Correction: Prasad et al. Patterns of Variation in the Usage of Fatty Acid Chains among Classes of Ester and Ether Neutral Lipids and Phospholipids in the Queensland Fruit Fly. Insects 2023, 14, 873.

Supplementary Table S3 in our recent publication [...].

Patterns of Variation in the Usage of Fatty Acid Chains among Classes of Ester and Ether Neutral Lipids and Phospholipids in the Queensland Fruit Fly.

Modern lipidomics has the power and sensitivity to elucidate the role of insects' lipidomes in their adaptations to the environment at a mechanistic molecular level. However, few lipidomic studies have yet been conducted on insects beyond model species such as Drosophila melanogaster. Here, we present the lipidome of adult males of another higher dipteran frugivore, Bactrocera tryoni. We describe 421 lipids across 15 classes of ester neutral lipids and phospholipids and ether neutral lipids and phospholipids. Most of the lipids are specified in terms of the carbon and double bond contents of each constituent hydrocarbon chain, and more ether lipids are specified to this degree than in any previous insect lipidomic analyses. Class-specific profiles of chain length and (un)saturation are broadly similar to those reported in D. melanogaster, although we found fewer medium-length chains in ether lipids. The high level of chain specification in our dataset also revealed widespread non-random combinations of different chain types in several ester lipid classes, including deficits of combinations involving chains of the same carbon and double bond contents among four phospholipid classes and excesses of combinations of dissimilar chains in several classes. Large differences were also found in the length and double bond profiles of the acyl vs. alkyl or alkenyl chains of the ether lipids. Work on other organisms suggests some of the differences observed will be functionally consequential and mediated, at least in part, by differences in substrate specificity among enzymes in lipid synthesis and remodelling pathways. Interrogation of the B. tryoni genome showed it has comparable levels of diversity overall in these enzymes but with some gene gain/loss differences and considerable sequence divergence from D. melanogaster.

Escape from cell-cell and cell-matrix adhesion dependence underscores disease progression in gastric cancer organoid models.

OBJECTIVE: Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells. DESIGN: We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix or both to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAP fusions, RHOA and CDH1, in modulating CC (CCi) or CM (CMi) adhesion independence. RESULTS: 97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to three public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOA mutation or ARHGAP fusions. Inducible knockout of ARHGAP fusions in CCi/CMi tumour organoids led to resensitisation to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype and inhibited xenograft formation. Normal gastric organoids engineered with CDH1 or RHOA mutations became CMi or CCi, respectively. CONCLUSIONS: The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.

Development and validation of the EHS-COPD model to predict sex-specific risk of chronic obstructive pulmonary disease (COPD) in older Chinese adults: Hong Kong's Elderly Health Service Cohort.

BACKGROUND: No screening program is recommended for chronic obstructive pulmonary disease (COPD) in adults based on current clinical practice guidelines. Risk prediction models for COPD developed in Western settings may not be directly applicable to older Chinese adults. To evaluate the performance of an existing risk prediction model for COPD developed in a Western setting in Chinese adults and investigate whether a new risk prediction model performs better in predicting 5-year risk of COPD (EHS-COPD). METHODS: This study is based on 135,822 participants aged 65+ years from Hong Kong's Elderly Health Service (EHS) cohort. We assessed the performance of an existing risk prediction model in the entire cohort, and in a random sub-sample of 91,133 participants, we recalibrated the existing model and derived a new model using extended Cox proportional hazards regression. Candidate risk predictors from the literature and the EHS cohort were considered for inclusion. Risk prediction performance, discrimination, and calibration of the newly derived models were assessed in the remaining 44,689 participants. RESULTS: The existing risk prediction model overestimated the 5-year risk of COPD in older Chinese adults (65+ years); after recalibration, it still overestimated the 5-year risk of COPD for both men and women. The new EHS-COPD risk prediction model, including time-varying factors (i.e., age and smoking status) and time-invariant factors (i.e., education level, public assistance, alcohol use, body mass index, physical activity, existing hypertension, recent falls, cognitive function, and self-rated health status), had an improved performance. For men, EHS-COPD explained 19.5% of COPD risk, the D statistic was 23.1, and Harrell's C statistic was 0.93. The corresponding values for women were 8.5%, 21.1, and 0.93. CONCLUSIONS: The existing COPD risk prediction model overpredicted COPD risk in older Chinese and could not be recalibrated to predict well. A revised prediction model using time-invariant and time-varying factors provides a better tool for identifying older Chinese adults at high risk of developing COPD.

