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1.  Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model 
Scientific Reports  2016;6:33781.
Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1–42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1–42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.
PMCID: PMC5031964  PMID: 27653553
2.  Subwavelength imaging through ion-beam-induced upconversion 
Nature Communications  2015;6:8832.
The combination of an optical microscope and a luminescent probe plays a pivotal role in biological imaging because it allows for probing subcellular structures. However, the optical resolutions are largely constrained by Abbe's diffraction limit, and the common dye probes often suffer from photobleaching. Here we present a new method for subwavelength imaging by combining lanthanide-doped upconversion nanocrystals with the ionoluminescence imaging technique. We experimentally observed that the ion beam can be used as a new form of excitation source to induce photon upconversion in lanthanide-doped nanocrystals. This approach enables luminescence imaging and simultaneous mapping of cellular structures with a spatial resolution of sub-30 nm.
Combining high-resolution microscopic techniques with luminescent probes is important for biological imaging. Here, Mi et al. demonstrate subwavelength imaging by combining lanthanide-doped upconversion nanocrystals with ionoluminescence, revealing cellular structure and particle spatial distribution at high resolution.
PMCID: PMC4660043  PMID: 26560858
3.  Identification of Valid Reference Genes for the Normalization of RT-qPCR Expression Studies in Human Breast Cancer Cell Lines Treated with and without Transient Transfection 
PLoS ONE  2015;10(1):e0117058.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a powerful technique for examining gene expression changes during tumorigenesis. Target gene expression is generally normalized by a stably expressed endogenous reference gene; however, reference gene expression may differ among tissues under various circumstances. Because no valid reference genes have been documented for human breast cancer cell lines containing different cancer subtypes treated with transient transfection, we identified appropriate and reliable reference genes from thirteen candidates in a panel of 10 normal and cancerous human breast cell lines under experimental conditions with/without transfection treatments with two transfection reagents. Reference gene expression stability was calculated using four algorithms (geNorm, NormFinder, BestKeeper and comparative delta Ct), and the recommended comprehensive ranking was provided using geometric means of the ranking values using the RefFinder tool. GeNorm analysis revealed that two reference genes should be sufficient for all cases in this study. A stability analysis suggests that 18S rRNA-ACTB is the best reference gene combination across all cell lines; ACTB-GAPDH is best for basal breast cancer cell lines; and HSPCB-ACTB is best for ER+ breast cancer cells. After transfection, the stability ranking of the reference gene fluctuated, especially with Lipofectamine 2000 transfection reagent in two subtypes of basal and ER+ breast cell lines. Comparisons of relative target gene (HER2) expression revealed different expressional patterns depending on the reference genes used for normalization. We suggest that identifying the most stable and suitable reference genes is critical for studying specific cell lines under certain circumstances.
PMCID: PMC4305315  PMID: 25617865
4.  Reliability and Validity of the CogState Battery Chinese Language Version in Schizophrenia 
PLoS ONE  2013;8(9):e74258.
Cognitive impairment in patients with schizophrenia is a core symptom of this disease. The computerized CogState Battery (CSB) has been used to detect seven of the most common cognitive domains in schizophrenia. The aim of this study was to examine the reliability and validity of the Chinese version of the CSB (CSB-C), in Chinese patients with schizophrenia.
Methodology/Principal Findings
Sixty Chinese patients with schizophrenia and 58 age, sex, and education matched healthy controls were enrolled. All subjects completed the CSB-C and the Repeated Battery for the Assessment of Neuropsychological Status (RBANS). To examine the test-retest reliability of CSB-C, we tested 33 healthy controls twice, at a one month interval. The Cronbach α value of CSB-C in patients was 0.81. The test-retest correlation coefficients of the Two Back Task, Gronton Maze Learning Task, Social Emotional Cognition Task, and Continuous Paired Association Learning Task were between 0.39 and 0.62 (p<0.01) in healthy controls. The composite scores and all subscores for the CSB-C in patients were significantly (p<0.01) lower than those of healthy controls. Furthermore, composite scores for patients on the RBANS were also significantly lower than those of healthy controls. Interestingly, there was a positive correlation (r  =  0.544, p<0.001) between the composite scores on CSB-C and RBANS for patients. Additionally, in the attention and memory cognitive domains, corresponding subsets from the two batteries correlated significantly (p<0.05). Moreover, factor analysis showed a two-factor model, consisting of speed, memory and reasoning.
The CSB-C shows good reliability and validity in measuring the broad cognitive domains of schizophrenia in affected Chinese patients. Therefore, the CSB-C can be used as a cognitive battery, to assess the therapeutic effects of potential cognitive-enhancing agents in this cohort.
PMCID: PMC3759436  PMID: 24023931
5.  P. aeruginosa Lipopolysaccharide-Induced MUC5AC and CLCA3 Expression Is Partly through Duox1 In Vitro and In Vivo 
PLoS ONE  2013;8(5):e63945.
We have previously found that reactive oxygen species (ROS) are involved in Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) induced MUC5AC in airway epithelial cells. Dual oxidase1 (Duox1), a member of NADPH oxidase(Nox), is known to be responsible for ROS production in respiratory tract epithelial cells. Our aim was to clarify whether Duox1 was also involved in the PA-LPS-induced MUC5AC and calcium dependent chloride channel 3(Clca3), another recognized marker of goblet cell hyperplasia and mucus hyper-production.
PA-LPS-induced Duox1 mRNA levels were examined in A549 cells, primary mouse tracheal epithelial cells (mTECS) and lung tissues of mice. Nox inhibitors diphenyleneiodonium chloride (DPI) and Duox1 siRNA were used to investigate whether Duox1 is involved in PA-LPS-induced MUC5AC and Clca3 expression both in vitro and in vivo.
Duox1 is induced by PA-LPS in A549 cells, primary mTECs and lung tissues of mice. DPI significantly inhibited PA-LPS-induced up-regulation of Duox1, Muc5ac and Clca3 in primary mouse trachea epithelial cells and lung tissues of mice. Knockdown of Duox1 markedly inhibited PA-LPS-induced MUC5AC expression via a ROS-TGF-α cascade in A549 cells. Furthermore, DPI significantly inhibited PA-LPS-induced increases in inflammatory cells accumulated in mouse lungs.
We demonstrate for the first time that PA-LPS-induced MUC5AC and Clca3 expression is partly through Duox1, and provide supportive evidence for Duox1 as a potential target in treatments of mucin over-production diseases.
PMCID: PMC3653940  PMID: 23691121
6.  The impact of educational status on the clinical features of major depressive disorder among Chinese women 
Journal of Affective Disorders  2012;136(3):988-992.
Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting.
Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD.
Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide.
Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample.
The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.
PMCID: PMC3314924  PMID: 21824664
Major depressive disorder; Education; Socio-economic status; Symptom
7.  Mitochondrial Changes in Ageing Caenorhabditis elegans – What Do We Learn from Superoxide Dismutase Knockouts? 
PLoS ONE  2011;6(5):e19444.
One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the “vicious cycle” theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the “vicious cycle” theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the “vicious cycle” theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed.
PMCID: PMC3097207  PMID: 21611128
Depression and Anxiety  2011;29(1):10-15.
A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD.
We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30–60 years of age. Odds Ratios were calculated by logistic regression.
Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous.
The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states. Depression and Anxiety 0:1–6, 2011. © 2011 Wiley-Liss, Inc.
PMCID: PMC3429856  PMID: 22065525
major depression; family history; symptom; life events

Results 1-8 (8)