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Palladium hydride (PdHx) is one of the well-known electrocatalytic materials, yet its synthesis is still a challenge through an energy-efficient and straightforward method. Herein, we propose a new and facile cyanogel-assisted synthesis strategy for the preparation of PdH0.649 at a mild environment with NaBH4 as the hydrogen source. Unlike traditional inorganic Pd precursors, the unique Pd-CN-Pd bridge in Pdx[Pd(CN)4]y â aH2O cyanogel offers more favourable spatial sites for insertion of H atoms. The characteristic three-dimensional backbone of cyanogel also acts as a support scaffold resulting in the interconnected network structure of PdH0.649. Due to the incorporation of H atoms and interconnected network structure, the PdH0.649 achieves a high half-wave potential of 0.932â V, a high onset potential of 1.062â V, and a low activation energy, as well as a long-term lifetime for oxygen reduction reaction. Theoretical calculation demonstrates a downshift of the d-band centre of Pd in PdH0.649 owing to the dominant Pd-H incorporation that weakens the binding energies of the *OH intermediate species. Zn-air batteries (ZAB) based on PdH0.649 exhibits high power density, competitive open circuit voltage, and good stability, exceeding that of commercial Pt black. This work not only opens up a new avenue for the development of high-efficiency Pt-free catalysts but also provides an original approach and insight into the synthesis of PdHx.
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Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.
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Biomarcadores , Chaperón BiP del Retículo Endoplásmico , Exposición Materna , Estrés Oxidativo , Ácidos Ftálicos , Placenta , Humanos , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/orina , Femenino , Estrés Oxidativo/efectos de los fármacos , Embarazo , Masculino , Placenta/efectos de los fármacos , Placenta/metabolismo , Biomarcadores/orina , Estudios Prospectivos , Adulto , Exposición Materna/efectos adversos , Factores Sexuales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Estudios de CohortesRESUMEN
In response to the challenges of intermediate poisoning and the high cost of noble metal catalysts in the hydrogen evolution reaction (HER), we develop a Ru-doped SnO2 catalyst. This Ru-SnO2 catalyst has the characteristics of low Ru loading and a hollow structure, which endow it with good electrocatalytic activity and stability for the HER.
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BACKGROUND: Lymphatic metastatic size was proved to predict prognosis in different types of carcinomas, except in head and neck squamous cell carcinoma (HNSCC) located in hypopharynx, oropharynx and supraglottic region et al. The aim of this study is to evaluate the prognostic value of lymphatic metastatic size in HNSCC, which may guide clinical decision-making in practice. METHODS: From 2008 to 2022, 171 patients, who were diagnosed as HNSCC in our center, were included. The demographic data, clinicopathological characteristics and lymphatic metastatic size were recorded and analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS: Among 171 patients, 107 cases were hypopharyngeal cancer, 38 cases supraglottic cancer and 26 cases oropharyngeal cancer. The median of lymphatic metastatic size was 8 mm (range 0-46). According to lymphatic metastatic size, the patients were assigned to three subgroups: Group I (0 mm), Group II ( ≤ 10 mm) and Group III (> 10 mm). Kaplan-Meier analysis with log rank test revealed that Group I and Group II had similar locoregional control rate, distant metastasis free probability, disease-free survival and overall survival (all p > 0.05), whereas Group III had significant worse prognosis. Adjusted for demographic and other clinicopathological characteristics, lymphatic metastatic size was an independent predictor of disease-free survival and overall survival in HNSCC. CONCLUSIONS: Lymphatic metastatic size was an independently prognostic factor in HNSCC, which may assist in postoperative adjuvant treatment decisions.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Carcinoma de Células Escamosas/patología , Metástasis LinfáticaRESUMEN
There is an urgent need to develop an economical and convenient method for the ultrasensitive detection of patulin (PAT), a mycotoxin that can potentially harm human health when it is found in fruits and their derivatives. In this study, we have developed a novel fluorescent aptasensor that utilizes nitrogen-doped carbon dots (N-CDs) as the fluorescent donor and hexagonal ß-Co(OH)2 nanoplates as the fluorescent acceptor. N-CDs were synthesized through the hydrothermal method, resulting in spherical particles with a diameter of 7.6 nm. These nanoparticles exhibited excellent water solubility and displayed a vibrant blue emission at 448 nm when excited at 360 nm. Cobalt hydroxide nanoplates with a beta crystal structure [ß-Co(OH)2] were synthesized using a simple co-precipitation method, exhibiting hexagonal plate-like shapes with uniform lateral sizes of 4-5 µm. The fluorescence of N-CDs can be efficiently quenched by hexagonal ß-Co(OH)2 nanoplates through Förster resonance energy transfer mechanism. The maximum quenching-recovery capability can be achieved when the concentrations of N-CDs-Apt and ß-Co(OH)2 nanoplates are 150 nmol/L and 100 µg/mL, respectively. The pH of the TE buffer should be 8.0, and the incubation time should be 10 min at 25 °C. The developed fluorescent aptasensor displayed an excellent selectivity for PAT determination with a detection limit of 0.57 pg/mL in the linear range of 1.25 pg/mL-100 ng/mL. The rapid PAT determination in fruit juice samples was realized with good recoveries (96.9-105.8%). The developed fluorescent aptasensor based on the interaction between N-CDs and hexagonal ß-Co(OH)2 nanoplates can be a promising method for the rapid and ultrasensitive detection of PAT in agricultural products.
