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The experiment was to study the effects of dietary isochlorogenic acid (ICGA) on early growth performance, intestinal structure, immune performance, and microbial diversity of broilers. 400 one-day-old Kebao broilers, half in male and half female, were randomly divided into five groups with eight replicates in each group and 10 chickens in each replicate. Each group was fed with basal diet (control group), basal diet + 500 mg/kg ICGA (T1 group), basal diet + 1 000 mg/kg ICGA (T2 group), basal diet + 2 000 mg/kg ICGA (T3 group), and basal diet + 3 000 mg/kg ICGA (T4 group). The trial period was 21 days. The results showed that the average daily feed intake (ADFI), average daily gain (ADG), and feed-to-weight ratio (F/G) were not significantly different among the groups (P>0.05). The apparent metabolic rate of crude protein (CP) in T3 group and T4 group was significantly higher than that in control group and T2 group (P<0.05), and the apparent metabolic rate of calcium (Ca) in all experimental groups was extremely higher than that in the control group (P<0.01). The ileal pH value of T3 group was significantly lower than that of other groups (P<0.05). Serum complement C3 content of broilers in each experimental group was significantly higher than that in the control group (P<0.05), and serum immunoglobulin G (IgG) and immunoglobulin M (IgM) content of broilers in T3 group were significantly higher than that in other groups (P<0.05). The villus height of T3 group was significantly higher than that of the control group and T1 group (P<0.05), and the villus-saphenous ratio of T3 group was significantly higher than that of the control group, T1 group, and T2 group (P<0.05). Subdoligranulum&lowbar;variabile in T2 group and T3 group was significantly higher than that in control group and T1 group (P<0.05). Subdoligranulum&lowbar;variabile in T2 group was extremely higher than that in the control group (P<0.01). The study indicates that the nutrient apparent metabolic rate, immune performance, intestinal structure, and intestinal flora were improved by adding ICGA in the diet. The appropriate level of ICGA in the diet of broilers is 2 000 mg/kg. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Kinetics of the hydrogen–oxygen catalytic recombination reaction was studied. • Changes of reaction intensity and Temp Rise with initial temperature are discrepant. • Oxygen flow rate affects the reaction temperature but not its direction of transfer. • Effects of hydrogen diffusion time on reaction temperature are complex and diverse. • Hydrogen elimination effect isn't affected by reaction parameters of this experiment. Hydrogen-oxygen catalytic recombination reaction, as a promising technology for hydrogen elimination in the confined environment, can spontaneously eliminate the leaking hydrogen in the environment. However, the kinetics characteristics of this reaction process under different environmental factors have been poorly reported. A series of hydrogen–oxygen catalytic recombination experiments are performed in a little cylindrical container using Platinum-Carbon powder as the catalyst, to investigate the effects of the initial temperature, oxygen flow rate, and hydrogen diffusion time on the temperature characteristics. In addition, the amount of residual hydrogen at the end of the reaction is also taken into account. The results show that the reaction intensity increases with the increase of the initial temperature, and the first temperature peak P T1 is gradually smaller than P T2 and finally disappears. However, the intensity of temperature increase caused by the reaction exotherm does not enhance continuously with the increase of the reaction intensity. With the decrease in oxygen flow rate, the reaction temperature gradually reduces and the temperature peak gradually forms before the end of oxygen inflow. Nevertheless, the direction of temperature transfer is hardly affected by the oxygen flow rate and the heat is still accumulating below the catalyst. The effect of hydrogen diffusion time on the reaction at hydrogen-poor, stoichiometric ratio hydrogen, and hydrogen-rich is diverse and complex, but the temperature–time profile on the catalyst surface has been changed accordingly. In addition, under any conditions, the hydrogen can be completely reacted below the stoichiometric ratio. [ABSTRACT FROM AUTHOR]

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction. [ABSTRACT FROM AUTHOR]

[Display omitted] • By recrystallization method, Cu and CuO are combined with a new material, 5AT. • Pyrolysis models for 5AT in each stage are deduced by Coats-Redfern method. • 5AT can undergo isomeric interconversion in the presence of metal catalysts. • The overall catalytic effect of copper is superior to that of copper oxide. As a new amino tetrazole compound, 5-Amino-1H-Tetrazole (5AT) has been widely used in propellants, blunt explosives, and airbags considering its advantages as high gas yield, environmentally friendly product, and low allergenicity. Yet, deficiencies such as wide pyrolysis range and low ignition temperature still exist in 5AT. So it is necessary to take some measures to improve its performance. Metal oxides and metals have been well established as catalysts in the field of energy-containing materials. In order to investigate the effect of Cu elements on the performance of 5AT pyrolysis, Cu and CuO are selected as catalysts for comparative analysis in this paper. It is found that the second stage of 5AT pyrolysis disappears in the presence of the catalysts, leaving only two stages. The activation energy of 5AT is reduced by about 30 kJ/mol and the pyrolysis model remains unchanged (still the F2 model) for the first stage. This indicates that the catalysts have a minimal effect on the first stage of 5AT. Due to the lower activation energy of 5AT-Cu and the SEM-EDS results showing that Cu is more tightly bound to 5AT, it could be inferred that Cu is more effective than CuO in the first stage. For the third stage, the activation energy of 5AT is reduced by the catalyst over 100 kJ/mol, with the pyrolysis model changing from F1 to D3, suggesting that the catalysts mainly act in the third stage. Since the activation energy of 5AT differs by no more than 3 % between the two catalysts, the pyrolysis model remains the same (both are D3). That means that the effects of the two catalysts are compatible. In terms of overall effectiveness, the effect catalyst Cu is superior to CuO. This paper can provide a reference for the choice of catalyst type, compounding method as well as the further combustion process of 5AT. [ABSTRACT FROM AUTHOR]

