RESUMO
Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.
Assuntos
Neurônios , Parvalbuminas , Animais , Camundongos , Parvalbuminas/metabolismo , Neurônios/metabolismo , Células Piramidais/metabolismo , Transmissão Sináptica , Sono , MamíferosRESUMO
BACKGROUND: Artemisia selengensis, classified within the genus Artemisia of the Asteraceae family, is a perennial herb recognized for its dual utility in culinary and medicinal domains. There are few studies on the chloroplast genome of A. selengensis, and the phylogeographic classification is vague, which makes phylogenetic analysis and evolutionary studies very difficult. RESULTS: The chloroplast genomes of 10 A. selengensis in this study were highly conserved in terms of gene content, gene order, and gene intron number. The genome lengths ranged from 151,148 to 151,257 bp and were typical of a quadripartite structure with a total GC content of approximately 37.5%. The chloroplast genomes of all species encode 133 genes, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Due to the contraction and expansion of the inverted repeats (IR), the overlap of ycf1 and ndhF genes occurred at the inverted repeats B (IRB) and short single copy sequence (SSC) boundaries. According to a codon use study, the frequent base in the chloroplast genome of A. selengensis' third codon position was A/T. The number of SSR repeats was 42-44, most of which were single nucleotide A/T repeats. Sequence alignment analysis of the chloroplast genome showed that variable regions were mainly distributed in single copy regions, nucleotide diversity values of 0 to 0.009 were calculated by sliding window analysis, 8 mutation hotspot regions were detected, and coding regions were more conserved than non-coding regions. Analysis of non-synonymous substitution (Ka) and synonymous substitution (Ks) revealed that accD, rps12, petB, and atpF genes were affected by positive selection and no genes were affected by neutral selection. Based on the findings of the phylogenetic analysis, Artemisia selengensis was sister to the genus Artemisia Chrysanthemum and formed a monophyletic group with other Artemisia genera. CONCLUSIONS: In this research, the present study systematically compared the chloroplast genomic features of A. selengensis and provided important information for the study of the chloroplast genome of A. selengensis and the evolutionary relationships among Asteraceae species.
Assuntos
Artemisia , Genoma de Cloroplastos , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Artemisia/genética , Artemisia/classificação , Composição de Bases , Repetições de Microssatélites , Evolução Molecular , Uso do CódonRESUMO
BACKGROUND: As indispensable reserves for the nursing workforce, undergraduate nursing students must possess self-directed learning abilities to consistently update their professional knowledge and adapt to the evolving demands of professional development. The acquisition of self-directed learning abilities can help undergraduate nursing students augment their theoretical knowledge and refine their clinical practice skills, thus fulfilling the demand from patients for high-quality nursing services. Hence, comprehending and investigating the factors that influence the development of self-directed learning abilities in nursing students is of paramount importance for nursing education and advancement of the nursing profession. OBJECTIVES: This study investigated the status of and associations between perceived stress, psychological capital, and self-directed learning abilities among undergraduate nursing students. Additionally, it examines the mediating role of psychological capital in the relationship between perceived stress and self-directed learning abilities. Thus, aiming to provide nursing educators with new directions for enhancing self-directed learning abilities. DESIGN: A cross-sectional descriptive study. METHODS: In February and March 2023, 900 undergraduate nursing students from 10 nursing schools completed an online questionnaire. The questionnaire included measures of perceived stress, psychological capital, and self-directed learning ability. Data were analyzed using SPSS 27.0 and the PROCESS macro tool. RESULTS: The scores for perceived stress, psychological capital, and self-directed learning ability among undergraduate nursing students were 40.07 ± 5.90, 99.89 ± 16.59, and 87.12 ± 9.20, respectively. Self-directed learning abilities were negatively correlated with perceived stress (r = -0.415, p < 0.001) and positively correlated with psychological capital (r = 0.465, p < 0.001). Perceived stress was negatively correlated with psychological capital (r = -0.630, p < 0.001). Psychological capital partially mediated the relationship between perceived stress and self-directed learning abilities among undergraduate nursing students, with a mediation effect of -0.166, accounting for 49.55% of the total effect. CONCLUSION: This study found that undergraduate nursing students perceived high levels of stress, possessed low levels of psychological capital, and had moderate levels of self-directed learning. Perceived stress and psychological capital directly influenced undergraduate nursing students' self-directed learning abilities, and perceived stress indirectly affected self-directed learning abilities through psychological capital. Nursing managers and educators should alleviate the perceived stress of undergraduate nursing students and cultivate their positive psychological capital to enhance self-directed learning abilities.
