene/pure water, polypropylene/seawater, and polystyrene/seawater. All the QSPR models show good fitting ability (R2 = 0.811–0.939), predictive ability (Q2ext = 0.835–0.910, RMSEext = 0.369–0.752), and robustness (Qcv2 = 0.882–0.957). They can be used to predict the Kd values of organic pollutants (such as polychlorinated biphenyls, chlorobenzene, polycyclic aromatic hydrocarbons, antibiotics perfluorinated compounds, etc.) under different pH conditions. The hydrophobic interaction has been indicated as an important mechanism for the adsorption of organic pollutants to microplastics. In sea waters, the role of hydrogen bond interaction in adsorption is considerable. For polystyrene, π–π interaction contributes to the partitioning. The developed models can be used to quickly estimate the adsorption capacity of organic pollutants on microplastics in different types of water, providing necessary information for ecological risk studies of microplastics.

Facile one-pot approach was established to fabricate chitosan-based supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking of the β-cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter (Dh) of 140 nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio of carrier:DOX at 25:10. They were stable in the simulated physiological medium with premature drug release of only 3% over 60 h, while a high cumulative release up to 82.3% was achieved within 84 h in a sustained manner without initial burst in the simulated tumor intracellular micro-environment. The MTT assays indicated that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced antitumor efficacy in comparison with the free DOX.

The new era with prosperous artificial intelligence (AI) and robotics technology is reshaping the materials discovery process in a more radical fashion. Here we present authentic intelligent robotics for chemistry (AIR-Chem), integrated with technological innovations in the AI and robotics fields, functionalized with modules including gradient descent-based optimization frameworks, multiple external field modulations, a real-time computer vision (CV) system, and automated guided vehicle (AGV) parts. AIR-Chem is portable and remotely controllable by cloud computing. AIR-Chem can learn the parametric procedures for given targets and carry on laboratory operations in standalone mode, with high reproducibility, precision, and availability for knowledge regeneration. Moreover, an improved nucleation theory of size focusing on inorganic perovskite quantum dots (IPQDs) is theoretically proposed and experimentally testified to by AIR-Chem. This work aims to boost the process of an unmanned chemistry laboratory from the synthesis of chemical materials to the analysis of physical chemical properties, and it provides a vivid demonstration for future chemistry reshaped by AI and robotics technology.

A facile one-pot approach has been developed to prepare novel pH-responsive ionic nanohydrogels with high drug-loading capacity and desirable size for tumor-specific intracellular triggered release of anticancer drug DOX, in which the ionic crosslinking of alginate (AL) or its derivatives (oxidized alginate (OAL) or PEGylated OAL (mPEG-OAL)) and the DOX-loading ocurred simultaneously. It was found that the modification was benificial to the formation of the DOX-loaded ionic nanohydrogels with smaller diameter and narrower size distribution, even with similar DOX loading capacity. Especially for the mPEG-OAL, the resultant mPEG-OAL/DOX ionic nanohydrogels showed a hydrodynamic diameter of 135 nm with very narrow size distribution. All the three DOX-loaded ionic nanohydrogels (AL/DOX, OAL/DOX, and mPEG-OAL/DOX) showed the pH-responsive characteristic, and the last one exhibited the best capacity for controlled release, in a sustained release mode.

Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. NMR was methylated by NSUN2 and might competitively inhibit methylation of potential mRNAs. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functions as an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.

PEGylated multi-walled carbon nanotubes (PEG-MWCNTs) were optimized as versatile vector for tumor-specific intracellular triggered release of doxorubicin (DOX), based on the effect of their length and PEGylation degree on the cytotoxicity and DOX-loading capacity. The length and surface carboxyl groups of the carboxylated multi-walled carbon nanotubes (CMWCNTs) were easily tailored by adjusting the oxidation time. The longer CMWCNTs or those with high carboxyl group content showed obvious cytotoxicity, while the PEG-MWCNTs ≤ 300 nm showed better cytocompatibility. The PEG-MWCNTs-3 of about 300 nm was selected as drug delivery vector, possessing a high drug-loading capacity of 0.55 mg/mg. They released DOX rapidly under lower pH media mimicking the tumor microenvironment with cumulative release of 57% within 24 h, while the premature leakage under the simulated physiological condition was only 10%. The WST-1 assays demonstrated the DOX-loaded PEG-MWCNTs-3 exhibited the enhanced inhibitory efficiency against HepG2 cells, in comparison with free DOX.

