The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed ...CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.
Introduction
The aim of our study was to evaluate the effect of low‐molecular‐weight heparin on pregnancy outcomes in women without thrombophilia during in vitro fertilization/intracytoplasmic sperm ...injection treatment.
Material and methods
We searched Pubmed, Web of Science, Embase, Cochrane and CNKI (from inception to 2 February 2018). Our study identified randomized controlled trials or quasi‐randomized controlled trials comparing low‐molecular‐weight heparin subcutaneous treatment with no treatment or only luteal support control. The outcomes included live birth rate, clinical pregnancy rate and miscarriage rate.
Results
Five trials, including 935 women receiving in vitro fertilization/intracytoplasmic sperm injection treatment, were included in meta‐analyses. There were 458 women receiving low‐molecular‐weight heparin and 477 in the control group. No significant differences for live birth rate, clinical pregnancy rate and miscarriage rate were found between the low‐molecular‐weight heparin and control groups. Of them, four trials reported live birth rate as an outcome and the risk ratio was 1.13 (95% confidence interval 0.88–1.43, p = 0.34). All five trials reported clinical pregnancy rate as an outcome, the risk ratio was 1.08 (95% confidence interval 0.87–1.32, p = 0.47). Three trials reported miscarriage rate and the risk ratio was 0.58 (95% confidence interval 0.30–1.10, p = 0.09). In women with two or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratio of live birth rate was 1.15 and the risk ratio of clinical pregnancy rate was 1.17. In women with three or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratios of live birth rate and clinical pregnancy rate were 1.36 and 1.35, respectively.
Conclusions
Our results suggested that low‐molecular‐weight heparin had no effect on pregnancy success rate in non‐thrombophilic women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. However, to justify the use of low‐molecular‐weight heparin in clinical practice, multicenter trials are still necessary.
Retinoblastoma (RB) is one of the most common primary intraocular malignancies in children. Emerging researches have shown that circular RNAs (circRNAs) play critical roles in a variety of cancers. ...As a novel circRNA, the function of circ_0000527 in RB remains unknown. In this work, expression level of circ_0000527 and miR‐646 in RB tissues and cell lines were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). RB cell lines (SO‐Rb50 and WERI‐Rb‐1) were used as cell models in functional experiments. CCK‐8 assay, TUNEL assay and transwell assay were employed to detect the biological influence of circ_0000527 and miR‐646 on cancer cells in vitro. qRT‐PCR, luciferase reporter assay, RIP assay and western blot were used for exploring the interactions among circ_0000527, miR‐646 and BCL‐2. It was demonstrated that expression level of circ_0000527 in RB samples was significantly up‐regulated compared to normal tissues, while miR‐646 was markedly down‐regulated. Overexpression of circ_0000527 promoted the viability, migration and invasion of RB cells, while miR‐646 transfection had the opposite effects. Circ_0000527 sponged miR‐646 to regulate the expression of BCL‐2. In conclusion, circ_0000527 could promote the development of RB by indirectly modulating BCL‐2 via absorbing miR‐646.
Significance of the study
Expression level of circ_0000527 in RB samples was significantly up‐regulated compared to normal tissues, while miR‐646 was markedly down‐regulated. Overexpression of circ_0000527 promoted the viability, migration and invasion of RB cells, while miR‐646 transfection had the opposite effects. Circ_0000527 sponged miR‐646 to regulate the expression of BCL‐2.
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•A novel monomer containing aromatic Schiff base was incorporated into PET.•Cross-linking reaction occurs among the CHN structure units at high temperature.•Cross-linking promotes ...char formation and melting viscosity increasing.•PET copolyesters with no-dripping and low smoke release show improved fire safety.
Bonding aryl groups with carbon-nitrogen double bond is a critical structural factor for the self-crosslinking of Schiff bases at high temperature. In this study, a novel aromatic Schiff base “5-(benzylidene-amino)-isophthalic acid dimethyl ester (BA)” has been designed as a self-crosslinking monomer for poly(ethylene terephthalate) (PET) based copolyesters (BAnPETs). The cross-linking behaviors, flame retardancy and non-dripping performance of BAnPETs have been investigated by simultaneous thermal analysis (TG-DSC), dynamic rheology, limiting oxygen index (LOI), UL-94 vertical burning and cone calorimetry tests. It is found that BA units can cross-link during combustion resulting in high melting viscosity and enhance char forming for BAnPETs, which endows the copolyesters with excellent flame retardancy and non-dripping behavior. Incorporating of BA with a low content (only 7.7 mol%), the LOI value of copolyester increases from 22.0% to 31.0%, and at the same time it achieves V-0 rating in the UL-94 vertical burning test. The mode action of Schiff bases on flame retardation and anti-dripping of copolyesters also has been investigated, and the results show that the aromatic Schiff base groups can lead copolyesters to form nitrogen-containing cross-linkable networks and further transform into compact char layer during combustion. The char layer which acts as an effective barrier, cuts off oxygen, hinders the volatilization of combustible gas and isolates unburned polymer from fire resource. This work suggests that using Schiff base as a self-crosslinkable monomer is a new and effective way for fire-safe polymeric materials.
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences ...among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese Control from cardiac centers in China) and analyzed by genome‐wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein–protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel “TOF‐specific CNVs” were identified with prevalence of CNVs of 21.5% in chromosomes 1‐20 and 37.0% including Chr21/22. In chromosomes 1‐20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF‐specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.
