Non-pharmacological interventions for preventing emergence delirium in children under general anesthesia: A scoping review.

PROBLEM: The phenomenon of emergence delirium in pediatric patients undergoing general anesthesia has garnered increasing attention in the academic community. While formal non-pharmaceutical interventions have demonstrated efficacy in mitigating this phenomenon, the diversity of intervention types and their varying degrees of effectiveness necessitate further discussion. A scoping review was conducted to identify and explicate the categorization, content elements, and outcomes measures of non-pharmacological interventions utilized to forestall the onset of emergence delirium in children undergoing general anesthesia. ELIGIBILITY CRITERIA: This review was conducted in accordance with the Arksey and O'Malley's methodology framework and PRISMA-ScR. It encompassed experimental and quasi-experimental studies that involved any non-pharmacological interventions during the perioperative period to prevent emergence delirium in children aged 0 to 18 years undergoing general anesthesia for elective surgery. SAMPLE: Thirty-two articles met the inclusion criteria, of which 29 were randomized controlled trials. The total sample size of the population was 4633. RESULTS: The scoping review revealed 10 non-pharmacological interventions, that included distraction intervention, visual preconditioning, virtual reality, parental participation, maternal voice, light drinking, acupuncture, auditory stimulation, monochromic light and breathing training. Emergence delirium, preoperative anxiety, and postoperative pain were the primary outcomes, and four assessment instruments were employed to measure the extent and incidence of emergence delirium. CONCLUSION: Numerous non-pharmacological interventions have been employed to prevent emergence delirium. Nevertheless, the effectiveness of some interventions is not yet evident. IMPLICATIONS: The utilization of visual preconditioning and distraction interventions appears to be an emerging area of interest.

Repression of GhTUBB1 Reduces Plant Height in Gossypium hirsutum.

The original 'Green Revolution' genes are associated with gibberellin deficiency. However, in some species, mutations in these genes cause pleiotropic phenotypes, preventing their application in dwarf breeding. The development of novel genotypes with reduced plant height will resolve this problem. In a previous study, we obtained two dwarf lines, L28 and L30, by introducing the Ammopiptanthus mongolicus (Maxim. ex Kom.) Cheng f. C-repeat-binding factor 1 (AmCBF1) into the upland cotton variety R15. We found that Gossypium hirsutum Tubulin beta-1 (GhTUBB1) was downregulated in L28 and L30, which suggested that this gene may have contributed to the dwarf phenotype of L28 and L30. Here, we tested this hypothesis by silencing GhTUBB1 expression in R15 and found that decreased expression resulted in a dwarf phenotype. Interestingly, we found that repressing AmCBF1 expression in L28 and L30 partly recovered the expression of GhTUBB1. Thus, AmCBF1 expression presented a negative relationship with GhTUBB1 expression in L28 and L30. Moreover, yeast one-hybrid and dual-luciferase assays suggest that AmCBF1 negatively regulates GhTUBB1 expression by directly binding to C-repeat/dehydration-responsive (CRT/DRE) elements in the GhTUBB1 promoter, potentially explaining the dwarf phenotypes of L28 and L30. This study elucidates the regulation of GhTUBB1 expression by AmCBF1 and suggests that GhTUBB1 may be a new target gene for breeding dwarf and compact cultivars.

Sialic acid plays a pivotal role in licensing Citrobacter rodentium's transition from the intestinal lumen to a mucosal adherent niche.

Enteric bacterial pathogens pose significant threats to human health; however, the mechanisms by which they infect the mammalian gut in the face of daunting host defenses and an established microbiota remain poorly defined. For the attaching and effacing (A/E) bacterial family member and murine pathogen Citrobacter rodentium, its virulence strategy likely involves metabolic adaptation to the host's intestinal luminal environment, as a necessary precursor to reach and infect the mucosal surface. Suspecting this adaptation involved the intestinal mucus layer, we found that C. rodentium was able to catabolize sialic acid, a monosaccharide derived from mucins, and utilize it as its sole carbon source for growth. Moreover, C. rodentium also sensed and displayed chemotactic activity toward sialic acid. These activities were abolished when the nanT gene, encoding a sialic acid transporter, was deleted (ΔnanT). Correspondingly, the ΔnanT C. rodentium strain was significantly impaired in its ability to colonize the murine intestine. Intriguingly, sialic acid was also found to induce the secretion of two autotransporter proteins, Pic and EspC, which possess mucinolytic and host-adherent properties. As a result, sialic acid enhanced the ability of C. rodentium to degrade intestinal mucus (through Pic), as well as to adhere to intestinal epithelial cells (through EspC). We thus demonstrate that sialic acid, a monosaccharide constituent of the intestinal mucus layer, functions as an important nutrient and a key signal for an A/E bacterial pathogen to escape the colonic lumen and directly infect its host's intestinal mucosa.

