Pancreatic agenesis and altered m6A methylation in the pancreas of PDX1-mutant cynomolgus macaques

As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal diabetes mellitus.However,the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models.In this study,three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology,all of which succumbed shortly postpartum,exhibiting pancreatic agenesis.Notably,one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4)developed a pancreas,whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation.RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions,indicating developmental delay and PDX1haploinsufficiency.A marked change in m6A methylation was identified in the M4 pancreas,confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.

Influence of preoperative comprehensive education on anxiety,depression,pain,and sleep in elderly patients operated under general anesthesia

BACKGROUND Owing to the particularities of their physical characteristics,older patients undergoing surgery under general anesthesia experience great surgical traumas.Thus,exploring more refined and individualized nursing approaches is an urgent need to mitigate the negative effects of surgery on such patients.AIM To analyze the influence of preoperative comprehensive education on anxiety,depression,pain,and sleep in older patients who underwent surgery under general anesthesia.METHODS In total,163 older adults who underwent surgery under general anesthesia between June 2022 and November 2023 were selected,77 of them received routine nursing care(control group),and 86 received preoperative comprehensive education(research group).Subsequently,comparative analyses were performed from the following perspectives:Surgical indicators(operation time,time to complete regain of consciousness,and temperature immediately after the procedure and upon recovery from anesthesia)before and after nursing care;negative emotions[self-rating anxiety scale(SAS)/self-rating depression scale(SDS)];pain severity[visual analog scale(VAS)];sleep quality[Pittsburgh sleep quality index(PSQI)];incidence of sleep disturbances(difficulties in falling asleep for the first time,falling asleep again after waking up frequently at night,falling asleep again after waking up early,and falling asleep all night);and incidence of adverse events(airway obstruction,catheter detachment,aspiration,and asphyxia).RESULTS The research group had significantly lower operation time and time to complete regain of consciousness than the control group after nursing care and markedly better recovery of postoperative body temperature and body temperature at awakening.In addition,more notable decreases in SAS,SDS,VAS,and PSQI scores were observed in the research group than in the control group.Furthermore,the incidence rate of sleep disturbance(8.14%vs 29.87%)and adverse events(4.65%vs 19.48%)were lower in the research group than in the control group.CONCLUSION Preoperative comprehensive education in older patients who underwent surgery under general anesthesia can improve postoperative indicators,effectively reduce the occurrence of anxiety and depression,alleviate postoperative pain,and improve sleep quality.

Reforming of CH_4 with CO_2 over Co/Mg–Al oxide catalyst

A series of Co/Mg-Al oxide samples, CoMgAl-x （x = （Mg ＋ Co）]AI molar ratio of 1-5）, were prepared by the self-combustion method followed by H2 reduction. The catalytic performance and stability of the samples were studied in dry reforming ofCH4. XRD and H2-TPR characterization results showed that the reduced CoMgAl-x samples mainly consisted of solid solution and spinel phases with cobalt particles. The spinel phases contained COB04 and ConMgl-nAl204 （0 〈 n 〈 1 ） varying with the （Mg ＋ Co）/AI ratio, The effect of （Mg ＋ Co）/A1 molar ratio on the catalytic behavior was investigated in detail and CoMgAI-3 exhibited the highest catalytic activity and stability among the catalysts studied.