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Objective The objective of this study was to assess the incidence and risk factors of major adverse cardiovascular events (MACEs) in patients with systemic sclerosis (SSc). Methods We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1379 patients with SSc and 2758 non-SSc individuals in the analysis. We assessed the association between SSc and MACEs, using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates, and investigated risk factors for MACEs in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% CIs. Results SSc was not significantly associated with the risk of MACEs (aHR 1.04; 95% CI 0.77–1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction [incidence rate ratio (IRR) 1.76; 95% CI 1.08–2.86] and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84–4.74) but not of ischaemic stroke (IRR 0.89; 95% CI 0.61–1.29). Factors independently associated with MACEs in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), RA (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31). Conclusions The risk of MACEs was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACEs in SSc patients. Additionally, patients with SSc exhibited higher risks of myocardial infarction and peripheral arterial occlusion disease but not of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. Methods: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. Results: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01–0.12, p = 0.016; right, 0.09, 95% CI 0.04–0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02–0.15, p = 0.008; right, 0.11, 95% CI 0.05–0.18, p = 0.001). Conclusion: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs. [ABSTRACT FROM AUTHOR]

The stabilities of hafnium and zirconium oxide ferroelectric orthorhombic phases, oIII-phase (Pca21) and oIV-phase (Pmn21), under shear strain are investigated theoretically by atomic modeling with density functional theory calculations. The results indicate that oIV-phase serves as a buffer state preventing oIII-phase from transforming into m-phase (P21/c) under structural distortion caused by shear strain and meanwhile preserves the remanent polarization to some certain degree. Shear strain will also induce the reduction in coercive field of the HZO film due to the distortion of oIII-phase or phase transition into oIV-phase. It is very possible to identify oIV-phase with careful analysis of high-resolution transmission electron microscopy and high-angle annular dark-field STEM images at the region having a crystal tilt angle smaller than 86°. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between appendicitis and the risk of systemic lupus erythematosus (SLE). Methods: Using claims data from the 2003–2013 Taiwanese National Health Insurance Research Database, we selected 6054 patients with newly diagnosed SLE from 2007 to 2012 and 36,324 age-, sex- and year of SLE diagnosis date-matched (1:6) non-SLE controls. After controlling for potential confounders, a multivariable conditional logistic regression model was used to calculate the adjusted odds ratio (aOR) with 95% confidence interval (CI) for the association of appendicitis history with SLE. Sensitivity analyses were conducted using various definitions of appendicitis. Subgroup analyses were conducted to examine possible modification effects by age, gender, level of urbanization, income and Charlson Comorbidity Index (CCI). Results: The average age of patients was 38 years old in both groups. The proportion of females was 86.5%. 75 (1.2%) of SLE cases and 205 (0.6%) of non-SLE controls had appendicitis history before the index date. After adjusting for potential confounding factors, appendicitis was associated with a higher risk of SLE (aOR, 1.84; 95% CI, 1.34–2.52), and such association remained robust after variation of appendicitis definition. No significant modification effects were found for the association between appendicitis and SLE by age, gender, urbanization level, income and CCI. Conclusion: This nationwide, population-based case–control study demonstrates an association between appendicitis and incident SLE. Lack of individual smoking status is a major limitation. Key Points • Appendicitis was significantly associated with an increased risk of SLE. • Such association remained robust using various definitions of appendicitis. [ABSTRACT FROM AUTHOR]

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan. [ABSTRACT FROM AUTHOR]

To present the natural course of keratoconus (KC) and compare pediatric and adult patients. Design A retrospective cohort study. Setting Hospital-based. Patient Population In total, 152 patients (288 eyes) diagnosed with KC at Chang Gung Memorial Hospital, Taiwan, were included. Previously managed patients and those with missing optical data were excluded. Observation Procedures Patients were divided into pediatric (≤ 18 years) and adult (> 18 years) groups. Demographics, clinical data, and optical variables were collected, including corrected distance visual acuity (CDVA), refractive error, and keratometric readings (K). Main Outcome Measure Optical variables at the final follow-up before aggressive treatment. Results In total, 20 pediatric (37 eyes) and 132 adults (251 eyes) patients were eligible for this study. The mean follow-up time was 2.98 years. Male predominance was observed in both groups. Both groups had similar clinical characteristics and optical variables at the initial diagnosis. Pediatric patients progressed significantly more rapidly in refractive errors, including spheres and cylinders, spherical equivalence, steep K, and flat K during the follow-up. However, significant change between the two study groups was only seen in sphere refractive error spherical equivalence. Conclusion Pediatric patients had more rapidly progressive KC than adult patients, so early detection and frequent follow-up for prompt interventions are necessary for these patients. [ABSTRACT FROM AUTHOR]

Via the density functional theory, the phase diagrams of HZO thin film in MFM (M = TiN, F = HZO) and MFI (I = α -SiO2) structures are constructed with dependences on grain size and temperature. In both MFM and MFI, the region for orthorhombic phase (o-phase) in phase diagram grows when HZO thickness gets thinner. Comparing to MFM, HZO/ α -SiO2 interface in MFI suppresses the growth of tetragonal phase (t-phase) to the region of very small grain size ∼1.2 nm. The simulation results agree with the experimental observation by Cheema et al, that the enhanced FE property was obtained in a MFIS (S = silicon) device with ultrathin HZO film (<2 nm). Simulation model indicates more chemical bonds forming between HZO and α -SiO2 interface could stabilize o-phase to greatly enhance the FE property in a MFIS device. [ABSTRACT FROM AUTHOR]

