Multifunctional hydrogel for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer recurrence and wound infection.

Metastatic recurrence and postoperative wound infection are two major challenges for breast cancer patients. In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer and wound infection. The hydrogel system was obtained by cross-linking Prussian blue-modified N-carboxyethyl chitosan (PBCEC) and oxidized sodium alginate using the amino and aldehyde groups on the polysaccharides, resulting in the formation of responsive dynamic imine bonds. Conditioned stimulation (e.g., acid microenvironment) enabled the controlled swelling of hydrogels as well as subsequent slow release of loaded doxorubicin (DOX). Additionally, this hydrogel system decomposed endogenous reactive oxygen species into oxygen to relieve the hypoxic tumor microenvironment and promote the healing of infected-wounds. Both in vitro and in vivo experiments demonstrated the synergistic reoxygenation and chemo/photothermal effects of the PB/DOX hydrogel system against metastatic breast cancer and its recurrence, as well as postoperative wound infection. Thus, the combination of reoxygenation and chemo/photothermal therapy represents a novel strategy for treating and preventing tumor recurrence and associated wound infection.

Copper-Catalyzed Fluoroalkylphosphorothiolation of Alkynes for the Synthesis of (E)-ß-Fluoroalkyl Vinyl Phosphorothioates.

A convenient copper-catalyzed three-component radical-based fluoroalkylphosphorothiolation of terminal alkynes with (iPrO)2P(O)SH and fluoroalkylation reagent for the synthesis of a variety of (E)-ß-fluoroalkyl vinyl phosphorothioates with excellent regioselectivity and stereoselectivity has been developed. All the starting materials used in this reaction are highly stable and readily available. Thus, this process features with mild reaction conditions, simple operation and good functional group tolerance (>40 examples). Furthermore, this modular reaction system allows the late-stage functionalization of bioactive molecules.

Genetically Engineering Escherichia coli to Produce Xylitol from Corncob Hydrolysate without Lime Detoxification.

Before fermentation with hemicellulosic hydrolysate as a substrate, it is generally necessary to detoxify the toxic substances that are harmful to microorganism growth. Cyclic AMP receptor protein (CRP) is a global regulator, and mutation of its key sites may have an important impact on E. coli virulence tolerance. Using corncob hydrolysate without ion-exchange or lime detoxification as the substrate, shake flask fermentation experiments showed that CRP mutant IS5-dG (I112L, T127G, A144T) produced 18.4 g/L of xylitol within 34 h, and the OD600 was 9.7 at 24 h; these values were 41.5% and 21.3% higher than those of the starting strain, IS5-d, respectively. This mutant produced 82 g/L of xylitol from corncob hydrolysate without ion-exchange or lime detoxification during fed-batch fermentation in a 15-L bioreactor, with a productivity of 1.04 g/L/h; these values were 173% and 174% higher than the starting strain, respectively. To our knowledge, this is the highest xylitol concentration and productivity produced by microbial fermentation using completely non-detoxified hemicellulosic hydrolysate as the substrate to date. This study also showed that alkali neutralization, high temperature sterilization, and fermentation of the hydrolysate had important effects on the xylose loss rate and xylitol production.

Fabrication of porous ZnO/Co3O4 nanohybrids for the application of surface enhanced Raman scattering.

With the growing use of various pesticides, it is important to develop facile and sensitive method to detect pesticides residues in food. Here, a semiconductor/magnetic hybrid material was used as surface enhanced Raman scattering (SERS) substrate to detect simulated residues. The representative sample of porous ZnO/Co3O4 nano-cube was fabricated by pyrolysis and calcination of Zn-Co ZIF, successively. The obtained hybrid of ZnO/Co3O4 was employed as substrate to detect of crystal violet (CV) and Rhodamine B (Rh B), and showed remarkable SERS performance. The detection limit of Rh B was 1 × 10-10 M as well as CV of 1 × 10-9 M. The results indicated that it was an ideal choice to improve the SERS property of transition metal oxide substrates by doping semiconductor. The semiconductor/magnetic hybrid material highlighted the obvious characteristics of low cost, facile preparation and ultra-low detection limit in the SERS measurements. The hybrids with the combination of semiconductor/magnetic properties showed a further widely application and development in SERS detection of pesticides residues.

Metabolic Behaviors of Aconitum Alkaloids in Different Concentrations of Aconiti Lateralis Radix Praeparata and Effects of Aconitine in Healthy Human and Long QT Syndrome Cardiomyocytes.