Climate stress resistance in male Queensland fruit fly varies among populations of diverse geographic origins and changes during domestication.

BACKGROUND: The highly polyphagous Queensland fruit fly (Bactrocera tryoni Froggatt) expanded its range substantially during the twentieth century and is now the most economically important insect pest of Australian horticulture, prompting intensive efforts to develop a Sterile Insect Technique (SIT) control program. Using a "common garden" approach, we have screened for natural genetic variation in key environmental fitness traits among populations from across the geographic range of this species and monitored changes in those traits induced during domestication. RESULTS: Significant variation was detected between the populations for heat, desiccation and starvation resistance and wing length (as a measure of body size). Desiccation resistance was correlated with both starvation resistance and wing length. Bioassay data for three resampled populations indicate that much of the variation in desiccation resistance reflects persistent, inherited differences among the populations. No latitudinal cline was detected for any of the traits and only weak correlations were found with climatic variables for heat resistance and wing length. All three stress resistance phenotypes and wing length changed significantly in certain populations with ongoing domestication but there was also a strong population by domestication interaction effect for each trait. CONCLUSIONS: Ecotypic variation in heat, starvation and desiccation resistance was detected in Australian Qfly populations, and these stress resistances diminished rapidly during domestication. Our results indicate a need to select source populations for SIT strains which have relatively high climatic stress resistance and to minimise loss of that resistance during domestication.

Development of indirect ELISA for the detection of canine adenovirus type 2 antibodies in dog sera.

BACKGROUND: Canine adenovirus type 2 (CAV-2) induces infectious laryngotracheitis in members of the family Canidae, including dogs. To date, no ELISA kits specific for CAV-2 antibody have been commercialized for dogs in Korea. OBJECTIVES: We aimed to develop new indirect enzyme-linked immunosorbent assay (I-ELISA) to perform rapid, accurate serological surveys of CAV-2 in dog serum samples. METHODS: In total, 165 serum samples were collected from dogs residing in Chungbuk and Gyeongbuk provinces between 2016 and 2018. The Korean CAV-2, named the APQA1701-40P strain, was propagated in Madin-Darby canine kidney cells and purified in an anion-exchange chromatography column for use as an antigen for I-ELISA. The virus-neutralizing antibody titers of CAV-2 in the dog sera were measured by virus neutralization (VN) test. RESULTS: We compared the results obtained between the VN and new I-ELISA tests. The sensitivity, specificity, and accuracy of new I-ELISA were 98.6%, 86.4% and 97.0% compared with VN test, respectively. New I-ELISA was significantly correlated with VN (r = 0.91). CONCLUSIONS: These results indicate that new I-ELISA is useful for sero-surveillance of CAV-2 in dog serum.

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer.

Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They are the aetiological agents of almost all cervical cancers as well as a sub-set of other anogenital and head and neck cancers. Hijacking of host cellular pathways is essential for virus pathogenesis; however, a major challenge remains to identify key host targets and to define their contribution to HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating the function of the transcription factor YAP. Increased YAP expression has been observed in cervical cancer but the mechanisms driving this increase remain unclear. We found significant down-regulation of the master Hippo regulatory kinase STK4 (also termed MST1) in cervical disease samples and cervical cancer cell lines compared with healthy controls. Re-introduction of STK4 inhibited the proliferation of HPV positive cervical cells and this corresponded with decreased YAP nuclear localization and decreased YAP-dependent gene expression. The HPV E6 and E7 oncoproteins maintained low STK4 expression in cervical cancer cells by upregulating the oncomiR miR-18a, which directly targeted the STK4 mRNA 3'UTR. Interestingly, miR-18a knockdown increased STK4 expression and activated the Hippo pathway, significantly reducing cervical cancer cell proliferation. Our results identify STK4 as a key cervical cancer tumour suppressor, which is targeted via miR-18a in HPV positive tumours. Our study indicates that activation of the Hippo pathway may offer a therapeutically beneficial option for cervical cancer treatment.

Establishment of multiplex RT-PCR for differentiation between rabies virus with and that without mutation at position 333 of glycoprotein.

