There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10-15 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10-8 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10-15 ) and BMPER (rs17169634; p = 1.45 × 10-10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.
  Iron deficiency during early life could affect the developing lung and immune system, and influence child's respiratory or allergy outcomes in later life.
 
  To examine the associations of maternal iron status during early pregnancy with child's lung function, asthma, inhalant allergic sensitization, and physician-diagnosed inhalant allergy at school-age.
 
  In a population-based cohort study, among 3825 mother-child pairs, ferritin, transferrin concentrations, and transferrin saturation were measured from maternal venous blood samples during early pregnancy. In children at the age of 10 years, spirometry was used to determine child's lung function, current asthmaand physician-diagnosed inhalant allergy were assessed by questionnaires, and inhalant allergic sensitization was measured by skin prick tests. We used multivariable regression models to examine the associations.
 
  After adjustment for gestational age at maternal iron status measurement and sociodemographic or lifestyle-related confounders, a higher plications need to be explored.Introduction of cationic modifications into an oligonucleotide can increase its nuclease resistance and duplex- or triplex-forming abilities. In a recent study, we found that the nuclease resistance and RNA binding selectivity of an oligonucleotide containing a 5'-(R)-amino-5'-deoxy-5'-(R)-hydroxymethylthymidine residue were greater than those of the unmodified oligonucleotide. In this article, we describe the synthesis of 5'-amino-5'-deoxy-5'-hydroxymethylthymidine via dihydroxylation of the 5'-alkene derivative using either of two commercial AD (asymmetric dehydroxylation) mixes or via epoxidation and ring opening. We also provide detailed protocols for the syntheses of oligonucleotides containing 5'-amino-5'-deoxy-5'-hydroxymethylthymidine residues. © 2021 Wiley Periodicals LLC. Basic Protocol 1 Synthesis of 5'-amino-5'-deoxy-5'-hydroxymethylthymidine phosphoramidites 9a and 9b Basic Protocol 2 Synthesis of oligonucleotides 1 and 2 containing 5'-amino-5'-deoxy-5'-hydoxymethylthymidine residues (R T and S T).
  To describe the long-term (up to 18 years of age) respiratory outcomes of children and adolescents born at very low birth weight (VLBW;≤1500 g) in comparison with that of children born >1500 g.
 
  An observational, longitudinal, retrospective study comparing VLBW infants with matched controls, registered at a large health maintenance organization in Israel.  https://www.selleckchem.com/products/GDC-0449.html  Pulmonary outcomes collected anonymously from the electronic medical files included respiratory illness diagnoses, purchased medications for respiratory problems, office visits with either a pediatric pulmonologist or cardiologist and composite respiratory morbidity combining all these parameters.
 
  Our study included 5793 VLBW infants and 11,590 matched controls born between 1998 and 2012. The majority (99%) of VLBW infants were premature (born < 37 weeks' gestation), while 93% of controls were born at term. The composite respiratory morbidity was significantly higher in VLBW infants compared with controls in all age groups (relative risk [95% confife and declines afterward.The analysis of low molecular weight (LMW) compounds is of great interest to detect small pharmaceutical drugs rapidly and sensitively, or to trace and understand metabolic pathways. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) plays a central role in the analysis of high molecular weight (bio)molecules. However, its application for LMW compounds is restricted by spectral interferences in the low m/z region, which are produced by conventional organic matrices. Several strategies regarding sample preparation have been investigated to overcome this problem. A different rationale is centred on developing new matrices which not only meet the fundamental requirements of good absorption and high ionization efficiency, but are also vacuum stable and "MALDI silent", i. e., do not give matrix-related signals in the LMW area. This review gives an overview on the rational design strategies used to develop matrix systems for the analysis of LMW compounds, focusing on (i) the modification of well-known matrices, (ii) the search for high molecular weight matrices, (iii) the development of binary, hybrid and nanomaterial-based matrices, (iv) the advance of reactive matrices and (v) the progress made regarding matrices for negative or dual polarity mode.
  The real-world relationships between the demographic and clinical characteristics of asthma patients, their prehospitalization management and the frequency of hospitalization due to asthma exacerbation is poorly established.
 
  To determine the risk factors of recurrent asthma exacerbations requiring hospitalizations and evaluate the standard of baseline asthma care.
 
  A territory-wide, multicentre retrospective study in Hong Kong was performed. Medical records of patients aged ≥18 years admitted to 11 acute general hospitals from January 1 to December 31, 2016 for asthma exacerbations were reviewed.
 
  There were 2280 patients with 3154 admissions (36.7% male, median age 66.0 [interquartile range 48.0-81.0] years, 519 had ≥2 admissions). Among them, 1830 (80.3%) had at least one asthma-associated comorbidity, 1060 (46.5%) and 885 (38.9%) of patients had Accident and Emergency Department (AED) attendance and hospitalization in the preceding year, respectively. Patients with advancing age (incidence rate ratio [IRR] 1.