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Patulina , Humanos , Agricultura , Carbono , Colorantes , NitrógenoRESUMEN
Acute kidney injury (AKI) is common in patients with heart failure (HF), but studies have been inconsistent about the incidence of AKI in patients with HF. We conducted a meta-analysis to examine the incidence of AKI and its impact on mortality in patients with HF. We also looked at inpatient variables that could predict the development of AKI to identify potential risk factors, so that these can be used as a starting point for intervention and prevention in this group. The Embase, Medline, PubMed, Cochrane libraries, and Web of Science databases were used for searching articles from the inception of the database to October 2022. The EndNote software was used for screening. Meta-analysis was performed using Stata 16.0 software to combine effect sizes. A total of 37 studies were included. Of all the 3 533 583 patients with HF, 774 887 had AKI, with a pooled incidence of 33% [95% confidence interval (CI): 32-35%]. The incidence rate of AKI in acute HF and chronic HF was 36% (95% CI: 31-40%) and 30% (95% CI: 24-35%), respectively. Eleven studies found that AKI patients had higher in-hospital mortality than non-AKI patients [risk ratio (RR): 3.65; 95% CI: 3.04-4.39, P < 0.001]. Mortality was assessed in five studies, and it was found that mortality remained high at 1-year follow-up after onset of AKI (RR: 1.85, 95% CI: 1.54-2.22, P < 0.001). Fifteen admission variables were included and analysed in 13 studies. The combined results showed that diabetes, hypertension, history of chronic kidney disease, chronic HF systolic, age, N-terminal pro-B-type natriuretic peptide, creatinine > 1.0 mg/dL, index estimated glomerular filtration rate < 60 mL/min/1.73 m2 , blood urea nitrogen > 24 mg/dL, intravenous dobutamine, and serum albumin were predictor factors for HF patients with AKI (P < 0.05). In this meta-analysis, AKI occurred in approximately 33% of HF patients during hospitalization and the risk of dying in the hospital was tripled. Even during 1-year long-term follow-up, the risk of death remained high, and multiple inpatient variables showed that HF patients tended to have AKI. Early intervention and treatment are important to reduce the incidence of AKI and improve the prognosis.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Humanos , Incidencia , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Pronóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Factores de RiesgoRESUMEN
The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.
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Studies have shown that an organization's corporate social responsibility (CSR) activities affect customer behaviors such as loyalty and satisfaction. In spite of this, the role of social media in informing customers about a brand's CSR activities and in fostering customer advocacy behavior (CADB) has been underexplored. To fill this knowledge gap, this study investigates the relationship between the CSR-related communication of a banking organization and CADB. This study also examines how emotions such as customer-company identification (CCI) and gratitude as a mediator and a moderator. Using a self-administered questionnaire (n = 302), we collected data from banking customers. Hypotheses were evaluated by using structural equation modeling, which revealed that CSR positively predicts CADB, whereas there are mediating and moderating functions of CCI and GA. Theoretically, this study highlights the role of human emotions in behavior formation from the standpoint of social media. Practically, this study provides important insights for the banking sector's administrators to realize the important role of CSR communication, using different social networking websites, for converting customers into brand advocates.
