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Unscheduled R-loops are a major source of replication stress and DNA damage. R-loop-induced replication defects are sensed and suppressed by ATR kinase, whereas it is not known whether R-loop itself is actively involved in ATR activation and, if so, how this is achieved. Here, we report that the nuclear form of RNA-editing enzyme ADAR1 promotes ATR activation and resolves genome-wide R-loops, a process that requires its double-stranded RNA-binding domains. Mechanistically, ADAR1 interacts with TOPBP1 and facilitates its loading on perturbed replication forks by enhancing the association of TOPBP1 with RAD9 of the 9-1-1 complex. When replication is inhibited, DNA-RNA hybrid competes with TOPBP1 for ADAR1 binding to promote the translocation of ADAR1 from damaged fork to accumulate at R-loop region. There, ADAR1 recruits RNA helicases DHX9 and DDX21 to unwind R-loops, simultaneously allowing TOPBP1 to stimulate ATR more efficiently. Collectively, we propose that the tempo-spatially regulated assembly of ADAR1-nucleated protein complexes link R-loop clearance and ATR activation, while R-loops crosstalk with blocked replication forks by transposing ADAR1 to finetune ATR activity and safeguard the genome.
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Proteínas de Unión al ADN , Estructuras R-Loop , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de Ciclo Celular/metabolismo , Replicación del ADN , Proteínas de Unión al ADN/genética , ARN/genética , Humanos , Animales , RatonesRESUMEN
Objective: To elucidate the role of circVRK1 and its interaction with miR-4428 in regulating proliferation and apoptosis in acute lymphoblastic leukemia (ALL) cells. Methods: KOCL44 ALL cells were cultured in vitro, and experimental groups included pcDNA, pcDNA-circVRK1, anti-miR-NC, anti-miR-4428, si-NC, si-circVRK1, pcDNA-circVRK1+miR-NC, and pcDNA-circVRK1+miR-4428. The expression levels of circVRK1 and miR-4428 were detected using qRT-PCR. CCK-8 assays and flow cytometry were used to assess cell proliferation and apoptosis, respectively. The dual luciferase reporter assays were employed to investigate the interaction between circVRK1 and miR-4428, with groups categorized as WT-circVRK1+miR-NC, WT-circVRK1+miR-4428, MUT-circVRK1+miR-NC, and MUT-circVRK1+ miR-4428. Western blotting was utilized to detect the expression levels of Ki-67, cleaved caspase-3, and cleaved caspase-9 proteins. Results: Compared to the pcDNA group, circVRK1 expression was up-regulated in the pcDNA-circVRK1 group (P<0.05). Compared to transfection with pcDNA or anti-miR-NC, transfection with pcDNA-circVRK1 or anti-miR-4428 led to decreased cell viability and Ki-67 protein levels in KOCL44 cells (P<0.05), and increased apoptosis rates and levels of cleaved caspase-3 and cleaved caspase-9 (P<0.05). circVRK1 was found to negatively regulate miR-4428 expression, with this effect observed only in the WT-circVRK1 group. miR-4428 levels were lower in the pcDNA-circVRK1 group compared to the pcDNA group (P<0.05) and higher in the si-circVRK1 group compared to the si-NC group (P<0.05). Co-transfection with pcDNA-circVRK1+miR-4428 resulted in increased cell viability (P<0.05) and Ki-67 expression (P<0.05), and decreased apoptosis rates and levels of cleaved caspase-3 and cleaved caspase-9 (P<0.05) compared to co-transfection with pcDNA-circVRK1+miR-NC. Conclusion: Overexpression of circVRK1 reduces the proliferation ability of acute ALL cells and induces cell apoptosis by downregulating miR-4428 expression.
