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Respiratory diseases represent one of the most significant economic burdens on healthcare systems worldwide. The variation in the increasing number of cases depends greatly on climatic seasonal effects, socioeconomic factors, and pollution. Therefore, understanding these variations and obtaining precise forecasts allows health authorities to make correct decisions regarding the allocation of limited economic and human resources. We aimed to model and forecast weekly hospitalizations due to respiratory conditions in seven regional hospitals in Costa Rica using four statistical learning techniques (Random Forest, XGboost, Facebook's Prophet forecasting model, and an ensemble method combining the above methods), along with 22 climate change indices and aerosol optical depth as an indicator of pollution. Models were trained using data from 2000 to 2018 and were evaluated using data from 2019 as testing data. During the training period, we set up 2-year sliding windows and a 1-year assessment period, along with the grid search method to optimize hyperparameters for each model. The best model for each region was selected using testing data, based on predictive precision and to prevent overfitting. Prediction intervals were then computed using conformal inference. The relative importance of all climatic variables was computed for the best model, and similar patterns in some of the seven regions were observed based on the selected model. Finally, reliable predictions were obtained for each of the seven regional hospitals.
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Mudança Climática , Previsões , Costa Rica/epidemiologia , Humanos , Alta do Paciente/estatística & dados numéricos , Doenças Respiratórias/epidemiologia , Clima , Modelos Estatísticos , Estações do Ano , Hospitais , Poluição do Ar/análise , Hospitalização/estatística & dados numéricos , Aprendizado de Máquina , AlgoritmosRESUMO
Oxidative stress, characterized by an imbalance between oxidative and antioxidant processes, results in excessive accumulation of intracellular reactive oxygen species. Among these responses, the regulation of intracellular hydroxyl radicals (â¢OH) and glutathione (GSH) is vital for physiological processes. Real-time in situ monitoring these two opposing bioactive species and their redox interactions is essential for understanding physiological balance and imbalance. In this study, we developed a dual-site fluorescence chemosensor OG-3, which can independently image both exogenous and endogenous â¢OH and GSH in separate channels both within cells and in vivo, eliminating issues of spatiotemporal inhomogeneous distribution and cross-interference. With its imaging capabilities of monitoring â¢OH-GSH redox, OG-3 elucidated two different pathways for ferroptosis induction: (i) inhibition of system xc- to block cystine uptake (extrinsic pathway) and (ii) GPX4 inactivation, leading to the loss of antioxidant defense (intrinsic pathway). Moreover, we assessed the antiferroptotic function and effects of ferroptosis inhibitors by monitoring â¢OH and GSH fluctuations during ferroptosis. This method provides a reliable platform for identifying potential ferroptosis inhibitors, contributing to our understanding of relevant metabolic and physiological mechanisms. It shows potential for elucidating the regulation of ferroptosis mechanisms and investigating further strategies for therapeutic applications.
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Ferroptose , Corantes Fluorescentes , Glutationa , Radical Hidroxila , Oxirredução , Ferroptose/efeitos dos fármacos , Glutationa/metabolismo , Glutationa/análise , Humanos , Radical Hidroxila/metabolismo , Animais , Corantes Fluorescentes/química , Camundongos , Imagem ÓpticaRESUMO
INTRODUCTION AND IMPORTANCE: Direct carotid-cavernous fistulas (CCF) are primarily caused by head trauma. Some cases have also been attributed to iatrogenic injuries during endovascular procedures. However, the reports of functional endoscopic sinus surgery (FESS) associated with direct CCFs are extremely rare. PRESENTATION OF CASE: A 52-year-old male worker, who suffered from chronic sinusitis and underwent functional endoscopic sinus surgery (FESS) performed by an otolaryngologist. Intra-operative finding indicated a left sphenoid sinus wall injury without internal carotid artery bleeding, which was repaired using mucosa and tissue glue. One month after discharge, he began experiencing tinnitus, headache and swelling in his left eye. Cerebral angiography revealed a direct carotid-cavernous fistula (CCF) on the left side. The patient underwent transarterial and transvenous stent-assisted coiling using detachable coils and Onyx, which alleviated his symptoms. CLINICAL DISCUSSION: A cavernous-carotid fistula following FESS is an exceedingly rare occurrence first reported by Karaman et al. in 2009. The incidence of internal carotid artery injury during FESS or endonasal endoscopic surgery (EES) is estimated to be between 0 and 0.1 %. Currently, there is no definitive explanation for the development of a carotid-cavernous fistula (CCF) post-FESS. Previous studies suggest that procedures like transsphenoidal surgery and EES can induce pseudoaneurysms in the internal carotid artery. If the cavernous pseudoaneurysm ruptures, it could lead to the formation of a CCF. CONCLUSION: A direct cavernous-carotid fistula following functional endoscopic sinus surgery is a very rare. Consequently, when encountering patients with a carotid-cavernous fistula, relevant procedure history should be considered.
