Pharmacogenetic study of methadone treatment for heroin addiction: associations between drug-metabolizing gene polymorphisms and treatment efficacy.

OBJECTIVES: Opioid dependence is currently one of the most serious problems affecting the social norms and public health system. Methadone maintenance therapy (MMT) is being widely used in treating heroin-dependent patients. The mechanism of methadone metabolism and disposition has been shown to involve cytochrome P450 (CYP450) and P-glycoprotein. The aim of this study was to explore the relationships among genetic polymorphisms, BMI and effective dose of methadone used in MMT within a northern Taiwan cohort. METHODS: One hundred heroin-dependent patients were enrolled in the study. The clinical data gathered included methadone dose, sex and BMI. DNA was collected from the oral swab of the participants to analyze the relevant alleles. RESULTS: An effective methadone dose correlated with sex, BMI and the presence of ABCB1 2677GG (rs2032582) and CYP2B6 516GG (rs374527). Furthermore, the CYP2B6 516GG homozygote was related to a higher average dose of methadone (GG: 68.50 ± 32.43; GT: 52.28 ± 25.75; TT: 44.44 ± 29.64; P < 0.02), whereas the ABCB1 2677GG homozygote was related to a lower dose (GG: 51.09 ± 20.83; GT: 69.65 ± 37.51; TT: 62.52 ± 30.44; P < 0.05). We examined the predictive effect of polymorphisms combined with sex and BMI on methadone dose by conducting multiple linear regressions. Our data predicted the average dose of methadone in approximately 30% of heroin-dependent patients. CONCLUSION: The interactions between genetic polymorphisms and clinical features proved useful in identifying the effective dose of MMT for heroin-dependent patients in Taiwan more precisely.

The Therapeutic Effect of Acanthopanax senticosus Components on Radiation-Induced Brain Injury Based on the Pharmacokinetics and Neurotransmitters.

Acanthopanax senticosus (AS) is a medicinal and food homologous plant with many biological activities. In this research, we generated a brain injury model by 60Co -γ ray radiation at 4 Gy, and gavaged adult mice with the extract with AS, Acanthopanax senticocus polysaccharides (ASPS), flavones, syringin and eleutheroside E (EE) to explore the therapeutic effect and metabolic characteristics of AS on the brain injury. Behavioral tests and pathological experiments showed that the AS prevented the irradiated mice from learning and memory ability impairment and protected the neurons of irradiated mice. Meanwhile, the functional components of AS increased the antioxidant activity of irradiated mice. Furthermore, we found the changes of neurotransmitters, especially in the EE and syringin groups. Finally, distribution and pharmacokinetic analysis of AS showed that the functional components, especially EE, could exert their therapeutic effects in brain of irradiated mice. This lays a theoretical foundation for the further research on the treatment of radiation-induced brain injury by AS.

CNTs-CaP/chitosan-coated AZ91D magnesium alloy extract promoted rat dorsal root ganglia neuron growth via activating ERK signalling pathway.

Increasing attention has been paid on the application of biodegradable materials such as magnesium and its alloys in neuron repair. AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated in this study. To evaluate the bioactivity of these AZ91D-based composites, the extracts were prepared by immersing samples in modified simulated body fluid (m-SBF) for 0, 2, 8, 16, 24, 34, 44, 60, or 90 days. Immunofluorescence staining for neuronal class III ß-tubulin (TUJ1) revealed that both CNTs-CaP/CS-AZ91D and CaP/CS-AZ91D extracts promoted axon outgrowth of dorsal root ganglia (DRG) neurons, accompanied with increased expression of phosphorylated focal adhesion kinase (p-FAK) and growth associated protein-43 (GAP-43). Besides, the extracts increased the expression and the release of neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). ERK signalling was activated in DRG neurons after treating with either CNTs-CaP/CS-AZ91D or CaP/CS-AZ91D extracts, and its inhibition with U0126 counteracted the beneficial effects of these extracts on DRG neuron. Overall, the extracts from these AZ91D-based composites might promote DRG neuron growth via activating ERK signalling pathway. Notably, CNTs-CaP/CS-AZ91D extracts showed a better promoting effect on neuron growth than CaP/CS-AZ91D. Assessment of ion elements showed that the addition of CNTs coating enhanced magnesium corrosion resistance and reduced the deposition of calcium and phosphorus on the surface of CaP/CS-AZ91D alloy. These findings demonstrate that CNTs-CaP/CS-AZ91D likely provide a more suitable environment for neuron growth, which suggests a potential implantable biomaterial for the treatment of nerve injury. SIGNIFICANCE: AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated and their immersion extracts were prepared using modified simulated body fluid in this study. Both extracts from CNTs-CaP/CS and CaP/CS-coated AZ91D magnesium alloy promotes rat dorsal root ganglia (DRG) neuron growth via activating ERK signalling pathway. Notably, the addition of CNTs improves the performance of CaP/CS-AZ91D. For the first time, our research demonstrates that CNTs-CaP/CS-AZ91D likely provide a suitable environment for neuron growth, suggesting these AZ91D-based composites as potential implantable biomaterials for the treatment of nerve injury.