GhPYL9-5D and GhPYR1-3 A positively regulate Arabidopsis and cotton responses to ABA, drought, high salinity and osmotic stress.

BACKGROUND: Abscisic acid (ABA) receptor pyrabactin resistance 1/PYR1-like/regulatory components of ABA receptor proteins (PYR/PYL/RCARs) have been demonstrated to play pivotal roles in ABA signaling and in response to diverse environmental stimuli including drought, salinity and osmotic stress in Arabidopsis. However, whether and how GhPYL9-5D and GhPYR1-3A, the homologues of Arabidopsis PYL9 and PYR1 in cotton, function in responding to ABA and abiotic stresses are still unclear. RESULTS: GhPYL9-5D and GhPYR1-3A were targeted to the cytoplasm and nucleus. Overexpression of GhPYL9-5D and GhPYR1-3A in Arabidopsis wild type and sextuple mutant pyr1pyl1pyl2pyl4pyl5pyl8 plants resulted in ABA hypersensitivity in terms of seed germination, root growth and stomatal closure, as well as seedling tolerance to water deficit, salt and osmotic stress. Moreover, the VIGS (Virus-induced gene silencing) cotton plants, in which GhPYL9-5D or GhPYR1-3A were knocked down, showed clearly reduced tolerance to polyethylene glycol 6000 (PEG)-induced drought, salinity and osmotic stresses compared with the controls. Additionally, transcriptomic data revealed that GhPYL9-5D was highly expressed in the root, and GhPYR1-3A was strongly expressed in the fiber and stem. GhPYL9-5D, GhPYR1-3A and their homologs in cotton were highly expressed after treatment with PEG or NaCl, and the two genes were co-expressed with redox signaling components, transcription factors and auxin signal components. These results suggest that GhPYL9-5D and GhPYR1-3A may serve important roles through interplaying with hormone and other signaling components in cotton adaptation to salt or osmotic stress. CONCLUSIONS: GhPYL9-5D and GhPYR1-3A positively regulate ABA-mediated seed germination, primary root growth and stomatal closure, as well as tolerance to drought, salt and osmotic stresses likely through affecting the expression of multiple downstream stress-associated genes in Arabidopsis and cotton.

Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Highly Sensitive, Flow Cytometry-Based Measurement of Intestinal Permeability in Models of Experimental Colitis.

BACKGROUND & AIMS: Increased intestinal permeability is seen in a variety of inflammatory conditions such as enteric infections and inflammatory bowel disease. Because barrier function can provide a key biomarker of disease severity, it often is assayed in animal models. A common methodology involves gavaging mice with fluorescein isothiocyanate-conjugated dextran (FITC-D), followed by cardiac puncture to assay plasma fluorescence on a spectrophotometer. Although the FITC-D method is relatively simple, its sensitivity is limited and enables only a single measurement because the test requires killing the subject. Herein, we describe a novel flow cytometry-based method of intestinal permeability measurement based on detection of orally gavaged ovalbumin (OVA) that leaks out of the gut. Our approach uses minute blood volumes collected from the tail vein, permitting repeated testing of the same subject at multiple time points. By comparing this assay against the gold standard FITC-D method, we show the expanded utility of our OVA assay in measuring intestinal permeability. METHODS: We directly compared our OVA assay against the FITC-D assay by co-administering both probes orally to the same animals and subsequently using their respective methodologies to measure intestinal permeability by detecting probe levels in the plasma. Permeability was assessed in mice genetically deficient in intestinal mucus production or glycosylation. In addition, wild-type mice undergoing dextran sodium sulfate-induced colitis or infected by the enteric bacterial pathogen Citrobacter rodentium also were tested. RESULTS: The OVA assay showed very high efficacy in all animal models of intestinal barrier dysfunction tested. Besides identifying intestinal barrier dysfunction in mice with impaired mucin glycosylation, the assay also allowed for repeated tracking of intestinal permeability within the same animal over time, providing data that cannot be easily acquired with other currently applied methods. CONCLUSIONS: The OVA assay is a highly sensitive and effective method of measuring intestinal permeability in mouse models of barrier dysfunction and experimental colitis.