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Cyanobacteria can sense different light color by adjusting the components of photosynthetic pigments including chlorophyll a (Chl a), phycoerythrin (PE), and phycocyanin (PC), etc. Filamentous cyanobacteria are the main producer of 2-methylisoborneol (MIB) and many can increase their PE levels so that they are more competitive in subsurface layer where green light is more abundant, and have caused extensive odor problems in drinking water reservoirs. Here, we identified the potential correlation between MIB biosynthesis and ambient light color induced chromatic acclimation (CA) of a MIB-producing Pseudanabaena strain. The results suggest Pseudanabaena regulates the pigment proportion through Type III CA (CA3), by increasing PE abundance and decreasing PC in green light. The biosynthesis of MIB and Chl a share the common precursor, and are positively correlated with statistical significance regardless of light color (R2=0.68; p<0.001). Besides, the PE abundance is also positively correlated with Chl a in green light (R2=0.57; p=0.019) since PE is the antenna that can only transfer the energy to PC and Chl a. In addition, significantly higher MIB production was observed in green light since more Chl a was synthesized.
Assuntos
Cianobactérias , Clorofila A , Cianobactérias/fisiologia , Ficoeritrina , Ficocianina , AclimataçãoRESUMO
Knowledge of the parameters of the human spine is essential in designing ergonomic furniture. The purpose of this study was to evaluate spinal alignment in adolescents of various ages. The lengths, curvatures, and concave-convex spacings of the spine were investigated in 268 participants aged 9-18 years. Ten ages were classified, and the rate of increase of parameters was calculated for each age and age group. The results showed that spinal parameters, except for cervical lordosis, increased with age. Adolescents were classified as 9-10, 11-12, 13-15, and 16-18 years old. A rapid increment of lengths and concave-convex spacings occurred at ages 13-15, while that of curvatures occurred at ages 16-18. Spinal parameters differed significantly among the age groups (p < 0.05). Concave-convex spacings reflected differences in the spine more clearly than the other parameters. This study suggests the necessity of designing spine-related furniture based on spinal parameters, thus providing adaptive support for the adolescent spine, particularly the lumbar spine. Practitioner summary: This study examined spinal lengths, curvatures, and concave-convex spacings in adolescents aged 9-8 years and then divided them into four age groups. Concave-convex spacings effectively reflected spinal differences between age groups, particularly the lumbar spine. These results can inform the ergonomic design of spine-related furniture.HIGHLIGHTSSpinal parameters increased progressively between 9 and 18 years. Regression analysis showed good linear correlations between TK, LL, SK, TS, and LS with age.Age classification of adolescents was Group I (9-10 years), Group II (11-12 years), Group III (13-15 years), and Group IV (16-18 years). The rapid increment of lengths and concave-convex spacings were in Group III while that of curvatures were in Group IV.Concave-convex spacings were vital parameters to evaluate the global balance of the spine.The lumbar spine is an essential segment for characterizing spinal alignment.
Assuntos
Lordose , Escoliose , Adolescente , Humanos , Decoração de Interiores e Mobiliário , Coluna Vertebral , Vértebras LombaresRESUMO
Daptomycin is a new lipopeptide antibiotic for treatment of severe infection caused by multi-drug-resistant bacteria, but its production cost remains high currently. Thus, it is very important to improve the fermentation ability of the daptomycin producer Streptomyces roseosporus. Here, we found that the deletion of proteasome in S. roseosporus would result in the loss of ability to produce daptomycin. Therefore, transcriptome and 4D label-free proteome analyses of the proteasome mutant (Δprc) and wild type were carried out, showing 457 differential genes. Further, five genes were screened by integrated crotonylation omics analysis. Among them, two genes (orf04750/orf05959) could significantly promote the daptomycin synthesis by overexpression, and the fermentation yield in shake flask increased by 54% and 76.7%, respectively. By enhancing the crotonylation modification via lysine site mutation (K-Q), the daptomycin production in shake flask was finally increased by 98.8% and 206.3%, respectively. This result proved that the crotonylation modification of appropriate proteins could effectively modulate daptomycin biosynthesis. In summary, we established a novel strategy of gene screen for antibiotic biosynthesis process, which is more convenient than the previous screening method based on pathway-specific regulators. KEY POINTS: ⢠Δprc strain has lost the ability of daptomycin production ⢠Five genes were screened by multi-omics analysis ⢠Two genes (orf04750/orf05959) could promote the daptomycin synthesis by overexpression.