[Display omitted] • By recrystallization method, Cu and CuO are combined with a new material, 5AT. • Pyrolysis models for 5AT in each stage are deduced by Coats-Redfern method. • 5AT can undergo isomeric interconversion in the presence of metal catalysts. • The overall catalytic effect of copper is superior to that of copper oxide. As a new amino tetrazole compound, 5-Amino-1H-Tetrazole (5AT) has been widely used in propellants, blunt explosives, and airbags considering its advantages as high gas yield, environmentally friendly product, and low allergenicity. Yet, deficiencies such as wide pyrolysis range and low ignition temperature still exist in 5AT. So it is necessary to take some measures to improve its performance. Metal oxides and metals have been well established as catalysts in the field of energy-containing materials. In order to investigate the effect of Cu elements on the performance of 5AT pyrolysis, Cu and CuO are selected as catalysts for comparative analysis in this paper. It is found that the second stage of 5AT pyrolysis disappears in the presence of the catalysts, leaving only two stages. The activation energy of 5AT is reduced by about 30 kJ/mol and the pyrolysis model remains unchanged (still the F2 model) for the first stage. This indicates that the catalysts have a minimal effect on the first stage of 5AT. Due to the lower activation energy of 5AT-Cu and the SEM-EDS results showing that Cu is more tightly bound to 5AT, it could be inferred that Cu is more effective than CuO in the first stage. For the third stage, the activation energy of 5AT is reduced by the catalyst over 100 kJ/mol, with the pyrolysis model changing from F1 to D3, suggesting that the catalysts mainly act in the third stage. Since the activation energy of 5AT differs by no more than 3 % between the two catalysts, the pyrolysis model remains the same (both are D3). That means that the effects of the two catalysts are compatible. In terms of overall effectiveness, the effect catalyst Cu is superior to CuO. This paper can provide a reference for the choice of catalyst type, compounding method as well as the further combustion process of 5AT. [ABSTRACT FROM AUTHOR]

Abstract: Information routing is one of the most important problems in large communication networks. In this paper we propose a novel routing strategy in which the optimal paths between all pairs of nodes are chosen according to a cost function that incorporates degrees of nodes in paths. Results on large scale-free networks demonstrate that our routing strategy is more efficient than the shortest path algorithm and the efficient routing strategy proposed by Yan et al. [Phys. Rev. E 73, 046108 (2006)]. Furthermore our routing strategy has strong robustness against cascading failure attacks on networks. [Copyright &y& Elsevier]

Abstract: The synthetic DOX–LNA conjugate was characterized by proton nuclear magnetic resonance and mass spectrometry. In addition, the purity of the conjugate was analyzed by reverse-phase high-performance liquid chromatography. The cellular uptake, intracellular distribution, and cytotoxicity of DOX–LNA were assessed by flow cytometry, fluorescence microscopy, liquid chromatography/electrospray ionization tandem mass spectrometry, and the tetrazolium dye assay using the in vitro cell models. The DOX–LNA conjugate showed substantially higher tumor-specific cytotoxicity compared with DOX. [Copyright &y& Elsevier]

Options for treatment of chronic spontaneous urticaria beyond antihistamines are limited. This multicenter, randomized, sham-controlled trial from 3 teaching hospitals in China compared acupuncture, sham acupuncture, and waitlist control for treatment of chronic spontaneous urticaria. Visual Abstract. Efficacy of Acupuncture for Chronic Spontaneous Urticaria: Options for treatment of chronic spontaneous urticaria beyond antihistamines are limited. This multicenter, randomized, sham-controlled trial from 3 teaching hospitals in China compared acupuncture, sham acupuncture, and waitlist control for treatment of chronic spontaneous urticaria. Background: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. Objective: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. Design: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994) Setting: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. Participants: 330 participants diagnosed with CSU. Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). Measurements: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. Results: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was −8.2 (CI, −9.9 to −6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were −4.1 (CI, −5.8 to −2.4) and −2.2 (CI, −3.8 to −0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were −4.1 (CI, −6.5 to −1.8) and −6.1 (CI, −8.4 to −3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. Limitation: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. Conclusion: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. Primary Funding Source: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) can be induced by various injury factors, which is closely related to the inflammatory reaction and cellular ferroptosis reported recently. Glutathione peroxidase (GPX4) palys an important role in the inflammatory reaction, which also is the core regulatory protein of ferroptosis. Up-regulation of GPX4 can be helpful to inhibit the cellular ferroptosis and inflammatory reaction to treat ALI. mPEI/pGPX4 gene therapeutic system based on mannitol-modified polyethyleneimine (mPEI) was constructed. Compared with PEI/pGPX4 nanoparticles using commoditized gene vector PEI 25k, mPEI/pGPX4 nanoparticles achieved caveolae-mediated endocytosis and improved the gene therapeutic effect. mPEI/pGPX4 nanoparticles could up-regulate the gene expression of GPX4, inhibit inflammatory reaction and the cellular ferroptosis, thereby alleviating the ALI in vitro and in vivo. The finding indicated that gene therapy with pGPX4 is a potential therapeutic system for the effective treatment of ALI. [ABSTRACT FROM AUTHOR]

