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Carbon cloth (CC) was electrochemically activated using three electrochemical methods in different electrolytes. The gases released during the activation process etched the surface of the CC, thereby increasing its surface area of the activated CC (FCC). Moreover, functional groups such as oxygen-containing groups and N-doping have been introduced. The quantity and type of functional groups introduced during the activation process were related to the anions in the solution. FCC electrodes were used to construct electrochemical sensors for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The PFCC electrode activated by advanced cyclic voltammetry in (NH4)2HPO4 showed linear ranges for AA, DA, and UA concentrations of 0.1 to 2.1 mM, 0.5 to 11 µM, and 0.5 to 11 µM, respectively. The detection limits are 72.93, 0.22, and 0.42 µM, respectively. The good flexibility the PFCC electrode made it suitable for the preparation of flexible sensors. The simultaneous determination of AA, DA, and UA in fetal bovine serum showed a reliable recovery ratio. This study provides a simple and green approach for activating carbon cloth and constructing flexible electrochemical sensors with the potential to simultaneously detect AA, DA, and UA.
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Ácido Ascórbico , Carbono , Dopamina , Técnicas Eletroquímicas , Eletrodos , Ácido Úrico , Ácido Úrico/sangue , Ácido Úrico/análise , Ácido Ascórbico/sangue , Ácido Ascórbico/análise , Dopamina/sangue , Dopamina/análise , Animais , Bovinos , Carbono/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Limite de Detecção , Propriedades de SuperfícieRESUMO
The plum fruit moth, Grapholita funebrana Treitschke, is one of the most significant borer pests, often causing huge economic losses in fruit production. However, the potential distribution range of this economically important pest is still poorly understood. For this study, we simulated an ensemble species distribution model to predict the spatiotemporal distribution pattern of G. funebrana at a global scale. The results show that the suitable habitats for this moth, under current environmental conditions, are mainly distributed in Europe; East Asia, including China and Japan; Central Asia; and some parts of America. In future projections, the suitable habitats are predicted to generally expand northward, while the suitable area will remain unchanged overall. However, the area of highly suitable habitat will decrease to only 17.49% of that found under current conditions. None of the nine factors used were revealed to be predominant predictors in terms of contributing to the model, suggesting that the integrated effects of these variables shape G. funebrana's distribution. In this study, the distribution range that has been predicted, especially for the regions with a highly suitable habitat, poses a high risk of G. funebrana outbreaks, highlighting the urgency of pest management. Moreover, in the United States of America (USA) and Japan (for which G. funebrana distributions were not previously recorded), especially in areas highly suitable for this moth, monitoring and quarantine measures should be strengthened to prevent the colonization and further dispersal of this pest, as seen with its close relative G. molesta, which has become a cosmopolitan pest species, migrating from its native region (East Asia) to other continents, including the Americas.
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Prior to this cross-sectional study, the intrinsic capacity (IC) loss rates and protective factors in nursing homes for individuals aged 80 and older remained unexplored. Analysing 434 participants, this study found 86.9 % of individuals experienced the loss of at least one IC domain, with detailed losses in locomotion, vision, vitality, hearing, psychological, and cognitive capacities at rates of 83.2 %, 52.8 %, 50.9 %, 46.5 %, 44.9 %, and 44.0 %, respectively. Following latent class analysis (LCA), five distinct IC impairment patterns were noted, with locomotor impairment emerging as a central component across most classes. IC protective factors for persons aged 80 years and older included financial stability, being male or younger within the cohort, junior high school or higher education, being married, no smoking history, manageable comorbidity levels, minimal medication use, good sleep, and not using assistive devices. Based on these five classes, this study provides a potential practical framework alongside recommendations for IC care strategies in the oldest-old, emphasising the importance of locomotor function in maintaining the overall IC.
