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1.
Lancet ; 403(10438): 1808-1820, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38643776

RESUMEN

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Asunto(s)
Política de Salud , Adolescente , Niño , Femenino , Humanos , Masculino , Salud del Adolescente , Salud Infantil , China , Pueblos del Este de Asia , Necesidades y Demandas de Servicios de Salud
2.
J Asian Nat Prod Res ; 26(2): 269-279, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38078645

RESUMEN

Microbial transformation of dihydroresveratrol (DHRSV) using Beauveria bassiana has produced two new methylglucosylated derivatives of DHRSV (1 and 2), whose structures were characterized as 4'-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (4'-O-MG DHRSV, 1) and 3-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (3-O-MG DHRSV, 2) on the basis of spectroscopic methods. They showed moderate SIRT3 agonistic activity, and compound 2 exhibited the best deacetylation of 406.63% at 10 µM. The activity of 2 increased by 3.12-fold compared with that of DHRSV, since 2 performed better in molecular docking assay (GScore -8.445).


Asunto(s)
Bibencilos , Sirtuina 3 , Estilbenos , Metilglucósidos/química , Simulación del Acoplamiento Molecular , Estructura Molecular
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(3): 418-423, 2024 Jun 18.
Artículo en Zh | MEDLINE | ID: mdl-38864126

RESUMEN

OBJECTIVE: To explore the relationship between puberty timing and cardiovascular metabolic risk factors among primary and secondary students with different genders in Beijing. METHODS: Using the method of stratified cluster sampling by urban and rural areas and school sections, 3 067 students from 16 primary and secondary schools in Fangshan District of Beijing were selected in October 2012, with questionnaire survey, physical examination and serum laboratory testing. In this study, we controlled for confounding factors such as school segments, current residence of the family, birth weight, feeding method, only child, highest educational level of parents, and monthly family income, and then the associations between cardiovascular metabolic risk factors and puberty timing among the primary and secondary students was analyzed by multivariate Logistic analysis. To ensure the reliability of the data, this study adopted strict quality control. RESULTS: A total of 3 067 primary and middle school students aged 7 to 16 years were included in this study, including 1 575 boys and 1 492 girls. The prevalence of premature puberty was 14.73% among the boys and 12.89% among the girls, respectively. The prevalence of delayed puberty was 9.49% among the boys and 10.99% among the girls, respectively. The detection rates of central obesity, hypertension, hyperglycemia, and dyslipidemia among the primary and secondary students were 35.87%, 19.95%, 2.54% and 26.31%, respectively. The detection rates of 1 risk factor clustering, 2 risk factors clustering and more than 3 risk factors clustering were 29.21%, 16.17% and 9.36%, respectively. The difference in the detection rate of cardiovascular and metabolic risk factors in different youth stages was insignificant (P>0.05), the detection rate of risk factor aggregation of 0 was lower than that of the timely group and delayed group, and the detection rate of risk factors aggregation of 2 was higher than that of the timely group (P < 0.05).After adjusting the effects of learning stage, region, birth weight, feeding patterns, one-child, family income and the parents' educational levels, multivariate Logistic regression analysis showed that, compared with the on-time puberty group, the risk of 1 risk factor clustering, 2 risk factors clustering and more than 3 risk factors clustering increased by 1.94 times (95% CI=1.29-2.91), 2.97 times (95% CI=1.89-4.67) and 2.02 times (95% CI= 1.13-3.63) among the girls; It had not been found that the relationship between puberty timing and cardiovascular risk factor clustering among the boys (P>0.05). CONCLUSION: Premature puberty is an independent risk factor for the clustering of cardiometabolic risk factors in girls, and primary prevention strategies should be implemented to reduce the burden of cardiovascular metabolic diseases in the population.