The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000 via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system. 1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH 6.5â€"6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacy in vivo with no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Oxygen plasma treatment is often used to clean the surface or etch graphene for functional structures. Some unique properties such as photoluminescence (PL), energy bandgap engineering, and so on are presented in single‐layer graphene (SLG). Compared with SLG, few‐layer graphene (FLG) has higher luminescence intensity, slower decay rate, and better controllability. It is more universal in the application of new optoelectronic devices and transparent electrodes. So, a systematic study is provided to analyze the mechanism between chemical vapor deposition of few‐layer graphene and oxygen plasma process based on the optical characterization method. Surface morphology, structural defects, resistance change, chemical state, and PL are traced and investigated under different oxygen plasma treatment times. The CO and CO bonds on the surface of the FLG appear to increase and then decrease with oxygen plasma etching based on X‐ray photoelectron spectroscopy (XPS) characterization. A linear square resistance change is presented from 1.4 to 4.8 kΩ sq−1. Besides that, an obvious redshift–blueshift change is produced in fluorescence characteristic spectra. Herein, comprehensive research on the influencing mechanism of graphene and oxygen treatment is exhibited, which provides the potential to construct optoelectronic devices. [ABSTRACT FROM AUTHOR]

[Display omitted] • Use Pt/C catalyst to eliminate hydrogen pre-explosion at the ambient temperature. • The overall reaction process and temperature characteristics are discussed in detail. • The peak structure is impacted by hydrogen volume fraction and catalyst position. • The hydrogen elimination isn't affected by the catalyst position and usage condition. Hydrogen-oxygen recombination is a safe and effective method of eliminating hydrogen before the explosion occurs. Most existing studies have focused on material modification, but the dynamic response of this reaction is rarely reported. In this paper, a series of experiments catalyzed by the Platinum-Carbon catalyst was carried out in a cylindrical container of 250 cm3 to study the effects of hydrogen volume fraction, catalyst position, and catalyst usage status on the temperature characteristics and hydrogen conversion. The results show that the reaction temperature on the catalyst surface not only increases and then decreases with the increase of hydrogen volume fraction but also decreases as the distance between the catalyst and the bottom increases, except for the 40 vol% volume fraction of hydrogen, and the maximum value occurs at the hydrogen volume fraction of 70 vol%. Moreover, there is an uncertainty in the temperature relationship between the catalyst surface and below as the volume fraction of hydrogen increases. The temperature peak structure on the catalyst surface is only influenced by the catalyst position and hydrogen volume fraction, and two temperature peaks can be observed in most cases. However, the hydrogen conversion is not affected by the catalyst position and its usage status. [ABSTRACT FROM AUTHOR]

Abstract: Flavanoid kaempferol is mainly present as glucuronides and sulfates in rat plasma, and small amounts of the intact aglycone are also detected. In the this study, a rapid, specific and sensitive liquid chromatography–electrospray ionization-tandem mass spectrometry method (HPLC–MS/MS) was developed and validated for determination of kaempferol and its major metabolite glucuronidated kaempferol in rat plasma. A liquid–liquid extraction with acetic ether was involved for the extraction of kaempferol and internal standard. Analytes were separated on a C18 column (150mm×2.1mm, 4.5μm, Waters Corp.) with isocratic elution at a flow-rate of 0.3mlmin−1. The mobile phase was consisted of 0.5% formic acid and acetonitrile (50:50, v/v). The Quattro Premier HPLC–MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. The method was validated according to the FDA guidelines for validation of bioanalytical method. The validated method was successfully applied to the study of the pharmacokinetics in rats after oral administration of kaempferol with different doses. [Copyright &y& Elsevier]

Xanthotoxol, a biologically active linear furocoumarin, has been efficiently synthesized from 7-hydroxycoumarin in six steps. The key steps included two efficient rearrangements—Fries rearrangement and Claisen rearrangement—and a Baeyer–Villiger oxidation process. The overall yield of xanthotoxol was 29%. This approach also provided a new strategy to furnish easily furocoumarins with a hydroxyl group in the framework. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common malignant tumor with bone metastasis, and there is still no ideal treatment for bone metastasis of prostate cancer. In this study, a pH and GSH dual sensitive calcium phosphate-polymer hybrid nanoparticle (DTX@Cap/HP) was prepared to co-deliver zoledronate (ZOL) and docetaxel (DTX) to treat bone metastasis of prostate cancer. DTX@Cap/HP exhibited high bone binding affinity and released more DTX and ZOL in acidic and high GSH concentration environment. A large amount of DTX@Cap/HP was uptaken by PC-3 cell in acidic medium than that in neutral medium. DTX@Cap/HP obviously reduced PC-3 cell proliferation and bone lesion in in-vitro 3D model of bone metastases of prostate cancer. Besides, DTX@Cap/HP also exhibited stronger anti bone metastases of prostate cancer activity in vivo as compared with the same dose of DTX + ZOL, which resulted from the co-delivery of DTX and ZOL to bone metastases of prostate cancer by DTX@Cap/HP and the synergistic effects of DTX and ZOL. DTX@Cap/HP has great potential in the treatment of bone metastases of prostate cancer. [ABSTRACT FROM AUTHOR]

Background. As a central nervous system disease, migraine often coexists with gastrointestinal disorders, which suggests a disruption of brain-gut regulation. Clinical studies have confirmed that acupuncture and flunarizine not only alleviate migraine attacks but also substantially inhibit accompanying gastrointestinal symptoms. However, it is still not clear how acupuncture and flunarizine regulate the interactions of brain, gut, and microbiome. Therefore, this study will combine neuroimaging technology and gut microbiota detection technology to explore and compare the effects and brain-gut modulating mechanisms of acupuncture and flunarizine for migraine. Methods. This randomized clinical trial will recruit 66 patients with migraine without aura. Participants will be randomly assigned in a 1 : 1 ratio to an acupuncture group or a control group. The acupuncture treatment strategy is based on experience from our previous study and consensus meetings with clinical experts. Patients will receive 12 sessions of manual acupuncture treatment (once every other day to a total of three times per week, followed by a 2-day break). Flunarizine will be administered at a dose of 5 mg daily in the control group. Participants in both groups will receive treatment for a period of 4 weeks. The primary outcome is the change in frequency of migraine attacks, and the secondary outcomes include the changes in migraine days (days on which migraine attacks occurred), average migraine severity, gastrointestinal symptoms, psychiatric symptoms, and quality of life. Fresh stool samples will be collected, and 16S ribosomal RNA gene sequencing analysis will be used for gut microbiota. Magnetic resonance imaging will be applied to detect between-group changes in brain function. The abovementioned indicators will be collected at baseline, after a 4-week intervention, and at the 12-week follow-up. Discussions. From the perspective of brain-gut regulatory mechanisms, we will combine brain neuroimaging and gut microbiological data to partially reveal the similarities and differences of acupuncture and flunarizine on the treatment of migraine. The trial is registered with ChiCTR2000034417. [ABSTRACT FROM AUTHOR]

Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy. [ABSTRACT FROM AUTHOR]

Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy. [ABSTRACT FROM AUTHOR]

Background: Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. Results: A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. Conclusions: This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications. [ABSTRACT FROM AUTHOR]

Objective. Acupuncture is effective for irritable bowel syndrome (IBS); however, the mechanisms of action are not fully understood. We aim to explore the mechanism of electroacupuncture (EA) in the dual regulation of disorders of gut-brain interaction. Methods. A rat model of IBS was generated by chronic unpredictable mild stress (CUMS). Eight of 32 rats were assigned to the blank control group. The remaining 24 rats received CUMS for 14 days. Then, the rats surviving and successfully modelled were randomly divided into the CUMS group, the CUMS+EA group, and the CUMS+PB (pinaverium bromide) group. In the next 14 days of treatment, rats in the CUMS+EA group were acupunctured at ST25 (Tianshu), ST36 (Zusanli), SP6 (Sanyinjiao), and LR3 (Taichong) for 15 min every day. Rats in the CUMS+PB group were treated by the administration of gavage with 2.7 mg/mL pinaverium every day. Visceral pain threshold, the percentage of time spent in open arms (OT%) in the elevated plus maze test (EPMT), and the sucrose preference (SP%) in the sucrose preference test (SPT) were measured at baseline, day 15, and day 30. The expression of zonula occludens-1 (ZO-1), the morphology of the connective structure of intestinal epithelium, the CRF and CRF-R1 mRNA expression in the hypothalamus, and the double staining of intestinal mucosal mast cells (IMMC) and CRF-R1 were measured at the end of the experiment. Results. Compared with the blank control group, visceral pain threshold pressure, the expression of ZO-1, OT%, SP%, CRF, and CRF-R1 mRNA expression in the hypothalamus, and double staining of IMMC and CRF-R1 were decreased significantly in the CUMS group. Meanwhile, the morphology of the connective structure in the CUMS group was indistinct. Compared with the CUMS group, SP% was significantly increased in the CUMS+EA group, but there was no significant difference for it in the CUMS+PB group. The morphology of the connective structure in the two treatment groups was clear and seeable. And the expression of other parameters mentioned above was apparently increased in the two treatment groups. Compared with the CUMS+PB group, the expression of ZO-1 in the CUMS+EA group was significantly enhanced. And no obvious difference for other parameters was found between the two treatment groups. Conclusions. EA treatment can decrease the expression of hypothalamic CRF and CRF-R1, relieve anxiety and depression, meanwhile reduce the expression of CRF-R1 in the gastrointestinal mucosa, increase ZO-1 expression, and adjust tight junctions (TJs) to repair the intestinal mucosal barrier. The above roles suggest that EA may play a dual role in alleviating the gastrointestinal and psychological symptoms of IBS, suggesting a potentially dual therapeutic role for EA in regulating disorders of gut-brain interaction in IBS rats. [ABSTRACT FROM AUTHOR]

Background: Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI. Results: CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats. Conclusion: CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction. [ABSTRACT FROM AUTHOR]

In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and −15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis. [ABSTRACT FROM AUTHOR]

The amoxicillin-UCCs-2/TPP nanoparticles constructed with ureido-modified chitosan derivative UCCs-2 and sodium tripolyphosphate (TPP) played an important role to deliver drug to achieve more efficacious and specific eradication of Helicobacter pylori ( H . pylori ) in vitro . In this study, the anti- H . pylori effectiveness in vivo and uptake mechanism was investigated in details, including the effect of temperature, pH values and the addition of competitive substrate urea on uptake. Compared with unmodified nanoparticles, a more efficacious and specific anti- H . pylori activities were obtained in vivo by using this biological chitosan derivative UCCs-2. Histological staining and immunological analysis verified that the amoxicillin-UCCs-2/TPP nanoparticles could diminish the proinflammatory cytokines levels and alleviate the inflammatory damages caused by H . pylori infection. The uredio-modified nanoparticles also have favorable gastric retention property, which is beneficial for the oral drug delivery to targeted eradicate H . pylori infection in stomach. These findings suggest that this targeted drug delivery system may serve for specific treatment of H . pylori infection both in vitro and in vivo , which can also be used as promising nanocarriers for other therapeutic reagents to target H . pylori . [ABSTRACT FROM AUTHOR]

