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Electrochemical glucose sensors have garnered considerable attention because of their attractive prospect in point-of-care testing (POCT). In this review, we firstly introduce the principles and challenges of electrochemical glucose sensors. Subsequently, we present an overview of the application of electrochemical glucose sensors and discuss their advantages and drawbacks. Wearable and implantable devices based on diverse target biofluid and platforms provide a considerable prospect of accurate and continuous monitoring. Thus, we believe that the future development direction of electrochemical glucose sensors is non-invasive, wearable devices and implantable devices with minimally invasive for continuous glucose monitoring in real time. [ABSTRACT FROM AUTHOR]

Little is known about the difference between bacterial and fungal genetic and functional diversity in karst regions of south China. In this study, the genetic and functional diversity of bacteria and fungi in nine types of soil microenvironments in the karst region in Maolan National Nature Reserve in Guizhou were investigated by PCR-DGGE (Denaturing Gradient Gel Electrophoresis) and BIOLOG EcoPlates. Maolan National Nature Reserve is a UNESCO Biosphere Reserve and plays an important role in protecting the karst forest ecosystem and rare and endangered wild animals and plants in central Asia. The results showed that the diversity of both bacteria and fungi was high and the main factors influencing the diversity of bacteria and fungi were different. The bacterial community structure from different microhabitats under the same vegetation type had higher similarity than similar microhabitats in different vegetation types, which could indicate that the bacterial community structure was mainly controlled by vegetation. For fungi, similar microhabitat species under different vegetation types had higher similarities than different microhabitats species under the same vegetation type, which could indicate that the fungal community structure is mainly controlled by microhabitats. In addition, the metabolic patterns of similar microhabitats in different vegetation were different, while the metabolic patterns of different microhabitats in the same vegetation were not obviously different. In conclusion, the effect of vegetation types on soil microbial functional diversity was greater than that of microhabitats, and this difference was reflected by the different degrees of influence on soil microbial genetic diversity and community structure. [ABSTRACT FROM AUTHOR]

The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pKa = 7.06) with pH-dependent partition coefficient. The sphericalshaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is a common and disabling disorder. No current therapy can slow or reverse disease progression. An important aspect of research in this field is target validation, a systematic approach to evaluating the likelihood that modification of a certain molecule, mechanism or biological pathway may be useful for the development of pharmacological or molecular treatments for the disease. TorsinA, a member of the AAA+ family of chaperone proteins, has been proposed as a potential target of neuroprotective therapy. TorsinA is found in Lewy bodies in human PD, and can suppress toxicity in cellular and invertebrate models of PD. Here, we evaluated the neuroprotective properties of torsinA in mouse models of PD based on intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as recombinant adeno associated virus (rAAV) induced overexpression of alpha-synuclein (α-syn). Using either transgenic mice with overexpression of human torsinA (hWT mice) or mice in which torsinA expression was induced using an rAAV vector, we found no evidence for protection against acute MPTP intoxication. Similarly, genetic deletion of the endogenous mouse gene for torsinA (Dyt1) using an rAAV delivered Cre recombinase did not enhance the vulnerability of dopaminergic neurons to MPTP. Overexpression of α-syn using rAAV in the mouse substantia nigra lead to a loss of TH positive neurons six months after administration, and no difference in the degree of loss was observed between transgenic animals expressing forms of torsinA and wild type controls. Collectively, we did not observe evidence for a protective effect of torsinA in the mouse models we examined. Each of these models has limitations, and there is no single model with established predictive value with respect to the human disease. Nevertheless, these data do seem to support the view that torsinA is unlikely to be successfully translated as a target of therapy for human PD. [ABSTRACT FROM AUTHOR]

To evaluate novel mixed polymeric micelles based on monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) (mPEG-PLA) and Pluronic L61 for delivery of paclitaxel (PTX) to circumvent unfavorable effects resulting from Cremophore EL in Cremophore EL-based PTX formulation and overcoming multidrug resistance (MDR) in tumor cells at the same time. PTX-loaded plain micelles and mixed micelles were prepared and characterized by determining PTX release in vitro, MDR reversal effect in human breast cancer MDR MCF-7/ADR cell sublines and pharmacokinetics in vivo. Both PTX-loaded plain micelles and mixed micelles had similar in vitro release profile. Mixed micellar PTX significantly reduced IC50 of PTX in MCF-7/ADR cells compared to free PTX and plain micellar PTX, and mixed micelles substantially enhanced cellular accumulation of R 123 in MCF-7/ADR cells compared to free R123 and plain micelles. PTX-loaded mixed micelles with lower content of L61 exhibited comparable cytotoxicity to that observed with Cremophore EL-based PTX formulation in inhibiting the growth of MCF-7/ADR cells. Moreover, plain micelles and mixed micelles retained the pharmacokinetic characteristics of PTX in rats compared with Cremophore EL-based PTX formulation. This study suggested that the mixed micelles could enhance delivery of PTX and cell-killing effect for MDR MCF-7/ADR cells. [ABSTRACT FROM AUTHOR]