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Apoptosis , Proliferación Celular , MicroARNs , Leucemia-Linfoma Linfoblástico de Células Precursoras , ARN Circular , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Apoptosis/genética , Proliferación Celular/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Línea Celular Tumoral , Caspasa 3/metabolismo , Caspasa 3/genética , Caspasa 9/metabolismo , Caspasa 9/genéticaRESUMEN
Water reclamation is the most effective way to continuously provide clean water to combat catastrophic global water scarcity. However, current technology for water purification is not conducive to sustainability due to the high energy consumption and negative environmental impact. Here, we introduce an innovative method by utilizing the hierarchical microstructure of bamboo for water purification. Natural bamboo was delignified followed by freeze-drying to obtain a bamboo aerogel with a porosity of 72.0%; then, the bamboo aerogel was coated with silver nanoparticles to form a hierarchical bamboo/silver nanoparticle composite. The scanning electron microscopy images and energy-dispersive X-ray spectroscopy results indicated that the silver nanoparticles were uniformly attached to the parenchyma cell surface. By physical adsorption and catalytic reduction, the bamboo/silver nanoparticle composite was able to degrade methylene blue by more than 96.7%, which is mainly attributed to the large specific surface area of the bamboo providing more space for the purification reaction. This composite can be potentially used for board applications with its high porosity, mechanical reliability, and sustainability.
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OBJECTIVE: To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS. MATERIALS AND METHODS: This is a prospective case control study, 550 women recruited (aged 20-40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. RESULTS: The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS. CONCLUSION: The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.
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Hormonas Peptídicas , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/diagnóstico , Andrógenos , Hormona Antimülleriana , Androstenodiona , Estudios de Casos y Controles , Pueblos del Este de Asia , TestosteronaRESUMEN
Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in cancer cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120ub1 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation, and this process is not affected by H2AK119 ubiquitination catalyzed by PRC1. Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives cancer cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during tumor progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of tumor patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for cancer intervention.
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Carcinogénesis , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Peptidasa Específica de Ubiquitina 7/metabolismo , Animales , Femenino , Proteína Forkhead Box O1/metabolismo , Células HEK293 , Humanos , Ratones , Ratones Endogámicos BALB C , Células Sf9 , Ubiquitinación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
With the global spread of the novel coronavirus, avoiding human-to-human contact has become an effective way to cut off the spread of the virus. Therefore, contactless gesture recognition becomes an effective means to reduce the risk of contact infection in outbreak prevention and control. However, the recognition of everyday behavioral sign language of a certain population of deaf people presents a challenge to sensing technology. Ubiquitous acoustics offer new ideas on how to perceive everyday behavior. The advantages of a low sampling rate, slow propagation speed, and easy access to the equipment have led to the widespread use of acoustic signal-based gesture recognition sensing technology. Therefore, this paper proposed a contactless gesture and sign language behavior sensing method based on ultrasonic signals-UltrasonicGS. The method used Generative Adversarial Network (GAN)-based data augmentation techniques to expand the dataset without human intervention and improve the performance of the behavior recognition model. In addition, to solve the problem of inconsistent length and difficult alignment of input and output sequences of continuous gestures and sign language gestures, we added the Connectionist Temporal Classification (CTC) algorithm after the CRNN network. Additionally, the architecture can achieve better recognition of sign language behaviors of certain people, filling the gap of acoustic-based perception of Chinese sign language. We have conducted extensive experiments and evaluations of UltrasonicGS in a variety of real scenarios. The experimental results showed that UltrasonicGS achieved a combined recognition rate of 98.8% for 15 single gestures and an average correct recognition rate of 92.4% and 86.3% for six sets of continuous gestures and sign language gestures, respectively. As a result, our proposed method provided a low-cost and highly robust solution for avoiding human-to-human contact.
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COVID-19 , Ultrasonido , Humanos , Gestos , Lengua de Signos , AcústicaRESUMEN
Uveal melanoma (UM) is the most common intraocular malignant tumor in adults with an extremely high mortality rate. Genetic and epigenetic dysregulation contribute to the development of UM. Recent discoveries have revealed dysregulation of the expression levels of microRNAs (miRNAs) as one of the epigenetic mechanisms underlying UM tumorigenesis. Based on their roles, miRNAs are characterized as either oncogenic or tumor suppressive. This review focuses on the roles of miRNAs in UM tumorigenesis, diagnosis, and prognosis, as well as their therapeutic potentials. Particularly, the actions of collective miRNAs are summarized with respect to their involvement in major, aberrant signaling pathways that are implicated in the development and progression of UM. Elucidation of the underlying functional mechanisms and biological aspects of miRNA dysregulation in UM is invaluable in the development of miRNA-based therapeutics, which may be used in combination with conventional treatments to improve therapeutic outcomes. In addition, the expression levels of some miRNAs are correlated with UM initiation and progression and, therefore, may be used as biomarkers for diagnosis and prognosis.
