Macrophage derived foam cells in atherosclerotic plaques are the major factor responsible for the pathogenesis of atherosclerosis (AS). During advanced AS, macrophage-specific macroautophagy/autophagy is dysfunctional. 1, 25-dihydroxy vitamin D3 (VitD3) and its receptor VDR (vitamin D receptor) are reported to inhibit foam cell formation and induce autophagy; however, the role of VitD3-VDR-induced autophagy and foam cell formation in AS has not been explored. Here we find that VitD3 significantly recovered oxidized low-density lipoprotein-impaired autophagy, as well as increased autophagy-mediated lipid breakdown in mouse bone marrow-derived macrophages and human monocyte-derived macrophages, thus inhibiting the conversion of macrophages into foam cells. Importantly, VitD3 functions through its receptor VDR to upregulate autophagy and attenuate the accumulation of lipids in macrophages. Moreover, this study is the first occasion to report the interesting link between VitD3 signaling and PTPN6/SHP-1 (protein tyrosine phosphatase non-receptor type 6) in macrophages. VitD3-induced autophagy was abrogated in the presence of the PTPN6/Ptpn6 shRNA or inhibitor. VDR along with RXRA (retinoid X receptor alpha), and NCOA1 (nuclear receptor coactivator 1), are recruited to a specific response element located on the gene promoter and induce PTPN6 expression. PTPN6 contributes to VitD3-mediated autophagy by regulating autophagy-related genes via activation of MAPK1 (mitogen-activated protein kinase 1) and CEBPB (CCAAT enhancer binding protein beta). Furthermore, expression of PTPN6 is also crucial for VitD3-mediated inhibition of macrophage foam cell formation through autophagy.  https://www.selleckchem.com/products/sj6986.html  Thus, VitD3-VDR-PTPN6 axis-regulated autophagy attenuates foam cell formation in macrophages.
  Physiotherapy is a commonly prescribed intervention for people with Parkinson's disease (PD). Conventional types of physiotherapy have been studied extensively, while novel modalities are being developed and evaluated.
 
  To evaluate the effectiveness of conventional and more recent physiotherapy interventions for people with PD. The meta-analysis performed as part of the 2014 
  was used as the starting point and updated with the latest evidence.
 
  We performed a systematic search in PubMed, CINAHL, Embase, and Web of Science. Randomized controlled trials comparing any physiotherapy intervention with no intervention or sham treatment were included. Trials were classified into 12 categories conventional physiotherapy, resistance training, treadmill training, strategy training, dance, martial arts, aerobic exercises, hydrotherapy, balance and gait training, dual tasking, exergaming, and Nordic walking. Outcomes included motor symptoms, balance, gait, and quality of life, and are presented as standardized meanve efficacy of the various treatments.
 This meta-analysis provides a comprehensive overview of the evidence for the effectiveness of different physiotherapy interventions in the management of PD, allowing clinicians and patients to make an evidence-based decision for specific treatment modalities. Further work is needed to directly compare the relative efficacy of the various treatments.Although molecular targeted therapies have recently displayed therapeutic effects in acute myeloid leukemia (AML), limited response and acquired resistance remain common problems. Numerous studies have associated autophagy, an essential degradation process involved in the cellular response to stress, with the development and therapeutic response of cancers including AML. Thus, we review studies on the role of autophagy in AML development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML. Abbreviations AML acute myeloid leukemia; AMPK AMP-activated protein kinase; APL acute promyelocytic leukemia; ATG autophagy related; ATM ATM serine/threonine kinase; ATO arsenic trioxide; ATRA all trans retinoic acid; BCL2 BCL2 apoptosis regulator; BECN1 beclin 1; BET proteins, bromodomain and extra-terminal domain family; CMA chaperone-mediated autophagy; CQ chloroquine; DNMT, DNA methyltransferase; DOT1L DOT1 like histone lysine methyltransferase; FLT3 fms related receptor tyrosine kinase 3; FIS1 fission, mitochondrial 1; HCQ hydroxychloroquine; HSC hematopoietic stem cell; IDH isocitrate dehydrogenase; ITD internal tandem duplication; KMT2A/MLL lysine methyltransferase 2A; LSC leukemia stem cell; MDS myelodysplastic syndromes; MTORC1 mechanistic target of rapamycin kinase complex 1; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NPM1 nucleophosmin 1; PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3; PML PML nuclear body scaffold; ROS reactive oxygen species; RB1CC1/FIP200 RB1 inducible coiled-coil 1; SAHA vorinostat; SQSTM1 sequestosome 1; TET2 tet methylcytosine dioxygenase 2; TKD tyrosine kinase domain; TKI tyrosine kinase inhibitor; TP53/p53 tumor protein p53; ULK1 unc-51 like autophagy activating kinase 1; VPA valproic acid; WDFY3/ALFY WD repeat and FYVE domain containing 3.
  The availability of local, state, and national data on alcohol outlet density have important implications for policies and interventions aiming to reduce alcohol-related problems. High-quality data on locations of alcohol outlets is important to accurately inform community interventions and public health initiatives, but such data is often not maintained, readily available, or of sufficient quality. 
  This study aims to examine the discrepancies between alcohol outlet databases and how neighborhood characteristics (i.e. income, majority racial population, urbanicity) are associated with the discrepancies between databases. 
  Data was collected from national (
   = 1), local (
   = 2), and state databases (
   = 3). Negative binomial regression models were used to assess discrepancies in alcohol outlet count at the ZIP code level based on the data source. 
  The average density of alcohol outlets (per 1000 residents) ranged from 0.71 to 2.17 in Maryland, 1.65 to 5.17 in Wisconsin, and 1.09 to 1.22 in Oregon based on different sources of data.