(E)-3-(2-Fur­yl)-1-(2-hydroxy­phen­yl)prop-2-en-1-one

In the title mol­ecule, C13H10O3, an intra­molecular O—H⋯O hydrogen bond influences the mol­ecular conformation, and the benzene and furan rings form a dihedral angle of 8.35 (7)°. Weak inter­molecular C—H⋯O hydrogen bonds link mol­ecules into sheets parallel to the bc plane

Neurodegenerative Diseases Associated with Mutations in <em>SLC25A46</em>

Neurodegenerative diseases present substantial clinical challenges. Their processes have been linked with various genetic causes, including mutations of genes encoding proteins associated with mitochondrial dynamics. Biallelic mutations in SLC25A46 have been identified as novel causes of a wide spectrum of neurological diseases with recessive inheritance, including optic atrophy, Charcot-Marie-Tooth neuropathy (CMT) type 2A neuropathy, Leigh syndrome, progressive myoclonic ataxia, and lethal congenital pontocerebellar hypoplasia. SLC25A46 (solute carrier family 25 member 46) is a membrane transit protein that is expressed in the mitochondrial outer membrane where it plays a major role in mitochondrial dynamics and cristae maintenance. This chapter presents recent findings on: (1) the clinical heterogeneity of SLC25A46-related neuropathies; (2) the SLC25A46 mutation spectrum and associated genotype-phenotype correlation; and (3) pathophysiological functions of SLC25A46 as characterized in cells and mouse models. A better understanding of the etiology of SLC25146-linked diseases will elucidate therapeutic perspectives

Altered Tryptophan Metabolism as a Paradigm for Good and Bad Aspects of Immune Privilege in Chronic Inflammatory Diseases

The term “immune privilege” was coined to describe weak immunogenicity (hypo-immunity) that manifests in some transplant settings. We extended this concept to encompass hypo-immunity that manifests at local sites of inflammation relevant to clinical diseases. Here, we focus on emerging evidence that enhanced tryptophan catabolism is a key metabolic process that promotes and sustains induced immune privilege, and discuss the implications for exploiting this knowledge to improve treatments for hypo-immune and hyper-immune syndromes using strategies to manipulate tryptophan metabolism

2-Amino-4-(2-chloro­phen­yl)-5-oxo-5,6,7,8-tetra­hydro-4H-chromene-3-carbonitrile ethanol monosolvate

In the title compound, C16H13ClN2O2·C2H6O, the fused cyclo­hexene and pyran rings adopt envelope and flattened boat conformations, respectively. In the crystal, N—H⋯O and O—H⋯O hydrogen bonds link the chromene and ethanol solvent mol­ecules into infinite chains along the c axis, and N—H⋯N hydrogen bonds link these chains into a three-dimensional framework. Weak C—H⋯π inter­actions are also present

Systematic review and meta-analysis on the impact of COVID-19 pandemic-related lifestyle on myopia

Purpose: To conduct a systematic review and meta-analysis to assess the effects of coronavirus disease 2019 (COVID-19) pandemic–related lifestyle on myopia outcomes in children to young adults. Methods: A systematic search was conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases (with manual searching of reference lists of reviews). Studies included assessed changes in myopia-related outcomes (cycloplegic refraction) during COVID and pre-COVID. Of 367 articles identified, 7 (6 prospective cohorts; 1 repeated cross-sectional study) comprising 6327 participants aged 6 to 17 were included. Quality appraisals were performed with Joanna Briggs Institute Critical Appraisal Checklists. Pooled differences in annualized myopic shifts or mean spherical equivalent (SE) during COVID and pre-COVID were obtained from random-effects models. Results: In all 7 studies, SE moved toward a myopic direction during COVID (vs pre-COVID), where 5 reported significantly faster myopic shifts [difference in means of changes: −1.20 to −0.35 diopters per year, [D/y]; pooled estimate: −0.73 D/y; 95% confidence interval (CI): −0.96, −0.50; P<0.001], and 2 reported significantly more myopic SE (difference in means: −0.72 to −0.44 D/y; pooled estimate: −0.54 D/y; 95% CI: −0.80, −0.28; P<0.001). Three studies reported higher myopia (SE ≤−0.50 D) incidence (2.0- to 2.6-fold increase) during COVID versus pre-COVID. Of studies assessing lifestyle changes, all 4 reported lower time outdoors (pre-COVID vs during COVID: 1.1–1.8 vs 0.4–1.0 hours per day, [h/d]), and 3 reported higher screen time (pre-COVID vs during COVID: 0.7–2.8 vs 2.4–6.9 h/d). Conclusions: This review suggests more myopic SE shifts during COVID (vs pre-COVID) in participants aged 6 to 17. COVID-19 restrictions may have worsened SE shifts, and lifting restrictions may lessen this effect. Evaluations of the long-term effects of the pandemic lifestyle on myopia onset and progression in large studies are warranted to confirm these findings.info:eu-repo/semantics/publishedVersio