Asunto(s)
Enfermedades Cardiovasculares , Pubertad , Estudiantes , Humanos , Femenino , Masculino , Adolescente , Niño , China/epidemiología , Estudiantes/estadística & datos numéricos , Pubertad/fisiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Encuestas y Cuestionarios , Factores de Riesgo de Enfermedad Cardiaca , Hipertensión/epidemiología , Dislipidemias/epidemiología , Pubertad Precoz/epidemiología , Obesidad Abdominal/epidemiología , Prevalencia , Hiperglucemia/epidemiología , Factores de Edad
4.
Mol Breed ; 43(7): 57, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37457120

RESUMEN

In wheat, TaMYC8 is a negative regulator of cadmium (Cd)-responsive ethylene signaling. In this study, we functionally characterized TabHLH094, a basic helix-loop-helix (bHLH) transcription factor (TF) that inhibits the transcriptional activity of TaMYC8. The TabHLH094 protein was found in the nucleus of tobacco epidermal cells and exhibited transcriptional activation activity. Real-time quantitative PCR (RT-qPCR) indicated that TabHLH094 exhibited root-specific, Cd-responsive expression in wheat seedlings. Overexpression of TabHLH094 enhanced the tolerance of wheat seedlings to Cd exposure. The protein-protein interaction between TabHLH094 and TaMYC8 was verified by glutathione S-transferase (GST) pulldown, coimmunoprecipitation (Co-IP), yeast two-hybrid (Y2H), and bimolecular fluorescence complementation (BiFC) analyses. TabHLH094 was found to reduce the ability of TaMYC8 to bind to the TaERF6 promoter. Furthermore, TabHLH094 could also reduce aminocyclopropanecarboxylate oxidase (ACO) and ACC synthase (ACS) activities, both of which are necessary for ethylene biosynthesis. Taken together, these results indicate that TabHLH094 mediates Cd tolerance by regulating the transcriptional activity of TaMYC8 and decreasing ethylene production. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01404-1.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(1): 57-63, 2023 Feb.
Artículo en Zh | MEDLINE | ID: mdl-36861156

RESUMEN

Objective To evaluate the performance of contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) LR-5 in the diagnosis of hepatocellular carcinoma (HCC). Methods The clinical research reports with the application of CEUS LI-RADS in the diagnosis of HCC were collected from PubMed,Embase,Cochrane Library,CNKI,and Wanfang Data from inception to November 14,2021.Two researchers respectively screened the literature and extracted relevant information.The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of all the included articles.RevMan 5.4,Meta disc 1.4,and Stata 16.0 were employed to analyze the diagnostic performance of LR-5 for HCC in high-risk patients. Results Twenty original studies were included,involving a total of 6131 lesions,of which 5142 were HCC.The results of meta-analysis showed that the LR-5 in CEUS LI-RADS for diagnosing HCC in the high-risk population had the overall sensitivity of 0.72 (95%CI=0.66-0.77),the overall specificity of 0.93 (95%CI=0.87-0.96),the overall positive likelihood ratio of 9.89 (95%CI=5.31-18.41),the overall negative likelihood ratio of 0.30 (95%CI=0.25-0.37),and the area under the summary receiver operating characteristic curve of 0.88 (95%CI=0.85-0.91).There was heterogeneity among the included studies (I2=95.31,P<0.001).The funnel plot indicated the existence of publication bias (P=0.04). Conclusion The CEUS LI-RADS can effectively diagnose HCC in high-risk patients based on the LR-5 criteria.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Diagnóstico por Imagen , Ultrasonografía
6.
Hum Mol Genet ; 29(8): 1239-1252, 2020 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-32037456

RESUMEN

It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson's disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.


Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Proteínas de Unión al ADN/genética , Neuronas Dopaminérgicas/metabolismo , Enfermedad de Parkinson/genética , Proteínas Proto-Oncogénicas/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animales , Metilación de ADN/genética , Dioxigenasas , Modelos Animales de Enfermedad , Epigénesis Genética , Humanos , Masculino , Mesencéfalo/lesiones , Mesencéfalo/metabolismo , Ratones , Enfermedad de Parkinson/patología
7.
BMC Plant Biol ; 22(1): 342, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35836128

RESUMEN

BACKGROUND: Rhododendron molle (Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have been demonstrated to be the chemical basis for the analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in the leaves, flowers, roots, and fruits of R. molle, with low content. Currently the research on the biosynthesis of grayanoids is hindered, partially due to lack of the genomic information. RESULTS: In the present study, a total of 744 Mb sequences were generated and assembled into 13 chromosomes. An ancient whole-genome duplication event (Ad-ß) was discovered that occurred around 70 million years ago. Tandem and segmental gene duplications led to specific gene expansions in the terpene synthase and cytochrome P450 (CYP450) gene families. Two diterpene synthases were demonstrated to be responsible for the biosynthesis of 16α-hydroxy-ent-kaurane, the key precursor for grayanoids. Phylogenetic analysis revealed a species-specific bloom of the CYP71AU subfamily, which may involve the candidate CYP450s responsible for the biosynthesis of grayanoids. Additionally, three putative terpene biosynthetic gene clusters were found. CONCLUSIONS: We reported the first genome assembly of R. molle and investigated the molecular basis underpinning terpenoids biosynthesis. Our work provides a foundation for elucidating the complete biosynthetic pathway of grayanoids and studying the terpenoids diversity in R. molle.


