Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging.

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting.

Efficacy and safety of dulaglutide monotherapy compared with glimepiride in East-Asian patients with type 2 diabetes in a multicentre, double-blind, randomized, parallel-arm, active comparator, phase III trial.

Aims: To compare the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide 1.5 and 0.75 mg with glimepiride in East-Asian patients with type 2 diabetes (T2D).

Thermoregulation-Independent Regulation of Sleep by Serotonin Revealed in Mice Defective in Serotonin Synthesis.

A role for 5-hydroxytryptamine (5-HT) or serotonin in sleep has been known for decades but was challenged by recent papers that concluded that the apparent sleep phenotype was secondary to defective thermoregulation. Those studies used mice lacking serotonergic neurons resulting from the loss of function mutations in the gene encoding the LIM homeobox transcription factor 1 (). Here we show that, while mutants failed to keep the physiologic body temperature, they exhibited more activities at the room and elevated temperatures.

Substantia Nigra Echogenicity Associated with Clinical Subtypes of Parkinson's Disease.

Background: It is debatable whether transcranial sonography (TCS) could be a biomarker for monitoring disease progression. Various phenotypes of Parkinson's disease (PD) may be a major reason contributing to the inconsistency.

Objective: We classified PD patients into different subtypes and evaluated the correlation between SN echogenicity and disease progression.

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.

Genome-Wide Association and Functional Studies Identify and as Novel Susceptibility Genes for Coronary Artery Disease.

Objective: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD.

Approach And Results: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs (single nucleotide polymorphisms), rs9486729 ( [Scm polycomb group protein-like 4]; odds ratio, 1.

Argininosuccinate synthetase 1 contributes to gastric cancer invasion and progression by modulating autophagy.

Argininosuccinate synthetase 1 (ASS1) is a rate-limited enzyme in arginine biosynthesis. The oncogenic potential of ASS1 in terms of prognosis and cancer metastasis in arginine prototrophic gastric cancer (GC) remains unclear at present. We identify differentially expressed proteins in microdissected GC tumor cells relative to adjacent nontumor epithelia by isobaric mass tag for relative and absolute quantitation proteomics analysis.

Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson's disease or essential tremor.

Objectives The serum concentration of brain-derived neurotrophic factor (BDNF) was compared among patients with Parkinson's disease (PD), patients with essential tremor (ET), and healthy participants, and its association with clinical features of PD and ET was assessed. Methods Demographic and clinical data were collected from 60 patients with PD at different clinical stages, 60 patients with ET, and 60 controls. All participants' serum BDNF concentrations were measured.

Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.

Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials.

Objective: The main of this study is to clarify whether hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus monkeys that had received intramyocardial injections of 1×10 EGFP (enhanced green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group).

Non-Transition-Metal Catalytic System for N Reduction to NH: A Density Functional Theory Study of Al-Doped Graphene.

The prevalent catalysts for natural and artificial N fixation are known to hinge upon transition-metal (TM) elements. Herein, we demonstrate by density functional theory that Al-doped graphene is a potential non-TM catalyst to convert N to NH in the presence of relatively mild proton/electron sources. In the integrated structure of the catalyst, the Al atom serves as a binding site and catalytic center while the graphene framework serves as an electron buffer during the successive proton/electron additions to N and its various downstream NH intermediates.

Poor nighttime sleep is positively associated with dyskinesia in Parkinson's disease patients.

Background: Dyskinesia is a troublesome complication of long-term dopaminergic medications in Parkinson's disease (PD) patients. Many factors are reported to be associated with dyskinesia in PD.

Objective: To investigate the association between sleep quality and dyskinesia in patients with PD.

Magnitude of Soluble ST2 as a Novel Biomarker for Acute Aortic Dissection.

Background: Misdiagnosis of acute aortic dissection (AAD) can lead to significant morbidity and death. Soluble ST2 (sST2) is a cardiovascular injury-related biomarker. The extent to which sST2 is elevated in AAD and whether sST2 can discriminate AAD from other causes of sudden-onset severe chest pain are unknown.

Odor selectivity of hyposmia and cognitive impairment in patients with Parkinson's disease.

Objective: Hyposmia is one of the earliest non-motor features of Parkinson's disease (PD) and can precede the onset of motor symptoms by years. Most of the current olfactory detection tests are targeted at Western populations. The exact relationship between hyposmia and cognitive impairment is unknown.

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease.

Introduction: Loss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD.

Different iron deposition patterns in early- and middle-late-onset Parkinson's disease.

Background: Iron deposition may contribute to the clinical symptoms in Parkinson's disease (PD). With partial different clinical manifestations, the iron deposition patterns between patients with early-onset Parkinson's disease (EOPD) and middle-late-onset Parkinson's disease (M-LOPD) are still unclear. This study was designed to investigate the patterns of iron deposition and their clinical relevance in EOPD and M-LOPD patients, using quantitative susceptibility mapping technique.

Deletion of Angiotensin-Converting Enzyme-2 Promotes Hypertensive Nephropathy by Targeting Smad7 for Ubiquitin Degradation.

Angiotensin-converting enzyme-2 (ACE2) is downregulated in hypertensive nephropathy. The present study investigated the mechanisms whereby loss of ACE2 promoted angiotensin II-induced hypertensive nephropathy in ACE2 gene knockout mice. We found that compared with wild-type animals, mice lacking ACE2 developed much more severe hypertensive nephropathy in response to chronic angiotensin II infusion, including higher levels of blood pressure, urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation.

Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility.

Background: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages.

Methods: Bioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4).

Evaluation of Visual-Evoked Cerebral Metabolic Rate of Oxygen as a Diagnostic Marker in Multiple Sclerosis.

A multiple sclerosis (MS) diagnosis often relies upon clinical presentation and qualitative analysis of standard, magnetic resonance brain images. However, the accuracy of MS diagnoses can be improved by utilizing advanced brain imaging methods. We assessed the accuracy of a new neuroimaging marker, visual-evoked cerebral metabolic rate of oxygen (veCMRO₂), in classifying MS patients and closely age- and sex-matched healthy control (HC) participants.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

Background: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.

Methods: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks.

Urban-Rural Disparities in Energy Intake and Contribution of Fat and Animal Source Foods in Chinese Children Aged 4-17 Years.

Objective: Excessive energy intake and poor food choices are major health concerns associated with overweight and obesity risk. This study aims to explore disparities in energy intake and the contributions from fat and animal source foods among Chinese school-aged children and adolescents in different communities based on urbanization levels.

Design: Three consecutive 24 h recalls were used to assess dietary intake.

Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification.

Objective: Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.

Approach And Results: We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia.

Acupuncture Therapy and Incidence of Depression After Stroke.

Background And Purpose: We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression.

Methods: This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714).