Chirality-Mediated 1D-to-2D Phase Transition in Hybrid Lead Halide Perovskites.

Dimensionality engineering plays a pivotal role in optimizing the performance, ensuring long-term stability, and expanding the versatile applications of lead halide perovskites (LHPs). Currently, the manipulation of LHP dimensions primarily occurs during the synthesis stage, a procedure hampered by constraints, including synthetic complexity and irreversibility. This investigation successfully achieved a transition from one-dimensional (1D) to two-dimensional (2D) structures in chiral LHPs by applying hydrostatic pressure. Remarkably, this pressure-induced transition in dimensionality is absent in the racemic analogue due to the staggered arrangement of inorganic chains and the elevated steric hindrance posed by the organic cations. Notably, the hydrogen bonding between organic cations and the inorganic framework adopts a symmetrical arrangement in the racemic system but a helical configuration along the 1D chain direction in the chiral counterparts. This distinct helical arrangement induces a consequential distortion in the inorganic moiety, resulting in the emergence of a spin-polarized Rashba-Dresselhaus texture that explains the chirality's electronic spin origin. Furthermore, both experimental and density functional theory calculation results demonstrate that the 1D-to-2D phase transition in chiral halide perovskites can induce significant modifications in the electronic structures and associated optical emissions. In summary, the findings unveil novel avenues for manipulating optoelectronic properties in chiral perovskites through dimensionality engineering.

Preparation and study of a capillary electrochromatographic column prepared by conjugating ß-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing ß-cyclodextrin covalent organic frameworks (ß-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10 min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26% RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERK/FOXO1 signaling.

Skeletal muscle atrophy is often found in patients with type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. As the largest tissue in the body, skeletal muscle plays important roles in insulin resistance. Advanced glycation end products (AGEs) are a type of toxic metabolite that are representative of multiple pathophysiological changes associated with T2DM. Mice were exposed to AGEs. Forkhead box O1 (FOXO1) was silenced by using a constructed viral vector carrying siRNA. Skeletal muscle atrophy was evaluated by using hematoxylin-eosin (H&E), oil red O, myosin skeletal heavy chain (MHC), and laminin immunofluorescent stains. Reactive oxygen species (ROS) generation was assessed by using the dihydroethidium (DHE) stain. Western blotting was used to evaluate protein expression and phosphorylation. Insulin resistance was monitored via the insulin tolerance test and the glucose infusion rate (GIR). Mice exposed to AGEs showed insulin resistance, which was evidenced by reduced insulin tolerance and GIR. H&E and MHC immunofluorescent stains suggested reduced cross-sectional muscle fiber area. Laminin immunofluorescent and oil red O stains indicated increased intramuscular fibrosis and lipid deposits, respectively. Exposure to AGEs induced ROS generation, increased phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and FOXO1, facilitated FOXO1 nuclear translocation, and elevated expression of muscle atrophy F-box (MAFbx) in gastrocnemius muscle. foxo1 silencing significantly suppressed skeletal muscle atrophy and insulin resistance without affecting ROS production. AGEs exacerbated skeletal muscle atrophy and insulin resistance by activating the PERK/FOXO1 signaling pathway in skeletal muscle.NEW & NOTEWORTHY In this study, we proposed a molecular mechanism underlying the skeletal muscle atrophy-associated insulin resistance in type 2 diabetes mellitus (T2DM). Our investigation suggests that exposure to AGEs, which are characteristic metabolites of T2DM pathology, induces the activation of reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, leading to the upregulation of the protein kinase RNA-like ER kinase (PERK)/forkhead box O1 (FOXO1)/muscle atrophy F-box pathway and subsequent skeletal muscle atrophy, ultimately resulting in insulin resistance.

Preparation of ß-cyclodextrin covalent organic framework-immobilized poly(glycidyl methacrylate) nanoparticle-coated open tubular capillary electrochromatography column for chiral separation.