Co-morbidity of overweight,obesity and depression and its influencing factors among students in Inner Mongolia Autonomous Region / 中国学校卫生

Objective@#To analyze the prevalence of overweight, obesity and depression among students in the Inner Mongolia Autonomous Region in 2019-2022 and explore the relevant factors affecting the co-morbidity of overweight,obesity and depression among students, so as to provide scientific basis for the prevention of co-morbidity.@*Methods@#From September 2019 to 2022, used stratified random cluster sampling, 90 519,71 560,90 079,91 089 students were selected from all 12 leagues in Inner Mongolia Autonomous Region for questionnaire survey and physical examination. The χ 2 test was used for demographic characteristics and univariate analysis, and a binary Logistic regression model was used to explore the association between lifestyle behaviors and co-morbidity.@*Results@#The detection rate of overweight,obesity among students from 2019-2022 was 29.21%,34.38%,35.20%,34.61%, the detection rate of depression was 18.35%，17.53%，16.43%，16.00%, and the co-morbidity detection rate of the two was 5.52%，5.93%，5.76%，5.46%. The number of overweight,obesity and depression co-morbidity students in 2022 was 4 978 students, and the co-morbidity detection rates of the students were significantly different in terms of the school segments and the family structures ( χ 2=103.51, 99.90, P <0.01). Multivariate Logistic regression analysis showed that consuming sugar sweetened beverages or fried food ≥1 time/d, sometimes or never eat breakfast, watching computer or TV ≥2 h/d, and less than 1 h of moderate-to-vigorous physical activity on weekends were positively correlated with the occurrence of the co-morbidity of overweight,obesity and depression, with the value of OR ranging from 1.17 to 1.59 ( P <0.05). Eated fresh fruits or drinking milk and soy milk ≥1 time/d, outdoor activities ≥1 h/d, sleep ≥8 h/d, not smoking and not drinking alcohol were negatively correlated with the occurrence of comorbid overweight,obesity and depression, with the value of OR ranging from 0.47 to 0.92 ( P < 0.05).@*Conclusion@#The occurrence of overweight,obesity and depressive symptoms co-morbidity in students is associated with dietary, exercise and lifestyle behavior. Targeted measures should be taken to maintain students healthy weight and prevent the occurrence of depression from the aspects of diet, exercise and life habits.

Comorbidity of myopia and obesity and the moderating role of lifestyle among primary and secondary school students in Inner Mongolia Autonomous Region in 2021 / 中国学校卫生

Objective@#To describe the current status of the prevalence of co-morbid myopia and obesity among 7-18 years students in the Inner Mongolia Autonomous Region in 2021 and to analyze the moderating effect of lifestyle in this association ，so as to provide scientific basis for the establishment of the mechanism of Co-morbidity，Shared Etiology，and Shared Prevention of common diseases in children and adolescents.@*Methods@#A total of 139 630 primary and secondary school students aged 7-18 years from Inner Mongolia Autonomous Region were selected by stratified random cluster sampling method in September,2021. Myopia was determined using distance visual acuity examination and refractive error examination, and obesity was determined according to the BMI classification criteria for overweight, obesity screening of Chinese school age children and adolescents. Used a questionnaire, healthy lifestyles were determined according to the American Heart Association s Healthy Lifestyle Score by totaling the six scores for smoking, alcohol consumption, diet, exercise, screen time, and sleep duration.The χ 2 test was used to compare the association between group differences in the co-morbidity rate of myopia and obesity. The multivariable Logistic regression model was used to explore the influencing factors of the co-morbidity of myopia and obesity, and the stratified analysis was used to analyze the moderating effect of lifestyles on the prevalence of the co-morbidity.@*Results@#The prevalence of myopia and obesity co-morbidity among students aged 7-18 years old in the Inner Mongolia Autonmous Region in 2021 was 13.7%, higher among boys than girls ( 15.5 % vs. 11.8%), higher among those aged 10-12 years old than 7-9,13-15,and 16-18 years old (14.7%,13.7%, 13.3%, 12.0%), higher among other ethnic minorities than Han Chinese and Mongolians (15.3%, 14.0%, 12.5%), higher in urban areas than that in suburban areas(15.3%, 13.0%), and middle economic level tracts were higher than poor and good tracts (14.8%, 12.9 %, 12.6%) ( χ 2=392.37，115.73，62.80，119.02，121.60, P <0.05). Multivariable Logistic regression modeling showed that unhealthy lifestyles ( OR=1.24, 95%CI=1.19-1.29 ) and middle level of lifestyle score ( OR=1.15, 95%CI=1.10-1.19 ) students had higher prevalence of co-morbidity, and the results were statistically significant among both boys and girls, the age groups of 10- 12, 13-15, and 16-18 years old, as well as the Han and Mongolian ethnic groups (all P <0.05).@*Conclusion@#In 2021, the current situation of myopia and obesity co-morbidity and unhealthy lifestyles among primary and secondary school students in the Inner Mongolia Autonomous Region are not optimistic.

