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"Chang, Yun"
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Liver Fat, Hepatic Enzymes, Alkaline Phosphatase and the Risk of Incident Type 2 Diabetes: A Prospective Study of 132,377 Adults
Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35–79 who had two or more health examinations during 1996–2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.
Journal Article
Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases
Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.
Journal Article
Champions of winter survival
Evergreen conifers are champions of winter survival, based on their remarkable ability to acclimate to cold and develop cold hardiness. Counterintuitively, autumn cold acclimation is triggered not only by exposure to low temperature, but also by a combination of decreasing temperature, decreasing photoperiod and changes in light quality. These environmental cues control a network of signaling pathways that coordinate cold acclimation and cold hardiness in overwintering conifers, leading to cessation of growth, bud dormancy, freezing tolerance and changes in energy metabolism. Advances in genomic, transcriptomic and metabolomic tools for conifers have improved our understanding of how trees sense and respond to changes in temperature and light during cold acclimation and the development of cold hardiness, but there remain considerable gaps deserving further research in conifers. In the first section of this review, we focus on the physiological mechanisms used by evergreen conifers to adjust metabolism seasonally and to protect overwintering tissues against winter stresses. In the second section, we review how perception of low temperature and photoperiod regulate the induction of cold acclimation. Finally, we explore the evolutionary context of cold acclimation in conifers and evaluate challenges imposed on them by changing climate and discuss emerging areas of research in the field.
Journal Article
Robust, reproducible and quantitative analysis of thousands of proteomes by micro-flow LC–MS/MS
Nano-flow liquid chromatography tandem mass spectrometry (nano-flow LC–MS/MS) is the mainstay in proteome research because of its excellent sensitivity but often comes at the expense of robustness. Here we show that micro-flow LC–MS/MS using a 1 × 150 mm column shows excellent reproducibility of chromatographic retention time (<0.3% coefficient of variation, CV) and protein quantification (<7.5% CV) using data from >2000 samples of human cell lines, tissues and body fluids. Deep proteome analysis identifies >9000 proteins and >120,000 peptides in 16 h and sample multiplexing using tandem mass tags increases throughput to 11 proteomes in 16 h. The system identifies >30,000 phosphopeptides in 12 h and protein-protein or protein-drug interaction experiments can be analyzed in 20 min per sample. We show that the same column can be used to analyze >7500 samples without apparent loss of performance. This study demonstrates that micro-flow LC–MS/MS is suitable for a broad range of proteomic applications.
Mass spectrometry-based proteomics typically relies on highly sensitive nano-flow liquid chromatography (LC) but this can reduce robustness and reproducibility. Here, the authors show that micro-flow LC enables robust and reproducible high-throughput proteomics experiments at a very moderate loss of sensitivity.
Journal Article
Cryptococcus neoformans Overcomes Stress of Azole Drugs by Formation of Disomy in Specific Multiple Chromosomes
Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis. Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown. We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes. Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains. Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes. The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain. Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes. The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans. This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy.
Journal Article
Combination of Quantitative Parameters of Shear Wave Elastography and Superb Microvascular Imaging to Evaluate Breast Masses
This study aimed to evaluate the diagnostic value of combining the quantitative parameters of shear wave elastography (SWE) and superb microvascular imaging (SMI) to breast ultrasound (US) to differentiate between benign and malignant breast masses.
A total of 200 pathologically confirmed breast lesions in 192 patients were retrospectively reviewed using breast US with B-mode imaging, SWE, and SMI. Breast masses were assessed based on the breast imaging reporting and data system (BI-RADS) and quantitative parameters using the maximum elasticity (Emax) and ratio (Eratio) in SWE and the vascular index in SMI (SMI
). The area under the receiver operating characteristic curve (AUC) value, sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of B-mode alone versus the combination of B-mode US with SWE or SMI of both parameters in differentiating between benign and malignant breast masses was compared, respectively. Hypothetical performances of selective downgrading of BI-RADS category 4a (set 1) and both upgrading of category 3 and downgrading of category 4a (set 2) were calculated.
