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Clostridium autoethanogenum protein (CAP) is a promising protein source for aquaculture; however, how CAP influences fish quality is worth extensive research. We randomly allocated 630 turbot with initial body weights of about 180 g into 6 groups, with fishmeal-based control diet or diet with CAP replacing 15% (CAP15), 30% (CAP30), 45% (CAP45), 60% (CAP60), or 75% (CAP75) of fishmeal protein. After a 70-d feeding trial, the fillet yield (P = 0.015) and content of protein (P = 0.017), collagen (P < 0.001), hydroxyproline (P < 0.001), C20:5n-3 (P = 0.007), and ∑n-3/∑n-6 polyunsaturated fatty acids ratio (P < 0.001) in turbot muscle was found to decrease linearly with increasing CAP. However, turbot fed CAP15 diet maintained these parameters (P > 0.05). By contrast, the muscle hardness increased linearly with increasing CAP (P = 0.004), accompanied by linear reduction of muscle fiber area (P = 0.003) and expression of myogenesis-related genes, including cathepsin D (ctsd P < 0.001) and muscle ring finger protein 1 (murf 1, P < 0.001). Phosphorylation of protein kinase B (Akt, P < 0.001), target of rapamycin (TOR, P = 0.001), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, P < 0.001), and ribosomal protein S6 (S6, P < 0.001) decreased linearly; however, phosphorylation of AMP-activated protein kinase (AMPK, P < 0.001), eukaryotic initiation factor 2α (eIF2α, P < 0.001), and the abundance of activating transcription factor 4 (ATF4, P < 0.001) increased with increasing CAP, suggesting that the TOR signaling pathway was inhibited, and the amino acid response (AAR) and AMPK pathways were activated. Additionally, expression of genes related to protein degradation, including myogenic factor 5 (myf 5, P < 0.001), myogenic differentiation (myod, P < 0.001), paired box 7 (pax 7, P < 0.001), and ctsd (P < 0.001), decreased linearly with increasing CAP. In conclusion, CAP could be used to replace up to 15% of fishmeal without negatively impacting turbot quality. However, higher levels of CAP decreased fillet yield, muscle protein content, and muscle fiber diameter while increasing muscle hardness, which could be attributed to the inhibition of the TOR pathway and activation of the AAR and AMPK pathways.
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Legume-rhizobia symbiosis offers a unique approach to increase leguminous crop yields. Previous studies have indicated that the number of soybean nodules are increased under elevated CO2 concentration. However, the underlying mechanism behind this phenomenon remains elusive. In this study, transcriptome analysis was applied to identify candidate genes involved in regulating soybean nodulation mediated by elevated CO2 concentration. Among the different expression genes (DEGs), we identified a gene encoding small heat shock protein (sHSP) called GmHSP23.9, which mainly expressed in soybean roots and nodules, and its expression was significantly induced by rhizobium USDA110 infection at 14 days after inoculation (DAI) under elevated CO2 conditions. We further investigated the role of GmHSP23.9 by generating transgenic composite plants carrying GmHSP23.9 overexpression (GmHSP23.9-OE), RNA interference (GmHSP23.9-RNAi), and CRISPR-Cas9 (GmHSP23.9-KO), and these modifications resulted in notable changes in nodule number and the root hairs deformation and suggesting that GmHSP23.9 function as an important positive regulator in soybean. Moreover, we found that altering the expression of GmHSP23.9 influenced the expression of genes involved in the Nod factor signaling pathway and AON signaling pathway to modulate soybean nodulation. Interestingly, we found that knocking down of GmHSP23.9 prevented the increase in the nodule number of soybean in response to elevated CO2 concentration. This research has successfully identified a crucial regulator that influences soybean nodulation under elevated CO2 level and shedding new light on the role of sHSPs in legume nodulation.
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Dióxido de Carbono , Regulación de la Expresión Génica de las Plantas , Glycine max , Proteínas de Plantas , Nodulación de la Raíz de la Planta , Plantas Modificadas Genéticamente , Glycine max/genética , Glycine max/microbiología , Glycine max/metabolismo , Dióxido de Carbono/metabolismo , Nodulación de la Raíz de la Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nódulos de las Raíces de las Plantas/metabolismo , Nódulos de las Raíces de las Plantas/genética , Nódulos de las Raíces de las Plantas/microbiología , Simbiosis , Proteínas de Choque Térmico Pequeñas/genética , Proteínas de Choque Térmico Pequeñas/metabolismo , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. METHODS: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. RESULTS: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity. CONCLUSION: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.