Photocatalytic conversion of ethylenediaminetetraacetic acid dissolved in real electroplating wastewater to hydrogen in a solar light-responsive system.

A sustainable and multifunctional photocatalysis-based technology has been established herein for simultaneous hydrogen generation and oxidation of ethylenediaminetetraacetic acid (EDTA) in real electroplating wastewater. When the photocatalyst concentration was 4 g/L and electroplating wastewater pH was 6, optimal adsorptions of EDTA2-, H+, and H2O were observed, while hydrogen generation efficiency reached 305 µmol/(h g). Owing to EDTA oxidation and occupation of the active sites of the photocatalyst by Ni ions or Ni-EDTA chelates, the charge separation and adsorptions of H+ and H2O decreased, reducing hydrogen generation efficiency with time. The lower EDTA and Ni concentrations in treated wastewater showed that photocatalytic conversion of EDTA in real electroplating wastewater to enhance hydrogen generation efficiency can be a practical alternative energy production technology. This study provided a novel idea to enhance the value of electroplating wastewater, to build a hydrogen generation route with no consumption of a valuable resource, and to reduce EDTA and Ni concentrations in electroplating wastewater.

Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone.

BACKGROUND: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. METHODS: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. RESULTS: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. CONCLUSION: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

Vascular smooth muscle cell differentiation to an osteogenic phenotype involves matrix metalloproteinase-2 modulation by homocysteine.

Arterial calcification is common in vascular diseases and involves conversion of vascular smooth muscle cells (VSMCs) to an osteoblast phenotype. Clinical studies suggest that the development of atherosclerosis can be promoted by homocysteine (HCY), but the mechanisms remain unclear. Here, we determined whether increases in HCY levels lead to an increase in VSMC calcification and differentiation, and examined the role of an extracellular matrix remodeler, matrix metalloproteinase-2 (MMP-2). Rat VSMCs were exposed to calcification medium in the absence or presence of HCY (10, 100 or 200 µmol/L) or an MMP-2 inhibitor (10(-6) or 10(-5) mol/L). MTT assays were performed to determine the cytotoxicity of the MMP-2 inhibitor in calcification medium containing 200 µmol/L HCY. Calcification was assessed by measurements of calcium deposition and alkaline phosphatase (ALP) activity as well as von Kossa staining. Expression of osteocalcin, bone morphogenetic protein (BMP)-2, and osteopontin, and MMP-2 was determined by immunoblotting. Calcification medium induced osteogenic differentiation of VSMCs. HCY promoted calcification, increased osteocalcin and BMP-2 expression, and decreased expression of osteopontin. MMP-2 expression was increased by HCY in a dose-dependent manner in VSMCs exposed to both control and calcification medium. The MMP-2 inhibitor decreased the calcium content and ALP activity, and attenuated the osteoblastic phenotype of VSMCs. Vascular calcification and osteogenic differentiation of VSMCs were positively regulated by HCY through increased/restored MMP-2 expression, increased expression of calcification proteins, and decreased anti-calcification protein levels. In summary, MMP-2 inhibition may be a protective strategy against VSMC calcification.