Assuntos
Daptomicina , Streptomyces , Antibacterianos/farmacologia , Complexo de Endopeptidases do Proteassoma , Proteoma/metabolismo , Streptomyces/metabolismoRESUMO
Non-suicidal self-harm (NSSH) and chronic insufficient sleep are both major health problems during the transition from childhood to adolescence. We examined to identify sleep duration trajectories from childhood to adolescence and their associations with subsequent risk of NSSH. A cohort of children around the period of pubertal onset (7-9 years old) were followed from 2013 over 6 years. Group-based trajectory modeling was recruited to identify sleep duration trajectories derived from 5 repeated measures. Association between sleep duration trajectories with the risk of NSSH was examined using multivariate logistic regression model. Nonlinear dose-response associations between sleep duration and NSSH risk were also assessed using restricted cubic spline models. Of the 1973 participants included in the study (mean ± SD, 8.1 ± 0.9 years age at baseline, 41.1% female). Three sleep duration trajectories were identified: persistent sleeping ≥ 8 h/day (27.7%), moderately decreasing (60.8%) and rapidly decreasing (11.5%) sleep duration groups. After multivariable adjustment for covariates, compared with the persistent sleeping ≥ 8 h/day group, the odds ratio of NSSH was 2.58 (95% CI 1.92, 3.45) for the moderately decreasing group, and 4.16 (2.86, 6.04) for rapidly decreasing group. In dose-response analysis, sleep duration was associated with NSSH risk in a non-linear fashion (χ2 = 25.16, Pnonlinearity < 0.001). When compared with the reference (sleep duration = 8 h), the ORs (95% CI) for NSSH risks were 3.20 (1.93, 5.29), 2.37 (1.64, 3.41), 1.75 (1.39, 2.20) and 1.30 (1.18, 1.44) for sleep duration at 4 to 7 h, respectively. Also, we found sleep duration at 9 h [0.82 (0.75, 0.89)] and at 10 h [0.72 (0.57, 0.91)] significantly associated with decreased risk of NSSH. Longitudinal sleep duration patterns may assist in identification of adolescents at greatest risk of NSSH in the future, which could lead to improved targeting of prevention and intervention strategies. The findings also highlight a non-linear relationship between sleep duration and NSSH during the transition to adolescence.
Assuntos
Comportamento do Adolescente , Comportamento Autodestrutivo , Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Sono , Ideação SuicidaRESUMO
Evidence that common beverage consumption is associated with oral ecosystem. However, little is known about the effect of sugar-sweetened beverages (SSBs) on composition and functional potential of childhood oral microbiota. We aim to examine associations between SSBs consumption with oral microbiota diversity and function among school-aged children. Oral microbiota in buccal swab samples was collected from 180 children (11.3 ± 0.6 years) from an ongoing child growth and development cohort established in 2016, using 16S rDNA gene sequencing. Higher SSBs consumption (≥1 serving/day) was associated with lower oral microbiota richness and diversity. Children with higher SSBs consumption showed decreased abundance of genus Fusobacterium, Lachnoanaerobaculum, Soonwooa, Tannerella and Moraxella (p < 0.05). However, more SSBs intake selectively increases the dominance of aciduric bacteria (Neisseria and Streptococcus), which can lead to dental caries and other oral problems. Furthermore, PICRUSt analysis illustrated that oral microbiota was more conducive to the pathway activated of protein export (p = 0.020), D-glutamine and D-glutamate metabolism (p = 0.013), and pantothenate and CoA biosynthesis (p = 0.004), indicating vigorous microbial metabolism in oral bacterial community in higher SSBs intake groups. Overall, our finding suggests that higher SSBs consumption may disturb oral microecology and reduce diversity of microbiota during childhood, stimulating an increase in cariogenic genera, which contributes to increased susceptibility of SSBs-related oral diseases.