The purpose of this work was to investigate feasibility of a promising topical drug delivery system (TDDS) for sinomenine hydrochloride (SMH), extracted from the Chinese medicinal plant sinomenine acutum and currently used for the treatment of rheumatoid arthritis. It was found that SMH was a weak base (pKa, 7.98 ± 0.04) with pH-dependent solubility and partition coefficient. The result of in vitro permeation studies demonstrated that the permeation enhancer azone was the most effective. In contrast, spray had higher accumulative permeated amounts of SMH than patch, but permeated duration of spray was shorter than that of patch. The efficacy on Freund's complete adjuvant-induced arthritis suggested that there was near arthritis index for SMH spray with medium dose (i.e., 15 mg/rat) and oral solution at a dose of 12 mg/rat, indicating that topical SMH delivery system could achieve the similar anti-inflammatory efficacy with oral administration. Pharmacokinetic parameters including Cmax and AUC for both topical preparations were lower than those for oral preparation, which hinted that systemic side effect could be ignored. Therefore, the spray and patch were promising formulations for successful topical delivery of SMH through the skin instead of oral administration with side effects. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1790–1799, 2010 [ABSTRACT FROM AUTHOR]

Hereditary tyrosinemia type 1 (HT-1) is a rare autosomal recessive genetic disease with no effective cure at presen t. In recent years, gene-editing techniques such as base editor (BE) have been explored for treating HT-1. However, the delivery of nucleic acids faces challenges due to existing physiological barriers. In the present study, we constructed an asialoglycoprotein receptor (ASGPR)-targeted polymer-lipid nanoparticle to enhance the delivery efficiency of therapeutic nucleic acids for HT-1. To deliver BE plasmids, a biodegradable cationic polymer, acrylate-amino alcohol copolymer was synthesized and demonstrated superior transfection efficiency compared to the commercially available transfection reagent, Hieff TransTM. Subsequently, DOPE-PEG-GalNAc was combined with copolymer nanoparticles to enhance the hepatocyte delivery of the nanoparticles. Upon loading the recombinant BE plasmid, Fah-pCMV-ABE6.3-EGFP, the polymer-lipid nanoparticles exhibited remarkable hepatocyte selectivity, with a transfection efficiency over 70-fold higher than that of the free plasmid. The study suggested that polymer-lipid nanoparticles, in combination with liver-targeted ligands, could effectively enhance the liver-targeted delivery of therapeutic BE plasmids, providing a promising vector for gene therapy of HT-1. [ABSTRACT FROM AUTHOR]

Kentucky bluegrass (Poa pratensis L.), one of the most widely used cool‐season turfgrasses around the world, is sensitive to powdery mildew (PM; Blumeria graminis). The PM strain identification and regulation mechanisms of Kentucky bluegrass in response to pathogens still remain unclear. Through morphological and molecular analyses, we identified that the pathogen in Kentucky bluegrass was B. graminis f. sp. poae. The infection of B. graminis led to a reduction of the sclerenchyma area, expansion of vesicular cells and movement of chloroplasts. The infected leaves had significantly lower values in net photosynthesis, stomatal conductance and transpiration rate, maximal quantum yield of PSII photochemistry, photochemical quenching and non‐regulated energy dissipation compared to mock‐inoculated leaves. Expressions of light‐harvesting antenna protein genes LHCA and LHCB and photosynthetic electron transport genes petE and petH decreased significantly in infected leaves. Furthermore, upregulations of genes involved in plant‐pathogen interaction, such as HSP90, RBOH, and RPM and downregulations of EDS, RPS and WRKY were observed in infected leaves. The findings may help design a feasible approach to effectively control the PM disease in Kentucky bluegrass and other related perennial grass species. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) transition metal compound (TMC) monolayers, as well as their van der Waals heterostructures with unique properties, are fundamentally and technologically intriguing. Here, heterostructures consisting of a MoS2 monolayer and TM2CO2 (TM = Ti, Zr or Hf) monolayers are systematically researched by means of the density functional theory (DFT). Different from semiconductor/metal contacts, MoS2 and TM2CO2 monolayers are all semiconductors with band gaps ranging from 0.25–1.67 eV. According to rigorous screening of stacking patterns, MoS2/Zr2CO2 is shown to be an indirect type-II semiconductor with the maximum valence and minimum conduction bands spatially separated on opposite monolayers. Simultaneously, the interface charges transfer from Zr2CO2 to MoS2 results in a built-in field that separates the electrons and holes efficiently. Also, the smaller effective masses of electrons and the holes of band edges indicate the higher carrier mobility. Moreover, strain regulation can make the hetero-bilayer’s character a semiconductor–semimetal–metal transition. The physical insights pave the way for the good performance of MoS2/TM2CO2 in next-generation electronic devices and photocatalysts. [ABSTRACT FROM AUTHOR]