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Hiperparatiroidismo Primario , Hipocalcemia , Paratiroidectomía , Complicaciones Posoperatorias , Humanos , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/complicaciones , Femenino , Masculino , Paratiroidectomía/efectos adversos , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Estudios de Casos y Controles , Hipocalcemia/etiología , Hipocalcemia/sangre , Hipocalcemia/epidemiología , Hipocalcemia/diagnóstico , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Anciano , Calcio/sangre , Pronóstico , Biomarcadores/sangre , Adulto , Estudios de Seguimiento , Hormona Paratiroidea/sangreRESUMEN
We propose a mathematical framework for developing social-choice games that are designed to mediate decision-making processes for city planning, urban area redevelopment, and architectural configuration of urban housing complexes. The proposed framework features a digital serious gaming approach for participatory design to support transparency and inclusion in the process of decision-making and ensure an equitable balance of sustainable development goals in spatial design outcomes. The mathematical process consists of a Markovian design machine for balancing the design decisions of actors, a massing configurator equipped with fuzzy logic and multi-criteria decision analysis, algebraic graph-theoretical accessibility evaluators, and automated solar-climatic evaluators using geospatial computational geometry. We demonstrate the effectiveness of the framework by implementing a multi-player online game that facilitates a participatory decision-making workshop for forming multi-functional building complexes by providing a generative configurator equipped with automated appraisal/scoring mechanisms for revealing the aggregate impact of alternatives. The EquiCity game empowers a group of decision-makers to reach a fair consensual spatial design by mathematically simulating many rounds of reasonable trade-offs between their decisions, with different levels of interest or control over various types of investments. The novelty of the framework is in its capability to encompass decision-making about the most idiosyncratic aspects of a site related to its heritage status and cultural significance to the most generic aspects such as balancing access to sunlight for the site while respecting 'the right to sunlight' of the neighbours of the site, ensuring coherence of the entire configuration with regards to a network of desired closeness ratings, the satisfaction of a programme of requirements, and intricately balancing individual development goals in conjunction with communal goals and environmental design codes.
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Background: The global impact of the COVID-19 pandemic had significantly altered the daily routines of people worldwide. This study aimed to compare how sleeptime and depression among Chinese residents had differed between periods during and outside the epidemic. Furthermore, it delved into the interactive effect of age in this relationship. Method: Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) study in 2015 and the recently released data from 2020, which covered the pandemic period. Depression was assessed using Center for Epidemiologic Studies Depression Scale (CESD-10), considering a score of 10 or higher as indicative of depression. Participants were categorized based on age, specifically those aged 60 years and older. multivariate logistic regression and interaction analyses were employed to assess the interplay of age, supported by subgroup and sensitivity analyses to reinforce our findings. Results: The 2020 database comprised 19,331 participants, while the 2015 database had 10,507 participants. Our findings demonstrated a significant correlation between sleeptime and depression in both unadjusted models and models adjusted for all variables in both datasets (p<0.001). Upon stratifying by age and adjusting for relevant factors, we identified an interaction effect among age, sleeptime, and depression (p=0.004 for the interaction in the 2020 database, compared to 0.004 in 2015). The restricted cubic spline analysis in both datasets showcased a nonlinear relationship between sleeptime and depression. Conclusions: During both epidemic and non-epidemic periods in China, there existed a correlation between sleep duration and depression, which interacts with age.