Combining phytochemicals and nanotechnology to improve the unfavorable innate properties of phytochemicals and develop them into potent nanomedicines to enhance antitumor efficacy has become a novel strategy for cancer chemoprevention. Melanoma is the most aggressive, metastatic, and deadly disease of the primary cutaneous neoplasms. In this study, we fabricated phytoconstituent-derived zingerone nanoparticles (NPs) and validated their effects on cell adhesion and motility in melanoma B16F10 cells. Our data indicated that zingerone NPs significantly induced cytotoxicity and anti-colony formation and inhibited cell migration and invasion. Moreover, zingerone NPs dramatically interfered with the cytoskeletal reorganization and markedly delayed the period of cell adhesion. Our results also revealed that zingerone NPs-mediated downregulation of MMPs (matrix metalloproteinases) activity is associated with inhibiting cell adhesion and motility. We further evaluated the effects of zingerone NPs on Src/FAK /Paxillin signaling, our data showed that zingerone NPs significantly inhibited the protein activities of Src, FAK, and Paxillin, indicating that they play important roles in zingerone NP-mediated anti-motility and anti-invasion in melanoma cells. Accordingly, the phytoconstituent-zingerone NPs can strengthen the inhibition of tumor growth, invasion, and metastasis in malignant melanoma. Altogether, these multi-pharmacological benefits of zingerone NPs will effectively achieve the purpose of melanoma prevention and invasion inhibition. [Display omitted] • Nanosizing ginger phytoconstituent zingerone possesses superior anti-tumorigenesis. • Zingerone NPs promoted cytotoxicity and anti-cell adhesion in melanoma cells. • Zingerone NPs-mediated downregulation of cell invasion and MMPs activity. • Src/FAK/Paxillin signaling is involved in zingerone NP-mediated anti-cell motility. [ABSTRACT FROM AUTHOR]

Purpose. The present study investigated the risk factors for high myopia in adulthood, with a focus on the age at which children wore their first spectacles. Methods. Adults aged between 20 and 45 years were invited to complete a questionnaire about age, sex, current refractive error, high myopia in parents, early onset of myopia presented by the age of the first myopic spectacle prescription, refractive power of the first spectacles, and life habits at different educational stages. The associations between these factors and high myopia in adulthood were then evaluated and analyzed. Results. In total, 331 participants were enrolled. Their average refractive error was −4.03 diopters, and high myopia was noted in 27.5% of the study participants. Only 3.3% of participants had fathers with high myopia, while 6.0% had mothers with high myopia. The participants received their first myopic spectacle prescription at a mean age of 13.35 years, with a mean refractive error of −1.63 diopters. The significant risk factors for developing high myopia in adult life were earlier age of the first spectacles prescribed (p < 0.001), higher refractive power of the first spectacles (p < 0.001), mother with high myopia (p = 0.015), and after-school class attendance in senior high school (p = 0.018). Those who wore their first spectacles at <9 years of age were more predisposed to high myopia than those who did so at ≧13 years, with an odds ratio of 24.9. Conclusion. The present study shows that earlier onset of myopia, which is presented by the age of the first myopic spectacle prescription, higher myopic refraction of the first spectacles, mothers with high myopia, and after-school class attendance in senior high school are risk factors for high myopia in adulthood. It suggests that delaying the onset of myopia in children is important for the prevention of high myopia in later life. [ABSTRACT FROM AUTHOR]

Purpose. The present study investigated the risk factors for high myopia in adulthood, with a focus on the age at which children wore their first spectacles. Methods. Adults aged between 20 and 45 years were invited to complete a questionnaire about age, sex, current refractive error, high myopia in parents, early onset of myopia presented by the age of the first myopic spectacle prescription, refractive power of the first spectacles, and life habits at different educational stages. The associations between these factors and high myopia in adulthood were then evaluated and analyzed. Results. In total, 331 participants were enrolled. Their average refractive error was −4.03 diopters, and high myopia was noted in 27.5% of the study participants. Only 3.3% of participants had fathers with high myopia, while 6.0% had mothers with high myopia. The participants received their first myopic spectacle prescription at a mean age of 13.35 years, with a mean refractive error of −1.63 diopters. The significant risk factors for developing high myopia in adult life were earlier age of the first spectacles prescribed (p < 0.001), higher refractive power of the first spectacles (p < 0.001), mother with high myopia (p = 0.015), and after-school class attendance in senior high school (p = 0.018). Those who wore their first spectacles at <9 years of age were more predisposed to high myopia than those who did so at ≧13 years, with an odds ratio of 24.9. Conclusion. The present study shows that earlier onset of myopia, which is presented by the age of the first myopic spectacle prescription, higher myopic refraction of the first spectacles, mothers with high myopia, and after-school class attendance in senior high school are risk factors for high myopia in adulthood. It suggests that delaying the onset of myopia in children is important for the prevention of high myopia in later life. [ABSTRACT FROM AUTHOR]

In this work, the pathways for polarization switching of hafnium oxide (HfO2) orthorhombic phase were simulated via density functional theory. The energy barriers vary from 30.7 to 69.3 meV/atom depending on the transition states taken in the process of polarization switching. With further analysis, it is found that the pathway via transition state of the Pbcm phase is suitable for the domain-wall motion mechanism for polarization switching but bears the highest energy barrier. On the other hand, the pathways via the tetragonal-like transition state with the lowest energy barrier suggest the uniform switching mechanism. For HfO2 films composed of different sizes of grains, a uniform switching and domain-wall motion mechanism could be activated in small and large grains. [ABSTRACT FROM AUTHOR]