The acidic environment of the stomach is a threat to the curative effect of antimicrobial drugs for the eradication of Helicobacter pylori ( H. pylori ) in the infected area. The conventional clinical formulations of antibiotics have low specificity to H. pylori , which disrupts the normal balance of intestinal microbiomes. Therefore, oral drug delivery system with better stability at low pH as well as higher specificity to target H. pylori would provide more effective strategy to eradicate H. pylori and reduce the side effect of antibiotics. Based on the construction of UreI-mediated targeted drug delivery system developed by our group, in this work, using urea-modified UCCs-2 as targeting moiety to the UreI channel protein which is specifically expressed on H. pylori , pH-sensitive amoxicillin-loaded AMX-PLGA/UCCs-2 nanoparticles produced by UCCs-2 and PLGA for targeted treatment of H. pylori infection were established. The nanoparticles were prepared by double emulsion-solvent evaporation method. To achieve a promising drug delivery system with favorable pH-sensitive properties, we adopted an orthogonal design to obtain the optimal formulation. The results showed that the optimized AMX-PLGA/UCCs-2 nanoparticles were in a favorable pH sensitive manner and exhibited low cytotoxicity, higher specificity and better anti- H. pylori efficiency than amoxicillin and non-targeting AMX-PLGA/Cs nanoparticle both in vitro and in vivo , which can protect the antimicrobial drugs against acidic environment and deliver them to targeted eradicate H. pylori in the infected location. The cellular uptake mechanism showed that AMX-PLGA/UCCs-2 nanoparticles are an effective UreI-mediated targeted drug delivery system for anti- H. pylori treatment, which can also be used as promising nanocarriers for oral delivery of other therapeutic drugs to targeted treat H. pylori. [ABSTRACT FROM AUTHOR]

In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and −15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Tumor targeted combination nanoparticles was designed as effective therapeutic system for the drug resistant triple negative breast cancer and the anti-tumor effect in vitro and in vivo was demonstrated. [Display omitted] Breast cancer has become the malignant tumor with the largest incidence, especially the drug resistant triple negative breast cancer (TNBC). The combination therapeutic system can play a better role in resisting drug resistant TNBC. In this study, dopamine and tumor targeted folic acid modified dopamine were synthesized as carrier materials to construct melanin-like tumor targeted combination therapeutic system. The optimized nanoparticles of CPT/Fe@PDA-FA10 with efficient loading of camptothecin and iron was achieved, which showed tumor targeted delivery ability, pH sensitive controlled release, effective photothermal conversion performance and excellent anti-tumor efficacy in vitro and in vivo. CPT/Fe@PDA-FA10 plus laser could significantly kill the drug resistant tumor cells, inhibit the growth of the orthotopic drug resistant triple negative breast cancer through apoptosis/ferroptosis/photothermal treatment, and had no significant side effects on the main tissues and organs. This strategy provided a new idea for the construction and clinical application of triple-combination therapeutic system as effective treatment for drug resistant triple negative breast cancer. [ABSTRACT FROM AUTHOR]

The bone targeted miRNA delivery system PCA/miR-34a for miR-34a was developed for the gene therapy to bone-associated metastatic breast cancer. PCA/miR-34a showed specific bone-targeting ability and enhanced anti-tumor performance along with minor side effects, which provides a good strategy for the gene therapy of bone metastatic cancer in the clinic. [Display omitted] Bone metastatic cancer is the most common occurrence in breast cancer, and the treatment is also facing great challenges. MicroRNA-34a (miRNA-34a) is a promising anti-cancer miRNA for gene therapy to bone metastatic cancer patients. However, the lack of specificity to bone and low accumulation at the site of bone tumor remains the major challenge when used bone-associated tumor. To solve this problem, a bone-targeted vector for delivery of miR-34a to bone metastatic breast cancer was constructed by using the commonly used gene vector branched polyethylenimine 25 k (BPEI 25 k) as the skeleton and linking with alendronate (ALN) moieties for bone targeting group. The constructed gene delivery system PCA/miR-34a can efficiently prevent miR-34a from degradation during blood circulation and enhance the specific bone delivery and distribution. PCA/miR-34a nanoparticles can be uptake into tumor cells through clathrin and caveolae-mediated endocytosis, and directly regulate the expression of oncogenes, thus promoting tumor cell apoptosis and relieving bone tissue erosion. The results of experiments in vitro and in vivo confirmed that the constructed bone-targeted miRNA delivery system PCA/miR-34a can enhance the anti-tumor efficacy in bone metastatic cancer, and provide a potential strategy for gene therapy in bone metastatic cancer. [ABSTRACT FROM AUTHOR]

The covalently cross-linked chitosan-poly(ethylene glycol) 1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG 1540 -dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2 h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12 h. The results proved that the release-and-hold behavior of the cross-linked CS–PEG 1540 H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery. [ABSTRACT FROM AUTHOR]

[Display omitted] • The catalytic effect of PbO is better than SiO 2 and MnO 2. • The bond breakage processes in 5AT molecular structures are promoted by catalysts. • Catalysts mainly affect the escape of (NH 2) 2 CN but little effect on NH 2 CN and NH 3. • Pyrolysis models are converted into F 3/2 due to catalysts with conversion over 0.5. 5-Amino-1 H -Tetrazole (5AT), as a novel energetic material, has been widely applied in propellant, airbags, and fire extinguisher areas due to its excellent combustion properties. However, suboptimal combustion performance limits its extensive application. Thermal behaviors investigation could provide guidance on the control of combustion performance, which can be effectively optimized by adding catalysts. Therefore, exploring the thermal decomposition behaviors of 5AT is more beneficial to its combustion performance optimization, management and applications. Traditional catalysts for 5AT, such as coolants (CaCO 3), hydrohalide salts (HCl), and guanidine (CH 4 N 4 O 2) are easy to release harmful gas to destroy the environment when they catalyze the pyrolysis and combustion process. Moreover, different catalysts can play various catalytic mechanism. Therefore, a highly effective catalysts that are not easy to be occurred for pyrolysis on their own are required. In this study, three kinds of catalysts (acid oxide (SiO 2), alkaline oxide (PbO), amphoteric oxide (MnO 2)) are mixed with 5AT by means of ball milling, which is for the purpose of investigating the effect of multi-type oxides on the catalytic pyrolysis behaviors about 5AT. The TG test is conducted to analyze the thermal behaviors and the isoconversion method (Advanced Vyazovkin) is applied to evaluate the thermal activation energy ranging from 100 ∼ 300 ℃. The results reveal that the catalyst PbO embodies the best catalytic effect. The Criado method is employed to determine the pyrolysis model. The results indicates that the pyrolysis model is not governed by a specific model but all followed by F n model when the conversion is below 0.5 while the model is mainly charged by F 3/2 model when the conversion is over 0.5 with the addition of catalysts. Moreover, the TG-FTIR technology is also employed to capture the evolved gas products and further to infer the most likely pyrolysis route of 5AT. The conclusions in this study will provide a theoretical support for the storage, transportation, application, management, combustion investigation and the computer simulation of 5AT-based solid propellant. [ABSTRACT FROM AUTHOR]