Inhibition of TRPM7 Attenuates Rat Aortic Smooth Muscle Cell Proliferation Induced by Angiotensin II: Role of Genistein.

Transient receptor potential melastatin 7 (TRPM7) is a Ca, Mg permeable nonselective cation channel of the TRP channel superfamily and plays an important role in cell growth and proliferation. Compounds that alter the activity and expression of the channel protein might be of therapeutic interest. In this study, we investigated the effects of genistein on TRPM7 channels and the proliferation of rat aortic smooth muscle cells (RAoSMCs). In primary cultured RAoSMCs, acute genistein (50 µM) exposure inhibited native TRPM7 currents, whereas chronic expose to genistein (50 µM) downregulated TRPM7 protein expression. The downregulation of TRPM7 protein expression induced by genistein was mimicked by c-Src inhibitor (PP2), but not by epidermal growth factor receptor tyrosine kinase inhibitor (lavendustin A), or daidzein. Additionally, genistein (50 µM) attenuated angiotensin II-induced cell proliferation. This study is the first to demonstrate inhibition of TRPM7 by isoflavone genistein through c-Src tyrosine kinase inhibition in RAoSMCs. Our results not only provide a new modulation mechanism of TRPM7 but also suggest that TRPM7 may serve as a new therapeutic target of genistein in the treatment of vascular diseases.

Molecular characterization of the full-length L and M RNAs of Tomato yellow ring virus, a member of the genus Tospovirus.

Tomato yellow ring virus (TYRV), first isolated from tomato in Iran, was classified as a non-approved species of the genus Tospovirus based on the characterization of its genomic S RNA. In the current study, the complete sequences of the genomic L and M RNAs of TYRV were determined and analyzed. The L RNA has 8,877 nucleotides (nt) and codes in the viral complementary (vc) strand for the putative RNA-dependent RNA polymerase (RdRp) of 2,873 amino acids (aa) (331 kDa). The RdRp of TYRV shares the highest aa sequence identity (88.7 %) with that of Iris yellow spot virus (IYSV), and contains conserved motifs shared with those of the animal-infecting bunyaviruses. The M RNA contains 4,786 nt and codes in ambisense arrangement for the NSm protein of 308 aa (34.5 kDa) in viral sense, and the Gn/Gc glycoprotein precursor (GP) of 1,310 aa (128 kDa) in vc-sense. Phylogenetic analyses indicated that TYRV is closely clustered with IYSV and Polygonum ringspot virus (PolRSV). The NSm and GP of TYRV share the highest aa sequence identity with those of IYSV and PolRSV (89.9 and 80.2-86.5 %, respectively). Moreover, the GPs of TYRV, IYSV, and PolRSV share highly similar characteristics, among which an identical deduced N-terminal protease cleavage site that is distinct from all tospoviral GPs analyzed thus far. Taken together, the elucidation of the complete genome sequence and biological features of TYRV support a close ancestral relationship with IYSV and PolRSV.

The effect of limited proteolysis by different proteases on the formation of whey protein fibrils.

Four proteases: trypsin, protease A, pepsin, and protease M were selected to modify whey protein concentrate (WPC) at a low degree of hydrolysis (0.1, 0.2, and 0.3%) before adjusting to pH 2.0 and heating at 90°C to gain insight into the influence of proteolysis on fibril formation. The kinetics of fibril formation were performed on native and modified WPC using the fluorescent dye thioflavin T in conjunction with transmission electron microscopy and far-UV circular dichroism spectroscopy for the morphological and secondary structural analyses. The change in surface hydrophobicity and content of free sulfhydryl groups were also observed during the formation of fibrils for the native and modified WPC. The content of aggregation and thioflavin T kinetic data indicated that the ability of fibril formation was apparently different for WPC modified by the 4 proteases. Whey protein concentrate modified by trypsin aggregated more during heating and the fibril formation rate was faster than that of the native WPC. Whey protein concentrate modified by the other proteases showed slower aggregation with worse amyloid fibril morphology. Compared with the native WPC, the structure of WPC changed differently after being modified by proteases. The state of α-helix structure for modified WPC played the most important role in the formation of fibrils. Under the mild conditions used in this work, the α-helix structure of WPC modified by trypsin caused little destruction and resulted in fibrils with good morphology; the content of α-helices for WPC modified by other proteases decreased to 36.19 to 50.94%; thus, fibril formation was inhibited. In addition, it was beneficial for the modified WPC to form fibrils such that the surface hydrophobicity increased and the content of free sulfhydryl groups slightly decreased during heating.