The strain effect on the phase stability of bulk HfO2 is theoretically investigated with the density functional calculations. The origin of the ferroelectric (FE) characteristic in HfO2 is considered to be the formation of a non-centrosymmetric polar orthorhombic (PO) phase. The centrosymmetric nonpolar orthorhombic (O) phase is an antiferroelectric (AFE) structure, which has a smaller energy than PO-phase at unstrained condition. Applied biaxial strain can manipulate the relative stability among phases and also the ferroelectricity. Compressive strain is favored to transform HfO2 from monoclinic to PO-phase. The PO-phase HfO2 possesses the ferroelectricity with the remnant polarization of 66 µC/cm2 and the energy barrier of 70 meV/atom for the polarization switching from up to down. Tensile strain is found out to raise the relative energy of AFE state with respect to FE state. Furthermore, the Al doping in HfO2 could lower the energy barrier for polarization switching and also enhance the population of PO-phase. [ABSTRACT FROM AUTHOR]

We use the density functional theory method to study dry (1 × 1) α-quartz (0001) surfaces that have Frenkel-like defects such as oxygen vacancy and oxygen displacement. These defects have distinctively different effects on the water-silica interface depending on whether the adsorbent is a single water molecule, a cluster, or a thin film. The adsorption energies, bonding energies, and charge transfer or redistributions are analyzed, from which we find that the existence of a defect enhances the water molecule and cluster surface interaction by a large amount, but has little or even negative effect on water thin film-silica surface interaction. The origin of the weakening in film-surface systems is the collective hydrogen bonding that compromises the water-surface interaction in the process of optimizing the total energy. For clusters on surfaces, the lowest total energy states lower both the bonding energy and the adsorption energy. [ABSTRACT FROM AUTHOR]

Metabolic disorders hamper the brain metabolism and functions. The astrocytic glucose-derived lactate is known to fill the increased energy needs of neurons during synaptic transmission. However, whether systemic metabolism dysregulation affects the astrocytic lactate metabolism in the brain remain unexamined. To address this question, we adopt a 12-week high-fat diet to induce metabolic disorders in adult mice, and the effects of high-fat diet on the lactate metabolism in the hippocampus were examined. Results showed that a 12-week high-fat diet induced obesity and insulin resistance in mice. High-fat diet also decreased the lactate content levels and the expression of glial glutamate transporters, GLAST and GLT-1, in the hippocampus. Strong correlations between the lactate levels and the levels of GLAST and GLT-1 were evidenced. In conclusion, high-fat feeding induces metabolic disorders and disrupts lactate metabolism in the hippocampus. GLAST and GLT-1 may contribute to the HFD-induced abnormalities of the hippocampal lactate metabolism. [ABSTRACT FROM AUTHOR]

We demonstrate a new approach to synthesize several unique nanostructures by tuning the selective reactivities on individual symmetry-breaking segmented selenium nanorods (SBS-SeNRs). The segment-selective reactions from thiolated silane endowed the formation of float-like SBS-SeNR@SiO2 with a silica coating on the t-Se segment. Several other unique nanostructures were further synthesized by applying other selective reactions, such as Se chemical removal and nanogold deposition. Such a segmented nanomaterial of SBS-SeNRs acts as a new chemical template for preparing various segmented nanocomposites. [ABSTRACT FROM AUTHOR]

By using MPI-2 standard, we designed and implemented a new multiscale simulation architecture OPAL. It requires minimum modification to existing simulation code as maintaining the execution efficiency. The new architecture is capable of dynamical region identification, dynamical process spawning, and is grid-computing friendly. We demonstrated its usage and power with a simple test case: NaCl dissociation in water. The code shows excellent linear scaling capability, and no obvious degradation is observed. The communication time used by OPAL is negligible compared with its execution time, proving its high efficiency. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

Orchids are one of the most ecological and evolutionarily significant plants, and the Orchidaceae is one of the most abundant families of the angiosperms. Genetic databases will be useful not only for gene discovery but also for future genomic annotation. For this purpose, OrchidBase was established from 37,979,342 sequence reads collected from 11 in-house Phalaenopsis orchid cDNA libraries. Among them, 41,310 expressed sequence tags (ESTs) were obtained by using Sanger sequencing, whereas 37,908,032 reads were obtained by using next-generation sequencing (NGS) including both Roche 454 and Solexa Illumina sequencers. These reads were assembled into 8,501 contigs and 76,116 singletons, resulting in 84,617 non-redundant transcribed sequences with an average length of 459 bp. The analysis pipeline of the database is an automated system written in Perl and C#, and consists of the following components: automatic pre-processing of EST reads, assembly of raw sequences, annotation of the assembled sequences and storage of the analyzed information in SQL databases. A web application was implemented with HTML and a Microsoft .NET Framework C# program for browsing and querying the database, creating dynamic web pages on the client side, analyzing gene ontology (GO) and mapping annotated enzymes to KEGG pathways. The online resources for putative annotation can be searched either by text or by using BLAST, and the results can be explored on the website and downloaded. Consequently, the establishment of OrchidBase will provide researchers with a high-quality genetic resource for data mining and facilitate efficient experimental studies on orchid biology and biotechnology. The OrchidBase database is freely available at http://lab.fhes.tn.edu.tw/est. [ABSTRACT FROM AUTHOR]