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The widespread of patulin (PAT) and its potential hazards to human health call for alternative rapid assays to monitor it in food and the environment. Herein, we prepared chromium hydroxide [Cr(OH)3] nanoparticles via a one-pot chemical precipitation strategy and used them to fabricate a turn-on fluorescent aptasensor employing a morphological effect for sensitive PAT detection. Three Cr(OH)3 nanoparticle structures were synthesized by changing the solvent, and their structures and physicochemical properties were investigated. Then, we evaluated the effects of morphological structures on the fluorescence quenching-recovery capability of Cr(OH)3 nanoparticles before and after incubation with PAT. We found that the Cr(OH)3-3 nanoparticles efficiently absorbed the fluorescence dye 6-carboxyfluorescein labeled aptamer (FAM-Apt) and quenched the fluorophore through photoinduced electron transfer. Under optimal experimental conditions, the turn-on fluorescent aptasensor for PAT determination displayed two linear ranges (0.01-10 ng/mL and 1-200 ng/mL) with a low detection limit of 7.3 pg/mL. Moreover, the proposed aptasensor had no cross-reactivity with interferents that usually coexist with PAT and can be used to detect PAT in apple juices accurately. The results of the as-fabricated method were not significantly different from the high-performance liquid chromatography. Hence, we demonstrated that different Cr(OH)3 nanoparticles can be prepared by changing reaction conditions, and provided a novel strategy to improve the detection performance of fluorescent aptasensor by changing the morphological structure and crystalline properties of nano-quenchers.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas , Patulina , Humanos , Patulina/análisis , Cromo , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Límite de DetecciónRESUMEN
By mining the dimensional sentiment and dimension weight of the Ping An Health App reviews, this paper explores the changing trend of the influence of dimensions on user satisfaction and provides suggestions for the Ping An Health App operators to improve user satisfaction. Firstly, the topic model is used to identify the topic of user comments, and then the fine-grained sentiment analysis method is used to calculate the sentiment and weight of each dimension. Finally, the changing trend of the weight of each dimension and the changing trend of user satisfaction of each dimension are drawn. Based on the reviews of the Ping An Health App in the Apple App Store, users' concerns about Ping An Health App can be summarized into seven main dimensions: Usage, Bug report, Reliability, Feature information, Services, Other apps, and User Background. The "Feature information" dimension and "Reliability" dimension have a great impact on user satisfaction with the Ping An Health App, while the "Bug report" dimension has the lowest user satisfaction.
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Aplicaciones Móviles , Análisis de Sentimientos , Satisfacción Personal , ActitudRESUMEN
This cohort study sought to investigate the effects of phthalates exposure during pregnancy on offspring asthma and its association with placental stress and inflammatory factor mRNA expression levels. A total of 3474 pregnant women from the China Ma'anshan birth cohort participated in this study. Seven phthalate metabolites were detected in urine samples during pregnancy by solid phase extraction-high-performance liquid chromatography tandem mass spectrometry. Placenta stress and inflammation mRNA expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Early pregnancy may be the critical period when phthalates exposure increases the risk of asthma in infants and young children, and there is a certain gender difference in the risk of asthma in infants and young children. Moreover, through the placenta stress and inflammatory factor associated with infant asthma found anti-inflammatory factor of interleukin-10 (IL-10) mRNA expression will reduce the risk of 36-month-old male infant asthma. The expression of interleukin-4(IL-4) and macrophage (M2) biomarker cluster of differentiation 206(CD206) mRNA reduced the risk of asthma in 18-month-old female infants. Placental stress and inflammatory response were analyzed using mediating effects. Tumor necrosis factor-α (TNFα) showed a complete mediating effect between mono-benzyl phthalate (MBzP) exposure in early pregnancy and asthma in 12-month-old males, and IL-10 also showed a complete mediating effect between mono-n-butyl phthalate (MBP) exposure in early and late pregnancy and asthma in 36-month-old males. In summary, exposure to phthalates during pregnancy may contribute to the development of asthma in infants, which may be associated with placental stress and inflammation.