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BACKGROUND: Depression has gradually become a common psychological disorder among children and adolescents. Depression in children and adolescents affects their physical and mental development. Psychotherapy is considered to be one of the main treatment options for depressed children and adolescents. However, our understanding of the global performance and progress of psychological interventions for depression in children and adolescents (PIDCA) research is limited. AIM: To identify collaborative research networks in this field and explore the current research status and hotspots through bibliometrics. METHODS: Articles and reviews related to PIDCA from January 2010 to April 2023 were identified from the Web of Science Core Collection database. The Charticulator website, CiteSpace and VOSviewer software were used to visualize the trends in publications and citations, the collaborative research networks (countries, institutions, and authors), and the current research status and hotspots. RESULTS: Until April 16, 2023, 1482 publications were identified. The number of documents published each year and citations had increased rapidly in this field. The United States had the highest productivity in this field. The most prolific institution was the University of London. Pim Cuijpers was the most prolific author. In the context of research related to PIDCA, both reference co-citation analysis and keywords co-occurrence analysis identified 10 research hotspots, including third-wave cognitive behavior therapy, short-term psychoanalytic psychotherapy, cognitive behavioral analysis system of psychotherapy, family element in psychotherapy, modular treatment, mobile-health, emotion-regulation-based transdiagnostic intervention program, dementia risk in later life, predictors of the efficacy of psychological intervention, and risks of psychological intervention. CONCLUSION: This bibliometric study provides a comprehensive overview of PIDCA from 2010 to present. Psychological intervention characterized as psychological-process-focused, short, family-involved, modular, internet-based, emotion-regulation-based, and personalized may benefit more young people.
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The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.
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Proteínas Adaptadoras Transductoras de Señales , Núcleo Celular , Factor de Transcripción SOX9 , Factores de Transcripción , Proteínas Señalizadoras YAP , Humanos , Proteínas Señalizadoras YAP/genética , Proteínas Señalizadoras YAP/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/genética , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Transporte Activo de Núcleo Celular/genética , Ratones , Línea Celular Tumoral , Animales , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
BACKGROUND: The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis. However, its role in liver cirrhosis has not been reported. METHODS: Real-time PCR was used to detect miR-541 expression in the liver tissues and sera of liver cirrhosis patients and in the human LX-2. Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the activation of LX-2. Bioinformatics analysis and a luciferase reporter assay were conducted to investigate the target gene of miR-541. RESULTS: miR-541 was downregulated in the tissues and sera of patients with liver cirrhosis, which was exacerbated by deteriorating disease severity. Importantly, the lower expression of miR-541 was associated with more episodes of complications including ascites and hepatic encephalopathy, a shorter overall lifespan, and decompensation-free survival. Moreover, multivariate Cox's regression analysis verified lower serum miR-541 as an independent risk factor for liver-related death in cirrhotic patients (HR = 0.394; 95% CI: 0.164-0.947; P = 0.037). miR-541 was also decreased in LX-2 cells activated by TGF-ß and the overexpression of miR-541 inhibited the proliferation, activation and hydroxyproline secretion of LX-2 cells. JAG2 is an important ligand of Notch signaling and was identified as a direct target gene of miR-541. The expression of JAG2 was upregulated in the liver tissues of cirrhotic patients and was inversely correlated with miR-541 levels. A rescue assay further confirmed that JAG2 was involved in the function of miR-541 when regulating LX-2 activation and Notch signaling. CONCLUSIONS: Dysregulation of miR-541/JAG2 axis might be a as a new mechanism of liver fibrosis, and miR-541 could serve as a novel non-invasive biomarker and therapeutic targets for liver cirrhosis.
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Células Estrelladas Hepáticas , Cirrosis Hepática , MicroARNs , Humanos , Proliferación Celular/genética , Células Estrelladas Hepáticas/metabolismo , Proteína Jagged-2/metabolismo , Proteína Jagged-2/farmacología , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , MicroARNs/genética , MicroARNs/metabolismo , PronósticoRESUMEN
AIM: To explore the role of family meetings for individuals living with dementia and their family caregivers. DESIGN: Integrative review. METHODS: We conducted searches in the Cochrane Library, PubMed, CINAHL, and Embase databases (up to December 2022). Additionally, an ancestry search strategy was employed to supplement the retrieval of published literature related to family meetings or family conferences for people with dementia and their family caregivers. RESULTS: The review integrated 11 articles, comprising seven quantitative studies, two qualitative studies, and two case reports. The findings did not indicate a significant improvement in end-of-life quality for individuals with dementia in the family meetings group compared to those receiving usual care. Limited evidence suggested some improvement in mental health outcomes for family caregivers. Both intervention and control groups incurred high care costs. However, family meetings appeared to delay nursing home placements for individuals with dementia. Two qualitative studies provided insights into the experiences of families and healthcare professionals participating in family meetings, highlighting opportunities and challenges in implementing such meetings. Additionally, two case reports offered specific and illustrative accounts of typical family meetings. CONCLUSION: Family meetings can delay nursing home placements for elderly individuals with dementia. Families dealing with dementia perceive family meetings as an opportunity to collaborate with professionals in providing comprehensive care. Further research is needed to explore the effectiveness of family meetings in decision-making for families affected by dementia. Additionally, addressing timing and process coordination issues in family meetings is crucial for optimising their practices among families dealing with dementia. RELEVANCE TO CLINICAL PRACTICE: In order to make family meetings more accessible to families of individuals with dementia, we offer the following recommendations for future research and practice: Rather than a blanket rejection, the decision regarding the participation of individuals with dementia in family meetings should be based on their specific condition and the needs of their family. Coordination and harmonisation of opinions and perceptions among family members of individuals with dementia can sometimes be complex for healthcare professionals. The involvement of family coordinators may simplify this process. To determine the optimal timing for holding family meetings that can better assist families dealing with dementia, we propose that the right to initiate a meeting be granted to the family. This allows them to convene with healthcare professionals and address their concerns at their convenience.