We investigated whether maternal diabetes programs the offspring to develop hypertension and kidney injury in adulthood and examined potential underlying mechanisms. In a murine model we studied the offspring of three groups of dams (non-diabetic, diabetic, and diabetic treated with insulin). Mean systolic blood pressure in the offspring was monitored from 8 to 20 weeks. Body and kidney weights in the offspring of diabetic mothers were significantly lower than in offspring of non-diabetic mothers. Offspring of diabetic mothers developed hypertension, microalbuminuria, and glucose intolerance. Increased accumulation of extracellular matrix proteins in the glomeruli and marked upregulation of angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, transforming growth factor beta-1 (TGF-β1), and plasminogen activator inhibitor-1 (PAI-1) gene expression were evident in the renal cortex of hypertensive offspring of diabetic mothers. By contrast, angiotensin-converting enzyme-2 (ACE2) gene expression was lower in the hypertensive offspring of diabetic mothers than in that of non-diabetic mothers. These changes were prevented in the offspring of insulin-treated diabetic mothers. These data indicate that maternal diabetes induces perinatal programming of hypertension, renal injury, and glucose intolerance in the offspring and suggest a central role for the activation of the intrarenal renin–angiotensin system and TGF-β1 gene expression in this process. [ABSTRACT FROM AUTHOR]

Abstract: This paper proposes a new approach called rolling penetrate descriptor for shape description. It combines the advantage of the contour-based and the region-based methods, and provides an unified scheme to handle various shapes. The main process of the proposed method is to use a set of scanning lines that rotate around the shape centroid to collect information. During the rotating process, three feature functions are computed to reveal the inner structures of the candidate shape. The proposed method is very flexible and can be adapted for certain applications, while the scanning process serves as a framework. The rolling penetrate descriptor method is tested on several data sets with variations including common geometrical transform, noise, distortion and occlusion. Experimental results demonstrate that the proposed approach has strong capability in handling a variety of shapes. [Copyright &y& Elsevier]

We previously demonstrated that angiotensin II (Ang II) stimulates paired homeo box-2 (Pax-2) via the Ang II type 2 receptor (AT2R). The Pax-2 gene and N-myc play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation in embryonic mesenchymal cells and embryonic mouse kidneys. Since AT2R knock-out (KO) mice have a phenotype that is similar to that of humans with congenital renal and urinary tract anomalies (CAKUT) and develop hypertension in adulthood, these mice and wild-type controls were used for this study. Embryonic kidneys isolated from E12 to term gestation were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with or without Ang II (10−6 M) for 24 h ex vivo. Renal morphogenesis was histologically assessed. Mean glomerular tuft volume was determined by the method of Weibel and Gomez with the aid of image analysis software. Pax-2 and N-myc gene expression were determined by immunostaining as well as by Western blotting and real-time-quantitative polymerase chain reaction (RT-qPCR). Glomerular size was significantly smaller, and Pax-2 and N-myc expression down-regulated, in kidneys of AT2R KO mice compared with those of wild-type mice. In ex vivo studies, Ang II stimulated Pax-2 and N-myc mRNA expression in embryonic kidneys of wild-type mice, but this stimulatory effect was absent in embryonic kidneys of AT2R KO mice. Taken together, these data indicate that intrarenal AT2R plays an important role in nephrogenesis. Deficiency of AT2R may impair both Pax-2 and N-myc expression, eventually resulting in glomerular hyperfiltration that may, ultimately, lead to later development of hypertension. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2−/−/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD–induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3β pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways. ADAR2 KO mice are protected against several HFD–induced metabolic defects, show reduced hepatic lipid accumulation, improved hepatic insulin signaling, and increased pyruvate tolerance and glycogen synthesis, by activation of AMPK signaling pathways. [ABSTRACT FROM AUTHOR]

We investigated thin water films on quartz (0001) surfaces using first-principles density functional theory calculations. Interfacial structure and energetics were studied through a layer-by-layer deposition. From monolayer to multilayer, the low energy state configurations and adsorption sites show a transition due to formation of a highly stable bilayer membranelike structure. The water adsorption energy on a quartz surface coated by this membrane is of typical hydrogen bond strength for both dry and fully hydroxylated surfaces. The interactions between the surface and the water films are short-ranged due to shielding of the bilayer. [ABSTRACT FROM AUTHOR]

Reconstruction of α-quartz (0001) surfaces is studied using combined classical molecular dynamics and density functional theory. Five reconstruction patterns are identified, including three (2×1) patterns and two (1×1) patterns. The energetically most stable surface structure is found to be a (2×1) reconstruction pattern, and several patterns can coexist in a large-scale surface. A combination of structures can explain the experimentally observed (2×2) diffraction pattern. [ABSTRACT FROM AUTHOR]

