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Glucose oxidase (GOx)-based nanotheranostic agents hold great promise in tumor starvation and its synergistic therapy. Self-assembled plasmonic gold vesicles (GVs) with unique optical properties, large hollow cavity, and strong localized surface plasmon resonance, can be used as multi-functional nanocarriers for synergistic therapy. Herein, GOx-loaded GVs (GV-GOx) were developed for light-triggered GOx release as well as enhanced catalytic activity of GOx, achieving programmable photothermal/starvation therapy. Under near-infrared laser irradiation, the GV-GOx generated strong localized hyperthermia due to plasmon coupling effect of GVs, promoting the release of encapsulated GOx and increasing its catalytic activity, resulting in enhanced tumor starvation effect. In addition, the high photothermal effect improved the cellular uptake of GV-GOx and allowed an efficient monitoring of synergistic tumor treatment via photoacoustic/photothermal duplex imaging in vivo . Impressively, the synergistic photothermal/starvation therapy demonstrated complete tumor eradication in 4T1 tumor-bearing mice, verifying superior synergistic anti-tumor therapeutic effects than monotherapy with no apparent systemic side effects. Our work demonstrated the development of a light-triggered nanoplatform for cancer synergistic therapy.

International audience; The composition and structure properties of the CrOxNy films deposited by RF reactive magnetron sputtering were investigated and correlated with their optical properties. Two kinds of targets Cr2O3 and CrN compounds with variation of N2 and O2 gas flow were used to prepare two series of samples. The phase structure, chemical composition and optical properties of CrOxNy films were characterized by X-ray diffraction, X-ray photoelectron spectroscopy and ultraviolet-visible-near-infrared spectrophotometer, respectively. The films mainly consist of Cr2N and CrO3 phases. The Cr/ON ratio derived by XPS varies with the variation of nitrogen with Cr2O3 target. But only lower nitrogen content is detected with variation of oxygen using CrN target. TheCrOxNyy films with higher nitrogen content possess high absorbance around at 35% in the visible light range no matter the target.

The detection of fluoride ion (F−) in living subjects is of value for healthcare and environmental fields. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe composed of naphthalimide unit, namely LET-1, was developed for chemoselective photoacoustic detection (PAD) of F−. The response and mechanism of the interaction between F− and LET-1 were evaluated through kinetic optical studies, 1HNMR spectra analysis and docking calculations. The results demonstrated that LET-1 could rapidly recognize F− with good selectivity and high sensitivity. Upon the interaction with F−, this non-photoacoustic LET-1 probe could produce a turn-on PA signal at 680 nm, which was used as an indicator for PAD of F− in living subjects, such as soybean sprout and mouse. The present study provides a new approach for in vivo chemoselective PA detection of anions.

This study aimed to investigate the prevalence of T2DM and its risk factors in rural areas in Yinzhou District of Ningbo, China. A cross-sectional study with 4832 participants aged 18 years or older was conducted during the period of March 2013 to May 2013. Among the participants, 4760 completed a self-administered survey and physical examinations. Data collected included demographic characteristics, lifestyle, medical history, anthropometric measurements, and clinical assessment. After an overnight fasting of at least 10 h, participants also underwent an oral glucose tolerance test (OGTT) for diagnosing T2DM. Logistic regression analysis was performed to determine the risk factors associated with T2DM. The area under the receiver operating characteristic curve (AUROC) was used to assess the prediction ability of the models. The age-standardized prevalence of T2DM was 7.86% (95% confidence interval (95% CI = 7.10–8.62%), and the crude prevalence was 15.36%. In multivariate logistic regression models, age (≥ 65), obesity, and hypertension were the common risk factors of T2DM for both males and females. The AUROC of the T2DM model was 0.735 (95% CI = 0.709–0.762), indicating the accuracy of the model in predicting T2DM. Old age, obesity, hypertension, and elevated triglycerides and LDL-C were the risk factors for T2DM. And the predictive power of ROC curve we established for predicting T2DM had a good accuracy. Therefore, diabetes health education and early screening programs should be developed and strengthened for the prevention of T2DM in rural areas.