A new enantioselective open-tubular capillary electrochromatography was developed employing poly(glycidyl methacrylate) nanoparticles/ß-cyclodextrin covalent organic frameworks chemically immobilized on the inner wall of the capillary as a stationary phase. A pretreated silica-fused capillary reacted with 3-aminopropyl-trimethoxysilane followed by poly(glycidyl methacrylate) nanoparticles and ß-cyclodextrin covalent organic frameworks through a ring-opening reaction. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The electroosmotic flow was studied to evaluate the variation of the immobilized columns. The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. The influences of bonding concentration, bonding time, bonding temperature, buffer type and concentration, buffer pH, and applied voltage on the enantioseparation of four proton pump inhibitors were investigated. Good enantioseparation efficiencies were achieved for all enantiomers. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5-13.9. The column-to-column and inter- to intra-day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns.

ß-Cyclodextrin covalent organic framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation.

In this work, a new open-tubular capillary electrochromatography (OT-CEC) column was prepared using ß-cyclodextrin covalent organic framework (ß-CD COF) as a stationary phase. Polydopamine was used to assist fabrication of ß-CD COF on an inner wall of a fused-silica capillary. The coating layer on the capillary was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electroosmotic flow (EOF) was also studied to evaluate the variation of the inner wall of immobilized columns. Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by CEC using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The effects of bonding time and concentration of ß-CD COF, the type, concentration and pH of buffer, applied voltage were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of four analytes were resolved within 15 min with resolutions of 1.63-2.62. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75% and 4.24%, respectively. The results reveal that ß-CD COF has great potential as chiral-stationary phases for enantioseparation in CEC.

Sex effects on clinical features in LRRK2 G2385R carriers and non-carriers in Parkinson's disease.

BACKGROUND: Differences of genotypes between male and female have been studied in Parkinson's disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant. OBJECTIVE: The aim of this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD. METHODS: 613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex. RESULTS: Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135-0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167-0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361-0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228-0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428-0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078-2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102-0.849) compared with male. CONCLUSION: In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.

Ultrafast photophysical process of bi-exciton Auger recombination in CuInS2 quantum dots studied by transient-absorption spectroscopy.

Auger recombination is an ultrafast and unnegligible photophysical process in colloidal semiconductor quantum dots (QDs) due to competition with charge separation or radiative recombination processes, pivotal for their applications ranging from bio-labeling, light-emitting diodes, QD lasing to solar energy conversion. Among diverse QDs, ternary chalcopyrite is recently receiving significant attention for its heavy-metal free property and remarkable optical performance. Given deficient understanding of the Auger process for ternary chalcopyrite QDs, CuInS2 QDs with various sizes are synthesized as a representative and the bi-exciton lifetime (τBX) is derived by virtue of ultrafast time resolved absorption spectrum. The trend of τBX varying with size is consistent with the universal scaling of τBX versus QD volume (V): τBX = γV. The scaling factor γ is 6.6 ± 0.5 ps·nm-3 for CuInS2 QDs, and the bi-exciton Auger lifetime is 4-5 times slower than typical CdSe QDs with the same volume, suggesting reduced Auger recombination rate in ternary chalcopyrite. This work facilitates clearer understanding of Auger process and provides further insight for rational design of light-harvesting and emitting devices based on ternary chalcopyrite QDs.

Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity.

BACKGROUND: The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. METHODS: ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. RESULTS: ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19. CONCLUSION: These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.

Preparation of a polydopamine/ß-cyclodextrin coated open tubular capillary electrochromatography column and application for enantioseparation of five proton pump inhibitors.

An open tubular capillary electrochromatography column was prepared by immobilizing ß-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of ß-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/ß-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency.

P2X7R promotes angiogenesis and tumour-associated macrophage recruitment by regulating the NF-κB signalling pathway in colorectal cancer cells.

Overexpression of P2X7R has been observed in several tumours and is related to cancer advancement and metastasis. However, the role of P2X7R in colorectal cancer (CRC) patients is not well understood. In the current study, overexpression of P2X7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2X7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry. In this study, we found that overexpression of P2X7R increases in the in vivo growth of tumours. P2X7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2X7R up-regulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumour cells with P2X7R overexpression stimulated cytokines to recruit tumour-associated macrophage (TAMs) to increase the growth of tumours. We also found that the NF-κB signalling pathway is involved in P2X7R-induced cytokine up-regulation. P2X7R promotes NF-κB-dependent cytokine induction, which leads to TAM recruitment to control tumour growth and advancement and remodelling of the stroma. Our findings demonstrate that P2X7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.