Asunto(s)
Diterpenos , Ericaceae , Rhododendron , Cromosomas , Ericaceae/genética , Filogenia , Rhododendron/genética
8.
BMC Public Health ; 21(1): 1776, 2021 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-34592977

RESUMEN

BACKGROUND: Most studies of associations between parental support behaviours for physical activity (PA) and children's moderate-to-vigorous physical activity (MVPA) have been conducted in developed countries, and they have focused on maternal or parental support behaviours. Children's MVPA time (i.e., weekdays vs. weekends) has not been adequately differentiated. This paper investigated the associations of paternal and maternal support behaviours for PA with the proportion of children who met the MVPA recommendations on weekdays and weekends in China. METHODS: Cross-sectional data of 517 father-child dyads and 1422 mother-child dyads were analysed. The children recorded PA diaries on 7 consecutive days to assess their MVPA time. The father or mother completed a questionnaire concerning their support for children's PA. Multivariate logistic regression was used to investigate the independent effects of paternal and maternal support behaviours for PA on whether children met the MVPA recommendations for weekdays, weekends, and the whole week. RESULTS: Significantly fewer children met the MVPA recommendations on weekends (37.8%) than on weekdays (62.8%). Higher paternal (odds ratio [OR] = 1.098, 95% confidence interval [CI]: 1.009-1.195) and maternal (OR = 1.076, 95% CI: 1.021-1.134) total support behaviour scores were associated with higher odds of children meeting the MVPA recommendations on weekends, after controlling for covariates. Paternal PA knowledge-sharing with the child was positively associated with children meeting the MVPA recommendations on weekends (OR = 1.319, 95% CI: 1.055-1.649); it tended to be associated with children meeting the MVPA recommendations on weekdays and throughout the week, although these associations were not statistically significant. Maternal reservation of PA time for the child was positively associated with a higher likelihood of children meeting the MVPA recommendations on weekdays (OR = 1.160, 95% CI: 1.025-1.313), weekends (OR = 1.241, 95% CI: 1.097-1.403), and throughout the week (OR = 1.214, 95% CI: 1.076-1.369). CONCLUSIONS: Paternal and maternal support behaviours for PA should be enhanced on weekends to increase children's MVPA. Fathers should share PA knowledge with children and mothers should reserve PA time for children every day.


Asunto(s)
Ejercicio Físico , Padre , Acelerometría , Estudios Transversales , Femenino , Humanos , Masculino , Madres , Encuestas y Cuestionarios
9.
World J Microbiol Biotechnol ; 36(7): 106, 2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32638277

RESUMEN

As the most important member of antioxidant defense system, human Cu,Zn superoxide dismutase (hCu,Zn-SOD) protects cells against the free radicals produced by aerobic metabolism. hCu,Zn-SOD has been widely used in food, cosmetic and medicine industry due to its health benefits and therapeutic potentials. However, a more extensive application of hCu,Zn-SOD is limited by the challenge of expensive and low production of high-activity hCu,Zn-SOD in large scale. In this study, the codon-optimized hCu,Zn-SOD gene was synthesized, cloned into pET-28a( +) and transformed into Escherichia coli BL21(DE3). After induction with IPTG or lactose, hCu,Zn-SOD was highly expressed as soluble form in LB medium with 800 µM Cu2+ and 20 µM Zn2+ at 25 °C. The recombinant hCu,Zn-SOD was efficiently purified by nickel affinity chromatography. Through optimization of fed-batch fermentation conditions, 342 mg purified hCu,Zn-SOD was obtained from 1 L cultures fermented in a 3-L bioreactor. Furthermore, the recombinant hCu,Zn-SOD retained the enzymatic specific activity of 46,541 U/mg. This study has opened up an effective avenue for industrial production of hCu,Zn-SOD through microbial fermentation in the future.