Chemodynamic therapy (CDT) involves the catalytic generation of highly toxic hydroxyl radicals (. OH) from hydrogen peroxide (H2 O2 ) through metal-ion-mediated Fenton or Fenton-like reactions. Fe2+ is a classical catalyst ion, however, it suffers easy oxidation and systemic side-effects. Therefore, the development of a controllable Fe2+ delivery system is a challenge to maintain its valence state, reduce toxicity, and improve therapeutic efficacy. Reported here is a near-infrared (NIR) light-triggered Fe2+ delivery agent (LET-6) for fluorescence (FL) and photoacoustic (PA) dual-modality imaging guided, photothermal primed CDT. Thermal expansion caused by 808 nm laser irradiation triggers the transformation of LET-6 to expose Fe2+ from its hydrophobic layer, which primes the catalytic breakdown of endogenous H2 O2 within the tumor microenvironment, thus generating . OH for enhanced CDT. LET-6 shows remarkable therapeutic effects, both in vitro and in vivo, achieving 100 % tumor elimination after just one treatment. This high-performance Fe2+ delivery system provides a sound basis for future synergistic metal-ion-mediated cancer therapy.

Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.

In this study, a novel gradient heating procedure was developed to fabricate the targeted metal-ion-imprinted thermo-responsive material, i.e. ion-imprinted thermo-responsive BC derivative (ITB), from bacterial cellulose using Cu2+ as a template and N-isopropylacrylamide (NIPAM) as a monomer; moreover, the structure and properties of ITB were analysed via various analytical techniques including FTIR spectroscopy, DSC, SEM, and Raman spectroscopy. The lower critical solution temperature (LCST) of ITB was 38.57 °C in the heating procedure, whereas it was 30.81 °C in the cooling procedure. The adsorption capacity of ITB for Cu2+ reached 95.20 mg g−1 at 45 °C (>LCST), the desorption rate was 98.81%, and desorption could be simply achieved by washing the adsorbents with water at 20 °C (

Diabetic cardiomyopathy (DCM) is diagnosed when patients with diabetes develop ventricular dysfunction but do not exhibit coronary atherosclerosis or hypertension. Cortex Mori (CM) Radicis,he epidermis of the root of Morus alba L, has been traditionally used for cough treatment in oriental medicine. In this study, we investigated the protection of myocardium by CM in streptozotocin (STZ)-induced diabetic rats and the underlying mechanisms. Diabetes was induced in rats by an injection of STZ at 25mg/kg. The animals were randomly divided into 4 groups: control, diabetes, diabetes with CM treatment, diabetes with CM preventative treatment. Pathological changes were examined by hematoxylin-eosin staining. Extracellular matrix content was assessed by Masson's trichrome staining and Western blot. Endoplasmic reticulum (ER) stress-associated molecules and main components of the mitogen-activated protein kinase (MAPK) pathway were also measured by Western blot. Myocardial damages were induced by the injection of STZ as evidenced by abnormal blood glucose and pathological cardiac changes. Administration of CM markedly ameliorated myocardial damages such as cardiac hypertrophy and fibrosis. ER stress was down-regulated, and p38 and ERK were suppressed by CM. Thus, CM may have therapeutic potential in the treatment of DCM by attenuating ER stress and ERK and p38 MAPK activation.

Lytic and cell-penetrating peptides (CPPs) are both membrane-active peptides sharing similar physicochemical properties. Although their respective functions have been intensively investigated, the difference of intrinsic properties between these two types of peptides is rarely discussed. In this study, we designed a series of analogs of a recently discovered CPP ZXR-1 (FKIGGFIKKLWRSKLA) by varying the charge distributions both on the helical wheel projection and along the sequence. These peptides showed different functions on cell membranes, including membrane lytic (peptide Z1), cell-penetrating (peptide ZXR-1, Z2 and Z3), and inactive (peptide Z4) peptides. The three groups of peptides displayed different interactions with model lipid monolayer, and found that peptide insertion might be an important dynamic step to distinguish lytic and cell penetrating functions. Based on the analysis of charge distribution patterns, it was proposed that the charge distributions on the helical wheel and along the sequence are both able to influence the functions of the membrane-active peptides. This finding provides a further understanding about the effect of charge distribution on the functions of membrane-active peptides, and will be helpful for the design of functional peptides.