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Asma , Contaminantes Ambientales , Ácidos Ftálicos , Niño , Humanos , Masculino , Femenino , Embarazo , Lactante , Preescolar , Estudios de Cohortes , Interleucina-10 , Placenta/metabolismo , Ácidos Ftálicos/toxicidad , Asma/inducido químicamente , Asma/epidemiología , Inflamación , ARN Mensajero , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/análisisRESUMEN
Familial renal glucosuria (FRG) is a rare genetic condition featured by isolated glucosuria without hyperglycemia or other kidney diseases. It is caused by pathogenic mutations of the SGLT2 (Sodium-Glucose Cotransporter 2) gene, whose protein product is responsible for reabsorbing the majority of glucose in the early proximal convoluted tubule. Hitherto, quite an array of variants of SGLT2 have been identified in patients of FRG. In this study, we performed whole exome sequencing on three Chinese pediatric patients with FRG and uncovered three compound heterozygous variants of SGLT2: c.1333C > T (p.Q445X) and c.1130-5 C > G; c.1438G > T (p.V480F) and c.346G > A (p.V116M); c.1175C > G (p.S392C) and c.1333C > T (p.Q445X). Among the total of five variants, c.1333C > T (p.Q445X), c.1438G > T (p.V480F) and c.1175C > G (p.S392C) represented novel variants that had not been reported in any genetic databases. All five variants had extremely low allele frequencies and the amino acids loci affected by missense variants were highly conserved in vertebrate species. Bioinformatic tools predicted that all five variants might disrupt the function of SGLT2, which were likely to be causal for FRG in these patients. Our findings expand the variant spectrum of SGLT2 associated with FRG and provide novel insights into mechanism of action of this transporter, which will aid in the development of novel SGLT2 inhibitors for treatment of type 2 diabetes and cardiovascular diseases.
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Background: There is great mental stress due to the coronavirus disease 2019 (COVID-19) pandemic. However, there are no detailed psychological studies of the children with chronic kidney disease (CKD) and their guardians during the COVID-19 pandemic. Objective: This study explores the psychological pressure on children with CKD and their guardians. Methods: An online survey was conducted at 20 of the largest pediatric nephropathy departments in China, including the Rutter Parent Questionnaire, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Overall, 885 children (589 children with CKD associated with 296 children of the control group) completed the survey together with their guardians. Results: There was no statistical difference between CKD children and control children regarding their Rutter behavior scores and abnormal behaviors. Nevertheless, the abnormal behavior of children might aggravate the anxiety and depression of guardians in both CKD and control groups (p < 0.05). We confirmed that the anxiety and depression of guardians in the CKD group were both significantly higher than those in the control group (p < 0.05). The guardians in the CKD group with lower annual income were more likely to experience anxiety (p < 0.05). Furthermore, the guardians whose children were older than 11 years old might be more anxious than those who were 6-11 years old. Besides, the guardians in the CKD group who watched the news for 30-60 min daily were less likely to have depression than those who watched < 10 min (p < 0.05). The subgroup results showed that the gender, the time of watching the news, the annual income of guardians, and children's age might be the most critical factors influencing guardians' psychological burden. Conclusion: The guardians in the CKD group have more severe anxiety and depression during the pandemic. The children's abnormal behavior, adolescents' pressure, low household income, and the panic about the pandemic may be the main reasons for the anxiety and depression of guardians.
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COVID-19 , Insuficiencia Renal Crónica , Niño , Adolescente , Humanos , Pandemias , COVID-19/epidemiología , Ansiedad/epidemiología , Ansiedad/psicología , Estrés Psicológico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Simultaneously engineering a bowl-like and ultrafine nano-size structure offers an attractive route to not only increase the utilization efficiency of noble metals, the specific surface areas and the availability of active sites, but also boost the structural robustness and long-term stability. However, a great challenge remains in terms of the methods of synthesis. Herein, we report a facile one-pot hydrothermal method for the preparation of hollow porous Pt nanobowls (NBs) assembled from ultrafine particles. N,N'-methylenebisacrylamide (MBAA) acts as a structure-directing agent that forms a self-template with Pt ions and drives the nucleation and assembly of Pt metals, resulting in the fabrication of Pt NBs from ultrafine particles. By virtue of their unique structure and morphology, the optimized Pt NBs exhibited enhanced electrocatalytic methanol oxidation reaction (MOR) activity with 3.1-fold greater mass activity and 2.6-fold greater specific activities compared with those of commercial Pt black catalysts, as well as excellent stability and anti-poisoning ability.