Assuntos
Cárie Dentária , Microbiota , Bebidas Adoçadas com Açúcar , Bebidas/análise , Criança , Cárie Dentária/etiologia , Humanos , Instituições AcadêmicasRESUMO
Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.
Assuntos
Nanocompostos , Quercetina , Animais , Inflamação/tratamento farmacológico , Ativação de Macrófagos , MacrófagosRESUMO
BACKGROUND: The earliest onset of puberty had shifted downward, which may be due to the role of early growth and development factors in childhood. METHODS: All of 1575 Kindergarten Two (K2) children from Anhui province, China were followed up to elementary school. Girls (n = 342) with available data on AR and breast development were included for this analysis. Polygenic risk score (PRS) was computed based on 17 single nucleotide polymorphisms for early puberty. Accelerate failure time (AFT) model was used to describe thelarche timing by early AR among girls with different polygenic susceptibility. RESULTS: After adjustment for perinatal anthropometric, household income, parental education and prepuberty BMI-Z score, puberty started 4.12-month earlier in early AR girls compared with normal AR girls (TR: 0.96; 95% CI: 0.95, 0.98, p < 0.001). Furthermore, this puberty-accelerating effect was observed among girls with high (6.06-month earlier, TR: 0.94; 95% CI: 0.90, 0.99) and moderate PRS (4.20-month earlier, TR: 0.96; 95% CI: 0.93, 0.98). No similar results were observed in the low PRS groups (TR: 1.00; 95% CI: 0.96, 1.04). CONCLUSIONS: Girls with early AR displayed younger age at thelarche; however, this accelerating effect was only observed among those with genetic susceptibility to early puberty. IMPACT: Early AR plays a more important role in predicting earlier thelarche among girls with high and moderate PRS. This study combined with the hot topics of pubertal-related polygenic risk score (PRS) for pubertal timing to examine the longitudinal association between early AR with accelerated pubertal onset. Our results mean that accelerating growth in the early childhood years after birth might forecast early puberty only among girls with genetic predisposition to early puberty. Prevention strategies and management options should be emphasized to target early childhood to address secular trend for early puberty observed in the past decades in China.
Assuntos
Adiposidade , Puberdade Precoce , Puberdade , Antropometria , Índice de Massa Corporal , Mama/fisiologia , Mama/fisiopatologia , Criança , China/epidemiologia , Feminino , Seguimentos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Receptores Androgênicos/genética , RiscoRESUMO
BACKGROUND: Rapid socio-economic development makes China a unique laboratory for examining how lifestyle changes affect adolescent mental health. This study aims to identify joint trajectories of modifiable lifestyle indicators during pubertal transition and its associations with psychopathological outcomes. METHODS: A cohort of 1974 children aged 7-9 years were recruited in Anhui Province, China during March 2013. The assessment of lifestyle behaviors (screen time, physical activity, sleep duration and beverage intake) and depressive symptoms were conducted from Wave 1 to Wave 4 (2018). Suicide ideation, non-suicidal self-harm (NSSI) and alcohol use were self-reported at Wave 4. Longitudinal trajectories of lifestyle patterns were defined using group-based multi-trajectory models in 2019. RESULTS: Four lifestyle trajectories were identified: persistent healthy (39.9%), suboptimal healthy (25.3%), unhealthy mitigation (17.2%), and persistent unhealthy (17.7%). Compared with persistent healthy group, the risk of subsequent suicide ideation [odds ratio (OR): 2.86, 95%CI: 2.15-3.81], depressive symptoms (OR: 2.16, 95%CI: 1.39-3.35), alcohol use (OR: 2.53, 95%CI: 1.78-3.61) and non-suicidal self-harm (OR: 1.35, 95%CI: 1.09-1.67) was significantly higher in persistent unhealthy group. CONCLUSIONS: This study provided convincing evidence that unhealthy lifestyle trajectory during adolescence is associated with more than two-fold elevated odds for multiple domains of psychopathological outcomes over 5 years.