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Background: Both pre-or post-COVID-19, older adults residing in nursing homes are at significant risk for social isolation, which is negatively associated with cognitive ability. Currently, the elderly aged 80 years and older are the fastest-growing age group globally. The extent of social isolation within this group post-COVID-19 and its impact on cognitive abilities remain inadequately explored. Objective: This research aimed to evaluate the prevalence of social isolation among the oldest old in Chinese nursing homes post-COVID-19 and to investigate the mediating and moderating roles of basic activities of daily living (BADL), depression, and subjective socioeconomic status in the relationship between social isolation and cognitive ability. Methods: This cross-sectional study included 453 participants aged 80 years and older from 11 nursing homes in Ningbo, Zhejiang Province, China. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive ability using the Mini-Mental State Examination (MMSE), BADL using the Barthel Index (BI), and depression using the Patient Health Questionnaire-9 items (PHQ-9). Mediation and moderation effects were statistically analyzed using SPSS 23.0 and PROCESS 3.5. Results: The mean age of the study sample was 87.1 ± 3.8 years, among whom 60.3% (n = 273) were female, and 56.1% experienced social isolation, with 41.1% and 63.1% being isolated from family and friends, respectively. Social isolation indirectly affected cognitive ability through BADL and depression, respectively, and through the chain mediation effect of BADL and depression. Subjective socioeconomic status moderated the relationships between social isolation and BADL and between social isolation and depression. However, no moderating effect of subjective socioeconomic status was found between social isolation and cognitive ability. Conclusion: This study deepens our understanding of the current state of social isolation and its mechanisms of action in the oldest old post-COVID-19 and provides a new basis for future public health policy development and related research.
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Iron is a crucial micronutrient, and its deficiency can have detrimental effects on the health of infants. Dietary polysaccharide-iron (III) complexes (PICs) are promising for addressing iron deficiency due to their minimal adverse reactions and high iron absorption rate. This study aimed to investigate the effects of dietary Enteromorpha prolifera polysaccharide-Fe (III) complex (EP-Fe) on newborns, using 3-day weaned piglets as the iron-deficiency model. Results showed that EP-Fe improved iron levels and promoted intestinal development in piglets. Transcriptome sequencing revealed that EP-Fe increased the survival of intestinal epithelial cells under hypoxia by upregulating the expression of genes that promote the development of the vascular system. Additionally, EP-Fe enhanced the mucosal barrier functions by inhibiting myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signaling pathway to increase the expression of intestinal tight junction proteins. Furthermore, the 16S rRNA gene sequencing of gut microbiota showed that EP-Fe promoted the enrichment of Bacteroides_fragilis and other gut microbes that can metabolize carbohydrates. In conclusion, EP-Fe is an effective iron supplement for newborns, and it can be developed as a comprehensive nutritional supplement.
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Background: The diagnosis of major depressive disorder (MDD) mainly depends on subjective clinical symptoms, without an acceptable objective biomarker for the clinical application of MDD. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) showed a high specificity as biomarker for the diagnosis and treatment of MDD. The present study aimed to investigate differences in plasma ITIH4 in two different aged MDD patients and underlying pathological mechanisms of plasma ITIH4 in the occurrence and development of MDD. Methods: Sixty-five adult MDD patients, 51 adolescent MDD patients, and 64 healthy controls (HCs) were included in the present study. A 14-days' antidepressive treatment was conducted in all MDD patients. Psychological assessments were performed and plasma ITIH4 and astrocyte-related markers were detected for all participants. Results: (1) Plasma levels of ITIH4 in adult MDD patients were significantly higher than adolescent MDD patients and HCs, and significantly increased plasma ITIH4 levels was observed in adolescent MDD patients compared with HCs (2). There were positive correlations between plasma ITIH4 levels and 24-item Hamilton Depression Scale (HAMD-24) scores and plasma glial fibrillary acidic protein (GFAP) levels in MDD patients, however, plasma ITIH4 levels were significantly correlated with age just in adult MDD patients (3). Plasma ITIH4 showed area under the curve values of 0.824 and 0.729 to differentiate adult MDD patients and adolescent MDD patients from HCs, respectively (4). There was significant decrease in plasma levels of ITIH4 between before and after antidepressive treatment in adult MDD patients, but not in adolescent MDD patients (5). Changed value of ITIH4 levels were correlated with the changed value of GFAP levels and changed rate of HAMD-24 scores in adult MDD patients following antidepressive treatment. Conclusion: Plasma ITIH4 may be potential plasma biomarkers of MDD with age-related specificity, which was associated with depressive symptoms astrocyte-related pathologic changes, and antidepressive treatment efficacy.