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Nanozymes show great promise in bioanalysis and therapeutics, which largely rely on high catalytic efficiency and selectivity. Inspired by the interfacial electronic interaction between noble metals and transition metal carbides, Pt nanozymes are modified with Ti3C2 MXene nanosheets to construct Ti3C2/Pt hybrids with synergistically enhanced catalytic activity. Although Ti3C2 does not have oxidase and peroxidase-like activity, it can greatly selectively enhance the peroxidase-like activity of Pt nanozymes. Near-infrared irradiation can further increase specifically the peroxidase-like activity of Ti3C2/Pt. The optimal peroxidase-like activity of Ti3C2/Pt is 6 times higher than Pt in the dark and 7.9 times higher than Pt under illumination. This catalytic enhancement is attributed to the interplay of the strong interfacial electron effect and unique photothermal effect of Ti3C2. Using the superior peroxidase-like activity of Ti3C2/Pt, dual mechanism colorimetric methods based on cascade reaction and inhibitory effect are developed for specific detection of glucose and glutathione with a limit of detection of 1.0 µM and 0.0089 µM, respectively. Our work provides an effective means to improve the catalytic activity and selectivity of nanozymes by introduction of an ideal supporter, which will be of value for the design of efficient nanozymes.
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Colorimetría , Titanio , Catálisis , Colorimetría/métodos , Glucosa/análisis , PeroxidasasRESUMEN
BACKGROUND: Studies on the impact of Se levels in different pregnancy periods on placental function are limited. AIM: This cohort study sought to investigate the levels of the trace element Se and to assess their effects on placental oxidative stress (OS) and mRNA expression of inflammatory genes during pregnancy. METHODS: The study population consisted of 2519 pregnant women from the Ma'anshan birth cohort. Se levels were measured in the first and second trimesters of pregnancy and in cord blood using inductively coupled plasma-mass spectrometry (ICP-MS). Placental stress and mRNA expression of inflammatory genes were assessed using RT-PCR. RESULTS: A statistically significant negative association was noted between Se levels in the second trimester of pregnancy and mRNA expression of placental HO-1(ß = -0.009, p < .01), HIF1α (ß = -0.005, p = .010), GRP78 (ß = -0.011, p < .001), CRP (ß = -.007, p = .033) and CD68 (ß = -0.006, p = .019). A negative association was noted between Se levels in cord blood and mRNA expression of placental HO-1 (ß = -0.007, p = .004), HIF1α (ß = -0.006, p = .005) and GRP78 (ß = -0.009, p = .004). We found that prenatal Se status was associated with placental stress and mRNA expression of inflammatory genes. CONCLUSION: Se deficiency during pregnancy, especially in the second trimester, leads to the production of OS and an increase in inflammatory mediators, affecting the growth and development of the fetus. Monitoring of pregnant women's nutritional status is necessary to prevent nutritional imbalances and deficiencies in important micronutrients in the fetal.
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Selenio , Femenino , Embarazo , Humanos , Placenta/metabolismo , Estudios de Cohortes , Estudios Prospectivos , Estrés Oxidativo , Inflamación/metabolismo , ARN Mensajero/metabolismoRESUMEN
Purpose: Macrophage polarization contributes to the mechanisms of treating knee osteoarthritis (KOA). In previous studies, fire needling acupuncture has been shown to affect KOA favorably. However, the mechanism of fire needling acupuncture on macrophage polarization is not well-defined. Thus, this study was conducted to determine that fire needling acupuncture exerts a therapeutic role in KOA by modulating macrophage polarization. Methods: Thirty mice were allocated at random into three groups of ten. The groups were labeled as "control", "model", and "fire needling acupuncture". Each group consisted of ten mice. From the second day of intra-articular injection MIA, the right "xiyan" (EX-LE5), "dubi" (ST35), "liangqiu" (ST34), and "xuehai" (SP10) acupoints were manipulated once every other day for two weeks in the fire needling acupuncture group. Mechanical withdrawal threshold and weight distribution were evaluated for behavioral testing in each group. The synovial morphology was monitored by HE staining. Pathological morphology was observed by HE staining, Saf-O staining, and toluidine blue staining. The polarization of macrophages in synovial tissue was detected using immunofluorescence (F4/80, CD86, and CD206). Results: Fire needling acupuncture increased the percentage weight-bearing difference and the mechanical withdrawal threshold, and improved synovial inflammation and cartilage damage in MIA-induced KOA mice. F4/80 and CD86 expression were downregulated by fire needling acupuncture, but CD206 was increased. Conclusion: Fire needling acupuncture decreases pain behaviors in KOA mice and improves synovial membrane injury and pathological cartilage damage. The macrophage polarization is involved in the mechanism of fire needling acupuncture's amelioration of articular cartilage damage.