Liquid hydrogenated nitrile-butadiene rubber (LH-NBR), hydrogenated nitrile-butadiene rubber (H-NBR) with number-averaged molecular weight of C C groups instead of the C N ones in the liquid nitrile-butadiene rubber (L-NBR) with narrow molecular weight distribution was conducted with palladium nanoparticles supported on macroporous hollow silica microspheres (Pd/MHS) catalyst, with the hydrogenation degree (HD%) > 95% for the 5th reuse.

A structurally stable silicon allotrope is predicted by means of first principles calculations. This new structure is composed of a six-membered ring, a five-membered ring and a three-membered ring with the space group PA and fvs topology, which is named fvs-Si48. The calculations of geometrical, vibrational, and electronic and optical properties reveal that fvs-Si48 has good mechanical stability with a mass density of 1.86 g cm−3. More importantly, it is a semiconductor with a direct band gap of 2.15 eV. From the analysis of its optical properties, there is the possibility of its synthesis in theory. This fvs-Si48 could have a wide range of applications in photo catalysts, optoelectronics, hydrogen storage and aerospace engineering.

Acetylation, as one of the most important post-translation modifications, plays a key role in a variety of biological functions, such as transcriptional regulation, cytokine signaling, and apoptosis. To understand the mechanism of acetylation profoundly, it is necessary to identify acetylation sites in proteins accurately. The existing methods for identifying protein acetylation sites can be divided into two major categories, i.e., mass spectrometry and computational methods. Mass spectrometry-based experimental methods are capable of discovering acetylation sites from eukaryotes, but can be time-consuming and expensive. Therefore, it is necessary to develop computational approaches that can effectively and accurately identify protein acetylation sites. The existing computational methods usually involve feature engineering, which may lead to redundancy and biased representations. While deep learning is capable of excavating the underlying characteristics from large-scale training data set via multiple-layer networks and non-linear mapping operations. In this paper, we propose a new method (named DeepAce) for predicting general and species-specific lysine acetylation sites based on deep neural network. We critically evaluate the performance of DeepAce and compare it with other existing predictors. The comparative results show the effectiveness of our Bi-modal deep architecture and also indicate that our method is very promising for predicting acetylation sites. The source code of DeepAce can be freely accessed at https://github.com/jiagenlee/DeepAce .

Novel porous polyaniline (PANI) modified MWNTs core-shell structure materials (porous CNTs-PANI) were fabricated by in situ polymerization using the “worm-like” MnO2 modified MWNTs (CNTs-MnO2) as the reactive template. The MnO2 layer on surface of MWNTs can act as the reactive template in the polymerization process. Meanwhile, the reactive etching of the MnO2 can form porous structure of PANI for fabrication of porous CNTs-PANI core-shell structure, which exhibits outstanding electrochemical performance among the CNTs-PANI and pure PANI materials. The porous CNTs-PANI materials possess an excellent specific capacitance of 406.5F/g at 0.5A/g, exhibit good rate capability of 84.7% even up to 50A/g, and keep 72% of its original value up to 1000 charge-discharge cycles at the current density of 10A/g, also maintain 55% capacitance retention at 2200 charge-discharge cycles. Furthermore, the porous CNTs-PANI materials exhibit an extremely high energy density of 55.6Wh/kg at the power density of 0.25kW/kg. The novel porous CNTs-PANI core-shell structure materials reveal promising applications in high performance supercapacitors. Keywords: Core-shell, PANI, Porous structure, Supercapacitor, High rate capability