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Regulación Neoplásica de la Expresión Génica , Melanoma/genética , MicroARNs/genética , Neoplasias de la Úvea/genética , Animales , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/patología , Progresión de la Enfermedad , Epigénesis Genética , Humanos , Melanoma/diagnóstico , Melanoma/patología , Pronóstico , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/patologíaRESUMEN
As part of ongoing efforts to contain the coronavirus disease (COVID-19) pandemic, understanding the role of asymptomatic patients in the transmission system is essential for infection control. However, the optimal approach to risk assessment and management of asymptomatic cases remains unclear. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) epidemic propagation model. The model was constructed based on epidemiological characteristics of COVID-19 in China and accounting for the heterogeneity of social contact networks. The early community outbreaks in Wuhan were reconstructed and fitted with the actual data. We used this model to assess epidemic control measures for asymptomatic cases in three dimensions. The impact of asymptomatic cases on epidemic propagation was examined based on the effective reproduction number, abnormally high transmission events, and type and structure of transmission. Management of asymptomatic cases can help flatten the infection curve. Tracing 75% of the asymptomatic cases corresponds to a 32.5% overall reduction in new cases (compared with tracing no asymptomatic cases). Regardless of population-wide measures, household transmission is higher than other types of transmission, accounting for an estimated 50% of all cases. The magnitude of tracing of asymptomatic cases is more important than the timing; when all symptomatic patients were traced, tested, and isolated in a timely manner, the overall epidemic was not sensitive to the time of implementing the measures to trace asymptomatic patients. Disease control and prevention within families should be emphasized during an epidemic. Note to Practitioners-This article addresses the urgent need to assess the risk of another COVID-19 outbreak caused by asymptomatic cases and to find the optimal, most practical approach to asymptomatic case management. Previous studies mostly focused on the clinical and statistical characteristics of asymptomatic cases; few have evaluated the impact of asymptomatic case measures using mathematical modeling at the community scale. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) propagation model based on local community structures and social contact networks, according to the development characteristics and trend of COVID-19 in a Chinese community. The conclusion provides theoretical support for emergency work of relevant departments in different periods of an epidemic. In the early stages of the epidemic, timely detection and isolation of symptomatic patients should be a priority. Where there are surplus resources for epidemic prevention, the authorities should consider increasing the proportion of asymptomatic patients being traced. Epidemic prevention measures among family members should be a primary focus of attention. This combination of strategies can help reduce the rate of viral transmission and result in extinguishing the epidemic.
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Insufficient mechanical properties of stereolithography (SLA)-printed architected polymer metamaterial limits its wide applications such as in the areas of biomedicine and aerospace. One effective solution is to reinforce the structures with micro- or nano- fibers/particles, but their interfaces are critical for the reinforcement. In this work, a carbon fiber-graphene oxide (CF-GO) polymer composite resin and a mild annealing postprocess have been rationally designed and applied into the manufacturing of oct-truss (OCT) lattices.In situcarbon fiber pulling-out experiment was conducted to exhibit the improve effect of GO on the crosslink of the CF and the polymer matrix interface. We found that the maximum reinforcement was realized when the CF-GO (CF: GO is about 3: 1) content is about 0.8 wt%, followed with annealing. Compared with pure polymer lattices, the compression strength of the CF-GO polymer OCT lattices has been significantly increased from â¼0.22 to â¼2.4 MPa, almost 10 times enhancement. Importantly, the compression strength of the CF-GO polymer OCT lattice (3.08 MPa) further increased by â¼30% after optimized annealing. This work suggests an efficient reinforce strategy for SLA-printed metamaterials, and thus can be valuable for advancing various practical applications of mechanical metamaterials.