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Relaxin-2 is a peptide hormone with important roles in human cardiovascular and reproductive biology. Its ability to activate cellular responses such as vasodilation, angiogenesis, and anti-inflammatory and antifibrotic effects has led to significant interest in using relaxin-2 as a therapeutic for heart failure and several fibrotic conditions. However, recombinant relaxin-2 has a very short serum half-life, limiting its clinical applications. Here, we present protein engineering efforts targeting the relaxin-2 hormone in order to increase its serum half-life while maintaining its ability to activate the G protein-coupled receptor RXFP1. To achieve this, we optimized a fusion between relaxin-2 and an antibody Fc fragment, generating a version of the hormone with a circulating half-life of around 3 to 5 days in mice while retaining potent agonist activity at the RXFP1 receptor both in vitro and in vivo.
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Receptores Acoplados a Proteínas G , Receptores de Peptídeos , Relaxina , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Animais , Relaxina/farmacologia , Receptores de Peptídeos/agonistas , Receptores de Peptídeos/metabolismo , Camundongos , Humanos , Meia-Vida , Engenharia de Proteínas/métodos , Células HEK293 , Fragmentos Fc das Imunoglobulinas/farmacologia , Camundongos Endogâmicos C57BL , MasculinoRESUMO
In the aquaculture system of ornamental fish, the interaction between bacterial microbiota and ciliate protozoa can prevent or promote disease outbreaks, and different physicochemical conditions will affect the relationships between them. We investigated the interaction between bacterial microbiota and the parasite Tetrahymena pyriformis when infecting Poecilia reticulata (guppy) under different physicochemical conditions. The abundance of T. pyriformis in water, the relative abundance of bacterial species, and histopathological observation were studied or monitored using environmental DNA (eDNA) extraction technology, the qPCR method, and 16s rRNA sequencing, respectively. The morphological identification and phylogenetic analysis of T. pyriformis were carried out. The infected guppy tissue was also stained by the hematoxylin and eosin methods. The results showed: (1) the bacterial communities of water samples were mainly composed of species assigned to Proteobacteria and Bacteroidetes, and Tabrizicola and Puniceicoccaceae were positively correlated with fish mortality, T. pyriformis abundance, and temperature. (2) Arcicella and Methyloversatilis universalis with different correlations between ciliates appeared in different treatment groups, the result of which proved that environmental factors affected the interaction between bacteria and T. pyriformis. (3) Lower temperatures and a higher pH were more beneficial for preventing disease outbreaks.
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BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.
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Doenças de Pequenos Vasos Cerebrais , Leucócitos , Análise da Randomização Mendeliana , Telomerase , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças de Pequenos Vasos Cerebrais/genética , China , População do Leste Asiático/genética , Predisposição Genética para Doença , Genótipo , Leucócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Telomerase/genética , Telômero/genéticaRESUMO
The inefficient delivery of herbicides causes unpleasant side effects on the ecological environment. Protoporphyrinogen oxidase (PPO)-inhibiting herbicides rely on the presence of external light to exert the activities and thus their performance in the field is extremely susceptible to the light environment. Here, taking acifluorfen (ACI) as a model PPO-inhibiting herbicide to enhance efficacy by boosting the utilization rate of sunlight, amphiphilic cationic CDs (CPC-CDs) from cetylpyridinium chloride (CPC) as a precursor, is first prepared as a supplementary light source generator, and subsequently co-assembled with ACI through non-covalent bond interactions to obtain the stable fluorescent nanoparticles (ACI@CPC-CDs). ACI@CPC-CDs with fascinating physicochemical properties can penetrate the leaves of weeds through the stomata and undergo a long-distance transport in the cell intervals. Under low light intensity, CPC-CDs can be applied as the internal light source to promote the formation of more singlet oxygen to damage the leaf cell membrane, consequently improving the herbicidal activity of ACI. Moreover, the safety evaluation of ACI@CPC-CDs demonstrates no risk to non-target organisms and the environment. Therefore, this work offers a promising strategy for the efficient delivery of light-dependent PPO-inhibiting herbicides and opens new insights into the application of CDs in the development of sustainable agriculture.