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[This corrects the article DOI: 10.1039/D2RA03435B.].
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This study investigates the influence of the quality of the "deep squat" movement, adapted from the Functional Movement Screen (FMS) system, on the lower extremity movement pattern during baseball throwing, and its potential impact on throwing performance and propulsion efficiency. Twenty-two baseball players were recruited and categorized into two groups: 13 in the high-score squat group (HSS) and 9 in the low-score squat group (LSS), based on their deep squat screening results. This research explored disparities in ball velocity, propulsion efficiency, propulsion ground reaction force (GRF) characteristics, and throwing kinematics between these two groups. The findings revealed no significant difference in ball velocity between the groups. However, the LSS group demonstrated a lower propulsion GRF efficiency (p < 0.030, ES = 0.46), along with a higher vertical peak GRF (p < 0.002, ES = 0.66). In the pivot leg, the HSS group exhibited significantly lower impulse forces in the Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.049, ES = 0.42), and vertical direction (p < 0.048, ES = 0.42). Additionally, the contribution to the ball velocity of the pivot leg was significantly greater in the HSS group, along with significantly better efficiency in Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.053, ES = 0.41), and vertical direction (p < 0.032, ES = 0.46). In the leading leg, the HSS group demonstrated significantly lower impulse forces in the Impulse Fresultant (p < 0.001, ES = 0.69), throwing direction (p < 0.007, ES = 0.58), and vertical direction (p < 0.001, ES = 0.70). Moreover, the contribution to the ball velocity of the leading leg was significantly greater in the HSS group, accompanied by significantly better efficiency in Impulse Fresultant (p < 0.003, ES = 0.63), throwing direction (p < 0.005, ES = 0.60), and vertical direction (p < 0.021, ES = 0.49). In conclusion, this study suggests that squat screening is a valuable tool for assessing propulsion efficiency. Coaches and trainers should be mindful of players with low squat quality but high throwing performance, as they may face increased impact and injury risks in the future.
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This study aims to investigate the different ground reaction force (GRF) characteristics from different stride types. This study included 30 Taiwanese elite college and professional baseball pitchers. Each pitcher was classified into one of the following stride types: tall and fall (TF), dip and drive (DD), or mixed (MX). Our findings indicated that DD pitchers pressed their bodies forward earlier than TF pitchers. In contrast, the GRF of the pivot leg of TF pitchers increased slowly in the first half of the stride phase and continued to increase even after the stride leg touched the ground. This type of continuous pressing in TF was different from that in DD and MX pitchers, which decreased rapidly into the arm-cocking & acceleration phases. We conclude that the lower extremities were used differently by TF, DD and MX pitchers. This information could serve as a training guideline for coaches and pitchers to enhance training effectiveness, while simultaneously lowering injury risks.
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Dengue transmission poses significant challenges for public health authorities worldwide due to its susceptibility to various factors, including environmental and climate variability, affecting its incidence and geographic spread. This study focuses on Costa Rica, a country characterized by diverse microclimates nearby, where dengue has been endemic since its introduction in 1993. Using wavelet coherence and clustering analysis, we performed a time-series analysis to uncover the intricate connections between climate, local environmental factors, and dengue occurrences. The findings indicate that multiannual dengue frequency (3 yr) is correlated with the Oceanic Niño Index and the Tropical North Atlantic Index. This association is particularly prominent in cantons located along the North and South Pacific Coast, as well as in the Central cantons of the country. Furthermore, the time series of these climate indices exhibit a leading phase of approximately nine months ahead of dengue cases. Additionally, the clustering analysis uncovers non-contiguous groups of cantons that exhibit similar correlation patterns, irrespective of their proximity or adjacency. This highlights the significance of climate factors in influencing dengue dynamics across diverse regions, regardless of spatial closeness or distance between them. On the other hand, the annual dengue frequency was correlated with local environmental indices. A persistent correlation between dengue cases and local environmental variables is observed over time in the North Pacific and the Central Region of the country's Northwest, with environmental factors leading by less than three months. These findings contribute to understanding dengue transmission's spatial and temporal dynamics in Costa Rica, highlighting the importance of climate and local environmental factors in dengue surveillance and control efforts.