Acute promyelocytic leukemia with FIP1L1::RARA fusion gene: The clinical utility of transcriptome sequencing and bioinformatic analyses

BackgroundAcute promyelocytic leukemia (APL) is typically characterized by the presence of coagulopathy and the PML::RARA fusion gene. The FIP1L1::RARA has been reported as a novel fusion gene, but studies on its pathogenesis are limited.ObjectivesA FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA sequencing (RNA-seq) of six patients (three cases of acute lymphoblastic leukemia (ALL), one case of myelodysplastic syndrome (MDS), one case of acute megakaryoblastic leukemia (M7), and one case of APL with FIP1L1::RARA) were performed.MethodsTranscriptome analysis of six patients was performed by RNA-seq. The heat map was used for showing the RNA expression profile, the volcano plot for identifying differential expression genes (DEGs), and the KEGG Orthology-Based Annotation System (KOBAS) online biological information database for KEGG pathway enrichment analysis.ResultsObvious differences between APL with FIP1L1::RARA and hematologic malignancies were identified. 1060 common differentially expressed genes (co-DEGs) were detected between APL with FIP1L1::RARA vs ALL and APL with FIP1L1::RARA vs myeloid neoplasms (MDS, M7), the up-regulated genes were mainly mapped into platelet activation, cancer, AMPK signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway. The down-regulated genes were significantly associated with TNF signaling pathway, Rap1 signaling pathway, Age-RAGE signaling pathway, and apoptosis.ConclusionA FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA-seq may provide a new diagnostic method when RARA rearrangements fail to be identified by conventional methods. In the analysis of co-DEGs between case vs ALL and case vs myeloid neoplasms, the up-regulated and down-regulated genes were enriched in different signaling pathways. Further experimental studies are needed to identify pathogenesis and treatment for APL with FIP1L1::RARA

PLASMA HEATING INSIDE INTERPLANETARY CORONAL MASS EJECTIONS BY ALFVÉNIC FLUCTUATIONS DISSIPATION

Nonlinear cascade of low-frequency Alfvénic fluctuations (AFs) is regarded as one of the candidate energy sources that heat plasma during the non-adiabatic expansion of interplanetary coronal mass ejections (ICMEs). However, AFs inside ICMEs were seldom reported in the literature. In this study, we investigate AFs inside ICMEs using observations from Voyager 2 between 1 and 6 au. It has been found that AFs with a high degree of Alfvénicity frequently occurred inside ICMEs for almost all of the identified ICMEs (30 out of 33 ICMEs) and for 12.6% of the ICME time interval. As ICMEs expand and move outward, the percentage of AF duration decays linearly in general. The occurrence rate of AFs inside ICMEs is much less than that in ambient solar wind, especially within 4.75 au. AFs inside ICMEs are more frequently presented in the center and at the boundaries of ICMEs. In addition, the proton temperature inside ICME has a similar "W"-shaped distribution. These findings suggest significant contribution of AFs on local plasma heating inside ICMEs

Targeting of the Human Coagulation Factor IX Gene at rDNA Locus of Human Embryonic Stem Cells

BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs) in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs) but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA) gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50%) and homologous recombination frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs

Association of low-level inorganic arsenic exposure from rice with age-standardized mortality risk of cardiovascular disease (CVD) in England and Wales

Adverse health outcomes, including death from cardiovascular disease (CVD), arising from chronic exposure to inorganic arsenic (iAs) are well documented. Consumption of rice is a major iAs exposure route for over 3 billion people, however, there is still a lack of epidemiological evidence demonstrating the association between iAs exposure from rice intake and CVD risks. We explored this potential association through an ecological study using data at local authority level across England and Wales. Local authority level daily per capita iAs exposure from rice (E-iAsing,rice) was estimated using ethnicity as a proxy for class of rice consumption. A series of linear and non-linear models were applied to estimate the association between E-iAsing,rice and CVD age-standardized mortality rate (ASMR), using Akaike's Information Criterion as the principle model selection criterion. When adjusted for significant confounders, notably smoking prevalence, education level, employment rate, overweight percentage, PM2.5, female percentage and medical and care establishments, the preferred non-linear model indicated that CVD risks increased with iAs exposure from rice at exposures above 0.3 μg/person/day. Also, the best-fitted linear model indicated that CVD ASMR in the highest quartile of iAs exposure (0.375–2.71 μg/person/day) was 1.06 (1.02, 1.11; p-trend <0.001) times higher than that in the lowest quartile (<0.265 μg/person/day). Notwithstanding the well-known limitations of ecological studies, this study further suggests exposure to iAs, including from rice intake, as a potentially important confounder for studies of the factors controlling CVD risks