Rabid raccoon dogs (Nyctereutes procyonoides koreensis) have been responsible for animal rabies in South Korea since the 1990s. A recombinant rabies vaccine strain, designated as ERAGS, was constructed for use as a bait vaccine. Therefore, new means of differentiating ERAGS from other rabies virus (RABV) strains will be required in biological manufacturing and diagnostic service centers. In this study, we designed two specific primer sets for differentiation between ERAGS and other RABVs based on mutation in the RABV glycoprotein gene. Polymerase chain reaction analysis of the glycoprotein gene revealed two DNA bands of 383 bp and 583 bp in the ERAGS strain but a single DNA band of 383 bp in the field strains. The detection limits of multiplex reverse transcription polymerase chain reaction (RT-PCR) were 80 and 8 FAID50/reaction for the ERAGS and Evelyn-Rokitnicki-Abelseth strains, respectively. No cross-reactions were detected in the non-RABV reference viruses, including canine distemper virus, parvovirus, canine adenovirus type 1 and 2, and parainfluenza virus. The results of multiplex RT-PCR were 100% consistent with those of the fluorescent antibody test. Therefore, one-step multiplex RT-PCR is likely useful for differentiation between RABVs with and those without mutation at position 333 of the RABV glycoprotein gene.

Bovine tongue epithelium-derived cells: A new source of bovine mesenchymal stem cells.

Mesenchymal stem cells (MSCs) possess the ability to differentiate into multiple cell lineages, and thus, confer great potential for use in regenerative medicine and biotechnology. In the present study, we attempted to isolate and characterize bovine tongue tissue epithelium-derived MSCs (boT-MSCs) and investigate the culture conditions required for long-term culturing of boT-MSCs. boT-MSCs were successfully isolated by the collagenase digestion method and their proliferative capacity was maintained for up to 20 or more passages. We observed a significant increase in the proliferation of boT-MSCs during the 20 consecutive passages under low-glucose Dulbecco's modified Eagle's medium culture condition among the three culture conditions. These boT-MSCs presented pluripotency markers (octamer-binding transcription factor 3/4 (Oct3/4) and sex determining region Y-box2 (Sox2)) and cell surface markers, which included CD13, CD29, CD44, CD73, CD90, CD105, CD166, and major histocompatibility complex (MHC) class I (MHC-I) but not CD11b, CD14, CD31, CD34, CD45, CD80, CD86, CD106, CD117, and MHC-II at third passage. Moreover, these boT-MSCs could differentiate into mesodermal (adipocyte, osteocyte, and chondrocyte) cell lineages. Thus, the present study suggests that the tongue of bovines could be used as a source of bovine MSCs.

Pyrethroid resistance in the pest mite, Halotydeus destructor: Dominance patterns and a new method for resistance screening.

An L1024F substitution in the para gene, which encodes a subunit of the voltage-gated sodium channel, has been implicated in pyrethroid resistance in a mite pest, Halotydeus destructor, which attacks rape and other grain crops. A high-resolution melt (HRM) genotyping assay was developed for testing the relative pyrethroid susceptibility of different para genotypes and for high-throughput field screening of resistant alleles. The L1024F mutation was found to be incompletely recessive in phenotypic laboratory bioassays with the pyrethroid pesticide, bifenthrin. While the resistance ratio of heterozygotes (RS) to susceptible homozygotes (SS) was <6 in 24 h bioassays, the resistant homozygotes (RR) (with a resistance ratio > 200,000) survived the recommended field rate of bifenthrin (100 mgL-1). HRM genotyping of mites from field populations across Australia indicated the presence of resistant alleles in Western Australia and South Australia, but not in Victoria and New South Wales. The assay developed will be useful for routine screening of pyrethroid resistance, and the dominance relationships established here point to useful resistance management strategies involving the maintenance of reservoirs of susceptible mites to dilute resistant homozygotes in a population.

Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

BACKGROUND: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). MATERIALS AND METHODS: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T). RESULTS: During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months, P = 0.0234, OS: 7.8 vs. 15.7 months, P = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months, P = 0.0437, OS: 20.5 vs. 18.2 months, P = 0.7820). CONCLUSIONS: Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.

Factors associated with prolonged length of stay for elective hepatobiliary and neurosurgery patients: a retrospective medical record review.

BACKGROUND: Patients with prolonged length of hospital stay (LOS) not only increase their risks of nosocomial infections but also deny other patients access to inpatient care. Hepatobiliary (HPB) malignancies have some of highest incidences in East and Southeast Asia and the management of patients undergoing HPB surgeries have yet to be standardized. With improved neurosurgery techniques for intracranial aneurysms and tumors, neurosurgeries (NS) can be expected to increase. Elective surgeries account for far more operations than emergencies surgeries. Thus, with potentially increased numbers of elective HPB and NS, this study seeks to explore perioperative factors associated with prolonged LOS for these patients to improve safety and quality of practice. METHODS: A retrospective cross-sectional medical record review study from January 2014 to January 2015 was conducted at a 1250-bed tertiary academic hospital in Singapore. All elective HPB and NS patients over 18 years old were included in the study except day and emergency surgeries, resulting in 150 and 166 patients respectively. Prolonged LOS was defined as above median LOS based on the complexity of the surgical procedure. The predictor variables were preoperative, intraoperative, and postoperative factors. Student's t-test and stepwise logistic regression analyses were conducted to determine which factors were associated with prolonged LOS. RESULTS: Factors associated with prolonged LOS for the HPB sample were age and admission after 5 pm but for the NS sample, they were functional status, referral to occupational therapy, and the number of hospital-acquired infections. CONCLUSION: Our findings indicate that preoperative factors had the greatest association with prolonged LOS for HPB and NS elective surgeries even after adjusting for surgical complexity, suggesting that patient safety and quality of care may be improved with better pre-surgery patient preparation and admission practices.

Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.

A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.

MTCH2 is a conserved regulator of lipid homeostasis.

OBJECTIVE: More than one-third of U.S. adults have obesity, causing an alarming increase in obesity-related comorbidities such as type 2 diabetes. The functional role of mitochondrial carrier homolog 2 (MTCH2), a human obesity-associated gene, in lipid homeostasis was investigated in Caenorhabditis elegans, cell culture, and mice. METHODS: In C. elegans, MTCH2/MTCH-1 was depleted, using RNAi and a genetic mutant, and overexpressed to assess its effect on lipid accumulation. In cells and mice, shRNAs against MTCH2 were used for knockdown and MTCH2 overexpression vectors were used for overexpression to study the role of this gene in fat accumulation. RESULTS: MTCH2 knockdown reduced lipid accumulation in adipocyte-like cells in vitro and in C. elegans and mice in vivo. MTCH2 overexpression increased fat accumulation in cell culture, C. elegans, and mice. Acute MTCH2 inhibition reduced fat accumulation in animals subjected to a high-fat diet. Finally, MTCH2 influenced estrogen receptor 1 (ESR1) activity. CONCLUSIONS: MTCH2 is a conserved regulator of lipid homeostasis. MTCH2 was found to be both required and sufficient for lipid homeostasis shifts, suggesting that pharmacological inhibition of MTCH2 could be therapeutic for treatment of obesity and related disorders. MTCH2 could influence lipid homeostasis through inhibition of ESR1 activity.

Cancer Mortality Risks from Long-term Exposure to Ambient Fine Particle.

BACKGROUND: Few studies have assessed long-term effects of particulate matter (PM) with aerodynamic diameter < 2.5 µm (PM2.5) on mortality for causes of cancer other than the lung; we assessed the effects on multiple causes. In Hong Kong, most people live and work in urban or suburban areas with high-rise buildings. This facilitates the estimation of PM2.5 exposure of individuals, taking into account the height of residence above ground level for assessment of the long-term health effects with sufficient statistical power. METHODS: We recruited 66,820 persons who were ≥65 in 1998 to 2001 and followed up for mortality outcomes until 2011. Annual concentrations of PM at their residential addresses were estimated using PM2.5 concentrations measured at fixed-site monitors, horizontal-vertical locations, and satellite data. We used Cox regression model to assess the HR of mortality for cancer per 10 µg/m(3) increase of PM2.5 RESULTS: PM2.5 was associated with increased risk of mortality for all causes of cancer [HR, 1.22 (95% CI, 1.11-1.34)] and for specific cause of cancer in upper digestive tract [1.42 (1.06-1.89)], digestive accessory organs [1.35 (1.06-1.71)] in all subjects; breast [1.80 (1.26-2.55)] in females; and lung [1.36 (1.05-1.77)] in males. CONCLUSIONS: Long-term exposures to PM2.5 are associated with elevated risks of cancer in various organs. IMPACT: This study is particularly timely in China, where compelling evidence is needed to support the pollution control policy to ameliorate the health damages associated with economic growth. Cancer Epidemiol Biomarkers Prev; 25(5); 839-45. ©2016 AACR.