Multi-responsive polymeric microspheres have attracted more and more interest as drug delivery system (DDS) for anti-tumor drugs because they could achieve “on-demand” drug release, triggered by the tumor micro-environment. Here the pH, temperature and reduction multi-stimuli responsive polymeric microspheres were fabricated via distillation–precipitation polymerization technique, with or without the middle hollow layer between their pH and reduction responsive poly(methacrylic acid) (PMAA) cores and temperature sensitive poly(N-isopropylacrylamide) (PNIPAM) shells. The effect of the hollow layer on their drug loading and drug release performance was investigated in detail. It was found that the PMAA/PNIPAM yolk/shell microspheres with hollow layer possessed a higher drug loading capacity, while the PMAA/PNIPAM core/shell microspheres without hollow layer exhibited a better controlled release behavior. This understanding must be helpful on designing intelligent anti-tumor DDS.

Drug self-delivery systems (DSDSs) have attracted intense attention due to their high drug content. However, their practical application still suffers from their premature drug leakage, slow drug release, and/or low antitumor efficacy of the released small molecular drugs. Here, acid-labile poly(Doxazolidine) (P(Doxaz)) is designed as a polyprodrug for the self-delivery of high antitumor chemotherapeutics (Doxazolidine (Doxaz)), with an ultrahigh Doxaz content of 92.45%. The P(Doxaz) nanoparticles could completely degrade into Doxaz within 10 h in the simulated tumor intracellular microenvironment, with a low drug leakage of 12.9% over 12 h in the normal physiological media. Owing to the ultrahigh drug content, fast acid-triggered degradation and drug release, and high antitumor efficacy of Doxaz, the proposed DSDS possesses an enhanced antiproliferation efficacy compared to the free DOX, demonstrating its potential in future tumor treatments.

Background Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers and affect the response to radiotherapy. This study focused on clarifying the underlying mechanism by which lncTUG1 affects the radiosensitivity of esophageal squamous cell carcinoma (ESCC). Methods lncTUG1, miR-144-3p and MET expression levels were detected in ESCC tissues and cells by qRT-PCR. Western blotting was used to examine the protein levels of MET, p-AKT and EGFR. The dual-luciferase reporter system and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between lncTUG1 and miR-144-3p or miR-144-3p and MET. MTT, colony formation and flow cytometry assays were applied to examine the behavioral changes in EC9706 and KYSE30 cells. Results lncTUG1 was upregulated in ESCC cells and tissues, and lncTUG1 expression was associated with an advanced pathological stage. The bioinformatics analysis revealed that lncTUG1 could specifically bind to miR-144-3p, which was downregulated in ESCC. There was a negative correlation between lncTUG1 and miR-144-3p. LncTUG1 inhibition retarded proliferation and colony formation and induced apoptosis in ESCC cells. Moreover, lncTUG1 knockdown dramatically improved the effect of radiotherapy on ESCC development both in vivo and in vitro. Furthermore, MET was revealed as a downstream target of miR-144-3p and is downregulated by it. LncTUG1 promoted the progression of ESCC and elevated radiotherapy resistance in ESCC cells, accompanied by a high level of MET expression. Moreover, we found that knockdown of lncTUG1 enhanced the radiosensitivity of ESCC cells via the p-AKT signaling pathway. Conclusion Our results indicate that lncTUG1 enhances the radiotherapy resistance of ESCC by lowering the miR-144-3p level and modulating the MET/EGFR/AKT axis.

Herein, a core–shell tellurium–selenium (Te–Se) nanomaterial with polymer‐tailed and lateral heterojunction structures is developed as a photothermal absorber in a bionic solar‐evaporation system. It is further revealed that the amorphous Se shell surrounds the crystalline Te core, which not only protects the Te phase from oxidation but also serves as a natural barrier to life entities. The core (Te)–shell (Se) configuration thus exhibits robust stability enhanced by 0.05 eV per Se atom and excellent biocompatibility. Furthermore, high energy efficiencies of 90.71 ± 0.37% and 86.14 ± 1.02% and evaporation rates of 12.88 ± 0.052 and 1.323 ± 0.015 kg m−2 h−1 are obtained under 10 and 1 sun for simulated seawater, respectively. Importantly, no salting out is observed in salt solutions, and the collected water under natural light irradiation possesses extremely low ion concentrations of Na+, K+, Ca2+, and Mg2+ relative to real seawater. Considering the tunable electronic structures, biocompatibilities, and modifiable broadband absorption of the solar spectrum of lateral heterojunction nanomaterials of Te–Se, the way is paved to engineering 2D semiconductor materials with supporting 3D porous hydrophilic materials for application in solar desalination, wastewater treatment, and biomedical ventures.