(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: −0.29 ± 0.44 vs. −0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = −0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells are in clinical testing against various tumor types, including multiple myeloma. In this study, we show that CIK cells have activity against subcutaneous and disseminated models of human myeloma (KAS-6/1), which can be enhanced by infecting the CIK cells with an oncolytic measles virus (MV) or by pretreating the myeloma cells with ionizing radiation (XRT). KAS-6/1 cells were killed by coculture with CIK or MV-infected CIK (CIK/MV) cells, and the addition of an anti-NKG2D antibody inhibited cytolysis by 50%. However, human bone marrow stromal cells can reduce CIK and CIK/MV mediated killing of myeloma cells (RPMI 8226, JJN-3 and MM1). In vivo, CIK and CIK/MV prolonged the survival of mice with systemic myeloma, although CIK/MV showed enhanced antitumor activity compared with CIK. Irradiation of the KAS-6/1 cells induced mRNA and protein expression of NKG2D ligands, MICA, and MICB in a dose-dependent manner and enhanced delivery of CIK/MV to the irradiated tumors. In both subcutaneous and disseminated myeloma models, XRT at 2 Gy resulted in superior prolongation of the survival of mice given CIK/MV therapy compared with CIK/MV with no XRT. This study demonstrates the potential of CIK against myeloma and that the combination of virotherapy with radiation could be used to further enhance therapeutic outcome using CIK cells. [ABSTRACT FROM AUTHOR]

This study provides a first attempt from a toxicological perspective to put forward, in general terms and explanations, the toxicity series of Cd(II), Cu(II) and Zn(II) to Thiobacillus thiooxidans BC1. Sulphur oxidation and sulphuric acid production are strongly related to microbial growth at pH less than 4. Dose–response analysis on chronic and acute toxicity (e.g. EC20, median effective dose EC50 and slope factor B) of divalent cadmium, copper and zinc cations suggests a toxicity series of Cu>Cd>>Zn to T. thiooxidans BC1. Zn(II) is termed non-toxic and the maximum treatment concentrations of Cd(II) and Cu(II) are approximately 300, 400 mg/l, respectively. This assessment clearly indicates viable operation ranges of metal bioleaching for mine wastewater treatment, suggesting a technological feasibility of biotreatment using acidophilic thiobacilli T. thiooxidans BC1. [Copyright &y& Elsevier]

Recent studies emphasize the importance of 5‐HT2C receptor (5‐HT2CR) signaling in the regulation of energy homeostasis. The 5‐HT2CR is the only G‐protein‐coupled receptor known to undergo post‐transcriptional adenosine to inosine (A‐to‐I) editing by adenosine deaminase acting on RNA (ADAR). 5‐HT2CR has emerged as an important role in the modulation of pancreatic β cell functions. This study investigated mechanisms behind the effects of palmitic acid (PA) on insulin secretion in different overexpressed 5‐HT2CR edited isoforms in pancreatic MIN6 β cells. Results showed that the expressions of 5HT2CR and ADAR2 were upregulated in the pancreatic islets of mice fed with high‐fat diet (HFD) compared to control mice. PA treatment significantly induced the expressions of 5‐HT2CR and ADAR2 in pancreatic MIN6 β cells. PA treatment significantly induced the editing of 5‐HT2CR in pancreatic MIN6 β cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5‐HT2CR edited isoforms in pancreatic MIN6 β cells. Overexpressed 5‐HT2CR edited isoforms showed reduced glucose‐stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5‐HT2CR edited isoforms displayed reduced endoplasmic reticulum (ER) calcium release and store‐operated calcium entry (SOCE) activation, probably through inhibition of stromal interaction molecule 1 trafficking under PA treatment. Altogether, our results show that PA‐mediated editing of 5‐HT2CR modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 β cells. [ABSTRACT FROM AUTHOR]