Total Structure Determination of the Largest Alkynyl-Protected fcc Gold Nanocluster Au110 and the Study on Its Ultrafast Excited-State Dynamics.

Great attention has been paid to nanoclusters having face-centered-cubic (fcc) metal kernels, because of the similarity of metal packing to that of bulk gold. So far, there is no precedent example of an all-alkynyl-protected fcc gold nanocluster with more than 100 gold atoms. We report the synthesis and total structure determination of an alkynyl-protected gold nanocluster [NEt3H]2[Au110(p-CF3C6H4C≡C)48] (Au110). It has an fcc Au86 kernel with 24 peripheral Au(C≡CR)2 staples. The Au86 kernel consists of six close packing layers in the pattern of Au6:Au16:Au21:Au21:Au16:Au6. Electronic absorption spectroscopy shows Au110 has a molecular-like discrete electronic structure, and transient absorption experiments reveal its nonmetallic nature.

Midbrain/pons area ratio and clinical features predict the prognosis of progressive Supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.

Baicalin Suppresses Bilirubin-Induced Apoptosis and Inflammation by Regulating p38 Mitogen-Activated Protein Kinases (MAPK) Signaling in Neonatal Neurons.

BACKGROUND Hyperbilirubinemia is associated with central nervous system damage in preterm neonates due to the neurotoxicity of bilirubin. This study explored the possible mechanisms of bilirubin's neurotoxicity, and the protective effect of baicalin (BAI) was also investigated. MATERIAL AND METHODS Isolated neonatal rat hippocampal neurons were exposed to free bilirubin (Bf). BAI was used to treat these neurons. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cell viability. Terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay was used to detect apoptosis. Contents of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Protein expression and phosphorylation levels were assessed by Western blotting. Nuclear translocation was observed by immunofluorescent staining. RESULTS Bf incubation significantly induced apoptosis and decreased viabilities of neurons. The phosphorylation levels of MAP kinase kinase (MKK)3, MKK6, p38 mitogen- activated protein kinases (MAPK), nuclear translocation level of p65, and the expression levels of cleaved caspase3 and tumor necrosis factor (TNF)alpha were found to be dramatically higher in Bf-incubated neurons. BAI pre-treatment, however, increased cell viability by reducing cell apoptosis. BAI pre-treatment also reduced phosphorylation levels of MKK3, MKK6, p38 MAPK, and nuclear translocation level of p65, as well as the expression levels of cleaved caspase3 and TNFalpha, in Bf- incubated neurons. CONCLUSIONS BAI suppressed bilirubin-induced neuron apoptosis and inflammation by deactivating p38 MAPK signaling.

Serum soluble lymphocyte activation gene-3 as a diagnostic biomarker in Parkinson's disease: A pilot multicenter study.

OBJECTIVE: Lymphocyte activation gene-3 (LAG-3) could mediate pathological α-synuclein transmission in neurodegeneration and may be involved in the pathogenesis of Parkinson's disease (PD). The aim of the present study was to explore soluble LAG-3 (sLAG-3) as a potential diagnostic biomarker for PD. METHODS: Serum sLAG-3 concentrations were measured by a quantitative ELISA for patients with PD, essential tremor (ET) and age- and sex-matched controls. The relationships between sLAG-3 and clinical phenotype were assessed via correlation analysis and logistic regression. RESULTS: Serum sLAG-3 levels in patients with PD were significantly higher than those in ET patients and age- and sex-matched controls. The area under the curve of serum sLAG-3 in differentiating PD from age- and sex-matched controls was 0.82. Serum sLAG-3 was associated with non-motor symptoms and excessive daytime sleep. CONCLUSION: sLAG-3 is a candidate novel biomarker for PD. © 2018 International Parkinson and Movement Disorder Society.

Association Between the Lipid Profile and Renal Dysfunction in the Heart Failure Patients.