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Background: X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 and is characterized by progressive kidney disease, hearing loss, and ocular abnormalities.The aim of this study was to identify gene mutations in a Chinese family with XLAS, confirm a diagnosis, and provide an accurate genetic counseling. Methods: The proband was a 5-year-old male with microscopic hematuria and a family history of renal disease in 5 relatives.His relatives had microhematuria with or without proteinuria. His maternal uncle developed renal failure at the age of 35 years. He was evaluated by renal biopsy,whole-exome sequencing (WES) and whole-genome sequencing (WGS) for Alport syndrome. RT-PCR and cDNA Sanger sequencing were performed on RNA extracted from the skin of the proband. Then, a splicing reporter minigene assay was used to examine the effect of the variation on the splicing of the primary transcript in transfected cells. Results: Pathological examination of the kidney of the proband revealed diffuse thinning of the glomerular basement membrane, and immunofluorescence analysis indicated normal expression of the α5 chain in the basement membrane. No phenotype-associated candidate variant was detected in the proband via WES. A novel deep intronic COL4A5 variant (c.385-716G > A), which is segregated with disease in this family, was identified using WGS. In-vitro minigene assay and in-vivo RT-PCR analysis demonstrated that the variant could produce both normal and abnormal transcripts. The abnormal transcripts showed that the variant activated a cryptic splice site, introducing a 147â bp pseudoexon into the mRNA sequence and consequently generating a premature termination codon (p.G129Afs*38) and leading to frameshifting and truncation of the α5 (collagen IV) protein. Conclusion: This is the first report of the novel c.385-716G > A splicing mutation in the COL4A5 gene, which illustrates the importance of performing WGS to find additional mutations in WES-negative patients with highly suspected forms of genetic diseases. The same results obtained from the in-vitro and in-vivo splicing experiments confirm the consistency between the minigene assay and RT-PCR analysis. In addition, this study highlights the importance of functional analysis in diagnosis and genetic counseling in AS.
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Thallium, a highly toxic heavy metal and priority pollutant, has been widely reported to cause neurodevelopmental toxicity in animals. However, accessible epidemiological studies concerning the neurodevelopmental toxicity of early-life thallium exposure in humans are limited. In a prospective birth cohort including 2164 mother-child pairs, we explored the effect of prenatal serum thallium exposure on cognitive development among preschool-aged children born in Ma'anshan, Anhui, China. Serum thallium concentrations were measured in the first trimester, second trimester, third trimester, and cord blood by inductively coupled plasma mass spectrometry (ICP-MS). Child cognitive development was appraised by the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) at 4.5 years old. Multiple informants generalized estimating equations (GEEs) were fit to jointly estimate the association between the four repeated measurements of thallium concentrations and the preschool-aged children's cognitive test scores. After adjusting for potential confounders, the visual spatial index (VSI) was 1.45 points lower in the highest tertile of serum thallium during the first trimester than in the lowest tertile (p for trend = 0.04). Moreover, children in the highest tertile of serum thallium during the third trimester had a significantly lower full-scale intelligence quotient (FSIQ) (ß = -1.51, 95% CI: -2.68, -0.35), VSI (ß = -1.79, 95% CI: -3.16, -0.42), fluid reasoning index (FRI) (ß = -1.41, 95% CI: -2.73, -0.10), and processing speed index (PSI) (ß = -1.47, 95% CI: -2.71, -0.24) scores than the children in the lowest tertile. When performing stratified analysis by child sex, the associations of first- and third-trimester thallium concentrations with cognitive test scores were more prominent in boys than in girls. Our findings revealed that maternal serum thallium exposure during the first and third trimesters, but not other periods, had detrimental effects on preschoolers' cognitive development, and these effects showed sex differences.