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Carbono , Herbicidas , Luz , Herbicidas/química , Herbicidas/farmacologia , Carbono/química , Cátions , Pontos Quânticos/química , Nanopartículas/química , Protoporfirinogênio Oxidase/metabolismo , Cetilpiridínio/farmacologia , Folhas de Planta/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacosRESUMO
BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.
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Aterosclerose , Carga Global da Doença , Humanos , Pessoa de Meia-Idade , Adulto , Feminino , Masculino , Adulto Jovem , Prevalência , Carga Global da Doença/tendências , Aterosclerose/epidemiologia , Idoso , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Fatores Etários , Anos de Vida Ajustados por Deficiência/tendências , Doença Arterial Periférica/epidemiologiaRESUMO
BACKGROUND: Craniofacial skeletal deformities can be addressed by applying tensile force to sutures to prompt sutural bone formation. The intricate process of mechanical modulation in craniofacial sutures involves complex biomechanical signal transduction. The small GTPase Ras homolog gene family member A (RhoA) functions as a key mechanotransduction protein, orchestrating the dynamic assembly of the cytoskeleton by activating the Rho-associated coiled-coil containing protein kinase (ROCK). Transcriptional coactivator with PDZ-binding motif (TAZ) serves as a crucial mediator in the regulation of genes and the orchestration of biological functions within the mechanotransduction signaling pathway. However, the role of RhoA/ROCK-TAZ in trans-sutural distraction osteogenesis has not been reported. METHODS: We utilized pre-osteoblast-specific RhoA deletion mice to establish an in vivo calvarial trans-sutural distraction model and an in vitro mechanical stretch model for pre-osteoblasts isolated from neonatal mice. Micro-CT and histological staining were utilized to detect the formation of new bone in the sagittal suture of the skull as well as the activation of RhoA, Osterix and TAZ. The activation of ROCK-limk-cofilin and the nuclear translocation of TAZ in pre-osteoblasts under mechanical tension were detected through Western blot, qRT-PCR, and immunofluorescence. RESULTS: The osteogenic differentiation of pre-osteoblasts was facilitated by mechanical tension through the activation of RhoA and Rho-associated kinase (ROCK), while ablation of RhoA impaired osteogenesis by inhibiting pre-osteoblast differentiation after suture expansion. Furthermore, inhibiting RhoA expression could block tensile-stimulated nuclear translocation of TAZ by preventing F-actin assembly through ROCK-LIM-domain kinase (LIMK)-cofilin pathway. In addition, the TAZ agonist TM-25659 could attenuate impaired osteogenesis caused by ablation of RhoA in pre-osteoblasts by increasing TAZ nuclear accumulation. CONCLUSIONS: This study demonstrates that mechanical stretching promotes the osteogenic differentiation of pre-osteoblasts in trans-sutural distraction osteogenesis, and this process is mediated by the RhoA/ROCK-TAZ signaling axis. Overall, our results may provide an insight for potential treatment strategies for craniosynostosis patients through trans-sutural distraction osteogenesis.