Asunto(s)
Escherichia coli/genética , Escherichia coli/metabolismo , Microbiología Industrial/métodos , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Técnicas de Cultivo Celular por Lotes , Cromatografía de Afinidad , Clonación Molecular/métodos , Cobre , Fermentación , Regulación Enzimológica de la Expresión Génica , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Superóxido Dismutasa/aislamiento & purificación , Zinc
10.
Biochem Biophys Res Commun ; 515(1): 201-206, 2019 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-31146911

RESUMEN

PURPOSE: Elevated levels of CXCL1 were observed in the cerebrospinal fluid of patients with early Alzheimer's disease, which may affect neural stem cells in the subventricular zone. We used APP/PS1 mice and neural stem cells to elucidate the role of CXCL1 in Alzheimer's disease. METHODS & RESULTS: We detected CXCL1 in cerebrospinal fluid (CSF), activated macrophages, and microglia suggesting that macrophages may contribute to elevated CXCL1 in the CSF of middle-aged APP/PS1 mice. Proliferation and differentiation of neural stem cells were further analyzed and the results suggested that CXCL1 promotes the proliferation of neural stem cells and inhibits their differentiation into astrocytes. In order to determine how CXCL1 exerts these effects, we analyzed intracellular reactive oxygen species, cell signaling, and performed in vivo recovery experiments. Our results suggest that CXCL1 promotes neural stem cell proliferation through a mechanism involving the production of reactive oxygen species and the PI3K/Akt pathway. CONCLUSION: In APP/PS1 mice, macrophage-derived CXCL1 can promote the proliferation of neural stem cells in the subventricular zone via the NOX2-ROS-PI3K/Akt pathway.


Asunto(s)
Proliferación Celular , Quimiocina CXCL1/metabolismo , Modelos Animales de Enfermedad , Células-Madre Neurales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Quimiocina CXCL1/líquido cefalorraquídeo , Humanos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Células-Madre Neurales/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
12.
Mar Drugs ; 16(2)2018 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-29495293

RESUMEN

A new spirotetronate glycoside tetrocarcin Q (1) and six known analogues tetrocarcin A (2), AC6H (3), tetrocarcin N (4), tetrocarcin H (5), arisostatin A (6), and tetrocarcin F1 (7) were isolated from the fermentation broth of the marine-derived actinomycete Micromonospora carbonacea LS276. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopy, as well as HR-ESI-MS analysis. The absolute configurations of their stereogenic carbons were determined by circular dichroism (CD) analysis. Compound 1 possesses 2-deoxy-allose, which is a unique sugar type at the C-9 position. This type has not been found in the previously reported spirotetronate glycosides. Compound 1 displayed moderate antibacterial activity against Bacillus subitlis ATCC 63501 with minimum inhibitory concentration (MIC) value of 12.5 µM.


Asunto(s)
Actinobacteria/química , Aminoglicósidos/química , Antibacterianos/química , Organismos Acuáticos/química , Micromonospora/química , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Glicósidos/química , Glicósidos/farmacología , Espectroscopía de Resonancia Magnética/métodos , Pruebas de Sensibilidad Microbiana/métodos
13.
Molecules ; 24(1)2018 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-30586935

RESUMEN

The ß-glycoside hydrolases (LXYL-P1-1 and LXYL-P1-2) from Lentinula edodes (strain M95.33) can specifically hydrolyze 7-ß-xylosyl-10-deacetyltaxol (XDT) to form 10-deacetyltaxol for the semi-synthesis of Taxol. Our previous study showed that both the I368T mutation in LXYL-P1-1 and the T368E mutation in LXYL-P1-2 could increase the enzyme activity, which prompted us to investigate the effect of the I368E mutation on LXYL-P1-1 activity. In this study, the ß-xylosidase and ß-glucosidase activities of LXYL-P1-1I368E were 1.5 and 2.2 times higher than those of LXYL-P1-1. Most importantly, combination of I368E and V91S exerted the cumulative effects on the improvement of the enzyme activities and catalytic efficiency. The ß-xylosidase and ß-glucosidase activities of the double mutant LXYL-P1-1V91S/I368E were 3.2 and 1.7-fold higher than those of LXYL-P1-1I368E. Similarly, the catalytic efficiency of LXYL-P1-1V91S/I368E on 7-ß-xylosyl-10-deacetyltaxol was 1.8-fold higher than that of LXYL-P1-1I368E due to the dramatic increase in the substrate affinity. Molecular docking results suggest that the V91S and I368E mutation might positively promote the interaction between enzyme and substrate through altering the loop conformation near XDT and increasing the hydrogen bonds among Ser91, Trp301, and XDT. This study lays the foundation for exploring the relationship between the structure and function of the ß-glycoside hydrolases.