ObjectiveTraditionally, the absence of insulin resistance risk factors (IRRFs) was considered a low risk for insulin resistance (IR). However, IR also existed in certain individuals without IRRFs; thus this study aims to explore predictors of IR targeted at the population without IRRFs.DesignCross-sectional survey.SettingNational Health and Nutrition Examination Survey.ParticipantsParticipants without regular IRRFs (IRRF-Free, n=2478) and a subgroup without optimal IRRFs (IRRF-Optimal, n=1414) were involved in this study.Primary and secondary outcome measureIRRFs and the optimal cut-off value of triglyceride (TG) to predict IR.ResultsOverall, the prevalence of IR was 6.9% and 5.7% in the IRRF-Free group and the IRRF-Optimal group, respectively. TG and waist circumference were independently associated with the prevalence of IR in both the groups (OR=1.010 to 10.20; pConclusionThere is an association between TG and IR even in the normal range of TG concentration. Therefore, normal TG could be used as an important indicator to predict the prevalence of IR in the absence of IRRFs.

A facile approach has been developed to prepare novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cy) prodrug nanohydrogels for tumor-specific intracellular triggered release of anticancer drug doxorubicin (DOX), by conjugating DOX via acid-labile Schiff base linkage into the alginate nanohydrogels crosslinked with bioreducible disulfide bonds. The uniform prodrug nanohydrogels, which were prepared with the oxidized alginate (OAL) with an oxidation degree of 20.0%, PEGylation degree of 7.5 mol%, and crosslinking degree of 94.0%, showed a favorable DOX content (22.7 ± 0.4%) with an average hydrodynamic diameter of about 170 nm. They released DOX rapidly in lower pH media mimicking the tumor microenvironment with a cumulative DOX release rate of 58.4% within 58 h with a sustained release behavior in long term release resulting from their nanohydrogel-micelle transformation, while the premature leakage under the simulated physiological conditions was only 15.5%. The MTT assay demonstrated that the mPEG-OAL-DOX/Cy prodrug nanohydrogels exhibited enhanced inhibitory efficiency against SKOV3 cells, in comparison with free DOX.

Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation, and simple esterification reaction and self-assembled into stimuli-regulated amphiphilic micelles in aqueous solution. On the basis of the optimization of the morphology and particle size of the micelles via modulating the number of the photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from PEG43-b-P(AA76-co-NBA35-co-tBA9) with an average hydrodynamic diameter (Dh) of 163 nm was selected as a potential drug delivery system (DDS) for UV-triggered delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX-loading. Most importantly, the DOX-loaded PEG43-b-P(AA76-co-NBA35-co-tBA9) micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated physiological medium within 6 days without UV-irradiation, indicating t...

Fluorescent poly(methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate-co-N′-rhodamine B-acrylhydrazine) (P(MAA-co-PEGMA-co-RhBAh), PMPR) nanoparticles were designed as pH/reduction dual stimuli-responsive drug delivery system (DDS) for anti-cancer drug via facile distillation-precipitation copolymerization with bio-reducible disulfide-containing crosslinker. As a carrier for doxorubicin (DOX), high drug-loading capacity (DLC) and drug-loading efficiency (DLE) of 53.1% and 97.3% were achieved respectively, via the strong electrostatic interaction between the carboxyl groups of PMAA segments and the amino group of DOX. Due to the disulfide crosslinking structure and their drug-loading mode, the DOX-loaded PMPR nanoparticles were relatively stable under extracellular conditions with low drug leakage, while a rapid intracellular drug release took place in acidic and reductive environment of tumor cells. The fluorescence microscope analysis showed that the DOX-loaded PMPR nanoparticles could be successfully endocytosed by HepG2 cells and the released DOX was mainly accumulated in cell nuclei. These features make them potential DDS for tumor-environment-responsive controlled release. Furthermore, the PMPR nanoparticles showed strong fluorescence only at low pH media, which might be used for the real-time fluorescent imaging in cancer diagnosis as a potential theranostic nanoplatform for imaging-guided therapy of cancer.