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Osteogênese por Distração , Osteogênese , Crânio , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP , Animais , Proteína rhoA de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Camundongos , Crânio/metabolismo , Osteoblastos/metabolismo , Osteoblastos/citologia , Diferenciação Celular , Transdução de Sinais , Mecanotransdução Celular , Suturas Cranianas/metabolismo , Fator de Transcrição Sp7/metabolismo , Fator de Transcrição Sp7/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas Adaptadoras de Transdução de SinalRESUMO
The off-target loss of pesticide formulations caused by volatilization and leaching has reduced effective utilization and increased risks to the ecological environment and human health. Self-assembly of pesticides has been widely concerned due to the improved bioactivity and environmental compatibility. Herbicidal ionic liquids (HILs) could effectively decrease off-target loss and increase efficacy and environmental safety by improving the physicochemical properties of herbicides. Herein, HILs were prepared by pairing dicamba with quaternary ammonium salts containing different alkyl chain lengths and aromatic groups and subsequently self-assembled into spherical nanoparticles (HIL NPs) via electrostatic interaction and hydrophobic effect. Compared with dicamba, the obtained HIL NPs with an average particle size of 6-55â¯nm exhibited improved physicochemical properties, including high zeta potential values (+20.3 to +27.8â¯mV), low volatilization rate (2.4-3.9â¯%) and surface tension (22.83-33.07 mN m-1), decreased contact angle (32.25-41.55°) and leaching potential (76.2-86.5â¯%), and high soil adsorption (12.1-23.8â¯%), suggesting low risks to the environment. The control efficacy against Amaranthus retroflexus of HIL3 NPs pairing dicamba with octadecyl-trimethyl ammonium chloride was better than that of dicamba sodium salt at different concentrations. Therefore, the ionic liquid self-assembly developed by a facile and green preparation approach to reduce the volatility and leaching of pesticides would have enormous potential in sustainable agriculture.
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Dicamba , Herbicidas , Líquidos Iônicos , Tamanho da Partícula , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Herbicidas/química , Herbicidas/farmacologia , Dicamba/química , Dicamba/farmacologia , Nanopartículas/química , Propriedades de Superfície , Eletricidade Estática , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , AdsorçãoRESUMO
The synthesis mechanisms and function evaluation of selenium(Se)-enriched microorganism remain relatively unexplored. This study unveils that total Se content within A. oryzae A02 mycelium soared to an impressive 8462 mg/kg DCW, surpassing Se-enriched yeast by 2-3 times. Selenium exists in two predominant forms within A. oryzae A02: selenoproteins (SeMet 32.1 %, SeCys 14.4 %) and selenium nanoparticles (SeNPs; 53.5 %). The extensive quantitative characterization of the elemental composition, surface morphology, and size of SeNPs on A. oryzae A02 mycelium significantly differs from those reported for other microorganisms. Comparative RNA-Seq analysis revealed the upregulation of functional genes implicated in selenium transformation, activating multiple potential pathways for selenium reduction. The assimilatory and dissimilatory reductions of Se oxyanions engaged numerous parallel and interconnected pathways, manifesting a harmonious equilibrium in overall Se biotransformation in A. oryzae A02. Furthermore, selenium-enriched A. oryzae A02 was observed to primarily upregulate peroxisome activity while downregulating estrogen 2-hydroxylase activity in mice hepatocytes, suggesting its potential in fortifying antioxidant physiological functions and upholding metabolic balance.