Aconiti Lateralis Radix Praeparata (Fu Zi) is the processed lateral root of Aconitum carmichaelii Debx, which is widely used in emergency clinics. Poisoning incidents and adverse reactions occur with the improper intake of Fu Zi. Metabolic characteristics of aconitum alkaloids of Fu Zi may vary, and the effects of Fu Zi in healthy and Long QT syndrome (LQTS) patients is unknown. In this experiment, 24 Sprague Dawley rats were randomly divided into three groups: 2.0, 1.0, and 0.5 g/kg dose groups, and blood samples were collected after the oral administration of Fu Zi extract. We used an ultra-high performance liquid chromatography-tandem mass spectrometry system to detect the concentrations of six aconitum alkaloids. Cell toxicity, calcium imaging, and patch-clamp recordings of human induced pluripotent stem cells-cardiomyocytes (hiPSC-CMs) of aconitine in healthy and LQTS were observed. We found that the AUC(0-48h), Cmax, and t1/2 of the six compounds increased with the multiplicative dosages; those in the high group were significantly higher than those in the low group. Aconitine concentration-dependently decreased the amplitude, which has no significant effect on the cell index of normal hiPSC-CMs. Aconitine at 5.0 µM decreased the cell index between 5-30 min for LQTS hiPSC-CMs. Meanwhile, aconitine significantly increased the frequency of calcium transients in LQTS at 5 µM. Aconitine significantly shortened the action potential duration of human cardiomyocytes in both normal and LQTS groups. These results show metabolic behaviors of aconitum alkaloids in different concentrations of Fu Zi and effects of aconitine in healthy and LQTS patients.

Photo-Responsive Micelles with Controllable and Co-Release of Carbon Monoxide, Formaldehyde and Doxorubicin.

Endogenous gases have attracted much attention due to their potent applications in disease therapies. The combined therapy, including gaseous molecules and other medicines that can create synergistic effects, is a new way for future treatment. However, due to the gaseous state, gas utilization in medical service is still limited. To pave the way for future usage, in this work, an amphiphilic block copolymer containing nitrobenzyl ether, 3-hydroxyflavone (3-HF) derivatives and ether linker was constructed. The nitrobenzyl ether group endows the polymer with a photo-responsive character. Upon light illumination, 3-HF derivatives can be triggered for carbon monoxide (CO) release. The ether linker can also be released emitting formaldehyde (FA). The self-assembly induced micelle can encompass medicine, e.g., doxorubicin (DOX), into it and a controlled release of DOX can be realized upon light illumination. As far as we know, there is no report on the combination donor of CO and DOX and this is the first attempt on the co-release of CO, FA and DOX.

Molecular dynamics study of lithium intercalation into -OH functionalized carbon nanotube bundle.

The influence of hydroxyl group (-OH) on carbon nanotube (CNT) interacting with lithium (Li) ions has been investigated via ab initio molecular dynamic (MD) simulations. Compared with the pure CNT, a higher efficiency has been observed for lithium intercalating into CNT-OH bundle. At lower Li ion density and CNT bundle density, CNT-OH exhibits higher intercalation efficiency than the pristine and ammonium functionalized CNTs. As the increasing of Li ion densities and CNT bundle densities, Li ions tend to intercalate into the interlayer between CNT-OH tubes instead of the interior of CNT-OH tubes. We also observe the destruction of hydroxyl groups during the intercalation of Li ions into interlayer of CNT-OH bundle. It is therefore suggested that eliminating the intercalation of Li ions into interlayer between tubes is important for the design of Li ion batteries.

A rational design of a cascaded DNA circuit for nanoparticle assembly and its application in the discrimination of single-base changes.

In the field of dynamic DNA nanotechnology, a designable DNA assembly circuit based on the toehold-mediated strand displacement reaction has demonstrated its ability to program the self-assembly of nanoparticles. However, the laborious work for the modification of nanoparticles with oligonucleotides, the long assembly time, and the circuit leakage prevent its further and scalable applications. To this end, cascaded circuits composed of two recycling circles are rationally designed in this study. Through the pre-initiation of the autonomous reaction, nanoparticles as sensing elements and no additionally exposed bases on the substrate hybridized with fuel strand, the real assembly time and signal leakage for diagnostic application can be effectively reduced and eliminated, thus offering a promising methodology for future point-of-care testing.

Efficacy of Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rat.