Chiral ligand conjugated transition metal oxide nanoparticles (NPs) are a promising platform for chiral recognition, biochemical sensing, and chiroptics. Herein, we present chirality-based strategy for effective sensing of mercury ions via ligand-induced chirality derived from metal-to-ligand charge transfer (MLCT) effects. The ligand competition effect between molybdenum and heavy metal ions such as mercury is designated to be essential for MLCT chirality. With this know-how, mercury ions, which have a larger stability constant ( K f ) than molybdenum, can be selectively identified and quantified with a limit of detection (LOD) of 0.08 and 0.12 nmol/L for D-cysteine and L-cysteine (Cys) capped MoO 2 NPs. Such chiral chemical sensing nanosystems would be an ideal prototype for biochemical sensing with a significant impact on the field of biosensing, biological systems, and water research-based nanotoxicology.

Acid-labile anhydride-linked doxorubicin-doxorubicin dimers (D-DOX) were designed as doxorubicin-doxorubicin conjugate-based drug self-delivery systems (DSDSs) with high drug content for tumor intracellular pH-triggered release, by conjugating doxorubicin (DOX) with various anhydrides, such as maleic anhydride (MAH), succinic anhydride (suc), and 2,3-dimethylmaleic anhydride (DMMAH). With the similar diameter of about 200 nm, the D-DOXMAH showed better pH-triggered DOX release and was thus selected for the further investigation. The D-DOX-5 nanoparticles with desirable average hydrodynamic diameter (Dh) of 162 nm and high drug content of 51.20% were obtained via self-assembly by a facile dialysis technique, with the PEGylated dimer (D-DOXMAH-S-PEG) as surfactant. The cumulative DOX release from the proposed D-DOX nanoparticles reached 40.6% within 36 h in the simulated tumor intracellular acidic micro-environment, while the premature drug leakage was only 4.5% in the simulated normal physiological medium. The MTT results indicated the proposed DSDS possessed an enhanced anti-tumor efficacy for the HepG2 cancer cell than the free DOX.

Facile approach was established to fabricate the hybrid cluster bombs of PEGylated chitosan encapsulated doxorubicin (DOX)-loaded superparamagnetic nanoparticles as tumor-specific theranostics for targeted DOX delivery and magnetic resonance (MR) imaging, by simply co-precipitation of poly(ethylene glycol) modified chitosan (CS-PEG), oleylamine modified Fe3O4 (OA-Fe3O4) nanoparticles and DOX. In presence of OA-Fe3O4, the particle size of the DOX/OA-Fe3O4@CS-PEG cluster bombs decreased to around 80 nm from 300 nm of the DOX/CS-PEG nanoparticles, with high drug-loading capacity (DLC) of 24.3% and saturation magnetization (Ms) of 4.11 emu/g, respectively. The in vitro evaluation results indicated that the blank OA-Fe3O4@CS-PEG clusters showed excellent cytocompatibility, while the DOX/OA-Fe3O4@CS-PEG clusters could be uptaken into HepG2 cells to deliver DOX into the cell nuclei with enhanced anti-cancer efficacy in comparison with free DOX. In the tumor intracellular micro-environment, the stimuli-responsive hybrid cluster bombs disassembled and re-self-assembled into the OA-Fe3O4 nanoparticle clusters with higher Ms for MR imaging-guided diagnosis, owing to the tumor-specific DOX release and dissolution of CS-PEG.