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Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.
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Interest in wearable and stretchable multifunctional sensors has grown rapidly in recent years. The sensing elements must accurately detect external stimuli to expand their applicability as sensors. However, the sensor's self-healing and adhesion to a target object have been major challenges in developing such practical and versatile devices. In this study, we prepared a hydrogel (LM-SA-PAA) composed of liquid metal (LM), sodium alginate (SA), and poly(acrylic acid) (PAA) with ultrastretchable, excellent self-healing, self-adhesive, and high-sensitivity sensing capabilities that enable the conformal contact between the sensor and skin even during dynamic movements. The excellent self-healing performance of the hydrogel stems from its double cross-linked networks, including physical and chemical cross-linked networks. The physical cross-link formed by the ionic interaction between the carboxyl groups of PAA and gallium ions provide the hydrogel with reversible autonomous repair properties, whereas the covalent bond provides the hydrogel with a stable and strong chemical network. Alginate forms a microgel shell around LM nanoparticles via the coordination of its carboxyl groups with Ga ions. In addition to offering exceptional colloidal stability, the alginate shell has sufficient polar groups, ensuring that the hydrogel adheres to diverse substrates. Based on the efficient electrical pathway provided by the LM, the hydrogel exhibited strain sensitivity and enabled the detection of various human motions and electrocardiographic monitoring. The preparation method is simple and versatile and can be used for the low-cost fabrication of multifunctional sensors, which have broad application prospects in human-machine interface compatibility and medical monitoring.
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Dengue fever is a vector-borne disease affecting millions yearly, mostly in tropical and subtropical countries. Driven mainly by social and environmental factors, dengue incidence and geographical expansion have increased in recent decades. Therefore, understanding how climate variables drive dengue outbreaks is challenging and a problem of interest for decision-makers that could aid in improving surveillance and resource allocation. Here, we explore the effect of climate variables on relative dengue risk in 32 cantons of interest for public health authorities in Costa Rica. Relative dengue risk is forecast using a Generalized Additive Model for location, scale, and shape and a Random Forest approach. Models use a training period from 2000 to 2020 and predicted climatic variables obtained with a vector auto-regressive model. Results show reliable projections, and climate variables predictions allow for a prospective instead of a retrospective study.
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Dengue , Animais , Humanos , Dengue/epidemiologia , Costa Rica/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Mosquitos Vetores , Surtos de Doenças , Aprendizado de Máquina , IncidênciaRESUMO
OBJECTIVES: We sought to evaluate the impact of the time interval from surgical resection to local recurrence (TTLR) on clinical outcomes in head and neck soft tissue sarcoma (HNSTS). METHODS: A total of 401 patients who underwent R0 resection for primary HNSTS were included in this study. Patients with local recurrence as the first event after their initial resection were divided into early local recurrence (ELR) or late local recurrence (LLR) groups according to TTLR. Multiple survival analyses were performed to identify the independent prognostic predictors of overall survival (OS) and survival after local recurrence (SAR). RESULTS: Two hundred and nine of the 401 patients (52.1%) developed local recurrence during a median follow-up period of 134.6 months. Patients in the ELR group had a shorter median OS time (35.0 vs. 120.6, p < 0.001) and lower 5-year OS rate (47.7% vs. 80.9%, p < 0.001) than those in the LLR group. Moreover, the ELR group exhibited worse SAR (p = 0.001) than the LLR group, and multivariate analyses demonstrated TTLR as an independent prognostic factor for SAR (p = 0.048) and OS (p = 0.004). Additionally, re-resection significantly prolonged SAR than other salvage interventions or no treatment (p < 0.001). CONCLUSION: In patients with HNSTS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TTLR could serve as a promising predictor for survival. Salvage therapies, especially the re-resection could improve SAR and should be recommended when there are surgical indications after recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2174-2182, 2023.
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Sarcoma , Humanos , Adulto , Estudos Retrospectivos , Prognóstico , Análise de Sobrevida , Fatores de Tempo , Recidiva Local de Neoplasia , Taxa de SobrevidaRESUMO
Objective: To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Methods: Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. Results: The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Conclusions: Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.