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Progesterone receptor membrane component 1 (PGRMC1) is mediating strong breast cancer cell proliferation induced by certain synthetic progestogens which we have shown within already published in vitro studies. Aim was now to use an animal model, to compare tumor growth using progesterone and its isomer dydrogesterone with norethisterone, which elicited in our in vitro studies the strongest proliferating effect. For the first time, we wanted to investigate if growth can be correlated both with blood concentrations and tissue expression of PGRMC1 to identify if PGRMC1 could be a new tumor marker. Prospective, randomized, blinded, placebo-controlled four-arm study (45-50 days); PGRMC1-transfected or empty-vector T47D- and MCF7-xenotransplants were each treated with estradiol (E2) +placebo; E2 + progesterone; E2 + norethisterone; E2 + dydrogesterone; blood PGRMC1 assessed by a novel ELISA, tissue expression by immunohistochemistry. PGRMC1-transfected tumors further increased with E2 + norethisterone but not with E2-dydrogesterone or E2-progesterone. In both PGRMC1-xenograft groups (T47D, MCF7) with E2/norethisterone, the blood concentrations and tissue expression of PGRMC1 were higher than in all other 14 groups (p < .05), with positive significant correlation between blood PGRMCI concentrations and tissue PGRMC1 expression. In the presence of PGRMC1, certain progestogens could increase the growth of breast tumor, which now also should be tested in clinical studies.
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Proliferación Celular/efectos de los fármacos , Didrogesterona/farmacología , Neoplasias Mamarias Experimentales/patología , Proteínas de la Membrana/metabolismo , Noretindrona/farmacología , Progesterona/farmacología , Receptores de Progesterona/metabolismo , Animales , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Femenino , Xenoinjertos , Humanos , Células MCF-7 , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Experimentales/sangre , Neoplasias Mamarias Experimentales/metabolismo , Proteínas de la Membrana/sangre , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Placebos , Distribución Aleatoria , Receptores de Progesterona/sangreRESUMEN
Soil salinization is a major cause of land degradation and hinders the effective utilization of agricultural land resources. Leymus chinensis (L. chinensis), as a dominant species with wide ecological amplitude, plays an important role in improving saline-alkali grasslands and indicating the degree of salinization. In this study, a sand culture experiment (nitrogen and phosphorus addition accompanied by saline-alkali stress) was designed to investigate the impact of different saline-alkali environments on the ecological stoichiometric homeostasis of L. chinensis with the aim of elucidating the saline-alkali resistance mechanisms. The results showed that the homeostasis indexes of N, P and N:P in the aboveground part of L. chinensis were generally higher than those in the belowground part under different saline-alkali conditions. Furthermore, the homeostasis index of N (HN) was greater than that of P (HP) in the aboveground part, whereas HN was less than HP in the belowground part. This indicates that the growth aboveground of L. chinensis was mainly dependent on N, whereas the growth belowground was mainly affected by P. The homeostasis index of the aboveground organs was 4.45-12.93 under pH 7-9.8. In contrast, HN and HN:P(+N) in the belowground organs did not conform to a homeostasis model when pH >â¯9.1. Consequently, when L. chinensis is subjected to high saline-alkali stress, the homeostasis reaction of the roots is more sensitive than that of the aboveground organs.