Prevalence trend and related factors of scoliosis and myopia co-morbidities among primary and middle school students in Inner Mongolia Autonomous Region from 2019 to 2022 / 中国学校卫生

Objective@#To analyze the prevalence trend of scoliosis among myopic students in Inner Mongolia Autonomous Region during 2019-2022, to explore the common etiology of myopia and scoliosis co-morbidities, so as to provide a reference for the development of relevant measures.@*Methods@#The method of stratified random cluster sampling was used to select 181 533, 141 552 , 200 987, 190 918 primary and secondary school students from 12 leagues(103 banners) in Inner Mongolia Atuonomous Region in September each year from 2019 to 2022. And scoliosis screening, vision examination and questionnaire survey were conducted among students in the included studies. The χ 2 test was used to analyze the data, and the binary multivariate Logistic regression model was used to screen the influencing factors of scoliosis and myopia co-morbidities.@*Results@#From 2019 to 2022, the myopia rate of primary and secondary school students in Inner Mongolia Autonomous Region was 55.55%-59.72%, scoliosis rate was 1.56 %-2.81% and the rates of scoliosis and myopia co-morbidities were 1.14%-1.95%, and the difference between different years was statistically significant ( χ 2=595.01, 775.56, 461.84, P < 0.05 ). In 2022, the co-morbidity rate was higher in girls than in boys(1.32% vs 0.97%), the rate of urban areas was higher than that of rural areas(2.57% vs 0.62%), the rate of students in vocational high school and high school was higher than that in junior high school and primary school (3.82%,2.47% vs 1.70%,0.42%), the rate of over developed areas was higher than that of poor areas (1.21% vs 0.99%)( χ 2=52.19, 1 269.82, 1 361.52, 17.29, P < 0.05 ). Logistic regression analysis showed that at least 1 h of moderate and high intensity exercise every day on weekends, the number of physical education classes per week was more than 3 sessions, the height of desks and chairs was adjusted according to height, resting outdoors, limiting screen time, and strictly requiring standing and sitting posture were the negative correlated with scoliosis and myopia, and the OR value was 0.65-0.90, reading books or electronic screens while participating in cram classes, walking or riding in the car were positively correlated with comorbid scoliosis and myopia, and the OR values were 1.27 and 1.13 ( P < 0.05), respectively.@*Conclusion@#Behavioral habits severely affect scoliosis and myopic of students. Prevention and control of scoliosis and myopia co-morbidity should start with students behavioral habits, early screening and early intervention.

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.

Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.

AmCBF1 Transcription Factor Regulates Plant Architecture by Repressing GhPP2C1 or GhPP2C2 in Gossypium hirsutum.

Dwarfism is a beneficial trait in many crops. Dwarf crops hold certain advantages over taller crops in lodging resistance, fertilizer tolerance, and yield. Overexpression of CBF/DREB transcription factors can lead to dwarfing in many plant species, but the molecular mechanism of plant dwarfing caused by overexpression of CBF/DREB in upland cotton (Gossypium hirsutum) remains unclear. In this study, we observed that overexpression of the Ammopiptanthus mongolicus AmCBF1 transcription factor in upland cotton R15 reduced plant height, whereas virus-induced gene silencing of AmCBF1 in the derived dwarf lines L28 and L30 partially restored plant height. Five protein phosphatase (PP2C) genes (GhPP2C1 to GhPP2C5) in cotton were identified by RNA-sequencing among genes differentially expressed in L28 or L30 in comparison with R15 and thus may play an important role in AmCBF1-regulated dwarfing in cotton. Gene expression analysis showed that the GhPP2C genes were down-regulated significantly in L28 and L30, and silencing of GhPP2C1 or GhPP2C2 in R15 inhibited the growth of cotton seedlings. Subcellular localization assays revealed that GhPP2C1 was localized to the cell membrane and nucleus, whereas GhPP2C2 was exclusively localized to the nucleus. Yeast one-hybrid and dual-luciferase assays showed that AmCBF1 was able to bind to the CRT/DRE elements of the upstream promoter of GhPP2C1 or GhPP2C2 and repress their expression. These findings provide insight into the mechanism of dwarfing and may contribute to the breeding of dwarf cultivars of upland cotton.