OBJECTIVE: To elucidate the protective effects of Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction (MI) through regulating myocardial autophagy. METHODS: Thirty-one male Sprague-Dawley rats were randomized into five groups (n = 6 or 7 for each). After treatment for 3 weeks, electrocardiogram ( ECG ) and cardiac function were recorded. Hematoxylin and eosin (HE) staining was used to detect pathological changes in the heart. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum B-type brain natriuretic peptide (BNP), cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), and serum inflammatory cytokines. Metabolomic analysis was used to identify differential biomarkers of MI in rats. Immunohistochemistry and western blotting were used to detect BNP, cTnT, TNF-α, LC3B, Beclin-1, p62, and adenosine monophosphate activated protein kinase (AMPK) expression in cardiac tissue. RESULTS: Fuzi (Radix Aconiti Lateralis Preparata) alone or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) markedly ameliorated cardiac dysfunction and abnormal ECGs, demonstrated by decreases in the heart weight/body weight ratio, BNP, and cTnT. Pro-inflammation cytokine interleukin (IL)-1α significantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen (Radix Ginseng) single or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) groups compared with the control group. HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen (Radix Ginseng) or Fuzi (Radix Aconiti Lateralis Preparata) alone. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) reversed these changes to different degrees in MI rats. Furthermore, Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) down-regulated LC3B, Beclin-1, and AMPK expression in cardiac tissue and upregulated p62 expression. CONCLUSIONS: Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) may have a greater effect on heart injury induced by MI in rats than Fuzi (Radix Aconiti Lateralis Preparata) treatment alone, and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects. These results provide fresh insight into the mechanism of co-treatment with Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) for MI.

Triple administration of osimertinib followed by chemotherapy for advanced lung adenocarcinoma: A case report.

BACKGROUND: Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor (EGFR) mutation positive advanced or metastatic non-small cell lung cancer (NSCLC). However, primary or acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) seems inevitable, and when drug-resistance occurs during treatment with osimertinib, the standard of care is to discontinue the TKI. CASE SUMMARY: A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration. An enhanced head magnetic resonance imaging scan showed brain metastases. An EGFR mutation (exon 21 L858R) was detected in pleural fluid. The patient was treated with oral osimertinib (80 mg once daily) from January 2018 but developed progressive disease on December 2018. She was then successfully treated with re-challenge and tri-challenge with osimertinib (80 mg once daily) by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib, and to date has survived for 31 mo. CONCLUSION: This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.

High-Performance Red-Light Photodetector Based on Lead-Free Bismuth Halide Perovskite Film.

In this study, we developed a sensitive red-light photodetector (RLPD) based on CsBi3I10 perovskite thin film. This inorganic, lead-free perovskite was fabricated by a simple spin-coating method. Device analysis reveals that the as-assembled RLPD was very sensitive to 650 nm light, with an on/off ratio as high as 105. The responsivity and specific detectivity of the device were estimated to be 21.8 A/W and 1.93 × 1013 Jones, respectively, which are much better than those of other lead halide perovskite devices. In addition, the device shows a fast response (rise time: 0.33 ms; fall time: 0.38 ms) and a high external quantum efficiency (4.13 × 103%). It is also revealed that the RLPD has a very good device stability even after storage for 3 months under ambient conditions. In summary, we suggest that the CsBi3I10 perovskite photodetector developed in this study may have potential applications in future optoelectronic systems.

Graphene oxide and creatine phosphate disodium dual template-directed synthesis of GO/hydroxyapatite and its application in drug delivery.

In this study, graphene oxide and creatine phosphate disodium acted as dual template and was employed to synthesize graphene oxide (GO)/hydroxyapatite (HA) hybrids as drug carriers. In the rapid preparation of GO/HA hybrids, creatine phosphate disodium salt (CPDS) severed as a phosphorus source and graphene oxide acted as a template in aqueous solution. The effects of the reaction temperature, time and pH value of the aqueous solution on the morphology of the product were investigated. The result showed that the hydrolysis of CPDS under hydrothermal condition played an important role in the formation of hierarchical hollow GO/HA hybrids. The GO nanosheets provided reactive sites for the binding of HA nanoparticles and absorbing ibuprofen (IBU) molecules. The GO/HA hybrids had ideal sustained drug-release behavior. It indicated that the prepared GO/HA hybrids may be promising materials for applications in biomedical area.

Nacre-like calcium carbonate controlled by ionic liquid/graphene oxide composite template.

Nacre-like calcium carbonate nanostructures have been mediated by an ionic liquid (IL)-graphene oxide (GO) composite template. The resultant crystals were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and X-ray powder diffractometry (XRD). The results showed that either 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) or graphene oxide can act as a soft template for calcium carbonate formation with unusual morphologies. Based on the time-dependent morphology changes of calcium carbonate particles, it is concluded that nacre-like calcium carbonate nanostructures can be formed gradually utilizing [BMIM]BF4/GO composite template. During the process of calcium carbonate formation, [BMIM]BF4 acted not only as solvents but also as morphology templates for the fabrication of calcium carbonate materials with nacre-like morphology. Based on the observations, the possible mechanisms were also discussed.