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Nitrógeno/metabolismo , Fósforo/metabolismo , Raíces de Plantas/metabolismo , Poaceae/metabolismo , Cloruro de Sodio/metabolismo , Álcalis , Ecosistema , Homeostasis , Concentración de Iones de Hidrógeno , Nutrientes , SueloRESUMEN
When a satellite performs complex tasks such as discarding a payload or capturing a non-cooperative target, it will encounter sudden changes in the attitude and mass parameters, causing unstable flying and rolling of the satellite. In such circumstances, the change of the movement and mass characteristics are unpredictable. Thus, the traditional attitude control methods are unable to stabilize the satellite since they are dependent on the mass parameters of the controlled object. In this paper, we proposed a reinforcement learning method to re-stabilize the attitude of a satellite under such circumstances. Specifically, we discretize the continuous control torque, and build a neural network model that can output the discretized control torque to control the satellite. A dynamics simulation environment of the satellite is built, and the deep Q Network algorithm is then performed to train the neural network in this simulation environment. The reward of the training is the stabilization of the satellite. Simulation experiments illustrate that, with the iteration of training progresses, the neural network model gradually learned to re-stabilize the attitude of a satellite after unknown disturbance. As a contrast, the traditional PD (Proportion Differential) controller was unable to re-stabilize the satellite due to its dependence on the mass parameters. The proposed method adopts self-learning to control satellite attitudes, shows considerable intelligence and certain universality, and has a strong application potential for future intelligent control of satellites performing complex space tasks.
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Vitamin B12 is an essential nutrient required for crucial metabolic processes in humans. Vitamin B12-producing lactic acid bacteria (LAB) have been attracting increased attentions currently because of the generally recognized as safe (GRAS) status. Most of recent studies focused on Lactobacillus, and little is known about B12-producing Enterococcus. In the present study, five Enterococcus strains isolated from infant feces were identified as vitamin B12 producers. Among them, Enterococcus faecium LZ86 had the highest B12 production (499.8 ± 83.7 µg/L), and the B12 compound from LZ86 was identified as the biological active adenosylcobalamin, using reversed phase high-performance liquid (RP-HPLC) chromatogram. We examined basic probiotic and safety properties of E. faecium LZ86 and found that it was able to survive harsh environmental conditions (hot temperature, cold temperature, ethanol and osmotic stresses), tolerate gastric acid (pH 2.0, 3 h) and bile salts (0.3%), and adhere to Caco-2 cells. We also showed that E. faecium LZ86 is devoid of transferable antibiotic resistance and potential virulence factors. Together, here we report a B12-producing E. faecium strain LZ86 firstly, which has desirable probiotic properties and may serve as a good candidate for vitamin B12 fortification in food industry.
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Enterococcus/aislamiento & purificación , Enterococcus/metabolismo , Probióticos/aislamiento & purificación , Vitamina B 12/biosíntesis , Antibacterianos/farmacología , Células CACO-2 , Cromatografía Líquida de Alta Presión , Cobamidas/aislamiento & purificación , Farmacorresistencia Microbiana , Enterococcus/efectos de los fármacos , Enterococcus/crecimiento & desarrollo , Heces/microbiología , Humanos , Lactante , Lactobacillus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Factores de Virulencia , Vitamina B 12/análisisRESUMEN
The grasslands of Western Jilin Province in China have experienced severe degradation during the last 50 years. Radial basis function neural networks (RBFNN) and support vector machines (SVM) were used to predict the carbon, nitrogen, and phosphorus contents of Leymus chinensis (L. chinensis) and explore the degree of grassland degradation using the matter-element extension model. Both RBFNN and SVM demonstrated good prediction accuracy. The results indicated that there was severe degradation, as samples were mainly concentrated in the 3rd and 4th levels. The growth of L. chinensis was shown to be limited by either nitrogen, phosphorus, or both during different stages of degradation. The soil chemistry changed noticeably as degradation aggravated, which represents a destabilization of L. chinensis community homeostasis. Soil salinization aggravates soil nutrient loss and decreases the bioavailability of soil nutrients. This, along with the destabilization of C/N, C/P and N/P ratios, weakens the photosynthetic ability and productivity of L. chinensis. This conclusion was supported by observations that L. chinensis is gradually being replaced by a Chloris virgata, Puccinellia tenuiflora and Suaeda acuminate mixed community.