Cholesterol derivatives M1 – M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1 – M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1 – M6 exhibited good transfection activity, and the transfection activity was parallel ( M2 and M4 ) or superior ( M1 and M6 ) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery. [ABSTRACT FROM AUTHOR]

The covalently modified ureido-conjugated chitosan/TPP multifunctional nanoparticles have been developed as targeted nanomedicine delivery system for eradication of Helicobacter pylori . H. pylori can specifically express the urea transport protein on its membrane to transport urea into cytoplasm for urease to produce ammonia, which protects the bacterium in the acid milieu of stomach. The clinical applicability of topical antimicrobial agent is needed to eradicate H. pylori in the infected fundal area. In this study, we designed and synthesized two ureido-conjugated chitosan derivatives UCCs-1 and UCCs-2 for preparation of multifunctional nanoparticles. The process was optimized in order to prepare UCCs/TPP nanoparticles for encapsulation of amoxicillin. The results showed that the amoxicillin-UCCs/TPP nanoparticles exhibited favorable pH-sensitive characteristics, which could procrastinate the release of amoxicillin at gastric acids and enable the drug to deliver and target to H. pylori at its survival region effectively. Compared with unmodified amoxicillin-chitosan/TPP nanoparticles, a more specific and effective H. pylori growth inhibition was observed for amoxicillin-UCCs/TPP nanoparticles. Drug uptake analysis tested by flow cytometry and confocal laser scanning microscopy verified that the uptake of FITC-UCCs-2/TPP nanoparticles was associated with urea transport protein on the membrane of H. pylori and reduced with the addition of urea as competitive transport substrate. These findings suggest that the multifunctional amoxicillin-loaded nanoparticles have great potential for effective therapy of H. pylori infection. They may also serve as pharmacologically effective nanocarriers for oral targeted delivery of other therapeutic drugs to treat H. pylori . [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a key pathological process of chronic liver diseases, caused by alcohol, toxic and aberrant energy metabolism. It progresses to cirrhosis or even hepatic carcinoma without effective treatment. Studies have shown that autophagy has important regulatory effects on hepatic stellate cells (HSCs) energy metabolism, and then affect the activation state of HSCs. Autophagy maintains hepatic energy homeostasis, and the dysregulation of autophagy can lead to the activation of HSCs and the occurrence and development of hepatic fibrosis. It is necessary to explore the mechanism of autophagy in energy metabolism-related hepatic fibrosis. Herein, the current study summarizes the regulating mechanisms of autophagy through different targets and signal pathways in energy metabolism-related hepatic fibrosis, and discusses the regulatory effect of autophagy by natural plant-derived, endogenous and synthetic compounds for the treatment of hepatic fibrosis. A better comprehension of autophagy in hepatic stellate cells energy metabolism-related hepatic fibrosis may provide effective intervention of hepatic fibrosis, explore the potential clinical strategies and promote the drug treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Alendronate-monoethyl adipate-(hydrazone)-doxorubicin conjugate ( ALN- MA-hyd- DOX) was synthesized to specifically deliver doxorubicin ( DOX) to bone tumor tissue. The binding kinetics of ALN- MA-hyd- DOX with hydroxyapatite ( HA) and natural bone were detected by using spectrophotometer. Cytotoxicity of ALN- MA-hyd- DOX on tumor cells was determined by MTT [3-(4,5-dimethylthiaol-2-yl)-2,5-diphenyl-tetrazolium bromide] method. The cellular uptake of ALN- MA-hyd- DOX was observed by using fluorescence microscopy. The in vivo antitumor activity of ALN- MA-hyd- DOX was investigated by using tumor-bearing nude mice model. The results indicated that ALN- MA-hyd- DOX was able to quickly bind with HA and natural bone. ALN- MA-hyd- DOX immobilized on the natural bone released more DOX in p H 5.0 medium than that in p H 6.0 or 7.4 medium. The cytotoxicity of ALN- MA-hyd- DOX toward A549 cells and MDA- MB-231/ ADR cells was greater than DOX. ALN- MA-hyd- DOX was rapidly uptaken by A549 cells and MDA- MB-231/ ADR cells. Compared with the same dose of free DOX, ALN- MA-hyd- DOX significantly decreased tumor volume of tumor-bearing nude mice. DOX mainly distributed in bone tumor tissue after ALN- MA-hyd- DOX was intravenously administered to tumor-bearing nude mice, whereas DOX distributed through the whole body after DOX was intravenously administered to tumor-bearing nude mice. These findings implied that the ALN- MA-hyd- DOX was a promising bone-targeted conjugate for treating bone neoplasms. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2293-2303, 2015 [ABSTRACT FROM AUTHOR]