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Development of novel sensors for the detection of lead ions (Pb2+) has attracted increasing interest due to their inherent toxic effects on human health and the environment. In this study, we describe two new polydiacetylene (PDA)-based liposome sensors for the colorimetric and fluorometric recognition of Pb2+ in aqueous solution. In the sensor system, a thymine-1-acetic acid (TAA) or orotic acid (OA) group was reasonably introduced into the diacetylene monomer to work as a strong binding site for Pb2+. The TAA- or OA-functionalized monomer and 10,12-pentacosadiynoic acid (PCDA) were incorporated into PDA liposomes in aqueous solution. After UV light-induced polymerization, deep blue colored liposome solutions were obtained. Upon the addition of a series of transition metal cations into the liposome solutions, only Pb2+ could induce a color change from blue to red observable by the naked eye and a large fluorescence enhancement. The results clearly showed that the PDA-EDEA-TAA and PDA-EDEA-OA liposomes could act as highly selective and sensitive probes to detect Pb2+ in aqueous solution. The detection limits of PDA-EDEA-TAA and PDA-EDEA-OA systems are 38 nM and 25 nM, respectively. The excellent selectivity of PDA liposomes could be attributed to the stronger complexation behavior of Pb2+ with TAA (or OA) and the carboxylic acid at the lipid-solution interface which could perturb the PDA conjugated backbone. In addition, the proposed sensors were successfully applied to detect trace amounts of Pb2+ in real water samples with excellent recovery, indicating that the developed method had a good accuracy and precision for the analysis of trace Pb2+ in practical samples.
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[ABSTRACT]. Objective. To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Methods. Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. Results. The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Conclusions. Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.
[RESUMEN]. Objetivo. Resumir los resultados de las investigaciones realizadas en Costa Rica en las que se aplicaron métodos matemáticos y estadísticos para estudiar la dinámica de transmisión de las enfermedades transmitidas por mosquitos. Métodos. Se seleccionaron y analizaron tres artículos con análisis matemáticos y estadísticos sobre enfermedades transmitidas por vectores en Costa Rica. En estos artículos se muestra el valor y la pertinencia de emplear diferentes métodos cuantitativos para comprender la dinámica de la enfermedad y brindar apoyo a la toma de decisiones. Resultados. Los resultados de estas investigaciones: 1) muestran la repercusión en los informes de casos de dengue cuando surge un segundo agente patógeno, como el chikunguña; 2) recuperan parámetros clave en la dinámica del Zika mediante la inferencia bayesiana; y 3) muestran el uso de los algoritmos de aprendizaje automático y las variables climáticas para pronosticar el riesgo relativo de dengue en cinco lugares diferentes. Conclusiones. Los modelos matemáticos y estadísticos permiten describir la dinámica de transmisión de las enfermedades transmitidas por mosquitos, mediante la provisión de información cuantitativa para brindar apoyo a los métodos de prevención y control y a la planificación de la asignación de recursos.
[RESUMO]. Objetivo. Resumir os resultados de estudos realizados na Costa Rica em que foram aplicados métodos matemáticos e estatísticos para estudar a dinâmica de transmissão de doenças transmitidas por mosquitos. Métodos. Foram selecionados e revisados três artigos com análises matemáticas e estatísticas sobre doenças transmitidas por vetores na Costa Rica. Esses artigos mostram o valor e a pertinência do uso de diferentes métodos quantitativos para compreender a dinâmica das doenças e apoiar a tomada de decisões. Resultados. Os resultados dessas investigações: 1) mostram o impacto nas notificações de casos de dengue quando surge um segundo patógeno, como o chikungunya; 2) recuperam parâmetros-chave na dinâmica do zika, usando a inferência bayesiana; e 3) mostram o uso de algoritmos de aprendizagem por máquina e variáveis climáticas para prever o risco relativo da dengue em cinco locais diferentes. Conclusões. A modelagem matemática e estatística permite a descrição da dinâmica de transmissão de doenças transmitidas por mosquitos ao oferecer informações quantitativas para apoiar métodos de prevenção e/ou controle e o planejamento da alocação de recursos.