Parkinson's Disease (PD) is an age-related, chronic neurodegenerative disorder. At present, there are no disease-modifying therapies to prevent PD progression. Activated microglia and neuroinflammation are associated with the pathogenesis and progression of PD. Accumulation of α-synuclein (α-SYN) in the brain is a core feature of PD and leads to microglial activation, inflammatory cytokine/chemokine production, and ultimately to neurodegeneration. Given the importance of the JAK/STAT pathway in activating microglia and inducing cytokine/chemokine expression, we investigated the therapeutic potential of inhibiting the JAK/STAT pathway using the JAK1/2 inhibitor, AZD1480. In vitro, α-SYN exposure activated the JAK/STAT pathway in microglia and macrophages, and treatment with AZD1480 inhibited α-SYN-induced major histocompatibility complex Class II and inflammatory gene expression in microglia and macrophages by reducing STAT1 and STAT3 activation. For in vivo studies, we used a rat model of PD induced by viral overexpression of α-SYN. AZD1480 treatment inhibited α-SYN-induced neuroinflammation by suppressing microglial activation, macrophage and CD4+ T-cell infiltration and production of proinflammatory cytokines/chemokines. Numerous genes involved in cell- cell signaling, nervous system development and function, inflammatory diseases/processes, and neurological diseases are enhanced in the substantia nigra of rats with α-SYN overexpression, and inhibited upon treatment with AZD1480. Importantly, inhibition of the JAK/STAT pathway prevented the degeneration of dopaminergic neurons in vivo. These results indicate that inhibiting the JAK/STAT pathway can prevent neuroinflammation and neurodegeneration by suppressing activation of innate and adaptive immune responses to α-SYN. Furthermore, this suggests the feasibility of targeting the JAK/STAT pathway as a neuroprotective therapy for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In this study, we investigated the association between the FasL -844T/C polymorphism and the risk of developing esophageal squamous cell carcinoma (ESCC) in South China. For the investigation, we randomly selected 248 patients suffering from ESCC from Southern China along with 297 healthy individuals as the control group. The relationship between the FasL gene -844T/C SNP and ESCC was studied using PCR-RFLP and immunohistochemistry. The Fas -1377G/A SNP was also selected for investigation to detect whether it interferes with the functional effect of the FasL -844C/T polymorphism in ESCC development. A significant difference in the FasL -844T/C genotypes between the patients and the control group was observed (P<0.05), with those expressing the C allele having a significantly reduced risk of developing ESCC, however elderly patients (>60 years) exhibited amoremalignant pathological grade if they were homozygous for the C allele. FasL -844 CC combined with the Fas -1377 G allele is a protective factor against ESCC. Having said this, even though the C allele has a protective effect prior to development of ESCC, once the host does develop the condition the tumour will develop faster and have a higher degree of malignancy than T carriers [ABSTRACT FROM AUTHOR]