Emax with a cutoff value of 86.45 kPa had the highest AUC value compared to Eratio of 3.57 or SMI
of 3.35%. In set 1, the combination of B-mode with Emax or SMI
had a significantly higher AUC value (0.829 and 0.778, respectively) than B-mode alone (0.719) (
< 0.001 and
= 0.047, respectively). B-mode US with the addition of Emax, Eratio, and SMI
had the best diagnostic performance of AUC value (0.849). The accuracy and specificity increased significantly from 68.0% to 84.0% (
< 0.001) and from 46.1% to 79.1% (
< 0.001), respectively, and the sensitivity decreased from 97.6% to 90.6% without statistical loss (
= 0.199).
Combining all quantitative values of SWE and SMI with B-mode US improved the diagnostic performance in differentiating between benign and malignant breast lesions.
Journal Article
Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis
BackgroundGenetic studies have shown that C9orf72, SOD1, TARDBP and FUS are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS.MethodsWe performed an extensive literature research to identify all original articles reporting frequencies of C9orf72, SOD1, TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis.Results111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the C9orf72 repeat expansions (FALS 33.7%, SALS 5.1%), followed by SOD1 (FALS 14.8%, SALS 1.2%), TARDBP (FALS 4.2%, SALS 0.8%) and FUS mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were SOD1 mutations (FALS 30.0%, SALS 1.5%), followed by FUS (FALS 6.4%, SALS 0.9%), C9orf72 (FALS 2.3%, SALS 0.3%) and TARDBP (FALS 1.5%, SALS 0.2%) mutations.ConclusionsThese findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.
Journal Article
Effects of 4-Week Inspiratory Muscle Training on Sport Performance in College 800-Meter Track Runners
Background and objectives: Respiratory muscle fatigue is one of the important factors limiting sports performance due to the metaboreflex. This reflex will cause a decrease in blood flow to the extremities and accelerate exercising limb fatigue. Previous studies found that inspiratory muscle training (IMT) can effectively enhance the respiratory muscle endurance and reduce fatigue during long-duration exercise or aerobic exercise, thereby enhancing athletic performance. However, the mechanism between inspiratory muscle strength, change of limb blood flow and sports performance still requires investigation, especially in short-duration exercise, anaerobic or both aerobic and anaerobic exercise. The purpose of this study was to investigate the effects of 4-week inspiratory muscle training on respiratory muscle strength, limb blood flow change rate and sports performance in recreational 800-m college runners. Materials and Methods: Twenty healthy 800-m college runners randomized into the IMT group (11 subjects) and control group (9 subjects). IMT consisted of 30 inspiratory efforts twice daily, 5 days a week, with intensity at 50%, 60%, 70% and 80% of maximum inspiratory pressure (MIP) for 4 weeks, while a control group kept 50% of MIP for 4 weeks. An 800-m trial test, limb blood flow change rate by using Impedance Plethysmography, and MIP were as the outcome measured variables and be evaluated. All measured variables were assessed before and after 4-week IMT training. Two-way ANOVA was conducted for statistical analysis. Results: The results showed significantly interaction between groups and pre-posttest. IMT group significantly decreased limb blood flow change rate from 19.91 ± 11.65% to 9.63 ± 7.62% after received the IMT training program (p < 0.05). The MIP significantly improved from 112.95 ± 27.13 cmH2O to 131.09 ± 28.20 cm H2O in IMT group, and the 800-m trial test also shorted the running time from 162.97 ± 24.96 s to 156.75 ± 20.73 s. But the control group no significantly changed in MIP and 800-m trial test. Conclusions: Our results indicated that the 4-week IMT training (twice a day, 5 days a week) significantly improves participants’ inspiratory muscle strength, 800-m running performance and decreases the limb blood flow change rate.
Journal Article