A genome‐wide association study (GWAS) in 605 subjects identified 119 novel tetralogy of Fallot (TOF)‐specific rare copy number variants (CNVs) in sporadic TOF in the Han Chinese with higher frequency than that reported in Western countries. The genotype–phenotype correlation was analyzed. These findings provide new insights into the contribution of CNVs to the genetic basis of TOF, give clear evidence of higher prevalence of CNV in the Han Chinese than in Caucasians, and identify new genetic loci potentially important to the pathogenesis of TOF that forms new basis for future diagnostic and therapeutic strategy in TOF.
Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system. Therefore, based on the regenerative capacity of stem cells, transplantation ...therapies of various stem cells have been tested in basic research and preclinical trials, and some have shown great prospects. This manuscript overviews the cellular and molecular characteristics of embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal stem/progenitor cells, mesenchymal stem/stromal cells, and their derivatives in vivo and in vitro as sources for regenerative therapy. These cells have all been considered as candidates to treat several major neurological disorders and diseases, owing to their self-renewal capacity, multi-directional differentiation, neurotrophic properties, and immune modulation effects. We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and age-related macular degeneration, as well as traumatic brain injury and glioblastoma. In spite of a few unsuccessful cases, risks of tumorigenicity, and ethical concerns, most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease. In summary, these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders. Thus, stem cells are a promising candidate for the treatment of nervous system diseases.
To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing ...spousal attitudes toward breastfeeding.
We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling.
(1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 "Newborns should be fed on time, not on demand" (42.6%) and Item 5 "Breastfeeding can prevent infant rickets" (49.5%). (2) The average score of spouses' infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 "Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk" (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education OR = 4.588, 95% CI (0.160 ∼ 3.598) and those with a master's degree or above OR = 18.278, 95% CI (3.471 ∼ 9.346).
(1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas'spouses with degrees below master's level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.
By incorporating an anthracene moiety into a framework, a multiresponsive luminescent metal–organic framework (1) has been synthesized, which exhibits both direct chemiluminescence (CL) and dual ...tunable photoluminescence. By utilizing the CL, 1 has been explored as a selective visual sensor for hydrogen peroxide. Moreover, 1 also exhibits tunable fluorescence response toward different analytes. For electron‐rich aromatics, “turn‐on” and “turn‐off” responses can be simply switched by varying the excitation wavelength. For nitroaromatics, 1 exhibits novel linear quantitative quenching response. Density functional theory (DFT) calculations and experiments have been carried out to study the unique fluorescence response. The multiple luminescence properties and dual tunable sensing response indicate that incorporating anthracene moieties into frameworks should be a promising strategy to develop unprecedented luminescent materials with remarkable sensing properties.
A 3D metal‐organic framework (MOF) consisting of an anthracene moiety is reported, which is the first example of a MOF exhibiting both direct chemiluminescence and dual tunable photoluminescence. The material is explored as a selective visual sensor for probing hydrogen peroxide, a dual sensor for aromatics, and a quantitative sensor for nitroaromatics.
To estimate the incidence of foodborne gastroenteritis caused by nontyphoidal Salmonella enterica, Shigella, and Vibrio parahaemolyticus in China, population surveys and sentinel hospital ...surveillance were implemented in six provinces from July 2010 to July 2011, and a multiplier calculation model for the burden of disease was constructed. The multiplier for salmonellosis and V. parahaemolyticus gastroenteritis was estimated at 4,137 95% confidence interval (CI) 2,320-5,663, and for shigellosis at 4,356 (95% CI 2,443-5,963). Annual incidence per 100,000 population was estimated as 245 (95% CI 138-336), 67 (95% CI 38-92), and 806 (95% CI 452-1,103) for foodborne salmonellosis, shigellosis, and V. parahaemolyticus gastroenteritis, respectively, indicating that foodborne infection caused by these three pathogens constitutes an important burden to the Chinese healthcare system. Continuous implementation of active surveillance of foodborne diseases, combined with multiplier models to estimate disease burden, makes it possible for us to better understand food safety status in China.
Pear (Pyrus spp) is an important fruit crop, grown in all temperate regions of the world, with global production ranked after grape and apples among deciduous tree crops. A high-density linkage map ...is a valuable tool for fine mapping quantitative trait loci (QTL) and map-based gene cloning. In this study, we firstly constructed a high-density linkage map of pear using SNPs integrated with SSRs, developed by the rapid and robust technology of restriction-associated DNA sequencing (RADseq). The linkage map consists of 3143 SNP markers and 98 SSRs, 3241 markers in total, spanning 2243.4 cM, with an average marker distance of 0.70 cM. Anchoring SSRs were able to anchor seventeen linkage groups to their corresponding chromosomes. Based on this high-density integrated pear linkage map and two years of fruit phenotyping, a total of 32 potential QTLs for 11 traits, including length of pedicel (LFP), single fruit weight (SFW), soluble solid content (SSC), transverse diameter (TD), vertical diameter (VD), calyx status (CS), flesh colour (FC), juice content (JC), number of seeds (NS), skin colour (SC), and skin smooth (SS), were identified and positioned on the genetic map. Among them, some important fruit-related traits have for the first time been identified, such as calyx status, length of pedicel, and flesh colour, and reliable localization of QTLs were verified repeatable. This high-density linkage map of pear is a worthy reference for mapping important fruit traits, QTL identification, and comparison and combination of different genetic maps.
A highly saturated pear genetic map was constructed using over 3000 SNP markers developed by RADseq integrated with anchored SSR markers. The reliable QTLs of several fruit traits were also identified.
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