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Aspergillus oryzae , Selênio , Aspergillus oryzae/metabolismo , Aspergillus oryzae/genética , Selênio/química , Selênio/metabolismo , Selênio/farmacologia , Animais , Camundongos , Selenoproteínas/metabolismo , Selenoproteínas/biossíntese , Micélio/metabolismo , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Nanopartículas/químicaRESUMO
BACKGROUND AND OBJECTIVES: Both hypoalbuminemia and inflammation were common in patients with inflammatory bowel diseases (IBD), however, the combination of the two parameters on hospital duration re-mained unknown. METHODS AND STUDY DESIGN: This is a retrospective two-centre study performed in two tertiary hospitals in Shanghai, China. Serum levels of C-Reactive Protein (CRP) and albumin (ALB) were measured within 2 days of admission. Glasgow prognostic score (GPS), based on CRP and ALB, was calculated as follows: point "0" as CRP <10 mg/L and ALB ≥35 g/L; point "1" as either CRP ≥10 mg/L or ALB <35 g/L; point "2" as CRP ≥10 mg/L and ALB <35 g/L. Patients with point "0" were classified as low-risk while point "2" as high-risk. Length of hospital stay (LOS) was defined as the interval between admission and discharge. RESULTS: The proportion of low-risk and high-risk was 69.3% and 10.5% respectively among 3,009 patients (65% men). GPS was associated with LOS [ß=6.2 d; 95% CI (confidence interval): 4.0 d, 8.4 d] after adjustment of potential co-variates. Each point of GPS was associated with 2.9 days (95% CI: 1.9 d, 3.9 d; ptrend<0.001) longer in fully adjusted model. The association was stronger in patients with low prealbumin levels, hypocalcaemia, and hypokalaemia relative to their counterparts. CONCLUSIONS: GPS was associated with LOS in IBD patients. Our results highlighted that GPS could serve as a convenient prognostic tool associated with nutritional status and clinical outcome.
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Proteína C-Reativa , Doenças Inflamatórias Intestinais , Tempo de Internação , Humanos , Masculino , Feminino , Estudos Retrospectivos , Prognóstico , Doenças Inflamatórias Intestinais/sangue , Adulto , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Proteína C-Reativa/análise , China , Albumina Sérica/análise , Hospitalização/estatística & dados numéricosRESUMO
In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Edição de Genes , Lipossomos , Pulmão , Nanopartículas , Células-Tronco , Animais , Humanos , Camundongos , Sistemas CRISPR-Cas , Fibrose Cística/terapia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/metabolismo , Terapia Genética/métodos , Pulmão/metabolismo , Organoides , Células-Tronco/metabolismoRESUMO
Ganoderma lucidum, renowned as an essential edible and medicinal mushroom in China, remains shrouded in limited understanding concerning the intrinsic mechanisms governing the accumulation of active components and potential protein expression across its diverse developmental stages. Accordingly, this study employed a meticulous integration of metabolomics and proteomics techniques to scrutinize the dynamic alterations in metabolite accumulation and protein expression in G. lucidum throughout its growth phases. The metabolomics analysis unveiled elevated levels of triterpenoids, steroids, and polyphenolic compounds during the budding stage (BS) of mushroom growth, with prominent compounds including Diplazium and Ganoderenic acids E, H, and I, alongside key steroids such as cholesterol and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol. Additionally, nutrients such as polysaccharides, flavonoids, and purines exhibited heightened presence during the maturation stage (FS) of ascospores. Proteomic scrutiny demonstrated the modulation of triterpenoid synthesis by the CYP450, HMGR, HMGS, and ERG protein families, all exhibiting a decline as G. lucidum progressed, except for the ARE family, which displayed an upward trajectory. Therefore, BS is recommended as the best harvesting period for G. lucidum. This investigation contributes novel insights into the holistic exploitation of G. lucidum.
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Proteômica , Reishi , Triterpenos , Reishi/metabolismo , Reishi/crescimento & desenvolvimento , Reishi/química , Triterpenos/metabolismo , Triterpenos/química , Proteômica/métodos , Metabolômica/métodos , Proteínas Fúngicas/metabolismoRESUMO
OBJECTIVE: The optimal choice for fusion strategy in Anterior Cervical Discectomy and Fusion (ACDF) remains an unresolved issue. This study aims to perform a network meta-analysis and systematic review of fusion rate and complication rate of various fusion strategies used in ACDF. METHODS: This study followed Prisma guidelines, and we searched PubMed, Embase, Cochrane Library, and Web of Science from inception to November 11, 2022, for Randomized Controlled trials comparing the efficacy and safety of fusion modalities in ACDF. The primary outcome was the fusion rate and complication rate. The PROSPERO number is CRD42022374440. RESULTS: This meta-analysis identified 26 Randomized Controlled trial studies with 1789 patients across 15 fusion methods. The cage with autograft + plating showed the highest fusion rate, surpassing other methods like iliac crest bone graft (ICBG) and artificial bone graft (AFG). The stand-alone cage with autograft (SATG) had the second highest fusion rate. Regarding complication rate, the cage with AFG (CAFG) had the highest rate, more than other methods. The ICBG had a higher complication rate compared to ICBG + P, AFG, stand-alone cage with artificial bone graft, SATG, and CALG. The SATG performed well in both fusion and complication rate. CONCLUSIONS: In this study, we conducted the first network meta-analysis to compare the efficacy and safety of various fusion methods in ACDF. Our findings suggest that SATG, with superior performance in fusion rate and complication rate, may be the optimal choice for ACDF. However, the results should be interpreted cautiously until additional research provides further evidence.