A combinational therapeutic system that simultaneously administrates various pathways is preferred for anti-cancer treatment. In the present study, we successfully constructed a co-delivery system, multivesicular liposomes (MVLs) co-encapsulating doxorubicin (DOX) and luminespib (AUY922). A simple and accurate dual-wavelength spectrophotometric method was established for the determination of DOX and AUY922 in liposomal formulation. MVL-loading drugs were prepared by a multi-emulsion solvent evaporation method, which exhibited excellent physicochemical properties, such as particle size of 3-8 μm and high entrapment efficiency above 95% for DOX and 73% for AUY922. The synergetic cytotoxic effect for these two drugs was evaluated in MDA-MB-231 cells. The in vitro antitumor studies demonstrated the superior anti-proliferation activity of DOX and AUY922 with a combination index of 0.43, indicating a great synergistic effect. The experimental data suggested that combinational use of DOX and AUY922 within liposomes could be an effective way to develop efficient treatments of cancers. [ABSTRACT FROM AUTHOR]

To study the soil genetic diversity of bacteria and fungi in different vegetation successions (grassland, shrubbery, primary forest and secondary forest) from the karst area, the Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) technology was applied. The results showed that: (1) the diversity of bacterial communities and the fungal communities in karst area were higher than non karst area in each vegetation succession. Compared with the survey from bacterial (the Shannon index was 2.97 in primary forest, 2.91 in secondary forest, 3.18 in shrubbery, 3.14 in grassland and 2.68 in non karst), fungal diversity between karst areas (the Shannon index was 3.56 in primary forest, 3.78 in secondary forest, 3.73 in shrubbery and 3.70 in grassland) and non karst areas (the Shannon index was 3.08) was more evident, which may be related to the alterations of the composition of plant community and the source of carbon in soil with the vegetation succession of karst ecosystem; (2) The comparation of bacterial diversity index and the richness comprehensively evaluated as follows: shrubbery > grassland > primary forest > secondary forest. The diversity index and the richness of fungal communities was as follows: secondary forest > shrubbery > grassland > primary forest. The results suggest that the fungal communities have been greatly changed via vegetation successions, but the diversity index and the richness of the bacterial communities have not been seriously affected. The results provide scientific basis for understanding karst surface ecosystem, which contributes to the future aim of protecting the karst from desertification. [ABSTRACT FROM AUTHOR]

In this study, liposomes were used to decorate bacterial outer membrane vesicles (OMVs), and decorated OMVs were evaluated in vitro. The OMVs of Pseudomonas aeruginosa were extracted by pressure-induced ammonium sulfate precipitation, and their particle size, distribution, zeta potential, protein content and stability were determined. Several types of liposomes were prepared by thin film dispersion method, and the OMVs were decorated by vortexing, sonication and extrusion, respectively. The interaction between liposome and OMV was studied with fluorescence resonance energy transfer (FRET) method. The results showed that the OMVs were spherical in shape and negatively charged. The vortexing method exerted little effect on the particle size and distribution of the decorated OMVs. The sonication process reduced the particle size and distribution of OMVs. FRET experiment indicated that the OMVs were decorated through membrane fusion. The above-mentioned results indicated that liposomes could successfully decorate OMVs, and decorated OMVs certainly widened their applications. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to explore the structure-activity relationship for the new amphiphilic material rhamnoside with antibacterial biofilm activity, and provide the basis for selecting rhamnoside with the optimum antibacterial biofilm activity. A series of alkyl rhamnosides with different carbon chain lengths were obtained by a simple and effective synthesis method. The structure was characterized by H NMR spectrum, and their critical micelle concentration (CMC) was measured by fluorescence probe method. The hydrophilic and lipophilic balance (HLB) value was obtained by calculation. The minimal inhibitory concentration (MIC) of Staphylococcus aureus was determined by the broth double dilution method. The effect of biofilm inhibition and biofilm disruption was assayed by crystal violet method. The results showed that with the increase of carbon chain length, the CMC and HLB of alkyl rhamnosides displayed a linear downward trend, indicating that the lipophilicity and surface activity of the alkyl rhamnoside were increased. At the same time, the antibacterial activity in vitro produced the maximum, ie, 12-hydroxydecanoyl rhamnoside had the strongest antibacterial activity in vitro. Similarly, this material also exhibited the strongest antibacterial biofilm activity in vitro. The results of this study demonstrated that the most potent active material was obtained through the structure-activity relationship and it could be applied antibacterial biofilms in clinical practice. [ABSTRACT FROM AUTHOR]

In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly(2-ethyl- 2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) with doxorubicin (PEOz-PLA-imi-DOX) to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLA via acid cleavable benzoic imine linker and characterized by 1H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be (14.84±3.85) mg/L. The conjugate micelles (denoted as PP-DOX-PM) formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles' distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth. [ABSTRACT FROM AUTHOR]