The problem of an aging society is becoming increasingly acute. Diseases related to aging also come with it. There are some diseases that people can&rsquo, t treat fundamentally. Therefore, people try to find a natural ingredient from natural medicine to treat these diseases and improve the quality of life of the elderly. With the screening of a large number of traditional Chinese medicines, we found that polysaccharides from Rehmannia glutinous (PRG) can prolong the lifespan of Caenorhabditis elegans (C. elegans). Neutral polysaccharide is the main component of PRG. In the present study, we used a C. elegans model to illustrate the stress resistance and lifespan extension effect and mechanism of two kinds of neutral polysaccharide fractions from Rehmannia glutinosa (NPRG), respectively called NPRRP and NPRR. Our data showed that two kinds of neutral polysaccharides fractions could extend the lifespan and delay senescence of wild-type worms. Moreover, the mechanism study revealed that NPRG was able to promote the nuclear localization of DAF-16 resulting in the activation of antioxidant enzymatic systems under oxidative stress. We also observed that NPRG didn&rsquo, t increase the lifespan of mutants with daf-16 portion loss of function, suggesting NPRG prolonging the lifespan partially required the daf-16 gene on the insulin/IGF-1 signaling pathway (IIS). NPRG was found to have no effect on Escherichia coli OP50 (E.coli OP50) growth and pharyngeal pump movement of nematodes, indicating that the anti‑aging effect of NPRG is not realized by the caloric restriction. However, mRNA levels of daf-2 were remarkably decreased after NPRG treatment. Thus daf-2 lost its inhibitory effect on the expression of daf-16 and had a continuous stimulation effect on the IIS, then prolonged the life of nematodes. Overall, our results illustrated the potential utilization of NPRG as a functional pharmaceutical ingredient to increase stress resistance and extend the life of C. elegans via the IIS, which could be developed as a natural supplement agent.

Background Propionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration. However, the underlying mechanism of P. acnes-induced CEP degeneration remains unclear. The objective of this study is to investigate the underlying mechanism of P. acnes-induced CEP degeneration. Methods We first examined MIF expression in degenerated human CEP samples by immunohistochemistry. We developed a P. acnes-induced rat model and detected MIF expression using immunohistochemistry. Additionally, we investigated the mechanism of P. acnes-induced CEP degeneration in CEP cells using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results We found that compared with the normal human CEP, the expression of MIF was increased in the degenerated human CEP. In a rat model, P. acnes induced CEP degeneration and upregulated MIF expression significantly. More importantly, we revealed the underlying mechanism of P. acnes-induced CEP degeneration in the rat CEP cells. Firstly, P. acnes induced the expression of MIF in a concentration-dependent manner. Then, MIF upregulated the expression of MMP-13 and promoted the secretion of IL-6 and IL-1β. Finally, P. acnes may promote MIF expression via NF-κB pathway rather than ERK1/2 pathway. Conclusion P. acnes-induced MIF expression via NF-κB pathway may be the underlying mechanism of CEP degeneration.

The problem of an aging society is becoming increasingly acute. Diseases related to aging also come with it. There are some diseases that people can’t treat fundamentally. Therefore, people try to find a natural ingredient from natural medicine to treat these diseases and improve the quality of life of the elderly. With the screening of a large number of traditional Chinese medicines, we found that polysaccharides from Rehmannia glutinous (PRG) can prolong the lifespan of Caenorhabditis elegans (C. elegans). Neutral polysaccharide is the main component of PRG. In the present study, we used a C. elegans model to illustrate the stress resistance and lifespan extension effect and mechanism of two kinds of neutral polysaccharide fractions from Rehmannia glutinosa (NPRG), respectively called NPRRP and NPRR. Our data showed that two kinds of neutral polysaccharides fractions could extend the lifespan and delay senescence of wild-type worms. Moreover, the mechanism study revealed that NPRG was able to promote the nuclear localization of DAF-16 resulting in the activation of antioxidant enzymatic systems under oxidative stress. We also observed that NPRG didn’t increase the lifespan of mutants with daf-16 portion loss of function, suggesting NPRG prolonging the lifespan partially required the daf-16 gene on the insulin/IGF-1 signaling pathway (IIS). NPRG was found to have no effect on Escherichia coli OP50 (E. coli OP50) growth and pharyngeal pump movement of nematodes, indicating that the anti-aging effect of NPRG is not realized by the caloric restriction. However, mRNA levels of daf-2 were remarkably decreased after NPRG treatment. Thus daf-2 lost its inhibitory effect on the expression of daf-16 and had a continuous stimulation effect on the IIS, then prolonged the life of nematodes. Overall, our results illustrated the potential utilization of NPRG as a functional pharmaceutical ingredient to increase stress resistance and extend the life of C. elegans via the IIS, which could be developed as a natural supplement agent.