Low MHR Is Associated with Hemorrhagic Transformation in Acute Large Artery Atherosclerosis Ischemic Stroke Patients with Intravenous Thrombolysis.

Background: Hemorrhagic transformation (HT) is a common complication of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) and may lead to neurological deterioration. This article discusses whether monocyte count to high-density lipoprotein ratio (MHR) level is associated with HT in AIS patients. Materials and methods: The clinical data of AIS patients who underwent rt-PA IVT treatment were continuously collected. According to whether HT occurred, patients were divided into HT group and non-HT group. Potential association between MHR and HT in different subtypes AIS was explored by using logistic regression. Results: A total of 444 AIS patients were retrospective analyzed. The MHR level was lower in HT group compared with the non-HT group in all AIS patients (0.28 vs 0.36, P = .031) and in large-artery atherosclerosis (LAA) type AIS patients (0.31 vs 0.37, P = .032). Low MHR was independently related to HT (OR:0.035, 95%CI:0.003-0.390, P = .006). Among all TOAST subtypes, low MHR was only independently associated with HT in patients of LAA-type AIS after adjusting for confounding factors (OR:0.01, 95%CI:0.00-0.62, P = .031), with an optimal cut-off value of 0.41, sensitivity of 85.7%, and specificity of 43.1%. MHR was not correlated with SVO, VE, and CE subtype AIS. Conclusion: Low MHR may be an independent predictor of HT in patients with AIS and this conclusion only existed in LAA-type AIS.

Target-independent hybridization chain reaction-fluorescence resonance energy transfer for sensitive assay of ctDNA based on Cas12a.

Circulating tumor DNA (ctDNA) is a noninvasive biomarker which offer valuable information for cancer diagnosis and prognosis. In this study, a target-independent fluorescent signal system, Hybridization chain reaction-Fluorescence resonance energy transfer (HCR-FRET) system, is designed and optimized. Combined with CRISPR/Cas12a system, a fluorescent biosensing protocol was developed for sensing assay of T790 M. When the target is absent, the initiator remains intact, opens the fuel hairpins and triggers the following HCR-FRET. At presence of the target, the Cas12a/crRNA binary complex specifically recognizes the target, and the Cas12a trans-cleavage activity is activated. As a result, the initiator is cleaved and subsequent HCR responses and FRET processes are attenuated. This method showed detection range from 1 pM to 400 pM with a detection limit of 316 fM. The target independent property of the HCR-FRET system endows this protocol a promising potential to transplant to the assay of other DNA target in parallel.

Synergetic effect of ß-asarone and cannabidiol against Aß aggregation in vitro and in vivo.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer's disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining ß-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aß) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aß40 aggregates in the presence of ß-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like ß-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.

Metagenomics insights into high-rate nitrogen removal from municipal wastewater by integrated nitrification, partial denitrification and Anammox at an extremely short hydraulic retention time.

To achieve high-rate nitrogen removal in municipal wastewater treatment through anaerobic ammonia oxidation (Anammox), the nitrification, partial denitrification, and Anammox processes were integrated by a step-feed strategy. An exceptional nitrogen removal load of 0.224 kg N/(m3·d) was achieved by gradient-reducing the hydraulic retention time (HRT) to 5 h. Metagenomic analysis demonstrated that Nitrosospira could express all genes encoding ammonia oxidation under low nitrogen and dissolved oxygen conditions (less than 0.5 mg/L), enabling complete nitrification. With the short of HRT, the relative abundance of Thauera increased from 2.8 % to 6.4 %. Frequent substrate exchanges at such extremely short HRT facilitated enhanced synergistic interactions among Nitrosospira, Thauera, and Candidatus Brocadia. These findings provide a comprehensive understanding of the utilization of Anammox combined processes for high-speed nitrogen removal in municipal wastewater treatment and the microbial interactions involved.