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Cuidadores , Demencia , Familia , Anciano , Humanos , Cuidadores/psicología , Personal de Salud , Casas de SaludRESUMEN
Introduction: Weeds are one of the main factors affecting crop growth, making weed control a pressing global problem. In recent years, interest in intelligent mechanical weed-control equipment has been growing. Methods: We propose a semantic segmentation network, RDS_Unet, based on corn seedling fields built upon an improved U-net network. This network accurately recognizes weeds even under complex environmental conditions, facilitating the use of mechanical weeding equipment for reducing weed density. Our research utilized field-grown maize seedlings and accompanying weeds in expansive fields. We integrated the U-net semantic segmentation network, employing ResNeXt-50 for feature extraction in the encoder stage. In the decoder phase, Layer 1 uses deformable convolution with adaptive offsets, replacing traditional convolution. Furthermore, concurrent spatial and channel squeeze and excitation is incorporated after ordinary convolutional layers in Layers 2, 3, and 4. Results: Compared with existing classical semantic segmentation models such as U-net, Pspnet, and DeeplabV3, our model demonstrated superior performance on our specially constructed seedling grass semantic segmentation dataset, CGSSD, during the maize seedling stage. The Q6mean intersection over union (MIoU), precision, and recall of this network are 82.36%, 91.36%, and 89.45%, respectively. Compared to those of the original network, the proposed network achieves improvements of 5.91, 3.50, and 5.49 percentage points in the MIoU, precision, and recall, respectively. The detection speed is 12.6 frames per second. In addition, ablation experiments further confirmed the impactful contribution of each improvement component on the overall semantic segmentation performance. Discussion: This study provides theoretical and technical support for the automated operation of intelligent mechanical weeding devices.
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WHAT IS KNOWN ON THE SUBJECT: Sleep problems are common among those with depression, and there is increasing evidence that sleep problems should be addressed during treatment simultaneously rather than treating depression alone. The first-line treatment for insomnia is cognitive behavioural therapy for insomnia (CBT-I), due to a lack of well-trained therapists and patient time constraints (travelling, work), CBT-I has not been popularized. The development of digital cognitive behavioural therapy for insomnia (dCBT-I) is making the treatment more accessible. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: Interventions for dCBT-I were significantly better than other control conditions in both reducing insomnia and improving depression in patients with depression and insomnia comorbidities. The effect was found to be related to the duration of the intervention and the severity of insomnia before the intervention and therapist-involved dCBT-I has less shedding than self-help. WHAT ARE THE IMPLICATIONS FOR PRACTICE: It's important for mental health practitioners to realize that insomnia in depressed people needs to be treated. Future trials may explore the effectiveness of therapist-guided dCBT-I in depressed populations and analyse the cost-effectiveness of this treatment. ABSTRACT: Aim The aim of the study was to systematically identify and synthesize the evidence for the effectiveness of digital cognitive behavioural therapy in insomnia with comorbid depression. Design Systematic review and metaanalysis. Methods A search was conducted on five English and four non-English databases from the inception of the databases to November 2023. This review adhered to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement 2020 and the included studies were evaluated using version 2 of the Cochrane risk of bias tool. This review examined sleep-related outcomes, including insomnia severity and sleep diaries, along with psychological outcomes, such as depression. We conducted a meta-analysis of each outcome using a random effects model. Heterogeneity was assessed by the I2 statistic. Results A total of seven articles with 1864 participants were included in this review. The results showed that the digital cognitive behavioural therapy group demonstrated a statistically significant amelioration in the severity of insomnia symptoms, as well as a reduction in depressive symptomatology compared with the control groups. The post-intervention effect was found to be related to the duration of the intervention and the severity of insomnia before the intervention. Conclusions Digital cognitive behavioural therapy for insomnia application in patients with depression and insomnia was demonstrated to be effective, less time-consuming and more accessible. Relevance to Clinical Practice We may consider incorporating nurses into treatment plans and conducting nurse-led interventions in specific programs. In the future, nurses may be able to provide exclusive digital behavioural therapy for insomnia to patients with depression to achieve greater effectiveness.