Sphingolipid synthesis inhibitor fumonisin B1 causes verticillium wilt in cotton.

Verticillium wilt caused by Verticillium dahliae is a major disease of cotton. Acidic protein-lipopolysaccharide complexes are thought to be the toxins responsible for its symptoms. Here, we determined that the sphingolipid biosynthesis inhibitor fumonisin B1 (FB1) acts as a toxin and phenocopies the symptoms induced by V. dahliae. Knocking out genes required for FB1 biosynthesis reduced V. dahliae pathogenicity. Moreover, we showed that overexpression of a FB1 and V. dahliae both downregulated gene, GhIQD10, enhanced verticillium wilt resistance by promoting the expression of brassinosteroid and anti-pathogen genes. Our results provide a new strategy for preventing verticillium wilt in cotton.

Silencing GhJUB1L1 (JUB1-like 1) reduces cotton (Gossypium hirsutum) drought tolerance.

Drought stress massively restricts plant growth and the yield of crops. Reducing the deleterious effects of drought is necessary for agricultural industry. The plant-specific NAC (NAM, ATAF1/2 and CUC2) transcription factors (TFs) are widely involved in the regulation of plant development and stress response. One of the NAC TF, JUNGBRUNNEN1 (JUB1), has been reported to involve in drought resistance in Arabidopsis. However, little is known of how the JUB1 gene respond to drought stress in cotton. In the present study, we cloned GhJUB1L1, a homologous gene of JUB1 in upland cotton. GhJUB1L1 is preferentially expressed in stem and leaf and could be induced by drought stress. GhJUB1L1 protein localizes to the cell nucleus, and the transcription activation region of which is located in the C-terminal region. Silencing GhJUB1L1 gene via VIGS () reduced cotton drought tolerance, and retarded secondary cell wall (SCW) development. Additionally, the expression of some drought stress-related genes and SCW synthesis-related genes were altered in the GhJUB1L1 silencing plants. Collectively, our findings indicate that GhJUB1L1 may act as a positive regulator in response to drought stress and SCW development in cotton. Our results enriched the roles of NAC TFs in cotton drought tolerance and laid a foundation for the cultivation of transgenic cotton with higher drought tolerance.

Comparative Metabolomics Analysis Reveals Sterols and Sphingolipids Play a Role in Cotton Fiber Cell Initiation.

Cotton fiber is a seed trichome that protrudes from the outer epidermis of cotton ovule on the day of anthesis (0 day past anthesis, 0 DPA). The initial number and timing of fiber cells are closely related to fiber yield and quality. However, the mechanism underlying fiber initiation is still unclear. Here, we detected and compared the contents and compositions of sphingolipids and sterols in 0 DPA ovules of Xuzhou142 lintless-fuzzless mutants (Xufl) and Xinxiangxiaoji lintless-fuzzless mutants (Xinfl) and upland cotton wild-type Xuzhou142 (XuFL). Nine classes of sphingolipids and sixty-six sphingolipid molecular species were detected in wild-type and mutants. Compared with the wild type, the contents of Sphingosine-1-phosphate (S1P), Sphingosine (Sph), Glucosylceramide (GluCer), and Glycosyl-inositol-phospho-ceramides (GIPC) were decreased in the mutants, while the contents of Ceramide (Cer) were increased. Detail, the contents of two Cer molecular species, d18:1/22:0 and d18:1/24:0, and two Phyto-Cer molecular species, t18:0/22:0 and t18:0/h22:1 were significantly increased, while the contents of all GluCer and GIPC molecular species were decreased. Consistent with this result, the expression levels of seven genes involved in GluCer and GIPC synthesis were decreased in the mutants. Furthermore, exogenous application of a specific inhibitor of GluCer synthase, PDMP (1-phenyl-2-decanoylamino-3-morpholino-1-propanol), in ovule culture system, significantly inhibited the initiation of cotton fiber cells. In addition, five sterols and four sterol esters were detected in wild-type and mutant ovules. Compared with the wild type, the contents of total sterol were not significantly changed. While the contents of stigmasterol and campesterol were significantly increased, the contents of cholesterol were significantly decreased, and the contents of total sterol esters were significantly increased. In particular, the contents of campesterol esters and stigmasterol esters increased significantly in the two mutants. Consistently, the expression levels of some sterol synthase genes and sterol ester synthase genes were also changed in the two mutants. These results suggested that sphingolipids and sterols might have some roles in the initiation of fiber cells. Our results provided a novel insight into the regulatory mechanism of fiber cell initiation.

Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)-producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

Sphingolipid Profile during Cotton Fiber Growth Revealed That a Phytoceramide Containing Hydroxylated and Saturated VLCFA Is Important for Fiber Cell Elongation.

Cotton fiber is a single-celled seed trichrome that arises from the epidermis of the ovule's outer integument. The fiber cell displays high polar expansion and thickens but not is disrupted by cell division. Therefore, it is an ideal model for studying the growth and development of plant cells. Sphingolipids are important components of membranes and are also active molecules in cells. However, the sphingolipid profile during fiber growth and the differences in sphingolipid metabolism at different developmental stages are still unclear. In this study, we detected that there were 6 classes and 95 molecular species of sphingolipids in cotton fibers by ultrahigh performance liquid chromatography-MS/MS (UHPLC-MS/MS). Among these, the phytoceramides (PhytoCer) contained the most molecular species, and the PhytoCer content was highest, while that of sphingosine-1-phosphate (S1P) was the lowest. The content of PhytoCer, phytoceramides with hydroxylated fatty acyls (PhytoCer-OHFA), phyto-glucosylceramides (Phyto-GluCer), and glycosyl-inositol-phospho-ceramides (GIPC) was higher than that of other classes in fiber cells. With the development of fiber cells, phytosphingosine-1-phosphate (t-S1P) and PhytoCer changed greatly. The sphingolipid molecular species Ceramide (Cer) d18:1/26:1, PhytoCer t18:1/26:0, PhytoCer t18:0/26:0, PhytoCer t18:1/h20:0, PhytoCer t18:1/h26:0, PhytoCer t18:0/h26:0, and GIPC t18:0/h16:0 were significantly enriched in 10-DPA fiber cells while Cer d18:1/20:0, Cer d18:1/22:0, and GIPC t18:0/h18:0 were significantly enriched in 20-DPA fiber cells, indicating that unsaturated PhytoCer containing hydroxylated and saturated very long chain fatty acids (VLCFA) play some role in fiber cell elongation. Consistent with the content analysis results, the related genes involved in long chain base (LCB) hydroxylation and unsaturation as well as VLCFA synthesis and hydroxylation were highly expressed in rapidly elongating fiber cells. Furthermore, the exogenous application of a potent inhibitor of serine palmitoyltransferase, myriocin, severely blocked fiber cell elongation, and the exogenous application of sphingosine antagonized the inhibition of myriocin for fiber elongation. Taking these points together, we concluded that sphingolipids play crucial roles in fiber cell elongation and SCW deposition. This provides a new perspective for further studies on the regulatory mechanism of the growth and development of cotton fiber cells.

HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma.

BACKGROUND: HER2 transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of HER2 TMD-mutant LUAD. METHODS: An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 HER2 V659E-mutant patients and an external cohort of 38 HER2-mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed. RESULTS: In Chinese LUAD, the prevalence of HER2 TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the HER2 V659E mutation. The most recurrent co-alteration was TP53 mutation (n=4, 25%) and HER2 amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P<0.001) and had poorer OS (median OS 10.0 vs. 61.6 months, HR =7.9, 95% CI: 1.0-61.0, P<0.001) than non-TMD mutations. The overall response rate of targeted therapy, chemo-based therapy, and immunotherapy was 57.1%, 22.2%, and 0%, respectively. We postulated to challenge the resistance of tyrosine kinase inhibitor (TKI) with another with stronger binding energy to HER2 and supported the conclusion with a successful case. Additionally, we demonstrated a three-month response to the off-label use of pyrotinib in fifth-line therapy. CONCLUSIONS: Comapred with non-TMD mtuations, HER2 TMD mutation is a rare driver mutation with poorer prognosis in LUAD. Targeted therapy is the dominant choice for patients harboring this targetable mutation and longer OS could possibly be achieved through rechallenge with TKI of stronger binding affinity. Response to fifth-line pyrotinib was observed.