In this work, three-dimensional trimetallic Pt–Pd–Co alloyed nanoflowers are fabricated by a facile one-pot solvothermal strategy, with the assistance of oleylamine as the solvent, surfactant, and reducing agents, along with cetylpyridinium chloride (CPC) as the co-surfactant and shape-directing agents. Their morphology and crystal structure were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning transmission electron microscope (STEM), and X-ray photoelectron spectra (XPS) in details. The respective electrochemically active surface area (ECSA) is estimated to be 32.53 m 2 g −1 , and current density is 132.91 mA cm −2 for the electrooxidation of ethylene glycol (EG). These values are much higher than those of PtPdCo nanoparticles, PtPd nanoparticles, commercial Pt black, and Pd black under the identical conditions, showing the improved catalytic activity of Pt–Pd–Co nanoflowers. The excellent performances are attributed to the specific structure and synergistic interactions of the trimetallic alloy. The as-prepared nanoflowers can serve as a promising electrocatalyst in fuel cells. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue with uncertain pathologic mechanism. Neuroimage may be an important key to unveil the central nervous system (CNS) mechanism in CFS. Although most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS, there are many factors that could affect GM volumes in CFS, including chronic pain, stress, psychiatric disorder, physical activity, and insomnia, which may bias the results. In this paper, through reviewing recent literatures, we discussed these interferential factors, which overlap with the symptoms of CFS. [ABSTRACT FROM AUTHOR]

PC407 is an effective COX-2 inhibitor in non-steroidal anti-inflammatory drug development but the poor solubility limits their usefulness. The aim of the study was to prepare and evaluate 4-oxo-4-[4-(5-(naphthalen-2-yl)-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzenesulfonamido]butyrate disodium, a derivative of PC407 with enhanced water solubility for injectable formulation. The prepared derivative displayed interesting high aqueous solubility (20.3 mg/mL, much superior to the parent compound PC407, 1.6 μg/mL) with confirmed in vivo analgesic activity. This derivative represents the profiles of prodrug and potential candidate of PC407 for the development of injectable COX-2 inhibitor due to extraordinary water solubility, low toxicity, and impressive analgesic activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Catalytic effect of boron powder mainly exerts on latter stages for 5AT pyrolysis. • Solution recrystallization method has better modification effect for 5AT pyrolysis. • Copper powder can optimize the pyrolysis behaviors for 5AT pyrolysis. • Kinetic models for 5AT in each stage have been deduced by model-fitting method. As a novel rich nitrogen content material, 5-Amino-1 H -Tetrazole (5AT) has been considerably popularized in the propellants area recently. The pyrolysis is deemed as the prelude of combustion for solid phase 5AT, which plays a crucial role in combustion process and grasping the pyrolysis characteristics will be more beneficial to further explore the combustion properties of 5AT-based propellant. In this paper, several efforts have been made to enhance the pyrolysis behaviors of 5AT, including employing metal particles as catalysts, and modifying the surface treatment method. Due to the calorific value, the boron and copper powder are selected as the potential catalysts. The solvent/non-solvent (S/NS) and solution recrystallization method are compared to explore the impact of these two modification methods. TG-FTIR technique is applied to capture evolved signals of organic compounds to further deduce the most probable decomposition pathway. Moreover, model-free and model-fitting methods are both employed to calculate the kinetic parameters. The results reveal that, for the modified 5AT samples with the same boron powder catalyst, the activation energies and reaction model (all governed by F4) in the initial stage (100–330 °C) are not significantly impacted by these two modification methods. However, during the latter stages (400–750 °C), the catalytic actions of boron powder appear to be more active, and solution recrystallization method exerts better modification effect, the activation energies was reduced 18.3 kJ/mol and 10.9 kJ/mol respectively for the latter stages compared to S/SN method. Also, the reaction model is transformed from n th -dimensional model (D3) to n th -order model (F1) in the third stage. Particularly, the catalytic actions of copper powder results in the simplification of decomposition steps for 5AT, the activation energies was 138.8 kJ/mol and the catalytic effect of which was improved about 25% compared to the catalytic effect of boron powder in the first stage and its reaction model is also found to be changed into F3. It illustrates that copper powder could embody a better catalytic effect than boron powder under the same modification method. The conclusions of this study could provide a worthwhile guidance for the understanding, designs and applications of the 5AT-based propellants. [ABSTRACT FROM AUTHOR]

A PEG-based, folate mediated, active tumor targeting drug delivery system using DOX-hyd-PEG-FA nanoparticles (NPs) were prepared. DOX-hyd-PEG-FA NPs showed a significantly faster DOX release in pH 5.0 medium than in pH 7.4 medium. Compared with DOX-hyd-PEG NPs, DOX-hyd-PEG-FA NPs increased the intracellular accumulation of DOX and showed a DOX translocation from lysosomes to nucleus. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was much higher than that of free DOX, DOX-ami-PEG-FA NPs and DOX-hyd-PEG NPs. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was attenuated in the presence of exogenous folic acid. The IC50 of DOX-hyd-PEG-FA NPs and DOX-hyd-PEG NPs on A549 cells showed no significant difference. After DOX-hyd-PEG-FA NPs were intravenously administered, the amount of DOX distributed in tumor tissue was significantly increased, while the amount of DOX distributed in heart was greatly decreased as compared with free DOX. Compared with free DOX, NPs yielded improved survival rate, prolonged life span, delayed tumor growth and reduced the cardiotoxicity in tumor bearing mice model. These results indicated that the acid sensitivity, passive and active tumor targeting abilities were likely to act synergistically to enhance the drug delivery efficiency of DOX-hyd-PEG-FA NPs. Therefore, DOX-hyd-PEG-FA NPs are a promising drug delivery system for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Aims To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. Methods and results Seven days post-permanent ligation, hearts from CD13 knockout (CD13KO) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13KO infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13KO mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13KO infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13KO infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. Conclusion In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing. [ABSTRACT FROM AUTHOR]

