Continuous-Flow Nanoprecipitation Method to Synthesize Degradable Hollow Mesoporous Organosilica Nanoparticles for Insecticide Delivery.

Degradable mesoporous organosilica nanoparticles (MONPs) are attracting significant attention in the area of designing smart drug carriers mainly due to their excellent stability and multiple functions. However, the efficient, controllable, and large-scale production of MONPs still faces huge challenges. Herein, a novel and facile continuous-flow nanoprecipitation strategy was reported to synthesize hollow MONPs with highly uniform and tailored properties. The synthesized hollow MONPs possessed a large surface area (SBET > 1070.1 m2 g-1), narrow size distribution, large hollow cavity, and thin shell. Interestingly, the incorporation of organic moieties into silica cross-linked networks led to the timely degradation of nanocarriers with the desired responsiveness. Moreover, the applicability of the as-obtained hollow MONPs has been demonstrated in the loading and pH-responsive release of thiamethoxam (THI). The resultant THI-loaded MONPs possessed long-term storage stability at a low temperature and showed release behaviors in response to a basic environment. Benefiting from the shielding property of MONPs, THI-loaded MONPs manifested superior stability against the photolysis as compared to that of the THI technical. This work provides a new consideration for promoting the advancement of nanotechnology in agricultural fields.

Bifunctional Polymer Brush Reactor for In Situ Synthesis of Hollow Silica-Supported Gold Nanocatalysts.

Gold nanoparticles (AuNPs) on carriers have received wide attention as catalysts as a result of their excellent stability and catalytic performance. Herein, we report the design and synthesis of hollow silica-supported gold nanocatalysts (SNPs@AuNPs) composed of highly dispersed AuNPs with approximately 4.30 nm using an in situ colloidal polyelectrolyte template strategy. The monodisperse polystyrene nanospheres accompanied by poly[(2-methacryloyloxyethyl)trimethylammonium chloride] brushes were first synthesized. Subsequently, the facile polymer-brush-engaged strategy for the synthesis of hollow SNPs@AuNPs involves in situ reduction of AuNPs, hydrolytic condensation of silica, and a chemical etching process. In combination with dynamic light scattering, transmission electron microscopy, small-angle X-ray scattering, X-ray powder diffraction, and Fourier transform infrared spectroscopy, the as-obtained polymer brushes were proven as effective versatile nanoreactors for the synthesis of AuNPs and silica nanoparticles without any catalysts. Benefiting from the structural advantages, the resultant hollow SNPs@AuNPs manifested superior catalytic activity and reusability for the reduction of p-nitrophenol by sodium borohydride in aqueous solution. With a delicate design, we believe that this synthetic strategy can be extended to fabricate multifunctional nanomaterials with diverse compositions, which would be of great interest in catalysis, energy, and many other important domains.

Immobilization of Gold Nanoparticles in Spherical Polymer Brushes Observed by Small-Angle X-ray Scattering.

Nanosized gold nanoparticles (AuNPs) are of great interest in areas such as catalysts or imaging but are easy to aggregate due to high surface activity. To stabilize AuNPs, two approaches were employed to immobilize AuNPs in spherical polymer brushes (SPBs), namely, the in situ preparation of AuNPs within the brush layer of SPBs and external addition of preprepared citrate-capped AuNPs. The distribution and stability of AuNPs in SPBs were studied by small-angle X-ray scattering (SAXS). SAXS results demonstrated that the in situ-prepared AuNPs were mainly located on the inner layer and their amount decreased from inside to outside. In the case of external addition of preprepared AuNPs, the cationic SPB showed obvious immobilization, while almost no AuNPs were immobilized in the anionic SPB. The stable immobilization of the AuNPs in SPBs was the result of multiple interactions including complexation and electrostatic interaction. SAXS was validated to be a distinctive and powerful characterization method to provide theoretical guidance for the stable immobilization of AuNPs.

Ultrasmall Pt Nanozymes Immobilized on Spherical Polyelectrolyte Brushes with Robust Peroxidase-like Activity for Highly Sensitive Detection of Cysteine.

Distinct platinum (Pt) nanozymes as peroxidase mimics have received extensive interest owing to their outstanding catalytic activity, high environmental tolerance, lower consumption, and great potential in replacing natural enzymes. However, easy agglomeration of Pt nanoparticles (Pt NPs) resulting from the high surface free energy significantly decrease their peroxidase-like activity. Herein, spherical polyelectrolyte brush (SPB)-stabilized ultrasmall Pt NPs (SPB@Pt NPs) were prepared by a novel synthetic strategy where the SPB not only performed as a nanoreactor for the synthesis of ultrasmall Pt NPs but also greatly stabilized Pt NPs against aggregation. The well-defined SPB@Pt NP nanozymes exhibited outstanding peroxidase-like activity for the catalytic oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB and were then used to establish a colorimetric sensor for rapid detection of cysteine, giving a limit of detection of 0.11 µM. Moreover, the colorimetric detection system was demonstrated with outstanding performance in sensitive and selective detection of cysteine in the presence of several interference molecules. From these results, SPB@Pt NPs have been regarded as promising peroxidase mimics for a large number of applications such as in biosensing, biomedicine, the food industry, and environmental chemistry.