Asunto(s)
Glicósido Hidrolasas/genética , Mutagénesis Sitio-Dirigida , Hongos Shiitake/enzimología , Biomasa , Cinética , Simulación del Acoplamiento Molecular , Mutación/genética , Recombinación Genética/genética , Saccharomyces cerevisiae/metabolismo , Especificidad por Sustrato , Taxoides/metabolismo , Xilosidasas/metabolismo
14.
Twin Res Hum Genet ; 20(4): 355-362, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28651682

RESUMEN

The Wuhan Pre/Post-Natal Twin Birth Registry (WPTBR) is one of the largest twin birth registries with comprehensive medical information in China. It recruits women from the first trimester of pregnancy and their twins from birth. From January 2006 to May 2016, the total number of twins enrolled in WPTBR is 13,869 twin pairs (27,553 individuals). The WPTBR initiated the Wuhan Twin Birth Cohort (WTBC). The WTBC is a prospective cohort study carried out through incorporation of three samples. The first one comprises 6,920 twin pairs, and the second one, 6,949 twin pairs. Both are population-based samples linked to the WPTBR and include pre- and post-natal information from WPTBR. The second sample includes neonatal blood spots as well. Using a hospital-based approach, we recently developed a third sample with a target enrolment of 1,000 twin pairs and their mothers. These twins are invited, via their parents, to participate in a periodic health examination from the first trimester of pregnancy to 18 years. Biological samples are collected initially from the mother, including blood, urine, cord blood, cord, amniotic fluid, placenta, breast milk and meconium, and vaginal secretions, and later from the twins, including meconium, stool, urine, and blood. This article describes the design, recruitment, follow-up, data collection, and measures, as well as ongoing and planned analyses at the WTBC. The WTBC offers a unique opportunity to follow women from prenatal to postnatal, as well as follow-up of their twins. This cohort study will expand the understanding of genetic and environmental influences on pregnancy and twins' development in China.


Asunto(s)
Bancos de Muestras Biológicas , Primer Trimestre del Embarazo , Embarazo , Sistema de Registros , Gemelos , China , Estudios de Cohortes , Femenino , Humanos , Masculino
15.
Molecules ; 22(12)2017 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-29207529

RESUMEN

The glycoside hydrolase LXYL-P1-2 from Lentinula edodes can specifically hydrolyze 7-ß-xylosyltaxanes to form 7-ß-hydroxyltaxanes for the semi-synthesis of paclitaxel. In order to improve the catalytic properties of the enzyme, we performed error-prone PCR to construct the random mutant library of LXYL-P1-2 and used the methanol-induced plate method to screen the mutants with improved catalytic properties. Two variants, LXYL-P1-2-EP1 (EP1, S91D mutation) and LXYL-P1-2-EP2 (EP2, T368E mutation), were obtained from the library and exhibited 17% and 47% increases in their catalytic efficiencies on 7-ß-xylosyl-10-deacetyltaxol. Meanwhile, compared with LXYL-P1-2, EP1 and EP2 showed elevated stabilities in the range of pH ≥ 6 conditions. After treatment at pH 12 for 48 h, EP1 and EP2 retained 77% and 63% activities, respectively, while the wild-type only retained 33% activity under the same condition. Molecular docking results revealed that the S91D mutation led to a shorter distance between the R-chain and the substrate, while the T368E mutation increased negative charge at the surface of the enzyme, and may introduce alterations of the loop near the active pocket, both of which may result in improved stabilities and catalytic activities of enzymes. This study provides a practical directed evolution method for exploring catalytically improved glycoside hydrolase.


Asunto(s)
Glicósido Hidrolasas/metabolismo , Catálisis , Evolución Molecular Dirigida , Glicósido Hidrolasas/genética , Simulación del Acoplamiento Molecular , Reacción en Cadena de la Polimerasa
16.
Am J Med Genet B Neuropsychiatr Genet ; 171(7): 931-7, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26710920

RESUMEN

Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the co-existence of these behavior problems. © 2015 Wiley Periodicals, Inc.