Folate-aminocaproic acid-doxorubicin (FA-AMA-DOX) was synthesized and characterized by H NMR spectroscopy and mass spectrometry. Cytotoxicity and cellular uptake experiments were performed in KB and HepG2 cells, which express folic acid receptor, and the cell line A549, which does not express folic acid receptor. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cellular uptake was monitored using fluorescence microscopy. The amount of DOX released from FA-AMA-DOX was much greater at pH 5.0 than that at pH 6.5 or 7.4. The cytotoxicity of FA-AMA-DOX toward KB and HepG2 cells was greater than that of DOX or AMA-DOX at the same concentrations, and cytotoxicity could be attenuated by FA in a dose-dependent manner. On the contrary, the cytotoxicity of FA-AMA-DOX and AMA-DOX toward A549 cells was lower than that of DOX at the same concentration, and cytotoxicity could not be reduced by FA. Compared with FA-AMA, FA-AMA-DOX increased the intracellular accumulation of DOX in KB cells. These results suggested that FA-AMA-DOX have suitable attributes for the active targeting of folate-receptor-positive tumor cells and for releasing the chemotherapeutic agent, DOX, in situ; it therefore has potential as a novel cancer therapeutic. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:530-540, 2013 [ABSTRACT FROM AUTHOR]

Abstract: Background: Whether acupuncture is effective for patients with functional constipation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using acupuncture to treat functional constipation. Design: A randomized, controlled, four-arm design, large-scale trial is currently undergoing in China. Seven hundred participants are randomly assigned to three acupuncture treatment groups and Mosapride Citrate control group in a 1:1:1:1 ratio. Participants in acupuncture groups receive 16 sessions of acupuncture treatment, and are followed up for a period of 9 weeks after randomization. The acupuncture groups are: (1) Back-Shu and Front-Mu acupoints of Large Intestine meridians (Shu-Mu points group); (2) He-Sea and Lower He-Sea acupoints of Large Intestine meridians (He points group); (3) Combining used Back-Shu, Front-Mu, He-Sea, and Lower He-Sea acupoints of Large Intestine meridians (Shu-Mu-He points group). The control group is Mosapride Citrate group. The primary outcome is frequency of defecation per week at the fourth week after randomization. The secondary outcomes include Bristol stool scale, the extent of difficulty during defecating, MOS 36-item Short Form health survey (SF-36),Self-Rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The first two of second outcomes are measured 1 week before randomization and 2, 4, and 8 weeks after randomization. Other second outcomes are measured 1 week before randomization and 2 and 4 weeks after randomization, but SF-36 is measured at randomization and 4 weeks after randomization. Discussion: The result of this trial (which will be available in 2012) will confirm whether acupuncture is effective to treat functional constipation and whether traditional acupuncture theories play an important role in it.Trials registration: Clinical Trials.gov NCT01411501 [ABSTRACT FROM AUTHOR]

Abstract: An efficient total synthesis of (R) and (S)-3-methyl 5-pentyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate in high optical purities is reported. The useful step is the resolution of racemic 2, 6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid by using commercially available Cinchona alkaloids cinchonidine and quinidine as the resolving agents. Under the optimum conditions, the optical purities for R- and S-enantiomers are extremely high (ee>99.5%). The further dihydropyridine receptor binding activity assay shows that the S-enantiomer is more potent than R-enantiomer both in rat cardiac (approximately 19times) and cerebral cortex membrane (12times). [Copyright &y& Elsevier]

The nano-delivery system HA-(BPEI-SS-Pt)-1/4 for cisplatin has been developed for effective cancer chemotherapy. HA-(BPEI-SS-Pt)-1/4 showed specific tumor-targeting ability, redox-responsive drug release manner, and more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin, which is of great significance for the chemotherapeutic drug in clinic. Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo , it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic. [ABSTRACT FROM AUTHOR]

In order to overcome drug resistant and enhance antitumor activity of DOX, a new pH-sensitive micelle (DOX/DQA-DOX@DSPE-hyd-PEG-AA) was prepared to simultaneously deliver DOX to nucleus and mitochondria. Drug released from DOX/DQA-DOX@DSPE-hyd-PEG-AA showed a pH-dependent manner. DOX/DQA-DOX@DSPE-hyd-PEG-AA induced the depolarization of mitochondria and apoptosis in MDA-MB-231/ADR cells and A549 cells, which resulted in the high cytotoxicity of DOX/DQA-DOX@DSPE-hyd-PEG-AA against MDA-MB-231/ADR cells and A549 cells. Confocal microscopy confirmed that DOX/DQA-DOX@DSPE-hyd-PEG-AA simultaneously delivered DQA-DOX and DOX to the mitochondria and nucleus of tumor cell. After DOX/DQA-DOX@DSPE-hyd-PEG-AA was injected to the tumor-bearing nude mice by the tail vein, DOX was mainly found in tumor tissue. But DOX was widely distributed in the whole body after the administration of free DOX. Compared with free DOX, the same dose of DOX/DQA-DOX@DSPE-hyd-PEG-AA significantly inhibited the growth of DOX-resistant tumor in tumor-bearing mice without obvious systemic toxicity. Therefore, dual subcellular compartment delivery of DOX greatly enhanced the antitumor activity of DOX on DOX-resistant tumor. DOX/DQA-DOX@DSPE-hyd-PEG-AA has the potential in target therapy for DOX-resistant tumor. [ABSTRACT FROM AUTHOR]

In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor. [ABSTRACT FROM AUTHOR]