Assuntos
Transtornos Mentais , Comportamento Autodestrutivo , Adolescente , Criança , Humanos , Estilo de Vida , Psicopatologia , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Ideação SuicidaRESUMO
Imatinib was the first BCR-ABL inhibitor used in clinical practice to treat chronic myeloid leukaemia (CML) and significantly improve the life expectancy of CML patients in the chronic phase. However, a portion of CML patients are resistant to imatinib. This study aimed to determine whether menadione (Vitamin K3) can improve imatinib efficacy in CML and to thoroughly explore the combination regimen mechanism between imatinib and menadione. Menadione improved imatinib efficacy in K562 cells by downregulating ABCB1 expression and increased the intracellular concentration of imatinib, which confirmed that this combination regimen is more effective than imatinib monotherapy. The results demonstrate that menadione and imatinib combination therapy may be a promising approach to refractory CML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Vitamina K 3/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Humanos , Mesilato de Imatinib/metabolismo , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Inibidores de Proteínas Quinases/metabolismoRESUMO
Hypertensive cardiac remodeling is a major cause of heart failure. The immunoproteasome is an inducible form of the proteasome and its catalytic subunit ß5i (also named LMP7) is involved in angiotensin II-induced atrial fibrillation; however, its role in deoxycorticosterone-acetate (DOCA)-salt-induced cardiac remodeling remains unclear. C57BL/6â¯J wild-type (WT) and ß5i knockout (ß5i KO) mice were subjected to uninephrectomy (sham) and DOCA-salt treatment for three weeks. Cardiac function, fibrosis, and inflammation were evaluated by echocardiography and histological analysis. Protein and gene expression levels were analyzed by quantitative real-time PCR and immunoblotting. Our results showed that after 21â¯days of DOCA-salt treatment, ß5i expression and chymotrypsin-like activity were the most significantly increased factors in the heart compared with the sham control. Moreover, DOCA-salt-induced elevation of blood pressure, adverse cardiac function, chamber and myocyte hypertrophy, interstitial fibrosis, oxidative stress, and inflammation were markedly attenuated in ß5i KO mice. These findings were verified in ß5i inhibitor PR-957-treated mice. Moreover, blocking of PTEN (the gene of phosphate and tensin homolog deleted on chromosome ten) markedly attenuated the inhibitory effect of ß5i knockout on DOCA-salt-induced cardiac remodeling. Mechanistically, DOCA-salt stress upregulated the expression of ß5i, which promoted the degradation of PTEN and the activation of downstream signals (AKT/mTOR, TGF-ß1/Smad2/3, NOX, and NF-κB), which ultimately led to cardiac hypertrophic remodeling. This study provides new evidence of the critical role of ß5i in DOCA-salt-induced cardiac remodeling through the regulation of PTEN stability, and indicates that the inhibition of ß5i may be a promising therapeutic target for the treatment of hypertensive heart diseases.
Assuntos
Hipertensão/metabolismo , Hipertensão/fisiopatologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Subunidades Proteicas/metabolismo , Remodelação Ventricular , Animais , Cardiomegalia/complicações , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Quimotripsina/metabolismo , Acetato de Desoxicorticosterona , Fibrose , Hipertensão/complicações , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
OBJECTIVE: To examine whether polygenic susceptibility for body mass index (BMI) interacts with cumulative stress exposure, potentially exacerbating and buffering the effects of chronic stress, to predict obesity during childhood. METHODS: Data were analyzed from an established prospective puberty cohort in Anhui province, China. A total of 1000 children (421 boys and 579 girls, mean (standard deviation) age 8.97 (0.86) years) who had complete DNA genotyping, hair cortisol concentration and BMI were eligible for the study. The polygenic susceptibility score (PSS) was computed based on 11 SNPs derived from a published genome-wide association study for child obesity. RESULTS: Children with different obesity polygenic susceptibility did not differ in BMI, obesogenic behaviors and HCC. The positive association between HCC with BMI was only found among children with highest PSS (r = 0.269, P < 0.001). When exposed in cumulative stress, children with highest PSS have higher BMI (ß = 1.46, 95% CI: 0.63, 2.29; P = 0.001) than those having lowest PSS. The reverse pattern was found among children without cumulative stress exposure, those with highest PSS showed lowest BMI (ß = -1.27, 95% CI: -2.17, -0.38; P = 0.001), compared to lowest PSS groups. Re-parameterized regression models provide strong support for the differential susceptibility hypothesis. CONCLUSIONS: The findings underlie the importance of shifting perspectives from gene vulnerability to gene plasticity in the field of childhood obesity prevention. Children carrying additional BMI-raising alleles are at heightened risk of obesity are at heightened risk of obesity; however, they seem to be protected against obesity when the adverse psychosocial environment is removed.