Highlights • HFD induces astrocyte activation in the hippocampus. • HFD represses the process arborization of the hippocampal astrocytes. • HFD downregulates the hippocampal expression of astrocytic glutamate transporters. • HFD induces depression-like behaviors in mice. Abstract Metabolic disorders induce adverse effects on brain functions. The hippocampus is one of the most vulnerable regions to metabolic disorders. Disrupted neuroplasticity is a major cause of hippocampus-related behavioral impairments, including memory loss, anxiety, and depression. Astrocytes support processes of neuroplasticity. However, whether metabolic disorders induce changes in astrocytes and their roles in affective disorders is relatively unclear. To answer this question, we fed 8-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to induce metabolic disruption and then examined their performance of hippocampus-related memory, and anxiety- and depression-like behaviors. The morphology of astrocytes and the expression of astrocytic neuroplasticity-related proteins in the hippocampus were also assessed. The results showed that HFD led to obesity, systemic insulin resistance and dysregulated lipid metabolism in mice. HFD induced depression-like behaviors, but not anxiety or memory impairment. Furthermore, HFD increased the expression of GFAP, shortened the processes of GFAP+ cells, and downregulated the expression of astrocytic neuroplasticity-related protein, GLAST, GLT-1, and connexin-43 in the hippocampi. In conclusion, HFD disturbs the function of hippocampal astrocytes and induces depression-like behaviors in mice. A decrease of hippocampal glutamate transporters may play a critical role in the pathogenesis of metabolic disorder-related depression. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diabetes is rapidly increasing worldwide and is highly associated with the incidence of cancers. In order to prevent diabetes, early diagnosis of prediabetes is important. However, biomarkers for prediabetes diagnosis are still scarce. The hedgehog-interacting protein (Hhip) is important in embryogenesis and is known to be a biomarker of several cancers. However, Hhip levels in subjects with diabetes are still unknown. Methods: In total, 314 participants were enrolled and divided into normal glucose tolerance (NGT; n = 75), impaired fasting glucose (IFG; n = 66), impaired glucose tolerance (IGT; n = 86), and newly diagnosed diabetes (NDD; n = 87) groups. Plasma Hhip levels were determined by an ELISA. The association between the Hhip and the presence of diabetes was examined by a multivariate linear regression analysis. Results: There were significant differences in the body mass index, systolic and diastolic blood pressure, fasting plasma glucose (FPG), post-load 2-h glucose, hemoglobin A1c (A1C), C-reactive protein, total cholesterol, triglyceride, and high- and low-density lipoprotein cholesterol levels among the groups. Concentrations of the Hhip were 2.45 ± 2.12, 4.40 ± 3.22, 4.44 ± 3.64, and 6.31 ± 5.35 ng/mL in subjects in the NGT, IFG, IGT, and NDD groups, respectively. In addition, we found that A1C and FPG were independently associated with Hhip concentrations. Using NGT as a reference group, IFG, IGT, and NDD were all independently associated with Hhip concentrations. Conclusions: Hhip was positively associated with prediabetes and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Lipotoxicity is associated with a high level of fatty acid accumulation in pancreatic β-cells. An overload of free fatty acids contributes to pancreatic β-cell apoptosis and dysfunction. Insulin secretion involves sequential ionic events upon glucose stimulation. ATP sensitive potassium (KATP) channels serve as glucose sensors and effectively initiate glucose-stimulated insulin secretion. This study investigated the effects of lipotoxicity on the trafficking of KATP channels in pancreatic β cells using chronic palmitic acid -injected mice and treated insulinoma cells. The chronic palmitic acid -injected mice displayed type II diabetic characteristics. The pancreatic sections of these mice exhibited a decrease in the expression of KATP channels. We then tested the time and dose effects of palmitic acid on the cell viability of INS-1 cells. We observed a significant decrease in the surface expression of KATP channels after 72 h of treatment with 0.4 mM palmitic acid. In addition, this treatment induced pancreatic β-cell apoptosis by increasing cleaved caspase 3 protein level. Our results demonstrated cotreatment with glibenclamide, the sulfonylurea compounds for type II diabetes mellitus, in palmitic acid -treated cells reduces cell death and recovers the glucose stimulated insulin secretion through increasing the surface expression of KATP channels. Importantly, glibenclamide also improved glucose tolerance, triglyceride concentration, and insulin sensitivity in the palmitic acid-injected mice. In conclusion, an increase in the surface expression of KATP channels restores insulin secretion, reduces pancreatic β-cell's apoptosis, highlighting correct trafficking of KATP channels is important in survival of β-cells during lipotoxicity. [ABSTRACT FROM AUTHOR]

Background: The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. Methods: We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol. Results: Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone. Conclusions: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D. [ABSTRACT FROM AUTHOR]

The increasing prevalence of hospital-acquired infection and the evolution and increasing resistance of pathogens toward antibiotics can cause serious health problems and disease-related mortality. In this study, we introduce a simple process and inexpensive method to synthesize CuO nanoparticles and silver-functionalized copper oxide (Ag@CuO) nanocomposites as well as to validate their potential antibacterial efficiency against the following three common nosocomial infection-associated bacterial pathogens: E. coli , S. enterica and S. aureus . We show that Ag@CuO significantly disturbs pathogen growth and viability compared with CuO. Further, we find that Gram-positive S. aureus is susceptible to CuO-induced cell structure damage, while Ag@CuO can induce more extensive architectural destruction and ROS generation in both Gram-positive and Gram-negative bacterial pathogens. This study indicates that Ag@CuO nanoparticles can act as a disinfection system and can be used in antibacterial applications for the future prevention of nosocomial infection in medical and/or health institutions. [ABSTRACT FROM AUTHOR]

The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic β-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene , was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells. [Display omitted] • An environmentally sensitive NIR fluorogenic dye was rationally designed to detect IAPP fibrils. • The probe exhibited an obvious fluorescence enhancement with a large hypsochromic shift after attaching to IAPP fibrils. • Uncharged AmySP-4-Nap-Ene demonstrated a higher binding affinity towards IAPP fibrils than conventionally used ThT. • AmySP-4-Nap-Ene can be utilized to image IAPP fibrils both in vitro and in cell milieu. • The designed probe showed distinct fluorescence emission profiles with different target proteins. [ABSTRACT FROM AUTHOR]

Exoglucanase/cellobiohydrolase (EC 3.2.1.176) hydrolyzes a β-1,4-glycosidic bond from the reducing end of cellulose and releases cellobiose as the major product. Three complex crystal structures of the glycosyl hydrolase 48 (GH48) cellobiohydrolase S (ExgS) from Clostridium cellulovorans with cellobiose, cellotetraose and triethylene glycol molecules were solved. The product cellobiose occupies subsites +1 and +2 in the open active-site cleft of the enzyme-cellotetraose complex structure, indicating an enzymatic hydrolysis function. Moreover, three triethylene glycol molecules and one pentaethylene glycol molecule are located at active-site subsites −2 to −6 in the structure of the ExgS-triethylene glycol complex shown here. Modelling of glucose into subsite −1 in the active site of the ExgS-cellobiose structure revealed that Glu50 acts as a proton donor and Asp222 plays a nucleophilic role. [ABSTRACT FROM AUTHOR]