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Doenças Transmitidas por Vetores , Modelos Teóricos , Saúde Pública , Costa Rica , Doenças Transmitidas por Vetores , Modelos Teóricos , Saúde Pública , Doenças Transmitidas por Vetores , Modelos Teóricos , Saúde PúblicaRESUMO
The ongoing poisoning of agricultural products has pushed the security problem to become an important issue. Among them, exceeding the standard rate of pesticide residues is the main factor influencing the quality and security of agricultural products. Moreover, the abuse of pesticides has introduced a large amount of residues in soil and drinking water, which will enter the food chain to the human body, leading to neurological disorders and cancer. Therefore, great efforts have been devoted to developing fluorescent sensors for detecting pesticide in a facile, quickly, sensitive, selective, accurate manner, which exhibit greater advantages than some traditional methods. In this review, we mainly focus on summarizing the non-biological fluorescent probes for organic pesticides detection with the detection limit of micromole to nanomole, including organic functional small molecules, calixarenes and pillararenes, metal organic framework systems, and nanomaterials. Meanwhile, we described the different sensing mechanisms for pesticides detection of these mentioned fluorescent sensors, the detection limit of each pesticide, the application in detecting actual samples, as well as their respective advantages and development prospects associated with present non-biological fluorescent sensors.
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Estruturas Metalorgânicas , Resíduos de Praguicidas , Praguicidas , Agricultura , Humanos , Resíduos de Praguicidas/análise , Praguicidas/análise , SoloRESUMO
ABSTRACT Objective. To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Methods. Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. Results. The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Conclusions. Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.
RESUMEN Objetivo. Resumir los resultados de las investigaciones realizadas en Costa Rica en las que se aplicaron métodos matemáticos y estadísticos para estudiar la dinámica de transmisión de las enfermedades transmitidas por mosquitos. Métodos. Se seleccionaron y analizaron tres artículos con análisis matemáticos y estadísticos sobre enfermedades transmitidas por vectores en Costa Rica. En estos artículos se muestra el valor y la pertinencia de emplear diferentes métodos cuantitativos para comprender la dinámica de la enfermedad y brindar apoyo a la toma de decisiones. Resultados. Los resultados de estas investigaciones: 1) muestran la repercusión en los informes de casos de dengue cuando surge un segundo agente patógeno, como el chikunguña; 2) recuperan parámetros clave en la dinámica del Zika mediante la inferencia bayesiana; y 3) muestran el uso de los algoritmos de aprendizaje automático y las variables climáticas para pronosticar el riesgo relativo de dengue en cinco lugares diferentes. Conclusiones. Los modelos matemáticos y estadísticos permiten describir la dinámica de transmisión de las enfermedades transmitidas por mosquitos, mediante la provisión de información cuantitativa para brindar apoyo a los métodos de prevención y control y a la planificación de la asignación de recursos.
RESUMO Objetivo. Resumir os resultados de estudos realizados na Costa Rica em que foram aplicados métodos matemáticos e estatísticos para estudar a dinâmica de transmissão de doenças transmitidas por mosquitos. Métodos. Foram selecionados e revisados três artigos com análises matemáticas e estatísticas sobre doenças transmitidas por vetores na Costa Rica. Esses artigos mostram o valor e a pertinência do uso de diferentes métodos quantitativos para compreender a dinâmica das doenças e apoiar a tomada de decisões. Resultados. Os resultados dessas investigações: 1) mostram o impacto nas notificações de casos de dengue quando surge um segundo patógeno, como o chikungunya; 2) recuperam parâmetros-chave na dinâmica do zika, usando a inferência bayesiana; e 3) mostram o uso de algoritmos de aprendizagem por máquina e variáveis climáticas para prever o risco relativo da dengue em cinco locais diferentes. Conclusões. A modelagem matemática e estatística permite a descrição da dinâmica de transmissão de doenças transmitidas por mosquitos ao oferecer informações quantitativas para apoiar métodos de prevenção e/ou controle e o planejamento da alocação de recursos.
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Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition.