BACKGROUND: Traditionally, absence of insulin resistance risk factors (IRRFs) is considered low risk for insulin resistance (IR). However, even individuals without IRRFs still have IR. This study aimed to explore the predictors of IR among the population who are non-smokers, non-diabetic and non-obese with normal blood pressure and lipids. METHODS: The data was derived from the 2007-2014 National Health and Nutrition Survey (NHANES). Participants without regular insulin resistance risk factors (IRRF-Free, n =2 317) and a subgroup without optimal insulin resistance risk factors (IRRF-Optimal, n =1 325) were involved to explore predictors of IR, which was indexed by homeostatic model assessment (HOMA). The logistic regression model and the areas under receiver operating characteristic curve (AUROC) were used to evaluate IRRFs and the predictive capacity, and Jordan index was performed to determine the optimal cut-off value of triglyceride (TG) to predict IR in IRRF-Free and IRRF-Optimal. FINDINGS: The prevalences of IR were 6.9% and 5.8% in IRRF-Free and IRRFOptimal respectively. TG and waist circumference (WC) were independently associated with the prevalence of IR (P

Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated oxidized alginate (mPEG-OAL) cross-linked with bioreducible disulfide bond. The effect of the complexation with cyclodextrins (α-CD and β-CD) before or after the cross-linking of the mPEG-OAL on the DOX content and controlled release performance was investigated. It was found that the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(CD)-OAL-DOX/Cys, prepared by cross-linking of the mPEG-OAL after complexation with cyclodextrins, exhibited better pH/reduction dual-responsive controlled release performance than the mPEG-OAL-DOX/Cys(CD) ones prepared by cross-linking of the mPEG-OAL before complexation with cyclodextrins, owing to the supramolecular cross-linking of the adjacent pseudopolyrotaxanes. Especially for the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(α-CD)-OAL-DOX/Cys, DOX was released rapidly under lower pH media mimicking the tumor microenvironment and completely released within 48 h, while the premature leakage under the simulated physiological condition was ∼40%, without burst release in both cases. The cellular toxicity and uptake results demonstrated that the mPEG(α-CD)-OAL-DOX/Cys prodrug nanohydrogels possessed similar inhibition against cancer cell growth in comparison with the free DOX and enhanced drug intracellular accumulation.

Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) (FA-PEG-NH2) and rhodamine B (RhB)-terminated poly(ethylene glycol) (RhB-PEG-NH2) modified oxidized alginate (OAL-g-PEG-FA/RhB) with cystamine (Cys), followed covalent conjugation of doxorubicin (DOX) via acid-labile Schiff base bond. Owing to the surface folic acid (FA) groups, disulfide crosslinking structure and Schiff base conjugation for DOX, the folate receptor (FR)-mediated targeting and pH/reduction dual responsive intracellular triggered release of DOX was achieved. The cytotoxicity and cellular uptake results clearly illustrated that most DOX was released and accumulated in the cell nuclei and killed the cancer cells efficaciously, due to the desirable targeting intracellular triggered release. Furthermore, the theranostic nanogels could be used for the real-time and noninvasive location tracking to cancer cells, owing to the pH-modulated fluorescence property of the pendant RhB groups.

Photonic crystal (PhC) lasers feature compact mode volume with high quality factor and they are promising candidates for ultra-fast and ultimate thresholdless lasing operation [1]. Until now, most photonic crystal lasers fabricated on silicon [2], III-V [3] and organic hybrid platforms [4] are limited by their natural rigidities. Here we report on a hybrid laser platform comprised of flexible organic supporting material PDMS and inorganic III-V material designed to operate in the spectral vicinity of 670 nm, which could be applied to ultra-small biosensors, flexible laser projection displays.

Drug content and releasing rate are the main determining factors for the drug delivery systems (DDSs). Here, doxorubicin dimer (D-DOXcar) was synthesized as drug-drug conjugate prodrug with high drug content of 86%, via an acid-triggered hydrolysable carbamate linker. The prodrug nanoparticles (D-DOXcar-NP) with different diameters were prepared as drug self-delivery system (DSDS) for intracellular pH-triggered slow release. They showed size- and concentration-dependent pH-triggered slow DOX release. For the D-DOXcar-sNP with smaller diameter, the cumulative release ratio reached 25.6% at pH 5.0 within 60 h. The MTT results demonstrated that the proposed DSDS showed similar tumor inhibition regardless of carboxylesterases, and an enhanced anti-tumor efficacy on the HepG2 cells in comparison with the free DOX.