Is Traditional Chinese Exercise Associated With Lower Mortality Rates in Older People? Evidence From a Prospective Chinese Elderly Cohort Study in Hong Kong.

The inverse association of aerobic exercise with death has been well documented. However, evidence on traditional Chinese exercise (TCE) and rate of death in older Chinese is limited. Multivariable Cox regression analysis was used to assess the associations of TCE and other types of physical activity with death from all causes and specific causes in a population-based prospective cohort of 66,820 Chinese persons (≥65 years of age) who were enrolled between July 1998 and December 2001 at all 18 Elderly Health Centers in Hong Kong and followed up until May 31, 2012. During an average of 10.9 years of follow-up, 19,845 deaths occurred. TCE was inversely associated with death from all causes (hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.74, 0.82), cardiovascular disease (HR = 0.77, 95% CI: 0.70, 0.85), cancer (HR = 0.84, 95% CI: 0.77, 0.92), and respiratory disease (HR = 0.71, 95% CI: 0.63, 0.80) but was not associated with death from accidents (excluding falls) (HR = 0.79, 95% CI: 0.44, 1.42), after adjustment for age, sex, socioeconomic position, alcohol use, smoking, body mass index, and health status. The associations did not vary by amount of TCE. Aerobic exercise had similar inverse associations as TCE, but associations for stretching exercises and walking slowly were less marked. Further studies of TCE are warranted in older Chinese.

Evaluation of biocompatible alginate- and deferoxamine-coated ternary composites for magnetic resonance imaging and gene delivery into glioblastoma cells.

BACKGROUND: This paper describes comparative studies in cytotoxicities, magnetic resonance imaging (MRI), and gene delivery into glioblastoma U87MG or U138MG cells with ternary composites that are consist of superparamagnetic iron oxide (SPIO) nanoparticles (NPs) (size: 8-10 nm) with different surface coatings, circular plasmid DNA (pDNA) (~4 kb) equipped with fluorescent/luminescent probe, and branched polyethylenimine (25 kDa, PDI 2.5). METHODS: Three types of SPIO-NPs were used, including: (I) naked iron oxide NPs with Fe-OH surface group (Bare-NP); (II) iron oxide NPs with a coating of alginate (Alg-NPs); and (III) iron oxide NPs with a coating of deferoxamine (Def-NPs). By tuning the polyethylenimine (PEI)/NP ratios and with a fixed DNA amount, different ternary composites were employed for NP/gene transfection into glioblastoma U87MG or U138MG cells, which were then characterized by Prussian blue staining, in vitro MRI, green fluorescence protein (GFP) fluorescence and luciferase assay. RESULTS: Among the composites prepared, 0.2 ng PEI/0.5 µg DNA/1.0 µg Bare-NP ternary composite possessed the best cellular uptake efficiency of NP to the cytoplasm, following the trend Bare-NP > Alg-NP > Def-NP. This observation was consistent to the MRI assessments with in vitro T 2 relaxivity (r 2) values of 46.0, 35.5, and 23.7 s(-1)·µM(-1)·Fe, respectively. For cellular uptake efficiency of the pDNA, all variations of PEI/NP ratios of the composites did not yield significant differences. However, cellular uptake efficiencies of pDNA in the ternary composites in U138MG cells were generally higher than that of U87MG cells by an order of magnitude. Exceptionally, the ternary composite 0.2 ng PEI/0.5 µg DNA/1.0 µg Bare-NP possessed a lowered luciferase activity RLU for gene expression in U138MG cells. A total of 0.2 ng PEI/0.5 µg DNA/0.1 µg Bare-NP would be uptaken to the cell nucleus with the highest luciferase activity. A working concentration range of PEI with at least 15% higher cell viabilities than lipofectamine was 0.1 to 0.2 ng/well. The cytotoxicities became significant when 0.5 ng/well PEI was present in the ternary composites. CONCLUSIONS: The as-prepared composites offer potential biomedical applications in simultaneous gene delivery, imaging contrast enhancement, and metabolism study.

FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development.