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Endocitose/fisiologia , Mucosa Intestinal , Lipídeos/toxicidade , Lipogênese/efeitos dos fármacos , Óxido de Zinco/farmacocinética , Ração Animal/toxicidade , Animais , Peixes-Gato , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Dieta , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/metabolismo , Intestinos/patologia , Lipídeos/farmacocinética , Redes e Vias Metabólicas/genética , Nanopartículas Metálicas/toxicidade , Regulação para Cima/efeitos dos fármacos , Zinco/metabolismo , Zinco/farmacocinética , Óxido de Zinco/química , Óxido de Zinco/toxicidadeRESUMO
The present study investigated the differences in the stride pattern of the lower extremities among different stride types in baseball pitchers with the aim of evaluating stride movement and skills to improve training effectiveness. Thirty elite male college baseball pitchers volunteered to pitch on an indoor-mound-like force plate, where motion data of their fastest strike trials were collected using an eight-camera motion analysis system at a 200-250 Hz sampling rate. Pelvis center trajectories of each participant were calculated and further categorized into three groups: tall-and-fall (TF), dip-and-drive (DD), and mixed (MX) pitchers. Motion analysis revealed that DD pitchers initiated pivot-knee extension and pivot-hip adduction earlier than TF pitchers and accelerated their bodies sooner than TF pitchers. In addition, TF pitchers accelerated their bodies forward by pivoting their legs until the middle of the arm-cocking and acceleration phases. The movement patterns of MX pitchers were similar to those of DD pitchers in terms of pivot leg, although this occurred a little later in the stride. Our findings are useful in developing training strategies for coaches, players, and trainers to better meet the demands of different pitching styles.
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Mice are the most widely used model organism for the study of gene functions and disease mechanisms through the generation of gene-modified mice. Since the 1980s, different genetic manipulation technologies have been developed to reveal gene functions in vivo, including homologous recombination strategies mediated by embryonic stem cells, transgenic strategies mediated by gametes, and the latest genetic modification strategies based on CRISPR/Cas9 technology. Semi-cloning technology mediated by "artificial spermatids" (androgenetic haploid embryonic stem cells, also termed sperm-like stem cells) is developed by Chinese scientists in 2012. In combination with CRISPR/Cas9, semi-cloning technology enables one-step generation of gene-modified mice through injection of "artificial spermatids" with specific gene modifications into oocytes. It has the characteristics of short construction cycle, high efficiency, low cost, and high application compatibility. In 2017, the Center for Excellence in Molecular Cell Science (CEMCS) of CAS has launched the genome tagging project (GTP) based on "artificial spermatid"-mediated semi-cloning technology. The ambitious goal of GTP is to tag every protein in mice and construct a unique mouse library that maintains the genome-wide protein-tagging mouse models. Subsequently, the GTP center was established at CEMCS to pursue the project. GTP center developed strategies to generate protein-tagging cells and mice. Briefly, a tag sequence is precisely inserted in a specific protein- coding gene endogenously in cultured "artificial spermatids"in vitro to build a cell library, in which, each cell line carrying a specific protein tag. The tagged cells could be further used as a sperm replacement to produce tagged mice in one step upon injection into oocytes. The tagged mouse library enables global analysis of protein expression, localization, and complexes using standard tag-based assays in vivo. By April 2021, the GTP center has generated 1532 tagged cell lines, 277 of which have been successfully used to produce tagged mice through oocyte injection. A total of 242 tagged mouse strains have been distributed to 66 research teams in 32 research institutions of 15 districts in 3 countries. The database of tagging product resources has been established and released regularly on the GTP website for scientists to inquire and order. Later, more information about GTP products, such as mouse breeding, protein tissue expression map, published literature, etc., will also be successively published on the GTP website. The GTP center will provide a standardized platform for protein function research, which may dramatically promote the development of life science and clinical transformation.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Genoma , Masculino , CamundongosRESUMO
The study characterized their regulatory functions of four znt members (znt1, znt2, znt6 and znt8) in Zn homeostasis in vertebrates. We found that the -1281/-1296 bp locus on the znt1 promoter, the -1/-16 bp locus on the znt2 promoter, the -825/-839 bp locus on the znt6 promoter, the -165/-180 bp locus and the -274/-292 bp STAT3 locus on the znt8 promoter were functional MTF-1 binding sites and had metal responsive element (MRE). Zn incubation increased activities of four znt promoters, which was mediated by MRE sites on znt1, znt2, znt6 and znt8 promoters and by STAT3 binding site on znt8 promoter. Moreover, Zn activated the transcription of these znts genes through MTF-1-MRE-dependent pathway. Zn incubation up-regulated the mRNA and total protein expression of ZnT1, ZnT2 and ZnT8 at both 24 h and 48 h. Overall, for the first time, this study offered novel insights for regulatory mechanism of Zn homeostasis in vertebrates.