A general strategy was developed to fabricate the chitosan-based micelles as smart drug delivery system (DDS) for anti-cancer drug doxorubicin (DOX), via modulating the feeding ratio of PEG (PEG(2000)-CHO) and molecular weight of chitosan. Typically, benefiting from the solubility of chitosan in media with different pH values as an "off-on" switch, the DOX/CS1000K-PEG(2) micelles possess spherical core with a narrow dispersed diameter of 64 nm and regular shell with a thickness of 14 nm in pH 7.4 PBS. Interestingly, the DOX/CS-PEG micelles exhibited drug leakage-free behavior in a physiological environment, with a cumulative release ratio of only 2.32% under pH 7.4 PBS, while achieving rapid drug release and a cumulative release ratio of 72.76% in the intracellular microenvironment. Moreover, the micelles transformed into the water-soluble CS100K-PEG(2) after the pH-triggered intracellular release of DOX, and it makes them easy to be biodegraded and eliminated by metabolic system. As revealed by MTT assays and CLSM images, DOX could be efficiently and rapidly transported into cell nuclei of tumor cells and showed significant cell inhibition. The simple fabrication and excellent properties make them intelligent and favorable on-demand DDS in cancer treatment (C) 2016 Elsevier B.V. All rights reserved.

Poly(doxorubicin) (PDOX) is synthesized with Mn of 1.66 × 104 and DOX content of 78% as prodrug for tumor-specific triggered release, via a facile condensation polymerization of DOX-SS-DOX and adipic dihydrazide. The PDOX nanoparticles (PDOX-NPs) could completely release DOX-SH within 1.5 days at the simulated tumor microenvironment, but no measurable leakage in the physiological media. The in vitro controlled release results show that the releasing rate is influenced by the dosage and independent of the particle size, while the solubility of the degraded products should be the main determining factor for the drug release from the PDOX-NPs. The PDOX-NPs are expected to be promising prodrug nanopharmaceutics for the on-demand self-delivery of DOX with enhanced anticancer efficacy in future tumor treatment.

Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.

A novel water-soluble pH stimuli-responsive fluorescent copolymer of P(PEGMA-b-(MAH-co-Rh6GEAm)) was synthesized by two-step sequential RAFT polymerization. The prodrug with drug content of 0.1560 mg/mg was prepared by coupling doxorubicin (DOX) onto the copolymer via acid-cleavable hydrazone bond, formed between the carbonyl group of DOX and abundant hydrazide functional groups in the copolymer. The amphiphilic DOX-conjugated prodrug (P(PEGMA-b-(MAH-DOX-co-Rh6GEAm))) could easily form a micelle in water with Dh of less than 100 nm. It could be transported into HepG2 cells and release DOX without burst release, while the leakage of DOX can be avoided in the simulated normal physiological media. Furthermore, its fluorescence intensity experienced a reversible change with the transformation of the media pH. The better biocompatibility, pH stimuli-responsiveness, and the strong fluorescence at low pH media make the nanoparticles a potential platform for the controlled release of anticarcinogens and real-time fluorescent imaging of tumor tissues.

Nitrosomethylisoamylamine (NMIA), a carcinogenic N-nitroso compound was synthesized from isoamylamine (IAA) in a glucose-ammonium nitrate medium after several days' incubation with fungi and subsequent nitrosation with sodium nitrate. The nitrosamine was not produced by control reactions which lacked either IAA or fungi. The yield of NMIA varied with the length of incubation after inoculation with the fungi, and with the concentrations of IAA and NaNO2, the duration of nitrosation, the pH of the medium and the species of the fungi. The optimum conditions for the formation of the nitrosamine are reported.