Binary transition metal oxides (BTMOs) have been explored as promising candidates in rechargeable lithium-ion battery (LIB) anodes due to their high specific capacity and environmental benignity. Herein, 2D ultrathin NiCo2O4 nanosheets vertically grown on a biomass-derived carbon fiber substrate (NCO NSs/BCFs) were obtained by a facile synthetic strategy. The BCF substrate has superior flexibility and mechanical strength and thus not only offers a good support to NCO NSs/BCFs composites, but also provides high-speed paths for electron transport. Furthermore, 2D NiCo2O4 nanosheets grown vertically present a large contact area between the electrode and the electrolyte, which shortens the ions/electrons transport distance. The nanosheets structure can effectively limit the volume change derived from Li+ insertion and extraction, thus improving the stability of the electrode material. Therefore, the synthesized self-supporting NCO NSs/BCFs electrode displays excellent electrochemical performance, such as a large reversible capacity of 1128 mA·h·g−1 after 80 cycles at a current density of 100 mA·g−1 and a good rate capability of 818.5 mA·h·g−1 at 1000 mA·g−1. Undoubtedly, the cheap biomass carbon source and facile synthesis strategy here described can be extended to other composite materials for high-performance energy-storage and conversion devices.

X-ray absorption spectroscopy (XAS) at the Co K edge was applied to investigate the chemical environment of Co atoms inside Co/Mo 2 C periodic multilayers. The results show a mixing between Co and Mo 2 C layers prior to any annealing process whereas following annealing from 300°C pure Co layers are observed. XAS results are in agreement with previous nuclear magnetic resonance spectroscopy results. They indicate that the pure Co content increases upon annealing, while it is absent in the as-deposited samples. The comparison of the results, based on the analysis of the data obtained on the multilayer samples and some reference materials, reveals that the ordering of Co atoms inside the Co layers increases upon annealing.

Many lytic peptides contain a heptad sequence with leucine or isoleucine residues at “a” and “d” positions. However, their roles in the peptide-induced cytolytic process remain unclear. We have recently reported an anticancer lytic peptide ZXR-2 (FKIGGFIKKLWRSLLA), which contains a shortened zipper-like sequence with Ile/Leu at “a” and “d” positions. To understand the roles of these Ile/Leu residues, a series of analogs were constructed by sequentially replacing the Ile or Leu residue with alanine (Ala). Significant reduction of the cytolytic activity was observed when the Ile (3rd and 7th) and Leu (10th and 14th) residues at the “a” and “d” positions were substituted, while the replacement of the separate Leu (15th) residue had less effect. Based on the quenching of the intrinsic fluorescence of the peptides and their induced surface pressure changes of lipid monolayer, it was conjectured that the peptide ZXR-2 might insert into cell membranes from the C-terminal and to a depth of the W11 position. Accordingly, I3, I7, and L10 residues which mainly exposed in aqueous solution were more responsible for the peptide self-association on cell membranes, while L14, together with L15, might help peptide insert and anchor to cell membranes. These results are significant to elucidate the crucial roles of such Ile/Leu residues at “a” and “d” positions in peptide–peptide and peptide–membrane interactions to exert the membrane disruption activity of lytic peptides. With further understanding about the structure–activity relationship of lytic peptides, it would be helpful for designing novel anticancer lytic peptides.

Long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and development. We previously demonstrated that lncRNA gastric cancer-associated transcript 3 (GACAT3) was positively correlated with TNM stages, tumor size, and distant metastasis of patients with gastric cancer. However, the role of GACAT3 in gastric cancer remains unclear. In this study, to investigate its function, we synthesized small interference RNAs (siRNAs) against GACTA3 and developed a GACAT3 overexpression vector (pcDNA3-GACAT3), respectively. The siRNA-mediated knockdown of GACAT3 significantly decreased cell proliferation of the gastric cancer HGC-27 cells, in which GACAT3 is overexpressed. Furthermore, GACAT3 overexpression in gastric cancer SGC-7901 cells promoted cell growth. Moreover, GACAT3 expression in HGC-27 cells was greatly upregulated by IL-6 treatment in a concentration-dependent manner. In contrast, siRNA-mediated knockdown of STAT3 decreased GACAT3 expression even in the presence of IL-6. These results demonstrated that as a downstream target of the IL6/STAT3 signaling, lncRNA GACAT3 promotes gastric cancer cell growth suggesting that GACAT3 is an inflammatory response gene and may be served as a valuable potential target for the treatment of gastric cancer.