Asunto(s)
Trastornos de Ansiedad/genética , Trastorno por Déficit de Atención con Hiperactividad/genética , Adolescente , Ansiedad/genética , Pueblo Asiatico/genética , Trastorno por Déficit de Atención con Hiperactividad/etiología , Niño , China , Depresión/genética , Enfermedades en Gemelos/genética , Ambiente , Femenino , Variación Genética , Humanos , Masculino , Gemelos/genética , Gemelos Dicigóticos , Gemelos Monocigóticos
17.
Mol Cell Proteomics ; 12(8): 2236-48, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23665501

RESUMEN

Paclitaxel, a natural antitumor compound, is produced by yew trees at very low concentrations, causing a worldwide shortage of this important anticancer medicine. These plants also produce significant amounts of 7-ß-xylosyl-10-deacetyltaxol, which can be bio-converted into 10-deacetyltaxol for the semi-synthesis of paclitaxel. Some microorganisms can convert 7-ß-xylosyl-10-deacetyltaxol into 10-deacetyltaxol, but the bioconversion yield needs to be drastically improved for industrial applications. In addition, the related ß-xylosidases of these organisms have not yet been defined. We set out to discover an efficient enzyme for 10-deacetyltaxol production. By combining the de novo sequencing of ß-xylosidase isolated from Lentinula edodes with RT-PCR and the rapid amplification of cDNA ends, we cloned two cDNA variants, Lxyl-p1-1 and Lxyl-p1-2, which were previously unknown at the gene and protein levels. Both variants encode a specific bifunctional ß-d-xylosidase/ß-d-glucosidase with an identical ORF length of 2412 bp (97% identity). The enzymes were characterized, and their 3.6-kb genomic DNAs (G-Lxyl-p1-1, G-Lxyl-p1-2), each harboring 18 introns, were also obtained. Putative substrate binding motifs, the catalytic nucleophile, the catalytic acid/base, and potential N-glycosylation sites of the enzymes were predicted. Kinetic analysis of both enzymes showed kcat/Km of up to 1.07 s(-1)mm(-1) against 7-ß-xylosyl-10-deacetyltaxol. Importantly, at substrate concentrations of up to 10 mg/ml (oversaturated), the engineered yeast could still robustly convert 7-ß-xylosyl-10-deacetyltaxol into 10-deacetyltaxol with a conversion rate of over 85% and a highest yield of 8.42 mg/ml within 24 h, which is much higher than those reported previously. Therefore, our discovery might lead to significant progress in the development of new 7-ß-xylosyl-10-deacetyltaxol-converting enzymes for more efficient use of 7-ß-xylosyltaxanes to semi-synthesize paclitaxel and its analogues. This work also might lead to further studies on how these enzymes act on 7-ß-xylosyltaxanes and contribute to the growing database of glycoside hydrolases.


Asunto(s)
Hongos Shiitake/enzimología , Taxoides/metabolismo , Xilosidasas/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Complementario/genética , ADN de Hongos/genética , Proteínas Fúngicas/genética , Datos de Secuencia Molecular , ARN de Hongos/genética , Hongos Shiitake/genética , Xilosidasas/genética , Levaduras/genética , Levaduras/metabolismo
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(3): 400-5, 2015 Jun 18.
Artículo en Zh | MEDLINE | ID: mdl-26080866

RESUMEN

OBJECTIVE: To study whether the socio-ecological model based on "student-school-family" three-level strategy is effective in obesity prevention. METHODS: A total of 3 175 students aged 7 to 18 from 16 schools (4 urban primary schools, 4 rural primary schools, 4 urban secondary schools and 4 rural secondary schools, of which 2 intervention schools were selected, respectively) were recruited by stratified cluster sampling method. A three-month intervention using "student-school-family" socio-ecological model was conducted through health education and environment improvement. The intervention contents included knowledge on obesity, healthy diet and physical activities. Their anthropometric indexes were recorded. RESULTS: The intervention prevented obesity (OR=1.12, P<0.05), and was effective in waist circumference (WC) and waist-hip ratio (WHR) (adjusted difference=0.63, 0.02, P<0.05). WC and WHR were reduced in girls (adjusted difference=0.52 & 0.02, P<0.05), and obesity was prevented in girls (OR=1.18, P<0.05). WC and WHR were reduced in boys (adjusted difference=0.73, 0.01, P<0.05). WHR were reduced in urban areas (adjusted difference=0.01, P<0.05). WC and WHR were reduced (adjusted difference=1.05, 0.02, P<0.05) and obesity was prevented (OR=1.18, P<0.05) in rural areas. WHR were reduced (adjusted difference=0.01, P<0.05) and obesity was prevented (OR=1.21, P<0.05) in primary schools. WHR were reduced in secondary schools (adjusted difference=0.02, P<0.05).The intervention effect was better in girls than in boys, in rural areas than in urban areas, and in primary schools than in secondary schools. The overweight and obesity prevalence went down after the intervention (χ2=11.01, P<0.01). CONCLUSION: Intervention strategy is effective in central obesity indexes such as WC and WHR, and it can be used widely.