Global analysis of protein succinylation modification of Nostoc flagelliforme in response to dehydration.

Nostoc flagelliforme is a type of terrestrial cyanobacteria that is distributed in arid or semi-arid steppes in China. To research the molecular mechanisms underlying the adaptation of N. flagelliforme to drought stress, the succinylated expression profile and changes in N. flagelliforme that resulted as a response to dehydration were analyzed by label-free proteomics. A total of 1149 succinylated sites, 1128 succinylated peptides, and 396 succinylated proteins were identified. Succinylated proteins were differentially involved in photosynthesis and energy metabolism, as well as in reactive oxygen species (ROS) scavenging. Motif-X analysis of succinylated sites determined a succinylation motif [KxxG]. N. flagelliforme adapts to dehydration by increasing glucose metabolism and pentose phosphate pathway flux, and decreasing photosynthetic rate, which some of the key proteins were succinylated. ROS scavenging was mainly involved in the regulation of the enzyme antioxidant defense system and non-enzymatic antioxidant defense system through succinylation modification, thus eliminating excessive ROS. Protein succinylation of N. flagelliforme may play an important regulatory role in response to dehydration. The results are foundational, as they can inform future research into the mechanisms involved in the succinylation regulation mechanism of N. flagelliforme in response to dehydration. SIGNIFICANCE: The global succinylation network involved in response to dehydration in N. flagelliforme has been established. We found that many succinylated proteins were involved in photosynthesis, glucose metabolism and antioxidation. The global survey of succinylated proteins and the changes of succinylated levels in response to dehydration provided effective information for the drought tolerance mechanism in N. flagelliforme.

Long Non-coding RNA MEG3 Alleviated Ulcerative Colitis Through Upregulating miR-98-5p-Sponged IL-10.

Ulcerative colitis (UC) is a refractory chronic colitis disease with the particularly complex cause. Recently, long noncoding RNAs (lncRNAs) have been reported to be related to the development of UC. LncRNA MEG3 has been proved to play an anti-inflammatory role in a variety of inflammatory diseases, which share similar pathogenesis with UC, indicating the potential involvement of lncRNA MEG3 in UC. This study aims to investigate the functional role and underlying mechanism of lncRNA MEG3 in UC. Gradient concentration of H2O2 (0, 20, 50, 100, and 200 µM) was used to induce Caco-2 damage models in vitro. Cell viability was detected by cell counting kit-8 (CCK-8) assay. LncRNA MEG3, miR-98-5p, and IL-10 levels in H2O2-treated Caco-2 cells were assessed by performing real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the binding relationship between lncRNA MEG3 and miR-98-5p, as well as the binding relationship between miR-98-5p and IL-10, was validated using dual-luciferase reporter assay. 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS) was applied to induce ulcerative colitis in young rats. The body weight, disease activity index (DAI), length and weight of the colons, pathological scores of UC rats, reactive oxygen species (ROS), and inflammatory cytokines were determined to evaluate the effects of lncRNA MEG3 on the progression of UC. Besides, hematoxylin-eosin (HE) staining was exploited to observe histological changes of UC rat colons. In addition, western blotting analysis was also performed to evaluate the apoptosis and pyroptosis-related protein levels. Moreover, lncRNA MEG3, miR-98-5p, and IL-10 levels in UC rat colons were further assessed by RT-qPCR. Meanwhile, IL-10 expression was determined using immunohistochemistry. LncRNA MEG3 and IL-10 levels were distinctly decreased while miR-98-5p was increased in Caco-2 damage models and UC rats. Bioinformatics analysis predicted the binding sites of lncRNA MEG3 to miR-98-5p and miR-98-5p to IL-10. Besides, dual-luciferase reporter assay validated the negative correlation between lncRNA MEG3 and miR-98-5p, miR-98-5p, and IL-10. Overexpressed lncRNA MEG3 reduced. DAI scores and colon weight/length ratio improved UC ulceration. In addition, upregulation of lncRNA MEG3 relieved oxidative stress, inflammatory response, apoptosis, and pyroptosis of UC rat colons. LncRNA MEG3 overexpression alleviates the serve ulceration of UC rat colons by upregulating IL-10 expression via sponging miR-98-5p. To sum up, this study reveals the protective role of lncRNA MEG3 in the development of UC and may provide potential therapeutic targets for UC.