The rate of neurogenesis is determined by 1) the number of neural stem/progenitor cells (NSCs), 2) proliferation of NSCs, 3) neuron lineage specification, and 4) survival rate of the newborn neurons. Aging lowers the rate of hippocampal neurogenesis, while exercise (Ex) increases this rate. However, it remains unclear which of the determinants are affected by aging and Ex. We characterized the four determinants in different age groups (3, 6, 9, 12, 21 months) of mice that either received one month of Ex training or remained sedentary. Bromodeoxyuridine (BrdU) was injected two hours before sacrificing the mice to label the proliferating cells. The results showed that the number of newborn neurons massively decreased (>95%) by the time the mice reached nine months of age. The number of NSC was mildly reduced during aging, while Ex delayed such decline. The proliferation rates were greatly decreased by the time the mice were 9-month-old and Ex could not improve the rates. The rates of neuron specification were decreased during aging, while Ex increased the rates. The survival rate was not affected by age or Ex. Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it. In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation. Although Ex increases the NSC number and neuron specification rates, it doesn't restore the massive decline of NSC proliferation rate. Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons. [ABSTRACT FROM AUTHOR]

We investigated whether overexpression of catalase (CAT) in renal proximal tubular cells (RPTCs) could prevent the programming of hypertension and kidney disease in the offspring of dams with maternal diabetes. Male offspring of nondiabetic and diabetic dams from two transgenic (Tg) lines (Hoxb7-green fluorescent protein [GFP]-Tg [controls] and Hoxb7/CAT-GFP-Tg, which overexpress CAT in RPTCs) were studied from the prenatal period into adulthood. Nephrogenesis, systolic blood pressure, renal hyperfiltration, kidney injury, and reactive oxygen species (ROS) generation were assessed. Gene expression of transforming growth factor-β1 (TGF-β1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and heme oxygenase-1 (HO-1) was tested in both in vitro and in vivo studies. Renal dysmorphogenesis was observed in offspring of Hoxb7-GFP-Tg dams with severe maternal diabetes; the affected male offspring displayed higher renal ROS generation and developed hypertension and renal hyperfiltration as well as renal injury with heightened TGF-β1 expression in adulthood. These changes were ameliorated in male offspring of diabetic Hoxb7/CAT-GFP-Tg dams via the Nrf2-HO-1 defense system. CAT promoted Nrf2 nuclear translocation and HO-1 gene expression, seen in both in vitro and in vivo studies. In conclusion, CAT overexpression in the RPTCs ameliorated maternal diabetes-induced perinatal programming, mediated, at least in part, by triggering the Nrf2-HO-1 defense system. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations of the biphalin molecule, (Tyr-D-Ala-Gly-Phe-NH), and the active tetrapeptide hydrazide, Tyr-D-Ala-Gly-Phe-NH-NH were performed to investigate the cause of the increased μ and δ receptor binding affinities of the former over the latter. The simulation results demonstrate that the acylation of the two equal tetrapeptide fragments of biphalin produces the constrained hydrazide bridges $$ {\hbox{C}}_4^{\alpha } - {{\hbox{C}}_4}\prime - {{\hbox{N}}_9} - {{\hbox{N}}_{{10}}} $$ and $$ {{\hbox{N}}_9} - {{\hbox{N}}_{{10}}} - {{\hbox{C}}_5}\prime - {\hbox{C}}_5^{\alpha } $$, which in turn increase the opportunity of conformations for binding to μ or δ receptors. Meanwhile, the connection of the two active tetrapeptide fragments of biphalin also results in the constrained side chain torsion angle χ at one of the two residues Phe. This constrained side chain torsion angle not only significantly increases the δ receptor binding affinity but also makes most of the δ receptor binding conformations of biphalin bind to the δ receptor through the fragment containing the mentioned residue Phe. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) 40: 560–566 Backgrounds:  MicroRNAs are small noncoding RNAs involved in posttranscriptional gene regulation, which play an important role in both physiological functioning and pathological progression. The miR‐221/miR‐222 microRNA family has been shown to be related to the neoplastic process in a number of different types of cancers; nevertheless, its function in oral squamous cell carcinoma (OSCC) remained uncertain. Materials and Methods:  Paired OSCC and matched noncancerous oral mucosa were examined for miR‐221/miR‐222 expression using quantitative reverse‐transcription PCR. Ectopic expression of miR‐221/miR‐222 by lentiviral infection was investigated to explore its in vitro and in vivo impact on the oncogenic phenotype and the expression of various target genes. The expression of Cip/Kip cell cycle regulator p27 in tumors was analyzed with immunohistochemistry. Results:  The expression levels of miR‐221 and miR‐222 were highly correlated in OSCC. Increased miR‐221/miR‐222 expression was found in 40% of OSCC tissues. The ectopic expression of miR‐221 or of miR‐222 increased growth and anchorage‐independent colony formation of OSCC cell lines. It also resulted in an increase in the tumorigenesis of an OSCC cell line in nude mice. Western blot analysis suggested that p27 and p57 might be the targets of miR‐221/miR‐222. p27 expression was reversely associated with the miR‐221 and miR‐222 expression level in OSCC tissues. Conclusions:  Our findings suggested that increased miR‐221/miR‐222 expression was associated with the OSCC cell growth. [ABSTRACT FROM AUTHOR]