BACKGROUND/AIMS: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. METHODS: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. RESULTS: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). CONCLUSION: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Asymmetrical damage growth of multilayer dielectric gratings induced by picosecond laser pulses.

We experimentally investigated the laser damage growth behavior of multilayer dielectric gratings (MLDGs) by the picosecond pulses at 1053nm. The damage growth threshold of 2.43J/cm2 is significantly lower than the 20/1 damage threshold of 3.06 J/cm2. Once the damage site is initiated, the damage area grows linearly with shot number and saturates after sufficient shots due to the Gaussian spot. The barycenter of the growing damage site deviates from the laser spot center and their distance increases with the shot number, which indicates the asymmetry of the damage growth along the laser propagation axis. The growth rate of the damage site along the laser propagation direction is larger than that in the reverse direction by a factor of ~1.8 for various fluences. The comparison of the experimental and numerical results reveals that the asymmetrical intensity modulation induced by the damage sites causes the asymmetry in growth. The revealed characteristics and mechanisms of the damage growth can be of great significance to predict the lifetime of the MLDGs in high-power laser systems.

Novel ASK1 Inhibitor AGI-1067 Attenuates AGE-Induced Fibrotic Response by Suppressing the MKKs/p38 MAPK Pathway in Human Coronary Arterial Smooth Muscle Cells.

The phenotype shifting of vascular smooth muscle cells (VSMCs) was indicated to play a role during the initial stage of atherosclerotic plaque formation by facilitating extracellular matrix deposition. This study was aimed at investigating the involvement of the apoptosis signal-regulating kinase 1 (ASK1) /mitogen-activated protein kinase (MAPK) kinases (MKKs) /p38 MAPK pathway in the advanced glycation end product (AGE) -induced fibrotic response of VSMCs. The effect of the novel ASK1 inhibitor AGI-1067 was also studied.Cultured human coronary smooth muscle cells (HCSMCs) were exposed to AGEs. AGI-1067 and siRNAs silencing mkk3, mkk6, and p38 mapk were used to treat the cells. The activation of MKK3, MKK6, and p38 MAPK was assessed by immunoblotting. Fibrotic response was assessed by the fluorescence immunohistochemistry staining of collagen I and collagen VIII. Activation of immunoprecipitation determined the association of ASK1 and its inhibitor thioredoxin. A kinase assay was used to determine ASK1 activity.AGE incubation significantly activated ASK1, MKK3, and MKK6, which led to activation of p38 MAPK, resulting in upregulated fibrotic response in HCSMCs. However, siRNAs knocking down mkk3, mkk6, and p38 mapk impaired this fibrotic response. AGI-1067 administration not only dramatically inhibited the activation of ASK1/MKKs/p38 MAPK but also suppressed the expression of the downstream proteins, including transforming growth factor-ß1, connective tissue growth factor, collagen I, and collagen VIII in HCSMCs exposed to AGEs.The ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to the fibrotic response in VSMCs. AGI-1067 reversed this process by maintaining the inactive state of ASK1.

WITHDRAWN: JIP3 deficiency protects mice from high fat diet-induced liver injury.

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Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. CASE PRESENTATION: A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. CONCLUSION: The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

Kinetics of volatile impurity removal from silicon by electron beam melting for photovoltaic applications.

A full domain control model is established for impurity transportation in the liquid phase, gas-liquid interface and gas phase of silicon to analyze the dynamic mechanics of impurity removal. The results show that the overall mass transfer coefficient mainly depends on the temperature and the chamber pressure. Its value increases with the increase of temperature or the decrease of chamber pressure. Under the same melting condition, the order of the overall mass transfer coefficients for P, Al and Ca is kP > kAl > kCa, indicating that P is easier to remove by evaporation. Mass transfer in the gas phase is the rate-controlling step for volatile impurity removal at the temperature above the melting point of silicon. The rate-controlling step transits to evaporation on the gas-liquid interface then to mass transfer in the liquid boundary layer as the temperature increases. During electron beam melting, the removal of P is controlled by both evaporation on the gas-liquid interface and mass transfer in the liquid boundary layer, and the removal of Al and Ca is controlled by evaporation on the gas-liquid interface.