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Terapia Cognitivo-Conductual , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Terapia Cognitivo-Conductual/métodos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Trastorno Depresivo/terapia , Comorbilidad , Depresión/terapiaRESUMEN
Coordination of filament assembly and membrane remodeling is required for the directional migration of cancer cells. The Wiskott-Aldrich syndrome protein (WASP) recruits the actin-related protein (ARP) 2/3 complex to assemble branched actin networks. The goal of our study was to assess the potential regulatory role exerted by the novel long noncoding RNA (lncRNA) LINC00869 on hepatocellular carcinoma (HCC) cells. We used HCC cells to overexpress or knockdown LINC00869, analyzed patient data from publicly available databases and Cancer Hospital Affiliated with Zhengzhou University, and used a xenograft mouse model of HCC to study the molecular mechanism associated with LINC00869 expression. We found that high levels of LINC00869 expression were associated with poor prognosis in patients with HCC. Next, we detected an interaction between LINC00869 and both WASP and ARP2 in HCC cells, and observed a modulatory effect of LINC00869 on the phosphorylation of WASP at Y291 and the activity of cell division control protein 42 (CDC42). These modulatory roles were required for WASP/CDC42 activity on F-actin polymerization to enhance membrane protrusion formation and maintain persistent cell polarization. This, in turn, promoted the migration and invasion abilities of HCC cells. Finally, we confirmed the role of LINC00869in vivo, using the tumor xenograft mouse model; and identified a positive correlation between LINC00869 expression levels and the phosphorylation levels of WASP in HCC samples. Overall, our findings suggest a unique mechanism by which LINC00869 orchestrates membrane protrusion during migration and invasion of HCC cells. IMPLICATIONS: LncRNA LINC00869 regulates the activity of CDC42-WASP pathway and positively affects protrusion formation in HCC cells, which expands the current understanding of lncRNA functions as well as gives a better understanding of carcinogenesis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Animales , Ratones , Carcinoma Hepatocelular/genética , Actinas , ARN Largo no Codificante/genética , Neoplasias Hepáticas/genética , Fosforilación , Complejo 2-3 Proteico Relacionado con la Actina/genética , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: This study assessed the safety, tolerability, and PK/PD of HSK7653 tablets in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a Phase IIa, multicenter, randomized, double-blind, placebo-controlled, and dose-increasing study with 48 Chinese diabetes patients. Subjects were randomly assigned to placebo and 10/25/50 mg dose groups, and they received oral administration once every two weeks for a total of six times. Safety and tolerability were assessed throughout this study, and PK/PD parameters were analyzed using non-compartment model with WinNonlin. RESULTS: The three doses of HSK7653 were well tolerated, and the incidence of TEAE and ADR was not significantly increased compared with the placebo group. Cmax increased linearly with the increasing dose, and the mean t1/2 was 64.0-87.0 h. The first dose and last dose PK parameters were similar. After oral administration of 10-50 mg HSK7653 every two weeks, the average Rac_Cmax and Rac_AUC were 0.9-1.0 and 1.0-1.1 respectively; therefore, HSK7653 was not accumulated in vivo. All three doses significantly inhibited DPP-4 activity and increased plasma GLP-1 level and serum insulin levels. When the plasma concentration of HSK7653 was ≥ 20.0 ng/mL, the DPP-4 inhibition rate in all subjects was maintained at > 80.0%. In 10 and 25 mg dose groups, the HbA1c levels maintained a downward trend compared with the placebo group. DISCUSSION: HSK7653 showed desirable pharmacokinetic and pharmacodynamic properties with good safety and tolerability in Chinese T2DM patients. DPP-4 inhibition rate and plasma GLP-1 levels were higher in each dose group than in placebo group. TRIAL REGISTRATION NUMBER: CTR20182505 (Drug Clinical Trial Registration and Information Disclosure Platform, www.chinadrugtrials.org.cn ).
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OBJECTIVE: Microwave ablation (MWA) has emerged as a minimally invasive technology for papillary thyroid microcarcinoma (PTMC), but it has not been widely applied to treat T1bN0M0 PTC with high-level evidence. This study was designed to compare the real-world efficacy and safety of MWA or surgery for treating T1bN0M0 PTC. METHODS: From December 2019 to April 2021, 123 continuous unifocal T1bN0M0 PTC patients without lymph node metastasis (LNM) or distant metastasis (DM) were included from 10 hospitals. Patients were allocated into the MWA or surgery group based on their willingness. The main outcomes were local tumour progression (LTP), new thyroid cancer, LNM, and DM. The secondary outcomes included changes in tumour size and volume, complications, and cosmetic results. Subgroup analyses were conducted to identify influencing factors. RESULTS: Fifty-two patients chose MWA, and 71 patients chose surgery. Patients had similar demographic information and tumour characteristics in the two groups. The follow-up durations after MWA and surgery were 10.6 ± 4.2 and 10.4 ± 3.4 months, respectively. The LNM rate was 5.8% in the MWA group and 1.4% in the surgery group (p = 0.177). No LTP, new thyroid cancer, or distant metastasis (DM) occurred in either group. Five (9.6%) of the 52 patients in the MWA group and 8 (11.3%) of the 71 patients in the surgery group had complications (p = 0.27). Better cosmetic results were found in the MWA group (p < 0.01). CONCLUSION: MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. CLINICAL RELEVANCE STATEMENT: MWA achieved comparable short-time treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC. KEY POINTS: ⢠MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. ⢠The complication rate in the surgery group was higher than that in the MWA group without a significant difference. ⢠There was no statistically significant difference in the LNM rate between the MWA and surgery groups.
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Microondas , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Microondas/uso terapéutico , Estudios Prospectivos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Metástasis Linfática , Ultrasonografía Intervencional , Estudios RetrospectivosRESUMEN
Objective: To explore the relationship between outdoor lighting and sports and the development of myopia, and to analyze the effects of outdoor lighting and exercise on the diopter of children with normal vision and myopia, so as to provide guidance for the prevention and treatment of myopia in children and adolescents in the future. Methods: A total of 201 children were divided into two groups according to myopia or not. Each group was randomly divided into 4 groups: outdoor exercise group, outdoor control group, indoor exercise group and indoor control group. Among them, the outdoor exercise group and indoor exercise group received moderate and high intensity aerobic exercise 3 times a week for 60 min each time for 12 months, while the outdoor control group and indoor control group had normal study and life during the corresponding period of time. No additional exercise intervention. At the end of the experiment, the diopter of each group was compared. Results: The diopter of all groups with normal vision and myopia decreased significantly after the experiment (p < 0.01). There were significant differences in diopter between outdoor exercise group and indoor control group (p < 0.01), between outdoor exercise group and indoor control group (p < 0.05), and between indoor exercise group and indoor control group (p < 0.01). There were significant differences in diopter between indoor exercise group and indoor control group (p < 0.01). The differences among myopic children after the experiment showed that there was significant difference in diopter between outdoor exercise group and indoor exercise group (p < 0.05), between outdoor exercise group and indoor control group (p < 0.01), and between outdoor control group and indoor control group (p < 0.05). There were significant differences in the changes of diopter between the outdoor control group and the indoor exercise group with normal vision and myopia before and after the experiment (p < 0.05). Conclusion: Outdoor light and exercise intervention can have a beneficial effect on children's vision, but because of whether children are myopic or not, the effect is different, outdoor light and exercise have a better effect on reducing the diopter of children with normal vision.
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Miopía , Deportes , Niño , Adolescente , Humanos , Iluminación , Ejercicio Físico , Miopía/prevención & control , Terapia por EjercicioRESUMEN
Whey-acidic-protein (WAP) four-disulfide core domain protein 3 (WFDC3) is one of the WAP family proteins. This protein family is associated with the development of solid tumors and affects the tumor immunological microenvironment. However, the prognostic value of WFDC3 in pancreatic adenocarcinoma (PAAD) and its effect on the tumor immune microenvironment is yet to be clarified. The Cancer Genome Atlas database and Genotype-Tissue Expression database were used to analyze the differential expression of WFDC3 between the tumor and adjacent tissues. The clinical significance of WFDC3 was analyzed in The Cancer Genome Atlas and International Cancer Genome Consortium database using WFDC3 transcripts and clinical information. In order to elucidate the underlying mechanisms, gene set enrichment analysis was conducted to determine potential activated pathways. Immune score evaluation and publicly available pharmacogenomics database [the Genomics of Drug Sensitivity in Cancer] were utilized to quantify immune cell infiltration and the effect on chemotherapeutic drug sensitivity. WFDC3 levels were higher in PAAD tissues than in normal pancreatic tissues. High levels of WFDC3 expression progressively increased as PAAD tumor stages progressed. Patients with elevated WFDC3 expression showed a poor prognosis. The gene set enrichment analysis analysis revealed that glutamate, arginine, and proline, and histidine metabolism levels were elevated in patients with a high WFDC3 expression phenotype. B, CD4+ T, and CD8+ T cell infiltration was diminished in PAAD tissues with elevated WFDC3 expression. According to pharmacogenomics, PAAD tissues with high WFDC3 expression are susceptible to gemcitabine. WFDC3 is highly expressed in PAAD, and patients with a high level of WFDC3 expression have a shorter overall survival time, indicating a poorer prognosis. High expression of WFDC3 may lead to the development of PAAD by affecting the amino acid metabolism and the tumor immunological microenvironment. WFDC3 may serve as a potential diagnostic and prognostic biomarker for PAAD patients.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , Biología Computacional , Expresión Génica , Pronóstico , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMEN
Blending octene random copolymer (ORC) with other polymers is a promising approach to improving ORC mechanical properties, such as tensile strength and elongation. In this study, octene block copolymer (OBC) with lower density than ORC and high-density polyethylene (HDPE) were used to blend with ORC. The effect of both OBC and HDPE on ORC was analyzed using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and small-angle X-ray scattering (SAXS). For ORC/OBC blends, a small amount of OBC can improve the crystallization ability of ORC. Meanwhile, for ORC/HDPE blends, the crystallization ability of ORC was significantly suppressed, attributed to good compatibility between ORC and HDPE as indicated by the homogeneous morphology and the disappearance of the α transition peak of ORC in ORC/HDPE blends. Therefore, the tensile strength and elongation of ORC/HDPE blends are significantly higher than those of ORC/OBC blends. For ORC/OBC/HDPE ternary blends, we found that when ORC:OBC:HDPE are at a ratio of 70:15:15, cocrystallization is achieved. Although HDPE improves the compatibility of ORC and OBC, the three-phase structure of the ternary blends can be observed through SAXS when HDPE and OBC exceed 30 wt%. Blending HDPE and OBC (≤30 wt%) could improve the mechanical property of ORC.
RESUMEN
Cancer is one of the leading causes of human death worldwide. One of the most common types of malignancy among women is breast cancer, which is the third most common cancer in the world after lung and stomach cancer. This study aimed to evaluate the expression level of Tissue Differentiation-Inducing Non-Protein Coding RNA (TINCR) in adjacent tumor and non-tumor tissues of 60 women with invasive ductal breast cancer. The relationship between TINCR expression and the clinical characteristics of patients has also been studied. For this purpose, total RNA was isolated from breast cancer patients' adjacent tumor and non-tumor tissue. RT Prime Script reagent was then used to convert total RNA to cDNA. The qRT-PCR quantified the TINCR expression level and analyzed the results by paired t-test. In addition, ROC curve analysis was used to evaluate the biomarker power of TINCR in breast cancer tumor tissues. According to the results, a decrease in the level of TINCR was obtained in the tumor tissue of breast cancer patients compared to the adjacent non-tumor tissue (P<0.001). TINCR expression was negatively correlated with tumor size and lymph node metastasis in breast cancer tumor tissue. In general, the decrease in the expression level of TINCR in the tumor tissue of breast cancer patients shows that its expression level can differentiate the adjacent tumor and non-tumor tissue from each other. In addition, TINCR has a lower expression level in breast cancer patients with large tumors, lymph node metastasis, and luminal subgroups A and B.
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Neoplasias de la Mama , ARN Largo no Codificante , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , ADN Complementario , Metástasis Linfática , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
The intestine is a host-pathogen interaction site and improved intestinal barrier function help to prevent disease in shrimp. Alginate oligosaccharides (AOS) are derived from resourceful brown algae. The intestine protection properties of AOS were widely recognized, and their benefits in fish have been reported. Nevertheless, there are no reports on AOS in shrimp and other crustaceans. In the present work, we measured the effects of AOS on growth performance and disease resistance in the white shrimp Litopenaeus vannamei and investigated their effects on intestinal health. Shrimps with an initial weight of about 2 g were fed with diets supplemented with 0 (control), 0.07%, 0.2%, 0.6%, or 1.2% of AOS for 56 days and were sampled and challenged with Vibrio parahaemolyticus. Dietary AOS did not significantly influence weight gain or feed utilization (P > 0.05). However, AOS considerably decreased the seven-day cumulative mortality after the challenge at any dose (P < 0.05). Dietary AOS improved the intestinal structure, significantly boosted the intestinal villus height at 0.6% and 1.2% levels, and increased intestinal wall thickness by 0.2%, 0.6%, and 1.2%. The alkaline phosphatase and maltase activities were also increased, suggesting that AOS improved the intestinal condition. Redox homeostasis in intestinal was improved by AOS, as expressed by the enhanced total antioxidant capacity and decreased malonaldehyde content, partly due to the increased superoxide dismutase and catalase activities. Compared with the antioxidant system, AOS's stimulating effects on immunity were more significant. At any level, AOS significantly activated lysozyme activity, the expression of propo and two antimicrobial peptide genes (pen-3 and crusin). However, the lowest concentration of AOS did not stimulate the gene expression of all three assayed pattern recognition receptors (LGBP, Toll, and IMD), and only the highest concentration of AOS increased the expression of imd. These findings suggest that AOS are highly efficient immunostimulants, and various immune pathways in shrimp are differentially sensitive to AOS. Finally, our findings suggest that AOS significantly alter the gut microbiota and their relative abundance at the phylum, family, and genus levels. In conclusion, AOS significantly enhances disease resistance in L. vannamei, possibly attributed to improved intestinal development, increased intestinal immunity and altered microbiota. These findings could provide a basis for future studies on the practical use of AOS and its mechanisms of action.
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Enfermedades Intestinales , Penaeidae , Vibrio parahaemolyticus , Animales , Resistencia a la Enfermedad , Antioxidantes/farmacología , Alginatos/farmacología , Inmunidad Innata , Dieta/veterinaria , Intestinos , Oligosacáridos/farmacología , Alimentación Animal/análisisRESUMEN
Moony viscosity of ethylene-propylene-diene monomers (EPDMs) can have effect on the crystallization dynamics, structure, and properties of EPDM/polypropylene (PP)-based thermoplastic vulcanizates (TPVs). TPVs with two different Moony viscosities are prepared via a twin-screw extruder, respectively. Crosslinked EPDM with lower Moony viscosity has a higher crosslinking density and the nucleation effect of its crosslink point improves the crystallization ability of PP in TPV, leading to PP phase crystallization at higher temperatures. For TPV with an EPDM of higher Moony viscosity, it has higher crystallinity and the EPDM phase crystallized earlier. Synchrotron radiation studies show that the EPDM with low Moony viscosity has no obvious crystalline structure, and the prepared TPV has an obvious phase separation structure, while the TPV with higher Mooney viscosity of the EPDM does not exhibit obvious phase separation, indicating that the longer EPDM chains have better compatibility with PP in TPV, also evidenced by the almost disappearance of the PP glass transition peak in TPV, from the dynamic mechanical analysis. The longer EPDM chains in TPV provide more physical entanglement and better interaction with PP molecules, resulting in a stronger strain hardening process, longer elongation at break, and higher tensile stress in TPV.