Abstract: A total of 142 sets of PM10 and PM2.5 aerosol particles collected from Taipei during a period from April 2003 to February 2004 were determined for atmospheric Pb concentrations. Among these samples, 77 sets of samples representing four seasons were selected for measuring Pb isotopic compositions to determine the relative contributions of various pollution sources. Results reveal an evident seasonality of high winter and low summer Pb concentrations, resembling those observed in Shanghai, China as well as many East Asian countries. Together with synoptic atmospheric conditions analysis, the seasonal pattern is attributable to the impact of long-range transport of Pb-rich anthropogenic aerosols from the Chinese pollution outflows in the northeast monsoon and to the effective removal by wet deposition in summer. Results of 206Pb/207Pb and 208Pb/207Pb isotope ratios show a minimum in summer, thereafter increasing progressively to fall to winter and reaching a maximum in spring. The summer values are similar to that of tunnel particles for 206Pb/207Pb ratio but dissimilar to that of tunnel particles for 208Pb/207Pb ratio. Here summer aerosols may represent a local pollution-influenced case, and tunnel particles represent a vehicle exhaust source for atmospheric Pb. Therefore apart from vehicle emissions of Pb for Taipei aerosols, other sources such as incineration, metalliferous industry and coal combustion of fire power plants need to be taken into account. The winter and spring Pb isotope ratios are quite comparable with those measured in China, especially Shanghai in the Yangtze Delta. Again this demonstrates northern Taiwan has already been affected by continental pollution of long-range transport during the northeast monsoon season beginning in early fall and ending in late spring. By employing a two end-member mixing model based on the assumption that the summer case represents the local source end-member, the relative contributions of long-range transport for anthropogenic Pb have been estimated to be 40% in fall, 50% in winter, and 75–85% in spring. [Copyright &y& Elsevier]

Patients with type 2 diabetes mellitus have more risk to develop depression. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is drug for mood and anxiety disorders. Previous studies showed that FLX could induce weight loss in non-depressed clinically overweight individuals. Although the anti-appetite effect of FLX is well-documented, its potential effects on metabolic abnormalities have not been investigated. In this study, we want to investigate whether FLX could be a therapeutic drug against high fat diet (HFD)-induced metabolic disorder. We generated metabolic disorders and depressed mouse model by feeding HFD for 12 weeks at the age of 8 weeks. Then, mice were intraperitoneally injected once daily with FLX (10 mg/kg or 20 mg/kg) for four weeks. Our results showed that FLX alleviated the HFD-induced metabolic dysfunctions and depressive phenotypes in mice. FLX improved systemic glucose homeostasis, at least in part, by improving visceral white adipose tissue (vWAT) insulin signaling. Moreover, FLX reduced circulating plasma leptin level, and decreased the expression of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor gamma (PPARγ) in vWAT. Our data revealed that FLX also reduced the triglyceride (TG) accumulation in vWAT. Therefore, these findings suggest that FLX exhibits significant potential on comorbidity of metabolic disorder and depression in mice. • Fluoxetine alleviated high-fat diet (HDF)-induced metabolic disorder in mice. • Fluoxetine reduced the HFD-induced upregulation of leptin levels. • Fluoxetine improved visceral white adipose tissue (vWAT) insulin signaling. • Fluoxetine reduced adipose triglyceride lipase (ATGL) expression in vWAT. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes is rapidly increasing worldwide and is highly associated with the incidence of depression. Pioglitazone, a Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is widely used for treating patients with type 2 diabetes. However, whether pioglitazone alleviates metabolic disorder-related depression and astrocytic deficits remains unclear. Here we showed that 12 weeks of high-fat diet (HFD) feeding (from 8- to 20-week-old) induced not only obesity and insulin resistance, but also depression-like behaviors in mice. Astrocytic activation, a sign closely associated with depression, was also evident in the ventral hippocampus. Four weeks of pioglitazone (10 or 20 mg/kg, daily, from 20- to 24-week-old) treatment alleviated the HFD-induced glucose-metabolic dysfunctions, upregulation of ventral hippocampal GFAP, reduction of the total process lengths and the number of branch points of the ventral hippocampal CA1 GFAP-immunoreactive astrocytes and depressive phenotypes but had no effect on anxiety-like behaviors or hippocampus-related learning and memory in mice. These findings suggest that pioglitazone could be a potential therapeutic agent for metabolic disorders and associated depression. • Pioglitazone alleviated high-fat diet (HDF)-induced depressive phenotypes in mice. • Pioglitazone reduced the HFD-induced upregulation of GFAP in hippocampal astrocytes. • Pioglitazone rescued HFD-disturbed the morphology of the hippocampal astrocytes. [ABSTRACT FROM AUTHOR]

Background: Antinuclear antibody pattern recognition is vital for autoimmune disease diagnosis but labor-intensive for manual interpretation. To develop an automated pattern recognition system, we established machine learning models based on the International Consensus on Antinuclear Antibody Patterns (ICAP) at a competent level, mixed patterns recognition, and evaluated their consistency with human reading. Methods: 51,694 human epithelial cells (HEp-2) cell images with patterns assigned by experienced medical technologists collected in a medical center were used to train six machine learning algorithms and were compared by their performance. Next, we choose the best performing model to test the consistency with five experienced readers and two beginners. Results: The mean F1 score in each classification of the best performing model was 0.86 evaluated by Testing Data 1. For the inter-observer agreement test on Testing Data 2, the average agreement was 0.849 (κ) among five experienced readers, 0.844 between the best performing model and experienced readers, 0.528 between experienced readers and beginners. The results indicate that the proposed model outperformed beginners and achieved an excellent agreement with experienced readers. Conclusions: This study demonstrated that the developed model could reach an excellent agreement with experienced human readers using machine learning methods. [ABSTRACT FROM AUTHOR]