Asunto(s)
Promoción de la Salud/métodos , Obesidad Infantil/prevención & control , Adolescente , Niño , Femenino , Educación en Salud , Humanos , Masculino , Obesidad Abdominal/prevención & control , Sobrepeso , Prevalencia , Población Rural , Instituciones Académicas , Estudiantes , Población Urbana , Circunferencia de la Cintura , Relación Cintura-Cadera
19.
Front Psychol ; 15: 1356554, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533221

RESUMEN

Background: The increasing prevalence of mental health issues among children and adolescents has prompted a growing number of researchers and practitioners to explore digital technology interventions, which offer convenience, diversity, and proven effectiveness in addressing such problems. However, the existing literature reveals a significant gap in comprehensive reviews that consolidate findings and discuss the potential of digital technologies in enhancing mental health. Methods: To clarify the latest research progress on digital technology to promote mental health in the past decade (2013-2023), we conducted two studies: a systematic review and meta-analysis. The systematic review is based on 59 empirical studies identified from three screening phases, with basic information, types of technologies, types of mental health issues as key points of analysis for synthesis and comparison. The meta-analysis is conducted with 10 qualified experimental studies to determine the overall effect size of digital technology interventions and possible moderating factors. Results: The results revealed that (1) there is an upward trend in relevant research, comprising mostly experimental and quasi-experimental designs; (2) the common mental health issues include depression, anxiety, bullying, lack of social emotional competence, and mental issues related to COVID-19; (3) among the various technological interventions, mobile applications (apps) have been used most frequently in the diagnosis and treatment of mental issues, followed by virtual reality, serious games, and telemedicine services; and (4) the meta-analysis results indicated that digital technology interventions have a moderate and significant effect size (g = 0.43) for promoting mental health. Conclusion: Based on these findings, this study provides guidance for future practice and research on the promotion of adolescent mental health through digital technology. Systematic review registration: https://inplasy.com/inplasy-2023-12-0004/, doi: 10.37766/inplasy2023.12.0004.

20.
Pest Manag Sci ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808769

RESUMEN

BACKGROUND: Cnaphalocrocis medinalis (C.medinalis) is an agricultural pest with recurrent outbreaks. The investigation into automated pest and disease detection technology holds significant value for in-field surveys. Current generic detection methods are inadequate due to arbitrary orientations and a wide range of aspect ratios in damage symptoms. To tackle these issues, we put forward a rotated two-stage detection method for in-field C.medinalis surveys. This method relies on an anchor-free rotated region proposal network (AF-R2PN), bypassing the need for hyper-parameter optimization induced by predefined anchor boxes. An in-field C.medinalis dataset is constructed during on-site pest surveys to validate the effectiveness of our method. RESULTS: The experimental results show that our method can accomplish 80% average precision (AP), surpassing the corresponding horizontal detector by 2.3%. The visualization results of our work showcase its exceptional localization capability over generic detection methods, facilitating inspection by plant protectors. Meanwhile, our proposed method outperforms other state-of-the-art rotated detection algorithms. The AF-R2PN module can generate superior arbitrary-oriented proposals even with a decreased number of proposals, balancing inference speed and detection performance among other rotated two-stage methods. CONCLUSION: The proposed method exhibits superiority in detecting C. medinalis damage under complex field conditions. It provides greater practical applicability during in-field surveys, enhancing their efficiency and coverage. The findings hold significance for pest and disease monitoring, providing important technical support for agricultural production. © 2024 Society of Chemical Industry.

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