Assuntos
Predisposição Genética para Doença/psicologia , Obesidade Infantil/genética , Estresse Psicológico/complicações , Índice de Massa Corporal , Criança , Feminino , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Obesidade Infantil/etiologia , Obesidade Infantil/psicologia , Estudos Prospectivos , Puberdade , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologiaRESUMO
MC13 is a novel coumarin compound found in Murraya, an economic crop whose leaves are widely used as condiment (curry) in cuisine. The aims of the present study were to investigate the neuroprotective effects of MC13 on microglia-mediated inflammatory injury model as well as potential molecular mechanism. Cell viability and apoptosis assay demonstrated that MC13 was not toxic to neurons and significantly protected neurons from microglia-mediated inflammatory injury upon lipopolysaccharide (LPS) stimulation. Results showed that MC13 markedly inhibited LPS-induced production of various inflammatory mediators, including nitrite oxide (Griess method), TNF-α and IL-6 (ELISA assay) in a concentration-dependent manner. Mechanism study showed that MC13 could suppress the activation of NF-κB, which was the central regulator for inflammatory response, and also decreased the interaction of TGF-ß-activated kinase 1 (TAK1)-binding protein (TAB2) with TAK1 and TNF receptor associated factor (TRAF6), leading to the decreased phosphorylation levels of NF-κB upstream regulators such as IκB and IκB kinase (IKK). MC13 also significantly down-regulated the phosphorylation levels of ERK and p38 MAPKs, which played key roles in microglia-mediated inflammatory response. Furthermore, MC13 inhibited Jak2-dependent Stat1/3 signaling pathway activation by blocking Jak2 phosphorylation, Stat1/3 phosphorylation, and nuclear translocation. Taken together, our results demonstrated that MC13 protected neurons from microglia-mediated neuroinflammatory injury by inhibiting TRAF6-TAK1-NF-κB, p38/ERK MAPKs, and Jak2-Stat1/3 pathways. Finally, MC13 might interact with LPS and interfere LPS-binding to cell membrane surface. These findings suggested that coumarin might act as a potential medicinal agent for treating neuroinflammation as well as inflammation-related neurodegenerative diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Inflamação/metabolismo , Microglia/efeitos dos fármacos , Murraya/química , Fármacos Neuroprotetores/farmacologia , Animais , Apoptose , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Camundongos , Microglia/citologia , Microglia/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
[To explore the effect of Humifuse Euphorbia Herb ( HEH) on alleviating insulin resistance in type 2 diabetic KK-Ay mice. Totally 40 KK-Ay mice fed with high-fat diet were divided into four groups: the metformin group, the model group, the HEH low-dose group and the HEH high-dose group, and orally administrated with metformin hydrochloride (250 mg x kg(-1)), distilled water, humifuse euphorbia herb 1 g x kg(-1) and 2 g x kg(-1). Besides, C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The oral administration for the five groups lasted for eight weeks. Before and after the experiment, weight, fasting glucose and insulin tolerance were determined. The morphological changes in pancreas were observed through hematoxylin-eosin (HE) staining on pancreatic tissue sections. The serum insulin, TNF-α, IL-6, adiponectin (ADPN) and leptin (LEP) were detected by ELISA. The results showed that HEH could reduce weight and fasting glucose in KK-Ay mice, alleviate hyperinsulinemia, reduce blood glucose-time AUC, increase 30-min blood glucose decline rate, relieve insulin resistance, significantly ameliorate the pathomorphological changes in pancreas in each group, decrease serum TNF-α, IL-6 and leptin levels in KK-Ay mice and rise serum ADPN level. This study proved that humifuse euphorbia herb can ameliorate the insulin resistance in KK-Ay mice, and its mechanism may be related to the effect on inflammatory factors and adipocytokines.