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Accumulating evidence demonstrates that cancer is an oxidative stress-related disease, and oxidative stress is closely linked with heat shock proteins (HSPs). Lipid oxidative stress is derived from lipid metabolism dysregulation that is closely associated with the development and progression of malignancies. This study sought to investigate regulatory roles of HSPs in fatty acid metabolism abnormality in ovarian cancer. Pathway network analysis of 5115 mitochondrial expressed proteins in ovarian cancer revealed various lipid metabolism pathway alterations, including fatty acid degradation, fatty acid metabolism, butanoate metabolism, and propanoate metabolism. HSP60 regulated the expressions of lipid metabolism proteins in these lipid metabolism pathways, including ADH5, ECHS1, EHHADH, HIBCH, SREBP1, ACC1, and ALDH2. Further, interfering HSP60 expression inhibited migration, proliferation, and cell cycle and induced apoptosis of ovarian cancer cells in vitro. In addition, mitochondrial phosphoproteomics and immunoprecipitation-western blot experiments identified and confirmed that phosphorylation occurred at residue Ser70 in protein HSP60, which might regulate protein folding of ALDH2 and ACADS in ovarian cancers. These findings clearly demonstrated that lipid metabolism abnormality occurred in oxidative stress-related ovarian cancer and that HSP60 and its phosphorylation might regulate this lipid metabolism abnormality in ovarian cancer. It opens a novel vision in the lipid metabolism reprogramming in human ovarian cancer.

Evidences have supported the pivotal roles of stem cells in mammary gland development. Many molecular markers have been identified to characterize mammary stem cells. Cellular fate mapping of mammary stem cells by lineage tracing has put unprecedented insights into the mammary stem cell biology, which identified two subtypes of mammary stem cells, including unipotent and multipotent, which specifically differentiate to luminal or basal cells. The emerging single-cell sequencing profiles have given a more comprehensive understanding on the cellular hierarchy and lineage signatures of mammary epithelium. Besides, the stem cell niche worked as an essential regulator in sustaining the functions of mammary stem cells. In this review, we provide an overview of the characteristics of mammary stem cells. The cellular origins of mammary gland are discussed to understand the stem cell heterogeneity and their diverse differentiations. Importantly, current studies suggested that the breast cancer stem cells may originate from the mammary stem cells after specific mutations, indicating their close relationships. Here, we also outline the recent advances and controversies in the cancer relevance of mammary stem cells.

Background. Mitochondria are the energy factories of cells. The abnormality of mitochondrial energy metabolism pathways is closely related to the occurrence and development of lung cancer. The abnormal genes in mitochondrial energy metabolism pathways might be the novel targets and biomarkers to diagnose and treat lung cancers. Method. Genes in major mitochondrial energy metabolism pathways were obtained from the KEGG database. The transcriptomic, mutation, and clinical data of lung cancers were obtained from The Cancer Genome Atlas (TCGA) database. Genes and clinical biomarkers were mined that affected lung cancer survival. Gene enrichment analysis was performed with ClusterProfiler and the gene set enrichment analysis (GSEA). STRING database and Cytoscape were used for protein-protein interaction (PPI) analysis. The diagnostic biomarker pattern of lung cancer was optimized, and its accuracy was verified with 10-fold cross-validation. The four genes screened by logistic regression model were verified by western blot in 5 pairs of lung cancer specimens collected in hospital. Results. In total, 188 mitochondrial energy metabolism pathway-related genes (MMRGs) were included in this study. GSEA analysis found that MMRGs in the lung cancer group were mainly enriched in the metabolic pathway of oxidative phosphorylation and electron respiratory transport chain compared to the control group. Age did not affect the mutation frequency of MMRGs. Comparative analysis of these 188 MMRGs identified 43 differentially expressed MMRGs (24 upregulated and 19 downregulated) in the lung cancer group compared to the control group. The survival analysis of these 43 differentially expressed MMRGs found that the survival time was better in the low-expressed GAPDHS group than that in the high-expressed GAPDHS group of lung cancers. The advanced age, high expression of GAPDHS, low expressions of ACSBG1 and CYP4A11, and ACOX3 mutation were biomarkers of poor prognosis in lung cancers. PPI analysis showed that proteins such as GAPDH and GAPDHS interacted with many proteins in mitochondrial metabolic pathways. A four-MMRG-signature model ( y = 0.0069 ∗ ACADL − 0.001 ∗ ALDH 18 A 1 − 0.0405 ∗ CPT 1 B + 0.0008 ∗ PPARG − 1.625 ) was established to diagnose lung cancer with the accuracy up to 98.74%, AUC value up to 0.992, and a missed diagnosis rate of only 0.6%. Western blotting showed that ALDH18A1 and CPT1B proteins were significantly overexpressed in the lung cancer group ( p < 0.05 ), and ACADL and PPARG proteins were slightly underexpressed in the lung cancer group ( p < 0.05 ), which were consistent with the results of their corresponding mRNA expressions. Conclusion. Mitochondrial energy metabolism pathway alterations are the important hallmarks of lung cancer. Age did not increase the risk of MMRG mutation. High expression of GAPDHS, low expression of ACSBG1, low expression of CYP4A11, mutated ACOX3, and old age predict a poor prognosis of lung cancer. Four differentially expressed MMRGs (ACADL, ALDH18A1, CPT1B, and PPARG) established a logistic regression model, which could effectively diagnose lung cancer. At the protein level, ALDH18A1 and CPT1B were significantly upregulated, and ACADL and PPARG were slightly underexpressed, in the lung cancer group compared to the control group, which were consistent with the results of their corresponding mRNA expressions.