The Snail family of transcription factors are core inducers of epithelial-to-mesenchymal transition (EMT). Here we show that the F-box protein FBXO11 recognizes and promotes ubiquitin-mediated degradation of multiple Snail family members including Scratch. The association between FBXO11 and Snai1 in vitro is independent of Snai1 phosphorylation. Overexpression of FBXO11 in mesenchymal cells reduces Snail protein abundance and cellular invasiveness. Conversely, depletion of endogenous FBXO11 in epithelial cancer cells causes Snail protein accumulation, EMT, and tumor invasion, as well as loss of estrogen receptor expression in breast cancer cells. Expression of FBXO11 is downregulated by EMT-inducing signals TGFß and nickel. In human cancer, high FBXO11 levels correlate with expression of epithelial markers and favorable prognosis. The results suggest that FBXO11 sustains the epithelial state and inhibits cancer progression. Inactivation of FBXO11 in mice leads to neonatal lethality, epidermal thickening, and increased Snail protein levels in epidermis, validating that FBXO11 is a physiological ubiquitin ligase of Snail. Moreover, in C. elegans, the FBXO11 mutant phenotype is attributed to the Snail factors as it is suppressed by inactivation/depletion of Snail homologs. Collectively, these findings suggest that the FBXO11-Snail regulatory axis is evolutionarily conserved and critically governs carcinoma progression and mammalian epidermal development.

Smoking and mortality in a prospective cohort study of elderly Chinese in Hong Kong.

BACKGROUND AND AIMS: Large cohort studies on smoking and mortality in elderly people are scarce, and few studies examined smokers aged 85+ years separately. We estimated the risks of all-cause and cause-specific mortality due to smoking in an elderly Chinese cohort in Hong Kong. DESIGN: A population-based prospective cohort of 65,510 Chinese enrolled from 1998 to 2001 and followed until May 2012. SETTING: All 18 Elderly Health Service centres in Hong Kong, China. PARTICIPANTS: Elderly people aged 65+ years. MEASUREMENTS: Self-reported smoking status was assessed at baseline interview and categorized as never, former and current smokers. FINDINGS: Compared with never smokers, after adjustment for sex, age, education, social security assistance, housing type, monthly expenditure, alcohol use, depressive symptoms and health status, the hazard ratio (HR) for current smokers was 1.89 [95% confidence interval (CI) = 1.81-1.98] for all participants aged 65+ years at baseline, corresponding to an attributable fraction (AF) of about 50%, which is based on AF = (HR-1)/HR. As the effect of smoking varied with age (P for age interaction <0.001), subgroup analysis by age group showed that the adjusted HR for current smokers aged 65-84 years was 1.93 (95% CI = 1.84-2.03), and for 85+ years was 1.29 (95% CI = 1.05-1.58). All the risk estimates did not vary by sex (P for sex interaction ranged 0.74-0.89). CONCLUSIONS: In Hong Kong, the risk of death from smoking appears to be the same for Chinese women as it is for men. Half of all deaths in Chinese smokers aged 65 years and older and a quarter of all deaths in Chinese smokers aged 85 years and older are caused by smoking-attributable diseases.

Self-rated health and mortality in a prospective Chinese elderly cohort study in Hong Kong.

OBJECTIVES: In the West, self-rated health reliably predicts death, but conceptualizations of health and cause-composition of mortality may be contextually specific. Little is known as to how self-rated health predicts death in non-Western settings. METHODS: Multivariable Cox regression analysis was used to assess the adjusted associations of age-comparative and self-comparative self-rated health with death from all- and specific-causes using a population-based cohort of 66,820 Chinese (65+years) enrolled from 1998 to 2001 at 18 Elderly Health Centers in Hong Kong, and followed until May 31, 2012. RESULTS: During an average of 10.9 years follow-up, 19,845 deaths occurred with 6336 from cancer. Worse age-comparative self-rated health, compared with better, was positively associated with death from all-causes (hazard ratio 1.68, 95% confidence interval 1.59, 1.77), cardiovascular disease (hazard ratio 1.83, 95% confidence interval 1.66, 2.02), stroke (hazard ratio 1.93, 95% confidence interval 1.63, 2.29), ischemic heart disease (hazard ratio 1.77, 95% confidence interval 1.51, 2.08), cancer (hazard ratio 1.17, 95% confidence interval 1.06, 1.30) and respiratory disease (hazard ratio 2.25, 95% confidence interval 2.01, 2.52), adjusted for age and sex. Self-comparative self-rated health was not associated with higher mortality. CONCLUSION: Age-comparative self-rated health predicted death in older people from a non-Western setting although the association was less marked than in Western settings.