Acanthopanax senticosus extract alleviates radiation-induced learning and memory impairment based on neurotransmitter-gut microbiota communication.

BACKGROUND: Acanthopanax senticosus (AS) is a medicinal and food plant with many physiological functions, especially nerve protection. Its extract has many functional components, including polysaccharides, flavonoids, saponins, and amino acids. Our previous study indicated that AS extract protected against nerve damage caused by radiation. However, little is known about the gut-brain axis mechanism of AS and its impact on radiation-induced learning and memory impairment. METHOD: In 60 Co-γ ray-irradiated mice, we investigated the changes in behavior, neurotransmitters and gut microbiota after different days of administration of AS extract as a dietary supplement. RESULTS: The AS extract improved learning and memory ability in mice, and the neurotransmitter levels in the hippocampus and colon started to change from the 7th day, which accompanied changes of the gut microbiota, a decreased abundance of Helicobacter on the 7th day and an increased abundance of Lactobacillus on the 28th day. Among the marker bacteria, Ruminococcus and Clostridiales were associated with 5-HT synthesis, and Streptococcus were associated with 5-HT and ACH synthesis. In addition, the AS extract increased the tight junction protein, inhibited inflammation levels in colon, and even increased the relative protein expression of BDNF and NF-κB and decreased the relative protein expression of IκBα in the hippocampus of irradiated mice. CONCLUSION: These results will lay the foundation for further study on the mechanism of the gut-brain axis of AS in preventing radiation-induced learning and memory impairment.

Sequential deacetylation/self-gelling chitin hydrogels and scaffolds functionalized with fucoidan for enhanced BMP-2 loading and sustained release.

Bone morphogenetic protein 2 (BMP-2) is a potent osteoinductive factor that promotes bone formation. A major obstacle to the clinical application of BMP-2 is its inherent instability and complications caused by its rapid release from implants. Chitin based materials have excellent biocompatibility and mechanical properties, making them ideal for bone tissue engineering applications. In this study, a simple and easy method was developed to spontaneously form deacetylated ß-chitin (DAC-ß-chitin) gels at room temperature through a sequential deacetylation/self-gelation process. The structural transformation of ß-chitin to DAC-ß-chitin leads to the formation of self-gelling DAC-ß-chitin, from which hydrogels and scaffolds were prepared. Gelatin (GLT) accelerated the self-gelation of DAC-ß-chitin and increased the pore size and porosity of the DAC-ß-chitin scaffold. The DAC-ß-chitin scaffolds were then functionalized with a BMP-2-binding sulfate polysaccharide, fucoidan (FD). Compared with ß-chitin scaffolds, FD-functionalized DAC-ß-chitin scaffolds showed higher BMP-2 loading capacity and more sustainable release of BMP-2, and thus had better osteogenic activity for bone regeneration.

Activation of propane C-H and C-C bonds by gas-phase Pt atom: a theoretical study.

The reaction mechanism of the gas-phase Pt atom with C(3)H(8) has been systematically investigated on the singlet and triplet potential energy surfaces at CCSD(T)//BPW91/6-311++G(d, p), Lanl2dz level. Pt atom prefers the attack of primary over secondary C-H bonds in propane. For the Pt + C(3)H(8) reaction, the major and minor reaction channels lead to PtC(3)H(6) + H(2) and PtCH(2) + C(2)H(6), respectively, whereas the possibility to form products PtC(2)H(4) + CH(4) is so small that it can be neglected. The minimal energy reaction pathway for the formation of PtC(3)H(6) + H(2), involving one spin inversion, prefers to start at the triplet state and afterward proceed along the singlet state. The optimal C-C bond cleavages are assigned to C-H bond activation as the first step, followed by cleavage of a C-C bond. The C-H insertion intermediates are kinetically favored over the C-C insertion intermediates. From C-C to C-H oxidative insertion, the lowering of activation barrier is mainly caused by the more stabilizing transition state interaction ΔE(≠) (int), which is the actual interaction energy between the deformed reactants in the transition state.

Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota.

Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the 60Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.

A toehold-mediated strand displacement cascade-based DNA assay method via flow cytometry and magnetic separation.

Sensitive assay of EGFR T790M, a circulating tumor DNA marker in non-small-cell carcinoma, provides critical information for the decision of clinical treatments, evaluation of radiotherapy effect, and monitoring the progress of recurrence and metastasis. In this report, a novel flow cytometry-based sensing method is proposed for detecting T790M. The toehold-sequence hybridizes with the biotin-labeled initiator sequence and forms IT-dsDNA. The presence of a target induces the displacement of initiator-sequence from IT-dsDNA. The targets are continuously set free with the aid of a helper hairpin sequence for the next cycle. In tandem, the free initiator sequence starts the hybridization chain reaction, which binds the serial of fluorescence-labeled probe sequences. The products of the hybridization chain reaction are captured and separated by magnetic beads, which are finally assayed via flow cytometry. The capability to distinguish single-nucleotide polymorphism and the tolerance of complex matrix in blood serum indicate that this strategy has the promising potential to be applied in the liquid biopsy of clinical samples.

Decreased Netrin-1 in Mild Cognitive Impairment and Alzheimer's Disease Patients.

BACKGROUND AND OBJECTIVE: Inflammatory mediators are closely associated with the pathogenesis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Netrin-1 is an axon guidance protein and despite its capacity to function as a neuroimmune guidance signal, its role in AD or MCI is poorly understood. In addition, the association among netrin-1, cognitive impairment and serum inflammatory cytokines such as interleukin-17 (IL-17) and tumor necrosis (TNF-α) remains unclear. The aim of this study was to determine serum levels of IL-17, TNF-α and netrin-1in a cohort of AD and MCI patients, and to study the relationship between these cytokines and cognitive status, as well as to assess the possible relationships between netrin-1 levels and inflammatory molecules. METHODS: Serum concentrations of netrin-1, TNF-α and IL-17 were determined in 20 AD patients, 22 MCI patients and 22 healthy controls using an enzyme-linked immunosorbent assay (ELISA). In addition, neuropsychological evaluations and psychometric assessments were performed in all subjects. RESULTS: Serum netrin-1 levels were decreased in AD and MCI patients and were positively correlated with Mini Mental State Examination (MMSE) scores. In contrast, serum TNF-α and IL-17 levels were elevated in AD and MCI cohorts and negatively correlated with MMSE scores. Serum netrin-1 levels were inversely related with TNF-α and IL-17 levels in AD, but not MCI, patients. CONCLUSION: Based on the findings reported here, netrin-1 may serve as a marker for the early recognition of dementia and predict cognitive impairment.

In situ phase transformation of polytypic zinc-blende/wurtzite copper indium sulfide via a facile polyol method to boost visible-light photocatalytic performance.

A zinc-blende/wurtzite (ZB/WZ) copper indium sulfide (CuInS2/CIS) polymorph with high visible-light absorption ability and high charge separation rate was developed by using a facile polyol method. Results showed that when thioacetamide served as a sulfur precursor, the crystalline phase of CIS was zinc-blende. Meanwhile, when thiourea served as a sulfur precursor, the crystalline phase of CIS was wurtzite, which exhibited good photocatalytic acid red 1 (AR1) dye decolorization efficiency. When the precursor/ethylene glycol ratio was 1/50-7/50, the AR1 decolorization efficiency followed the order: T-5-CIS > T-7-CIS > T-3-CIS > T-1-CIS, and the TOC removal efficiency of T-5-CIS was 45.7%. The PL and EIS analyses indicated that T-5-CIS showed the highest charge separation rate. Mott-Schottky analysis demonstrated that the remarkably enhanced photocatalytic decolorization rate was ascribed to the stronger reduction potential of CIS with the mixed ZB/WZ phases and the redox potential difference between the ZB and WZ phases, leading to a good oxidation ability and charge separation. The results indicated that O2- was the main reactive specie in this study, and this study provided a potential photocatalyst in the treatment of dye wastewater.