Lysosomal membrane permeabilization is involved in oxidative stress-induced apoptotic cell death in LAMP2-deficient iPSCs-derived cerebral cortical neurons

postprin

Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is an aggressive tumor, with a high mortality rate due to late symptom presentation and frequent tumor recurrences and metastasis. It is also a rapidly growing tumor supported by different metabolic mechanisms; nevertheless, the biological and molecular mechanisms involved in the metabolic reprogramming in HCC are unclear. In this study, we found that pyruvate kinase M2 (PKM2) was frequently over-expressed in human HCCs and its over-expression was associated with aggressive clinicopathological features and poor prognosis of HCC patients. Furthermore, knockdown of PKM2 suppressed aerobic glycolysis and cell proliferation in HCC cell lines in vitro. Importantly, knockdown of PKM2 hampered HCC growth in both subcutaneous injection and orthotopic liver implantation models, and reduced lung metastasis in vivo. Of significance, PKM2 over-expression in human HCCs was associated with a down-regulation of a liver-specific microRNA, miR-122. We further showed that miR-122 interacted with the 3UTR of the PKM2 gene. Re-expression of miR-122 in HCC cell lines reduced PKM2 expression, decreased glucose uptake in vitro, and suppressed HCC tumor growth in vivo. Our clinical data and functional studies have revealed a novel biological mechanism involved in HCC metabolic reprogramming.published_or_final_versio

The effects of a family-centered psychosocial-based nutrition intervention in patients with advanced cancer: the PiCNIC2 pilot randomised controlled trial

BACKGROUND: Malnutrition in advanced cancer patients is common but limited and inconclusive data exists on the effectiveness of nutrition interventions. Feasibility and acceptability of a novel family-based nutritional psychosocial intervention were established recently. The aims of this present study were to assess the feasibility of undertaking a randomised controlled trial of the latter intervention, to pilot test outcome measures and to explore preliminary outcomes.METHODS: Pilot randomised controlled trial recruiting advanced cancer patients and family caregivers in Australia and Hong Kong. Participants were randomised and assigned to one of two groups, either a family-centered nutritional intervention or the control group receiving usual care only. The intervention provided 2-3 h of direct dietitian contact time with patients and family members over a 4-6-week period. During the intervention, issues with nutrition impact symptoms and food or eating-related psychosocial concerns were addressed through nutrition counselling, with a focus on improving nutrition-related communication between the dyads and setting nutritional goals. Feasibility assessment included recruitment, consent rate, retention rate, and acceptability of assessment tools. Validated nutritional and quality of life self-reported measures were used to collect patient and caregiver outcome data, including the 3-day food diary, the Patient-Generated Subjective Global Assessment Short Form, the Functional Assessment Anorexia/Cachexia scale, Eating-related Distress or Enjoyment, and measures of self-efficacy, carers' distress, anxiety and depression.RESULTS: Seventy-four patients and 54 family caregivers participated in the study. Recruitment was challenging, and for every patient agreeing to participate, 14-31 patients had to be screened. The consent rate was 44% in patients and 55% in caregivers. Only half the participants completed the trial's final assessment. The data showed promise for some patient outcomes in the intervention group, particularly with improvements in eating-related distress (p = 0.046 in the Australian data; p = 0.07 in the Hong Kong data), eating-related enjoyment (p = 0.024, Hong Kong data) and quality of life (p = 0.045, Australian data). Energy and protein intake also increased in a clinically meaningful way. Caregiver data on eating-related distress, anxiety, depression and caregiving burden, however, showed little or no change.CONCLUSIONS: Despite challenges with participant recruitment, the intervention demonstrates good potential to have positive effects on patients' nutritional status and eating-related distress. The results of this trial warrant a larger and fully-powered trial to ascertain the effectiveness of this intervention.TRIAL REGISTRATION: The trial was registered with the Australian &amp; New Zealand Clinical Trials Registry, registration number ACTRN12618001352291 .</p

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells

published_or_final_versio

Automatic 3D tooth segmentation using convolutional neural networks in harmonic parameter space

Automatic segmentation of 3D tooth models into individual teeth is an important step in orthodontic CAD systems. 3D tooth segmentation is a mesh instance segmentation task. Complex geometric features on the surface of 3D tooth models often lead to failure of tooth boundary detection, so it is difficult to achieve automatic and accurate segmentation by traditional mesh segmentation methods. We propose a novel solution to address this problem. We map a 3D tooth model isomorphically to a 2D harmonic parameter space and convert it into an image. This allows us to use a CNN to learn a highly robust image segmentation model to achieve automated and accurate segmentation of 3D tooth models. Finally, we map the image segmentation mask back to the 3D tooth model and refine the segmentation result using an improved Fuzzy Clustering-and-Cuts algorithm. Our method has been incorporated into an orthodontic CAD system, and performs well in practice

Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

Peer reviewe

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe

Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

Peer reviewe

Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

Peer reviewe

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe