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Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.
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Metástase Neoplásica , RNA Circular , Neoplasias Urológicas , Humanos , RNA Circular/genética , RNA Circular/fisiologia , Animais , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Current density imaging is helpful for discovering interesting electronic phenomena and understanding carrier dynamics, and by combining pressure distributions, several pressure-induced novel physics may be comprehended. In this work, noninvasive, high-resolution two-dimensional images of the current density and pressure gradient for graphene ribbon and hBN-graphene-hBN devices are explored using nitrogen-vacancy (NV) centers in diamond under high pressure. The two-dimensional vector current density is reconstructed by the vector magnetic field mapped by the near-surface NV center layer in the diamond. The current density images accurately and clearly reproduce the complicated structure and current flow of graphene under high pressure. Additionally, the spatial distribution of the pressure is simultaneously mapped, rationalizing the nonuniformity of the current density under high pressure. The current method opens a significant new avenue to investigate electronic transport and conductance variations in two-dimensional materials and electrical devices under high pressure as well as for nondestructive evaluation of semiconductor circuits.
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Kidney fibrosis is a prominent pathological feature of hypertensive kidney diseases (HKD). Recent studies have highlighted the role of ubiquitinating/deubiquitinating protein modification in kidney pathophysiology. Ovarian tumor domain-containing protein 6 A (OTUD6A) is a deubiquitinating enzyme involved in tumor progression. However, its role in kidney pathophysiology remains elusive. We aimed to investigate the role and underlying mechanism of OTUD6A during kidney fibrosis in HKD. The results revealed higher OTUD6A expression in kidney tissues of nephropathy patients and mice with chronic angiotensin II (Ang II) administration than that from the control ones. OTUD6A was mainly located in tubular epithelial cells. Moreover, OTUD6A deficiency significantly protected mice against Ang II-induced kidney dysfunction and fibrosis. Also, knocking OTUD6A down suppressed Ang II-induced fibrosis in cultured tubular epithelial cells, whereas overexpression of OTUD6A enhanced fibrogenic responses. Mechanistically, OTUD6A bounded to signal transducer and activator of transcription 3 (STAT3) and removed K63-linked-ubiquitin chains to promote STAT3 phosphorylation at tyrosine 705 position and nuclear translocation, which then induced profibrotic gene transcription in epithelial cells. These studies identified STAT3 as a direct substrate of OTUD6A and highlighted the pivotal role of OTUD6A in Ang II-induced kidney injury, indicating OTUD6A as a potential therapeutic target for HKD.NEW & NOTEWORTHY Ovarian tumor domain-containing protein 6 A (OTUD6A) knockout mice are protected against angiotensin II-induced kidney dysfunction and fibrosis. OTUD6A promotes pathological kidney remodeling and dysfunction by deubiquitinating signal transducer and activator of transcription 3 (STAT3). OTUD6A binds to and removes K63-linked-ubiquitin chains of STAT3 to promote its phosphorylation and activation, and subsequently enhances kidney fibrosis.
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Hipertensão Renal , Nefrite , Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Angiotensina II/farmacologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Rim/metabolismo , Hipertensão Renal/metabolismo , Hipertensão Renal/patologia , Células Epiteliais/metabolismo , Fibrose , Neoplasias Ovarianas/metabolismo , Ubiquitinas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Photodynamic therapy (PDT) is receiving extensive attention as an antimicrobial strategy that does not cause drug resistance by reactive oxygen species (ROS). Herein, hierarchical Ag-ZnIn2S4 (Ag-ZIS) core-shell nanowires are synthesized by in situ Metal-Organic Framework derived method for efficient PDT of Candida albicans (C. albicans). The core-shell structure enables spatial synergy strategy to regulate the charge transfer pathway under visible light excitation, in which the Ag nanowires are like the highway for the photogenerated electrons. The enhanced charge carrier separation efficiency greatly increased the chances for the generation of ROS. As expected, the optimized Ag-ZIS nanowires exhibit excellent performance for inactivation of C. albicans under visible light irradiation (λ ≥ 420 nm, 15 min), and the effective sterilization concentration is as high as 107CFU mL-1. Moreover, in vivo infection experiments suggested that the PDT effect of Ag-ZIS nanowires on the mouse wound healing is better than that of the clinical Ketoconazole drug. The PDT antifungal mechanism of Ag-ZIS nanowires is also investigated, and superoxide anion is found to be the predominant active species to causes C. albicans damage. This work provides a new perspective for designing novel interface structures to regulate charge transfer to achieve efficient PDT antifungal therapy.
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Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.
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Neoplasias da Mama , Proliferação de Células , Células-Tronco Neoplásicas , Nucleofosmina , Proteínas Proto-Oncogênicas c-myc , RNA Nucleolar Pequeno , Proteína Ribossômica L3 , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Transdução de Sinais , Proteína Ribossômica L3/genética , Proteína Ribossômica L3/metabolismoRESUMO
When the electric field strength (E) surpasses a certain threshold, secondary droplets are generated during the coalescence between water droplets in oil and the oil-water interface (so-called the droplet-interface partial coalescence phenomenon), resulting in a lower efficiency of droplet electrocoalescence. This study employs molecular dynamics (MD) simulations to investigate the droplet-interface partial coalescence phenomenon under direct current (DC) electric fields. The results demonstrate that intermolecular interactions, particularly the formation of hydrogen bonds, play a crucial role in dipole-dipole coalescence. Droplet-interface partial coalescence is categorized into five regimes based on droplet morphology. During the contact and fusion of the droplet with the water layer, the dipole moment of the droplet exhibits alternating increases and decreases along the electric field direction. Electric field forces acting on sodium ions and the internal interactions within droplets promote the process of droplet-interface partial coalescence. High field strengths cause significant elongation of the droplet, leading to its fragmentation into multiple segments. The migration of hydrated ions has a dual impact on the droplet-interface partial coalescence, with both facilitative and suppressive effects. The time required for droplet-interface partial coalescence initially decreases and subsequently increases as the field strength increases, depending on the competitive relationship between the extent of droplet stretching and the electric field force. This work provides molecular insights into the droplet-interface coalescence mechanisms in water-in-oil emulsions under DC electric fields.
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Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.
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Indóis , Sistema de Sinalização das MAP Quinases , Mitocôndrias , Osteoclastos , Periodontite , Animais , Mitocôndrias/efeitos dos fármacos , Periodontite/tratamento farmacológico , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Indóis/farmacologia , Indóis/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Perda do Osso Alveolar/tratamento farmacológico , Camundongos Endogâmicos C57BL , Células RAW 264.7RESUMO
Members of the permease gene family are responsible for important biological functions in the growth and development of rice. Here, we show that OsAAP8 is a constitutive expression gene, and its translated protein is localized on the cell membrane. Mutation of the OsAAP8 can promote the expression of genes related to protein and amylopectin synthesis, and also promote the enlargement of protein bodies in its endosperm, leading to an increase in the protein, amylopectin, and total amino acid content of grains in OsAAP8 mutants. Seeds produced by the OsAAP8 mutant were larger, and the chalkiness traits of the OsAAP8 mutants were significantly reduced, thereby improving the nutritional quality and appearance of rice grains. The OsAAP8 protein is involved in the transport of various amino acids; OsAAP8 mutation significantly enhanced the root absorption of a range of amino acids and might affect the distribution of various amino acids. Therefore, OsAAP8 is an important quality trait gene with multiple biological functions, which provides important clues for the molecular design of breeding strategies for developing new high-quality varieties of rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01473-w.
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Cracks originating from thermal expansion and thermally induced phase transitions significantly hinder thermal conduction in certain energetic materials. For 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) crystals, a classic explosive, their temperature-dependent thermal conductivity serves as a crucial parameter determining safety and stability. In this work, the thermal conductivity of HMX single crystals before and after thermal damage under different heating conditions was measured and calculated, as well as the thermal conductivity of different regions of each single crystal. A threefold discrepancy in thermal conductivity was observed between room temperature and the phase transition temperature of the HMX crystal. The different effects of different types of damage and cracks, characterized by using 3D X-ray computed tomography (CT), on the thermal conduction process of the crystal were further analyzed. The results indicate that different heating methods influence the phase transformation of the crystals and the distributions of fast cracks and small cracks. The strong directivity of the fast cracks will significantly impact the thermal conductivity along two horizontal directions, whereas small cracks exert the greatest influence on the primary direction of heat conduction. The relevant conclusions were also verified by finite element analysis (FEA) modeling.
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PURPOSE: This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). MATERIALS AND METHODS: This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. RESULTS: A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P < 0.001). The AUC of CT values, ΔHU, and RatioHU for distinguishing AIS from OCI were 0.802, 0.896 and 0.878, respectively (all P < 0.001). Meanwhile, the AUC for distinguishing OCI from LA was 0.789, 0.883, and 0.857, respectively (all P < 0.001). Nevertheless, none of the parameters could distinguish AIS from LA. CONCLUSION: CT attenuation parameters can be utilized to differentiate between AIS and OCI or OCI and LA in indeterminate hypodense lesions on CT images. However, distinguishing AIS from LA remains challenging.
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Infarto Cerebral , Estudos de Viabilidade , AVC Isquêmico , Leucoaraiose , Tomografia Computadorizada por Raios X , Humanos , Leucoaraiose/diagnóstico por imagem , Masculino , Feminino , Idoso , Estudos Retrospectivos , AVC Isquêmico/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Infarto Cerebral/diagnóstico por imagem , Curva ROC , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.
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Displasia Cortical Focal , Imageamento por Ressonância Magnética Multiparamétrica , Nomogramas , Radiômica , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Displasia Cortical Focal/diagnóstico por imagem , Lateralidade Funcional , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Estudos RetrospectivosRESUMO
Subjective well-being is based on the unity of internal and external needs, as well as material and non-material needs. However, existing research lacks consideration of the impact of both objective material conditions and subjective psychological cognition on the subjective well-being of migrant workers. Thus, based on data from the 2017 China General Social Survey, this paper applies ordered logit models and OLS models to investigate the impact of social cognition and socioeconomic status on the subjective well-being of migrant workers and their intergenerational differences. The results indicate that: (1) Social cognition has a significant impact, and the impact of fairness perception is more pronounced than depression perception and class change perception; (2) among socioeconomic status, personal income did not have a significant effect as education level, car ownership and house property ownership; (3) there are intergenerational differences. The emotional state of the older generation is the most critical factor influencing their subjective well-being. In contrast, the new generation is more concerned with their feelings about future expectations. The older generation is more concerned with their house property ownership, while the increase in income, education and car ownership can significantly increase the subjective well-being of the new generation. For this reason, we believe that the Chinese government should gradually change the existing urban and rural management system to create a fair and just social environment; make migrant workers receive the same protection as urban residents and improve the income distribution mechanism; pay attention to the social security of the older generation of migrant workers and the development opportunities of the new generation of migrant workers and their ability to integrate into the city to improve their subjective well-being.
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Migrantes , Humanos , Cognição Social , Classe Social , Cidades , Emoções , ChinaRESUMO
OBJECTIVE: To predict the incidence of postoperative ileus in bladder cancer patients after radical cystectomy. METHODS: We retrospectively analyzed the perioperative data of 452 bladder cancer patients who underwent radical cystectomy with urinary diversion at the Second Hospital of Tianjin Medical University between 2016 and 2021. Univariate and multivariate logistic regression were used to identify the risk factors for postoperative ileus. Finally, a nomogram model was established and verified based on the independent risk factors. RESULTS: Our study revealed that 96 patients (21.2%) developed postoperative ileus. Using multivariate logistic regression analysis, we found that the independent risk factors for postoperative ileus after radical cystectomy included age > 65.0 years, high or low body mass index, constipation, hypoalbuminemia, and operative time. We established a nomogram prediction model based on these independent risk factors. Validation by calibration curves, concordance index, and decision curve analysis showed a strong correlation between predicted and actual probabilities of occurrence. CONCLUSION: Our nomogram prediction model provides surgeons with a simple tool to predict the incidence of postoperative ileus in bladder cancer patients undergoing radical cystectomy.
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Íleus , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Idoso , Cistectomia/efeitos adversos , Nomogramas , Estudos Retrospectivos , Derivação Urinária/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Íleus/epidemiologia , Íleus/etiologia , Íleus/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia. Embase, PubMed and Web of Science databases were searched from their inception to February 2024 (INPLASY:202430023). Data on the animal species, stroke model, drug dose, time of treatment, method of administration, study quality, and outcomes were extracted and pooled in a meta-analysis. The combined standardized mean difference (SMD) or mean difference (MD) estimates and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Thirteen eligible studies involving >200 animals fulfilled the inclusion criteria and were included in this meta-analysis. Meta-analyses demonstrated that bumetanide treatment significantly reduced cerebral infarct volume (SMD: -0.42; 95% CI: -0.75, -0.09; p < 0.01; n = 186 animals) and consistently relieved brain edema (SMD: -1.39; 95% CI: -2.06, -0.72; p < 0.01; n = 64 animals). Subgroup analyses demonstrated that bumetanide treatment reduced infarct volume in transient but not permanent cerebral ischemia models. When administered after the stroke, it was more effective than treatment initiation before the stroke. Eight studies assessed the effect of bumetanide on behavioral function and the results showed that bumetanide treatment significantly improved neurobehavioral deficits (SMD: -2.35; 95% CI: -2.72, -1.97; p < 0.01; n = 250 animals). We conclude that bumetanide appears to be effective in reducing infarct volume and brain edema and improving behavioral recovery in animal models of cerebral ischemia. This mechanism needs to be confirmed through further investigation.