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Pradera , Poaceae/química , Carbono/análisis , China , Aprendizaje Automático , Redes Neurales de la Computación , Nitrógeno/análisis , Fósforo/análisis , Suelo/química , Máquina de Vectores de SoporteRESUMEN
OBJECTIVE: To study gender differences in different measures of iron status in infants aged 4 and 6 months old. METHODS: Term delivery pregnant women with normal iron status were recruit with informed consent. Infants with normal birth weight were selected and exclusive breastfeeding were required. All infants were randomly assigned into one control group and one iron supplement group at 4 months old. The latter group were given a daily dose of iron supplement corresponding to 1 mg/kg body weight of elemental iron from 4 to 6 month. At 4 and 6 months old, vein blood were sampled to analyze hemoglobin (Hb), mean cell volume (MCV), serum ferritin (SF), and soluble transferrin receptors (sTfR) and the growth indices were measured. RESULTS: Data of infants at 4 months old (n = 178) and 6 months old (n = 85) were collected. At 4 months old, male infants had significantly lower MCV and SF and higher sTfR, male infants had lower Hb but with no significant difference. 6 months old, the trends of differences stayed the same as at 4 months old, and MCV remained significant. CONCLUSION: Male infants may have a higher risk to develop iron deficiency. Male infants may have a higher risk to develop iron deficiency. There needs to be respective diagnostical cut-off values and dietary iron requirement for male and female infants. At the same time, correct feeding is necessary.
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Anemia Ferropénica , Lactancia Materna , Hemoglobinas , Hierro de la Dieta , Suplementos Dietéticos , Femenino , Humanos , Lactante , Hierro , Masculino , Embarazo , Factores de Riesgo , Factores SexualesRESUMEN
At present, pulmonary fibrosis (PF) is a prevalent and irreversible lung disease with limited treatment options, and idiopathic pulmonary fibrosis (IPF) is one of its most common forms. Recent research has highlighted PF as a metabolic-related disease, including dysregulated iron, mitochondria, lipid, and glucose homeostasis. Systematic reports on the regulatory roles of glucose metabolism in PF are rare. This study explores the intricate relationships and signaling pathways between glucose metabolic processes and PF, delving into how key factors involved in glucose metabolism regulate PF progression, and the interplay between them. Specifically, we examined various enzymes, such as hexokinase (HK), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), pyruvate kinase (PK), and lactate dehydrogenase (LDH), illustrating their regulatory roles in PF. It highlights the significance of lactate, alongside the role of pyruvate dehydrogenase kinase (PDK) and glucose transporters (GLUTs) in modulating pulmonary fibrosis and glucose metabolism. Additionally, critical regulatory factors such as transforming growth factor-beta (TGF-ß), interleukin-1 beta (IL-1ß), and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were discussed, demonstrating their impact on both PF and glucose metabolic pathways. It underscores the pivotal role of AMP-activated protein kinase (AMPK) in this interplay, drawing connections between diabetes mellitus, insulin, insulin-like growth factors, and peroxisome proliferator-activated receptor gamma (PPARγ) with PF. This study emphasizes the role of key enzymes, regulators, and glucose transporters in fibrogenesis, suggesting the potential of targeting glucose metabolism for the clinical diagnosis and treatment of PF, and proposing new promising avenues for future research and therapeutic development.
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Glucosa , Glucólisis , Fibrosis Pulmonar , Humanos , Glucosa/metabolismo , Fibrosis Pulmonar/metabolismo , Animales , Transducción de SeñalRESUMEN
Human skin sensing of mechanical stimuli originates from transduction of mechanoreceptors that converts external forces into electrical signals. Although imitating the spatial distribution of those mechanoreceptors can enable developments of electronic skins capable of decoupled sensing of normal/shear forces and strains, it remains elusive. We report a three-dimensionally (3D) architected electronic skin (denoted as 3DAE-Skin) with force and strain sensing components arranged in a 3D layout that mimics that of Merkel cells and Ruffini endings in human skin. This 3DAE-Skin shows excellent decoupled sensing performances of normal force, shear force, and strain and enables development of a tactile system for simultaneous modulus/curvature measurements of an object through touch. Demonstrations include rapid modulus measurements of fruits, bread, and cake with various shapes and degrees of freshness.