BACKGROUND Oropharyngeal dysphagia is a common disorder after stroke. Physical therapy has been widely used in the rehabilitation of patients with dysphagia after stroke. Due to the lack of randomized trials directly comparing the efficacy of various physical therapies directly, the relative efficacy of these methods is difficult to determined. Therefore, we intend to conduct a network meta-analysis to evaluate the benefits of these physical therapies. METHODS According to the retrieval strategies, randomized controlled trials (RCTs) on physical therapies for stroke patients with dysphagia will be obtained from CNKI, Wan Fang Data, PubMed, Web of science, Embase databases and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed in Markov Chain Monte Carlo (MCMC) method and carried out with Stata14 and OpenBUGS14 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS This study will compare the efficacy of physical therapies in the treatment of stroke patients with dysphagia and suggests a reasonable clinical choice. CONCLUSION Our findings will provide references for future guidance developing and clinical decision.

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine-betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional

International audience; The Kossel effect is the diffraction by a periodically structured medium, of the characteristic X-ray radiation emitted by the atoms of the medium. We show that multilayers designed for X-ray optics applications are convenient periodic systems to use in order to produce the Kossel effect, modulating the intensity emitted by the sample in a narrow angular range defined by the Bragg angle. We also show that excitation can be done by using photons (X-rays), electrons or protons (or charged particles), under near normal or grazing incident geometries, which makes the method relatively easy to implement. The main constraint comes from the angular resolution necessary for the detection of the emitted radiation. This leads to small solid angles of detection and long acquisition times to collect data with sufficient statistical significance. Provided this difficulty is overcome, the comparison or fit of the experimental Kossel curves, i.e., the angular distributions of the intensity of an emitted radiation of one of the element of the periodic stack, with the simulated curves enables getting information on the depth distribution of the elements throughout the multilayer. Thus the same kind of information obtained from the more widespread method of X-ray standing wave induced fluorescence used to characterize stacks of nanometer period, can be obtained using the Kossel effect.

The feasibility of using GeTe based alloys in thermoelectric power generation has received a revived interest and has been extensively investigated through the approach of substitutional doping in recent times. Here, a systematic study of the thermoelectric properties of Sn doped GeTe prepared by DC magnetron co-sputtering using Sn and GeTe targets is presented. The effect of variation in Sn content was studied on the chemical bonds and of as-deposited films. Thermoelectric properties of as-deposited and fast annealed thin films at 280 °C in vacuum were measured. It is found that Sn forms bond with Te and increasing Sn content decreases the band gap of amorphous samples. The power factor was enhanced both at low temperature and high temperature through the reduction of the electrical resistivity and enhanced seebeck effect caused by changes in the carrier effective mass and carrier concentration. A competitively high power factor of 2.789 × 103 μW/K2m is reached at 300 K for the amorphous films and 1.423 × 103 μW/K2m at 718 K for the crystalline film. This provides a good basis for further enhancement of the power factor.

The adhesion strength between thin films has a significant effect on performance of micro-devices. It is introduced that the effects of three pre-treatment methods: acid, pulse reverse current and anodic current, on the adhesion performance of electrodeposited Ni films on Ni substrate. The adhesion strength, surface and fracture morphology of the Ni films were investigated. The dense oxide films on the Ni substrate were removed effectively by using the anodic dissolution current method in the acidic chloride solutions. Meanwhile, the Ni films treated with specific treatment conditions produced different roughness, which was responsible for the improved adhesion strength. The adhesion strength of the Ni films increased up to 629.8 MPa when substrates were treated with anodic current density of 30 mA/cm2 for 10 min, which is nearly two times higher than that of films treated by 5 vol % HCl for 10 min. The results indicate that the anodic current treatment method effectively improves the adhesion strength of Ni films.

The interface layer has great significance on the potential barrier height of the CdTe/GaAs heterointerface. In this study, the electronic properties of the CdTe/GaAs heterostructure prepared by molecular beam epitaxy was investigated in situ by synchrotron radiation photoemission spectroscopy for CdTe thicknesses ranging from 3.5 to 74.6 Å. During CdTe deposition, an As-Te and Ga-Te interface reaction occurred, which caused the out diffusion of Ga. As a result a stable GaTe interface dipole layer (more than 30 Å) was formed, which reduced the potential barrier height by 0.38 eV. The potential barrier height was in proportion to the chemical bonding density and thickness of the Ga-Te interface layer. These results provide a more fundamental understanding of the influencing mechanism of the interface layer on the potential barrier height of the CdTe/GaAs heterointerface.

A series of Pd/γ-Al2O3 catalysts modified by potassium salts were prepared and evaluated in the reductive cyclization of 2-nitro-2′-hydroxy-5′-methylazobenzene without additional base. These solid base-hydrogenation bifunctional catalysts were characterized and the results demonstrated that potassium salts could have an important impact on the properties and catalytic performance of Pd/γ-Al2O3.