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Bumetanida , Modelos Animais de Doenças , AVC Isquêmico , Bumetanida/uso terapêutico , Bumetanida/farmacologia , Animais , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/patologia , Edema Encefálico/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologiaRESUMO
As the cytoskeleton sustains cell and tissue forces, it incurs physical damage that must be repaired to maintain mechanical homeostasis. The LIM-domain protein zyxin detects force-induced ruptures in actin-myosin stress fibers, coordinating downstream repair factors to restore stress fiber integrity through unclear mechanisms. Here, we reconstitute stress fiber repair with purified proteins, uncovering detailed links between zyxin's force-regulated binding interactions and cytoskeletal dynamics. In addition to binding individual tensed actin filaments (F-actin), zyxin's LIM domains form force-dependent assemblies that bridge broken filament fragments. Zyxin assemblies engage repair factors through multi-valent interactions, coordinating nucleation of new F-actin by VASP and its crosslinking into aligned bundles by É-actinin. Through these combined activities, stress fiber repair initiates within the cores of micron-scale damage sites in cells, explaining how these F-actin depleted regions are rapidly restored. Thus, zyxin's force-dependent organization of actin repair machinery inherently operates at the network scale to maintain cytoskeletal integrity.
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Larvae are the most important feeding and developmental stage in the life cycle of insects. Correspondingly, the larval midguts, as the primary digestive organs, undergo diverse specialization among insect lineages. Larvae of Scarabaeoidae, commomly known as white grubs, exhibit diversity on feeding habits at the familial or subfamilial level. However, the ultrastructure of larval midguts is not yet satisfactorily understood. In this study, the larval midguts of Trypoxylus dichotomus and Anomala corpulenta were compared using light and transmission electron microscopy for the first time, to uncover the ultrastructural differences between the midguts of saprophagous and phytophagous white grubs. The larval midguts of both species are tubular with three circles of the gastric caeca, and share morphological similarities in midgut epithelial cells, layers of basal lamina, and the digestive and regenerative cells. However, the midguts of the two species differ significantly in the shape of the gastric caeca and exhibit slightly differences in muscle structure. The morphology of larval midgut is related to the feeding habits.
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Needle syringe irrigation is frequently used in root canal therapy, and the flow pattern during irrigation can be efficiently manipulated by means of passive flow control technique, resulting in expected irrigation performance improvement. Therefore, novel needles with composite flow control structures are numerically investigated and optimized in this study. Based on the 30G needle, six single/double side-vented needles with dimple and protrusion are proposed. Two flow rates in line with clinical applications, 5.3 and 8.6 m/s, are used in the analysis. Three performance parameters are investigated. The safety of the irrigation system is evaluated by the root canal apical pressure, whereas the irrigant extension and the flushing efficiency are evaluated by the extending depth and the effective cleaning area, respectively. The results demonstrate that the shear stress of the double-side-vented needle is higher while the irrigant extension is enhanced with a dimple structure. The performance of the double-side-vented needle with a dimple is superior to that of other designs, with up to 33% improvement in extending depth and a 22% increase in effective cleaning area over the prototype. New needles do not raise risk of irrigant extrusion. Furthermore, the effect of dimple depth and outlet angle are investigated. The needle with a dimple of 0.04 mm depth shows the highest extending depth within the confines of the investigation. The effective cleaning area is significantly influenced by the needle outlets, and the effective cleaning area expands with an increase in needle outlet angle, while the extending depth gradually declines.
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BACKGROUND AND PURPOSE: Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial. METHODS: In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used. RESULTS: Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135]. CONCLUSION: Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.
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Fibrinolíticos , AVC Isquêmico , Inibidores da Agregação Plaquetária , Ativador de Plasminogênio Tecidual , Humanos , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/farmacologia , Feminino , Masculino , AVC Isquêmico/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Inibidores da Agregação Plaquetária/administração & dosagem , Fibrinolíticos/administração & dosagem , Fibrinolíticos/farmacologia , Resultado do Tratamento , Terapia Antiplaquetária Dupla/métodos , Fatores Sexuais , Caracteres SexuaisRESUMO
We conducted a study to evaluate the impact of folic acid supplementation on the risk of Alzheimer disease (AD). A Mendelian randomization (MR) analysis model assessed the causal effects of folic acid supplementation on AD, utilizing data from recent genome-wide association studies. Effect estimates were scrutinized using various methods: inverse-variance weighted (IVW), simple mode, weighted mode, simple median, weighted median, penalized weighted median, and the MR-Egger method. The sensitivity analysis assessed heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs) using the IVW method with Cochran Q statistics and MR Egger intercept, respectively. Additionally, a leave-one-out sensitivity analysis determined potential SNP-driven associations. Both fixed-effect and random-effect IVW models in the MR analysis revealed a reduced risk of AD associated with folic acid supplementation (odds ratio, 0.930; 95% CI, 0.903-0.958, Pâ <â .001; odds ratio, 0.930; 95% CI, 0.910-0.950, Pâ <â .001) based on 7 SNPs as instrumental variables. The reverse MR analysis indicated no causal association between AD and folic acid supplementation. This study, utilizing genetic data, suggests that folic acid supplementation may potentially reduce the risk of AD and provides novel insights into its etiology and preventive measures.