The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2 (OCTN2) were constructed by combining carnitine conjugated poly(2 -ethyl-2-oxazoline)-poly(D,L-lactide) (Car-PEOz-PLA) with monomethoxy poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA). The structure of the synthesized Car-PEOz-PLA was confirmed by ¹H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

In this study, we developed a novel liposomal delivery system modified by Tat peptide and wheat germ agglutinin (WGA) with antimicrobial effect. Physicochemical parameters, in vitro antimicrobial, time-kill study, cellular uptake, biofilm formation inhibition and in vivo antibacterial efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Minimum inhibitory concentrations (MICs) and colony-forming units (CFUs) in the time-kill study for Tat-WGA-modified liposomal clarithromycin (CLA-TatWGALip) were lower than those of free and other modified liposomal CLA. Flow cytometry analysis disclosed that TatWGALip delivered more coumarin 6 into bacteria. Furthermore, Tat-WGA-modified liposomal CLA efficiently inhibited the formation of MRSA biofiom. CFU of MRSA in the abscess of mice treated with CLA-TatWGALip was significantly lower than that of any others (P<0.01). Collectively, liposomal delivery system modified by Tat and WGA could be a promising anti-resistant infection strategy. [ABSTRACT FROM AUTHOR]

To improve the oral absorption of poorly water-soluble drugs by overcoming the intestinal epithelium barrier, calcium carbonate nanoparticles targeting to intestine peptide transporter 1 (PepT1) were fabricated by modification of the surface of calcium carbonate nanoparticles with Gly-Sar. Gly-Sar-conjugated TPGS was successfully synthesized and characterized, and coumarin 6-loaded Gly-Sar modified calcium carbonate nanoparticles were then prepared and characterized to have a nano-scaled size of about 193 nm in diameter, cracked surface morphology under a scanning electron microscope, and high drug loading efficiency (60.5±5.9)%. Moreover, the Gly-Sar-modified calcium carbonate nanoparticles exhibited better drug loading stability during the process of their transcellular transport, and evidently enhanced intestinal absorption of poorly water-soluble agents. Therefore, the designed intestine PepT1-targeted calcium carbonate nanoparticles might have a promising potential for oral delivery of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

Corrections to the article "FasL Gene -844T/C Mutation of Esophageal Cancer in South China and Its Clinical Significance" are presented.

Ln(IO3)3 (Ln = Ce, Nd, Eu, Gd, Er, Yb) polycrystals were hydrothermally synthesized using lanthanide nitrate or lanthanide oxide and iodic add as precursors. X-ray diffraction was used to characterize the crystal structures of the Ln(IO3) 3 products. Scanning electron microscopy was carried out to observe the microscopic morphologies. The lattice spacings were studied by high-resolution transmission electron microscopy and selected area electron diffraction. We evaluated the photo-catalytic efficiency by decomposing methyl orange dye under ultraviolet light irradiation, and the Ln(IO3)3 products show excellent photocatalytic properties. To rule out the effect of photosensitization, 2,4-dichlorophenol was also photodegraded. As one of the key factors of photocatalysis, ultraviolet--visible diffuse reflectance spectra of the Ln(IO3) 3 samples were also studied, and all products have strong absorption in the ultraviolet region. [ABSTRACT FROM AUTHOR]

Accumulation of α-synuclein (a-syn) in the brain is a core feature of Parkinson disease (PD) and leads to microglial activation, produc-tion of inflammatory cytokines and chemokines, T-cell infiltration, and neurodegeneration. Here, we have used both an in vivo mouse model induced by viral overexpression of α-syn as well as in vitro systems to study the role of the MHCII complex in α-syn-induced neuroinflammation and neurodegeneration. We find that in vivo, expression of full-length human α-syn causes striking induction of MHCII expression by microglia, while knock-out of MHCII prevents α-syn-induced microglial activation, antigen presentation, IgG deposition, and the degeneration of dopaminergic neurons. In vitro, treatment of microglia with aggregated α-syn leads to activation of antigen processing and presentation of antigen sufficient to drive CD4 T-cell proliferation and to trigger cytokine release. These results indicate a central role for microglial MHCII in the activation of both the innate and adaptive immune responses to α-syn in PD and suggest that the MHCII signaling complex may be a target of neuroprotective therapies for the disease. [ABSTRACT FROM AUTHOR]