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Mecanorreceptores , Piel Artificial , Tacto , Dispositivos Electrónicos Vestibles , Humanos , Mecanorreceptores/fisiología , Células de Merkel/fisiología , Piel/inervación , Fenómenos Fisiológicos de la PielRESUMEN
Recent research has highlighted a growing focus on stimuli-responsive surfactant wormlike micelles (WLMs), particularly those with switchability. Here we report CO2-switchable WLMs based on the commercial anionic surfactant sodium dodecyl sulfate (SDS) and N,N,N',N'-tetramethyl-1,3-propanediamine (TMPDA) mixed in a mole ratio of 2:1. When CO2 is bubbled into an aqueous mixture of these reactants, the TMPDA molecules are protonated to form quaternary ammonium species, two of which in the same protonated TMPDA molecule "bridge" two SDS molecules by noncovalent electrostatic attraction, behaving like a pseudogemini surfactant and forming viscoelastic WLMs as verified by cryo-TEM. Upon removal of CO2, the quaternized spacers are deprotonated back to tertiary amines, dissociating the pseudogeminis back to conventional SDS molecules that form low-viscosity spherical micelles. Such a reversible sphere-to-worm transition could be repeated several cycles without a loss of response to CO2.
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Dióxido de Carbono/química , Tensoactivos/química , Sustancias Viscoelásticas/química , Micelas , Modelos Moleculares , Estructura MolecularRESUMEN
To realize a hyperconnected smart society with high productivity, advances in flexible sensing technology are highly needed. Nowadays, flexible sensing technology has witnessed improvements in both the hardware performances of sensor devices and the data processing capabilities of the device's software. Significant research efforts have been devoted to improving materials, sensing mechanism, and configurations of flexible sensing systems in a quest to fulfill the requirements of future technology. Meanwhile, advanced data analysis methods are being developed to extract useful information from increasingly complicated data collected by a single sensor or network of sensors. Machine learning (ML) as an important branch of artificial intelligence can efficiently handle such complex data, which can be multi-dimensional and multi-faceted, thus providing a powerful tool for easy interpretation of sensing data. In this review, the fundamental working mechanisms and common types of flexible mechanical sensors are firstly presented. Then how ML-assisted data interpretation improves the applications of flexible mechanical sensors and other closely-related sensors in various areas is elaborated, which includes health monitoring, human-machine interfaces, object/surface recognition, pressure prediction, and human posture/motion identification. Finally, the advantages, challenges, and future perspectives associated with the fusion of flexible mechanical sensing technology and ML algorithms are discussed. These will give significant insights to enable the advancement of next-generation artificial flexible mechanical sensing.
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Uranium extraction from radioactive nuclear waste is vital for sustainable energy supply and ecological security. Herein, a polyethyleneimine-chitosan composite microspheres n-PEI/ECH-CTS (n = 0.1, 0.2, 0.3, 0.4, 0.5) were synthetized for efficient and selective uranium adsorption. The prepared chitosan microspheres with uniform size, uniform dispersion and good mechanical strength combine cost-effectiveness and environmental benefits. The 0.4-PEI/ECH-CTS exhibits the highest adsorption capacity of 380.65 mg g-1 within only 4 h due to high nitrogen content of 6.57 mol kg-1. The DFT calculations confirms that the optimal coordination mode of UO22+ and 0.4-PEI/ECH-CTS is one UO22+ chelated with two -NH2 from two adsorption units, respectively. Adsorption efficiency of U(VI) from simulated nuclear wastewater achieves to 100%, and the Kd value is up to 1.1 × 104 mL g-1, which is 1.7 × 104-6.1 × 104 times that of coexisting ions. The CU(VI) reduces in simulated wastewater from 10.98 mg L-1 to 1 µg L-1, which is well below the US Environmental Protection Agency uranium limits for drinking water (30 µg L-1). Besides, 0.4-PEI/ECH-CTS still maintains above 95% adsorption efficiency after seven cycles. In short, the 0.4-PEI/ECH-CTS microspheres integrate high performance, practicality and cost-effectiveness, which has great advantages in practical industrial applications.