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Euphorbia/química , Resistência à Insulina , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Humanos , Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cephaleuros species are well-known as plant pathogens that cause red rust or algae spot diseases in many economically cultivated plants that grow in shady and humid environments. Despite their prevalence, the adaptive evolution of these pathogens remains poorly understood. We sequenced and characterized three Cephaleuros (Cephaleuros lagerheimii, Cephaleuros diffusus, and Cephaleuros virescens) chloroplast genomes, and compared them with seven previously reported chloroplast genomes. The chloroplast sequences of C. lagerheimii, C. diffusus, and C. virescens were 480,613 bp, 383,846 bp, and 472,444 bp in length, respectively. These chloroplast genomes encoded 94 genes, including 27 tRNA genes, 3 rRNA genes, and 64 protein-coding genes. Comparative analysis uncovered that the variation in genome size was principally due to the length of intergenic spacer sequences, followed by introns. Furthermore, several highly variable regions (trnY-GTA, trnL-TAG, petA, psbT, trnD-GTC, trnL-TAA, ccsA, petG, psaA, psaB, rps11, rps2, and rps14) were identified. Codon bias analysis revealed that the codon usage pattern of Cephaleuros is predominantly shaped by natural selection. Additionally, six chloroplast protein-coding genes (atpF, chlN, psaA, psaB, psbA, and rbcL) were determined to be under positive selection, suggesting they may play a vital roles in the adaptation of Cephaleuros to low-light intensity habitats.
Assuntos
Evolução Molecular , Genoma de Cloroplastos , Filogenia , Cloroplastos/genética , Uso do CódonRESUMO
The synergistic effects of plasma-activated water (PAW) and twin-screw extrusion (TSE) on the structural, physicochemical, antioxidant, and digestive properties of yam flour (YF) were studied. Compared to common TSE, PAW-TSE reduced the protein, starch, and polyphenol contents, swelling power, and gel property of YF, while PAW-TSE enhanced the flavonoid content, whiteness index, solubility, and antioxidant property of YF. Moreover, the results of structural characterization and differential scanning calorimetry indicated that the long-range or short-range ordering, and gelatinization enthalpy of starch in YF were reduced after PAW-TSE, while the structure ordering of proteins in YF increased. Furthermore, the in vitro digestibility results demonstrated a reduction in the rate of enzymatic hydrolysis, coupled with an increase in total contents of slowly digestible and resistant starch after PAW-TSE. It should be noted that TSE using PAW prepared by a longer plasma treatment resulted in a more significant improvement effect on YF.
RESUMO
The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H2O2 levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu3P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting â¢OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate-a metabolite in periodontal biofilm-into H2O2, further amplifying CDT's potential. In vitro Cu3P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu3P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue in vivo periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified via the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care. STATEMENT OF SIGNIFICANCE: The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H2O2 level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu3P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu3P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management.
RESUMO
Thermoplastic poly(ether/ester) elastomer (TPEE) has great potential as a mattress material due to its high resilience, breathability, and light weight. This study aimed to evaluate the feasibility of TPEE-3D fibrous material (T3DF), a three-dimensional block material made of TPEE fibers randomly aligned and loop-connected, for mattress application. After testing the compression properties of T3DF, the effects of T3DF structural layers on mattress firmness were investigated. The results showed that T3DF had good energy absorption capacity, broad indentation hardness range (126.94-333.82 N), and high compression deflection coefficient (2.79-4.39). The thickness and density of T3DF were the main factors influencing mattress firmness, and the impact of thickness was more significant (p < 0.05). Owing to the hard and soft segments contained in TPEE, T3DF could be used for both the padding and core layers of the mattress. The hardness value and Dsurface of the mattress with a T3DF padding layer increased with T3DF density but decreased with T3DF thickness. Moreover, the hardness value and Dsurface of the mattress with a T3DF core layer increased with T3DF density, while with T3DF thickness, its Dsurface increased and Dbottom decreased. Therefore, the thick and low-density T3DF padding layer could improve the comfort of the mattress surface, a thin T3DF core layer could satisfy both the softer surface and the firmer bottom of the mattress.