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Transplante Ósseo , Vértebras Cervicais , Discotomia , Metanálise em Rede , Fusão Vertebral , Fusão Vertebral/métodos , Humanos , Discotomia/métodos , Vértebras Cervicais/cirurgia , Transplante Ósseo/métodos , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Inflammation-related bone defects often lead to poor osteogenesis. Therefore, it is crucial to reduce the inflammation response and promote the osteogenic differentiation of stem/progenitor cells to revitalize bone physiology. Here, a kind of hybrid nano-hydroxyapatite was prepared using the confined phosphate ion release method with the participation of fucoidan, a marine-sourced polysaccharide with anti-inflammation property. The physicochemical analyses confirmed that the fucoidan hybrid nano-hydroxyapatite (FC/n-HA) showed fine needle-like architectures. With a higher amount of fucoidan, the crystal size and crystallinity of the FC/n-HA reduced while the liquid dispersibility was improved. Cell experiences showed that FC/n-HA had an optimal cytocompatibility at concentration of 50 µg/mL. Moreover, the lipopolysaccharide-induced cellular inflammatory model with PDLSCs was established and used to evaluate the anti-inflammatory and osteogenic properties. For the 1%FC/n-HA group, the expression levels of TNF-α and IL-1ß were significantly reduced at 24 h, while the expression of alkaline phosphatase of PDLSCs was significantly promoted at days 3 and 7, and calcium precipitates was enhanced at 21 days. In this study, the FC/n-HA particles showed effective anti-inflammatory properties and facilitated osteogenic differentiation of PDLSCs, indicating which has potential application in treating bone defects associated with inflammation, such as periodontitis.
Assuntos
Diferenciação Celular , Durapatita , Nanopartículas , Osteogênese , Ligamento Periodontal , Polissacarídeos , Células-Tronco , Humanos , Osteogênese/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Durapatita/química , Durapatita/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Nanopartículas/química , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Células CultivadasRESUMO
The interplay among frustrated lattice geometry, non-trivial band topology and correlation yields rich quantum states of matter in kagome systems1,2. A series of recent members in this family, AV3Sb5 (A = K, Rb or Cs), exhibit a cascade of symmetry-breaking transitions3, involving the 3Q chiral charge ordering4-8, electronic nematicity9,10, roton pair density wave11 and superconductivity12. The nature of the superconducting order is yet to be resolved. Here we report an indication of dynamic superconducting domains with boundary supercurrents in intrinsic CsV3Sb5 flakes. The magnetic field-free superconducting diode effect is observed with polarity modulated by thermal histories, suggesting that there are dynamic superconducting order domains in a spontaneous time-reversal symmetry-breaking background. Strikingly, the critical current exhibits double-slit superconductivity interference patterns when subjected to an external magnetic field. The characteristics of the patterns are modulated by thermal cycling. These phenomena are proposed as a consequence of periodically modulated supercurrents flowing along certain domain boundaries constrained by fluxoid quantization. Our results imply a time-reversal symmetry-breaking superconducting order, opening a potential for exploring exotic physics, for example, Majorana zero modes, in this intriguing topological kagome system.