The entropic force attracts a lot of interest for its multifunctional properties. For instance, Einstein's field equation, Newton's law of gravitation and the Friedmann equation can be derived from the entropic force. In this paper, utilizing a new kind of rainbow gravity model that was proposed by Magueijo and Smolin, we explore the quantum gravity corrections to the entropic force. First, we derive the modified thermodynamics of a rainbow black hole via its surface gravity. Then, according to Verlinde's theory, the quantum corrections to the entropic force are obtained. The result shows that the modified entropic force is related not only to the properties of the black hole but also the Planck length $\ell_p$, and the rainbow parameter $\gamma$. Furthermore, based on the rainbow gravity corrected entropic force, the modified Einstein's field equation and the modified Friedmann equation are also derived., Comment: 10 pages

Infection is a major cause of increased mortality after a liver transplant (LT). This study sought to identify the incidence, prevalence and risk factors of microbial infection for recipients who underwent LT using grafts from donors after cardiac death (DCD).We retrospectively analysed the frequency and characteristics of post-transplantation infections in 236 recipients who underwent DCD LT between 1 January 2010 and 31 December 2014 in our centre and evaluated the risk factors of post-transplantation infection.Overall, 162 recipients acquired at least one type of infection during hospitalisation after LT, and the morbidity rate was 68.6%. Moreover, 19 of the 236 recipients died, with an overall mortality rate of 8.1%. In total, 752 pathogens were isolated. Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 26.1% (196), 58.2% (438) and 15.7% (118) of the pathogens, respectively. Kaplan-Meier curves of 1-year survival showed that recipients with infection had a significantly lower cumulative survival rate compared with those without infection (83.2% vs. 90.6%, p 0.05). Multivariate analysis revealed that age 60 years (p = 0.010) and severe hepatitis (p = 0.036) were independent risk factors for infection during hospitalisation after LT.Infection is a common complication after a DCD-LT that could impair 1-year survival. We suggest physicians pay more attention to the infection of recipients post-LT, especially those recipients greater than 60 years of age and those who suffered from severe hepatitis.

Aims.To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).Methods and Results.Participants (n=808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87;P=0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72;P=0.002). No major bleeding events were observed in any participant.Conclusion.Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.

This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries.

In this paper, the modified entropic force law is studied by using a new kind of generalized uncertainty principle which contains a minimal length, a minimal momentum and a maximal momentum. Firstly, the quantum corrections to the thermodynamics of a black hole is investigated. Then, according to Verlinde's theory, the generalized uncertainty principle (GUP) corrected entropic force is obtained. The result shows that the GUP corrected entropic force is related not only to the properties of the black holes, but also to the Planck length and the dimensionless constants $\alpha _{\rm{0}}$ and $\beta _{\rm{0}}$. Moreover, based on the GUP corrected entropic force, we also derive the modified Einstein's field equation (EFE) and the modified Friedmann equation., Comment: 16 pages. arXiv admin note: substantial text overlap with arXiv:1604.04702

The Human Variome Project (HVP) is an international consortium of clinicians, geneticists, and researchers from over 30 countries, aiming to facilitate the establishment and maintenance of standards, systems, and infrastructure for the worldwide collection and sharing of all genetic variations effecting human disease. The HVP-China Node will build new and supplement existing databases of genetic diseases. As the first effort, we have created a novel variant database of BRCA1 and BRCA2, mismatch repair genes (MMR), and APC genes for breast cancer, Lynch syndrome, and familial adenomatous polyposis (FAP), respectively, in the Chinese population using the Leiden Open Variation Database (LOVD) format. We searched PubMed and some Chinese search engines to collect all the variants of these genes in the Chinese population that have already been detected and reported. There are some differences in the gene variants between the Chinese population and that of other ethnicities. The database is available online at http://www.genomed.org/LOVD/. Our database will appear to users who survey other LOVD databases (e.g., by Google search, or by NCBI GeneTests search). Remote submissions are accepted, and the information is updated monthly.

The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.