Exploring the FGFR3-related oncogenic mechanism in bladder cancer using bioinformatics strategy.

BACKGROUND: Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer. METHODS: The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed. Then, FGFR3-centered protein-protein interaction (PPI) and regulatory networks were constructed. Combined with the data retrieved from GSE31684, prognostic makers for bladder cancer were predicted. RESULTS: We identified a total of 2855 DEGs, and most of them were associated with blood vessel morphogenesis and cell division. In addition, KIAA1377, POLA2, FGFR3, and EPHA4 were the hub genes with high degree in the FGFR3-centered PPI network. Besides, 17 microRNAs (miRNAs) and 6 transcriptional factors (TFs) were predicted to be the regulators of the nodes in PPI network. Moreover, CSTF2, POLA1, HMOX2, and EFNB2 may be associated with the prognosis of bladder cancer patient. CONCLUSIONS: The current study may provide some insights into the molecular mechanism of FGFR3 as a mediator in bladder cancer.

Smart Protein-Based Fluorescent Nanoparticles Prepared by a Continuous Nanoprecipitation Method for Pesticides' Precise Delivery and Tracing.

It is highly desirable to develop smart and green pesticide nanoformulations for improving pesticide targeting and reducing their inherent toxicity. Herein, we demonstrate a continuous nanoprecipitation method to construct a novel type of enzyme-responsive fluorescent nanopesticides (denoted as ABM@BSA-FITC/GA NPs) based on abamectin, fluorescein isothiocyanate isomer (FITC)-modified protein, and food-grade gum arabic. The as-prepared ABM@BSA-FITC/GA NPs exhibit good water dispersibility, excellent storage stability, and enhanced wettability compared to commercial formulations. The controlled release of pesticides can be achieved through protein degradation caused by trypsin. Most importantly, the deposition, distribution, and transport of the ABM@BSA-FITC/GA NPs are precisely tracked on target plants (cabbage and cucumber) by fluorescence. Furthermore, the ABM@BSA-FITC/GA NPs show the high control efficacy against Plutella xylostella L., which is comparable with commercial emulsifiable concentrate formulation. In consideration of its eco-friendly composition and absence of organic solvent, this pesticide nanoformulation has promising potential in sustainable plant protection.

Scalable Manufacture of Curcumin-Loaded Chitosan Nanocomplex for pH-Responsive Delivery by Coordination-Driven Flash Nanocomplexation.

Metal coordination-driven nanocomplexes are known to be responsive to physiologically relevant stimuli such as pH, redox, temperature or light, making them well-suited for antitumor drug delivery. The ever-growing demand for such nanocomplexes necessitates the design of a scalable approach for their production. In this study, we demonstrate a novel coordination self-assembly strategy, termed flash nanocomplexation (FNC), which is rapid and efficient for the fabrication of drug-loaded nanoparticles (NPs) in a continuous manner. Based on this strategy, biocompatible chitosan (CS) and Cu2+ can be regarded anchors to moor the antitumor drug (curcumin, Cur) through coordination, resulting in curcumin-loaded chitosan nanocomplex (Cur-loaded CS nanocomplex) with a narrow size distribution (PDI < 0.124) and high drug loading (up to 41.75%). Owing to the excellent stability of Cur-loaded CS nanocomplex at neutral conditions (>50 days), premature Cur leakage was limited to lower than 1.5%, and pH-responsive drug release behavior was realized in acidic tumor microenvironments. An upscaled manufacture of Cur-loaded CS nanocomplex is demonstrated with continuous FNC, which shows an unprecedented method toward practical applications of nanomedicine for tumor therapy. Furthermore, intracellular uptake study and cytotoxicity experiments toward H1299 cells demonstrates the satisfied anticancer efficacy of the Cur-loaded CS nanocomplex. These results confirm that coordination-driven FNC is an effective method that enables the rapid and scalable fabrication of antitumor drugs.

Rapid Construction of Green Nanopesticide Delivery Systems Using Sophorolipids as Surfactants by Flash Nanoprecipitation.

Green delivery carriers of nanopesticides, like sophorolipid biosurfactants, are of great significance to reduce environmental pollution and promote sustainable agricultural development. However, the molecular diversity of an unisolated sophorolipid mixture with almost unpredictable self-assembly properties has limited the in-depth study of its structure-activity relationship and hindered the development of green pesticide delivery systems. In this work, the acidic and lactonic sophorolipids were successfully separated from the sophorolipid mixture through silica gel column chromatography. A series of cost-effective green nanopesticides loaded with lambda-cyhalothrin (LC) were rapidly fabricated based on a combination of the acidic and lactonic sophorolipids as surfactants by flash nanoprecipitation. The effects of the acidic-to-lactonic ratio on particle size, drug loading capacity, and biological activity against Hyphantria cunea of LC-loaded nanoparticles were systematically investigated. The resultant nanopesticides exhibited a better insecticidal efficacy than a commercial emulsifiable concentrate formulation. This work opens up a novel strategy to construct scalable, cost-effective, and environmentally friendly nanopesticide systems.

Identification of miRNA Regulatory Networks and Candidate Markers for Fracture Healing in Mice.

BACKGROUND: It is important to improve the understanding of the fracture healing process at the molecular levels, then to discover potential miRNA regulatory mechanisms and candidate markers. METHODS: Expression profiles of mRNA and miRNA were obtained from the Gene Expression Omnibus database. We performed differential analysis, enrichment analysis, protein-protein interaction (PPI) network analysis. The miRNA-mRNA network analysis was also performed. RESULTS: We identified 499 differentially expressed mRNAs (DEmRs) that were upregulated and 534 downregulated DEmRs during fracture healing. They were mainly enriched in collagen fibril organization and immune response. Using the PPI network, we screened 10 hub genes that were upregulated and 10 hub genes downregulated with the largest connectivity. We further constructed the miRNA regulatory network for hub genes and identified 13 differentially expressed miRNAs (DEmiRs) regulators. Cd19 and Col6a1 were identified as key candidate mRNAs with the largest fold change, and their DEmiR regulators were key candidate regulators. CONCLUSION: Cd19 and Col6a1 might serve as candidate markers for fracture healing in subsequent studies. Their expression is regulated by miRNAs and is involved in collagen fibril organization and immune responses.

A Cost-Effective Nano-Sized Curcumin Delivery System with High Drug Loading Capacity Prepared via Flash Nanoprecipitation.

Flash nanoprecipitation (FNP) is an efficient technique for encapsulating drugs in particulate carriers assembled by amphiphilic polymers. In this study, a novel nanoparticular system of a model drug curcumin (CUR) based on FNP technique was developed by using cheap and commercially available amphiphilic poly(vinyl pyrrolidone) (PVP) as stabilizer and natural polymer chitosan (CS) as trapping agent. Using this strategy, high encapsulation efficiency (EE > 95%) and drug loading capacity (DLC > 40%) of CUR were achieved. The resulting CUR-loaded nanoparticles (NPs) showed a long-term stability (at least 2 months) and pH-responsive release behavior. This work offers a new strategy to prepare cost-effective drug-loaded NPs with high drug loading capacity and opens a unique opportunity for industrial scale-up.

Three new phenylacetamide glycosides from Dracocephalum tanguticum Maxim and their anti-hyperglycemic activity.

Three new phenylacetamide glycosides (1-3) together with one known phenylacetamide glycoside (4) and two known flavonoid glycosides (5-6) were isolated from whole plants of Dracocephalum tanguticum. The structure of all compounds were elucidated based on spectroscopic data analysis and comparison with data reported in related literature. Compounds (1-3) were evaluated for their anti-hyperglycemic and anti-fungal (Candida albicans) activities, the results revealed that all of them showed moderate activity with 3T3-L1 adipocytes glucose consumption rate of 20.80 ± 1.47%, 21.48 ± 2.44%, and 21.57 ± 1.35%, respectively at the final concentration of 25 µM. However, none of them showed obvious Candida albicans inhibitory activity.

Two new xanthone glycosides from Swertia punicea Hemsl. and their anti-inflammatory activity.

Two new xanthone glycosides (1-2), together with seven known analogues (3-9), were isolated from whole herb of Swertia punicea. The structures of these metabolites were established on the basis of detailed spectroscopic analysis and comparison with data reported in the literature. In an in vitro test, all isolates were evaluated for their anti-inflammatory activity. The results revealed that all of them showed significant anti-inflammatory activity with IC50 values ranging from 1.237 to 3.319 mM. Compounds 3, 4, and 5 (IC50 values in the range 1.237-1.987 mM) displayed more potent anti-inflammatory activity than the positive control, indomethacin (IC50 value of 2.004 mM).

Cytosine 5-hydroxymethylation regulates VHL gene expression in renal clear cell carcinoma.

Cytosine5-hyxymethylation (5hmC)which is a new epigenetic modification form plays important roles in the development and progression of tumors. In the present study, we observed that levels of 5hmC in the promoter region of Von Hippel-Lindau (VHL) were lower in 97 samples of renal clear cell carcinoma tissue than in matched adjacent benign tissues. Moreover, when the cancer tissue samples were divided based on pathological staging, VHL expression and the level of 5hmC in the VHL promoter were both lower in pathological grade III tumors than in grades I or II. Correspondingly, expression of TET1, which catalyzes the formation of 5hmC, was also lower in grade III renal clear cell carcinomas than in grade I or II disease. These findings suggest the 5hmC level on VHL is a key determinant of the gene's expression and may participate in the occurrence and development of renal clear cell carcinoma. Thus the 5hmC level may be a useful indicator for early diagnosis and appropriate treatment of renal clear cell carcinoma.