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A digital workflow that can adjust the disc-condyle relationship rapidly and precisely is described. Cone beam computed tomography (CBCT), magnetic resonance imaging (MRI), and an intraoral scan at maximal intercuspal position are superimposed depending on the anatomic structure, and the disc-condyle relationship is adjusted on the fused display of the articular disc and condyle in the CBCT-MRI 3-dimensional spatial environment. An occlusal device is then directly designed and fabricated on the achieved maxillomandibular position, and the occlusal device is finely adjusted intraorally to improve function as needed. This technique can also be seamlessly integrated into the virtual environment to allow clinicians and dental laboratory technicians to design prostheses or treatment planning devices in a fully digital workflow.
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Background: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis. Case Presentation: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life. Conclusion: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients.
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Substituting mineral fertilizer with manure or a combination of organic amendments plus beneficial soil microorganisms (bio-manure) in agriculture is a standard practice to mitigate N2O and NO emissions while enhancing crop performance and nitrogen use efficiency (NUE). Here, we conducted a greenhouse trial for three consecutive vegetable growth seasons for Spinach, Coriander herb, and Baby bok choy to reveal the response of N2O and NO emissions, NUE, and vegetable quality index (VQI) to fertilization strategies. Strategies included solely chemical nitrogen fertilizer (CN), 20 (M1N4) and 50% (M1N1) substitution with manure, 20 (BM1N4) and 50% (BM1N1) substitution with bio-manure, and no fertilization as a control and were organized in a completely randomized design (n = 3). Manure decreased N2O emissions by 24-45% and bio-manure by 44-53% compared to CN. Manure reduced NO emissions by 28-41% and bio-manure by 55-63%. Bio-manure increased NUE by 0.04-31% and yields by 0.05-61% while improving VQI, attributed to yield growth and reduced vegetable NO3- contents. Improvement of root growth was the main factor that explained the rise of NUE; NUE declined with the increase of N2O emissions, showing the loss of vegetable performance under conditions when denitrification processes prevailed. Under the BM1N1, the highest VQI and the lowest yield-scaled N-oxide emissions were observed, suggesting that substitution with bio-manure can improve vegetable quality and mitigate N-oxide emissions. These findings indicate that substituting 50% of mineral fertilizer with bio-manure can effectively improve NUE and VQI and mitigate N-oxides in intensive vegetable production.
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Fertilizantes , Esterco , Nitrogênio , Solo , Verduras , Verduras/crescimento & desenvolvimento , Nitrogênio/metabolismo , Fertilizantes/análise , Solo/química , Agricultura/métodos , Óxido Nitroso/análise , Óxido Nitroso/metabolismoRESUMO
Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo. Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth. Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment. Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.
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Titânio , Terapia por Ultrassom , Titânio/química , Titânio/farmacologia , Animais , Camundongos , Humanos , Terapia por Ultrassom/métodos , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Fototerapia/métodos , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Induction of resistin-like molecule ß (Relm-ß) and mitofusin 2 (MFN2) mediated aberrant mitochondrial fission have been found to be involved in the pathogenesis of pulmonary arterial hypertension (PAH). However, the molecular mechanisms underlying Relm-ß regulation of MFN2 therefore mitochondrial fission remain unclear. This study aims to address these issues. Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. The results showed that Relm-ß promoted cells proliferation in PASMCs, this was accompanied with the upregulation of USP18, Twist1 and miR-214, and downregulation of MFN2. We found that Relm-ß increased USP18 expression which in turn raised Twist1 by suppressing its proteasome degradation. Elevation of Twist1 increased miR-214 expression and then reduced MFN2 expression and mitochondrial fragmentation leading to PASMCs proliferation. In vivo study, we confirmed that Relm-ß was elevated in MCT-induced PAH rat model, and USP18/Twist1/miR-214/MFN2 axis was altered similar as in vitro. Targeting this cascade by Relm-ß receptor inhibitor Calhex231, proteasome inhibitor MG-132, Twist1 inhibitor Harmine or miR-214 antagomiR prevented the development of pulmonary vascular remodeling and therefore PAH in MCT-treated rats. In conclusion, we demonstrate that Relm-ß promotes PASMCs proliferation and vascular remodeling by activating USP18/Twist1/miR-214 dependent MFN2 reduction and mitochondrial fission, suggesting that this signaling pathway might be a promising target for management of PAH.
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Proliferação de Células , GTP Fosfo-Hidrolases , MicroRNAs , Mitocôndrias , Ratos Sprague-Dawley , Transdução de Sinais , Proteína 1 Relacionada a Twist , Ubiquitina Tiolesterase , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , Ratos , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Proteína 1 Relacionada a Twist/metabolismo , Proteína 1 Relacionada a Twist/genética , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/patologia , Hipertensão Arterial Pulmonar/fisiopatologia , Monocrotalina/toxicidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/metabolismo , Proteínas MitocondriaisRESUMO
OBJECTIVES: To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. MATERIALS AND METHODS: Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. RESULTS: Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. CONCLUSION: For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.
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Estesioneuroblastoma Olfatório , Neoplasias Nasais , Humanos , Masculino , Feminino , Estesioneuroblastoma Olfatório/cirurgia , Estesioneuroblastoma Olfatório/mortalidade , Estesioneuroblastoma Olfatório/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Nasais/cirurgia , Neoplasias Nasais/mortalidade , Neoplasias Nasais/patologia , Adulto , Prognóstico , Idoso , Estadiamento de Neoplasias , Adulto Jovem , Taxa de Sobrevida , Endoscopia , Análise de Sobrevida , Adolescente , Cavidade Nasal/cirurgiaRESUMO
BACKGROUND: As of September 2023, more than 1,000 cases of monkeypox (mpox) have been reported in China. Based on the available evidence, men who have sex with men (MSM) are at high risk for mpox infection. This study aimed to analyses the self-reported infection status, knowledge, attitude and influencing factors of monkeypox among MSM in Jiaxing City, China. METHODS: A web-based cross-sectional survey was conducted in September 2023 to gather data on participants' socio-demographic profiles, mpox-related knowledge, sexual behavior characteristics, and other potentially related information to mpox knowledge. Multivariate regression modeling was employed to analyze the factors influencing the level of mpox-related knowledge. RESULTS: A total of 562 MSM were recruited; 4.3% self-reported being HIV-positive, 83.3% of respondents had heard of mpox, and 2.3% of them reported having suspected symptoms. 89.7% of respondents were willing to be vaccinated against mpox, but only 24.8% had a high level of knowledge about mpox. The main factors influencing knowledge of mpox were education level, household registration, homosexual anal intercourse in the past 6 months, and taking the HIV pre-exposure prophylaxis (PrEP). CONCLUSIONS: Knowledge of mpox among MSM living in the Jiaxing area needs to be enhanced, but willingness to get vaccinated is high. Educational level, household location, sexual behavior and PrEP use have important effects on knowledge of mpox. Individuals exhibiting symptoms indicative of suspected mpox had a diminutive consultation frequency, and it is imperative to augment screening efforts for mpox symptoms within specific demographic groups to prevent the underreporting of mpox cases.
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Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Mpox , Autorrelato , Humanos , Masculino , China/epidemiologia , Adulto , Homossexualidade Masculina/estatística & dados numéricos , Homossexualidade Masculina/psicologia , Estudos Transversais , Adulto Jovem , Pessoa de Meia-Idade , Mpox/epidemiologia , Adolescente , Fatores de RiscoRESUMO
The release of rubber-derived chemicals (RDCs) in road surface runoff has received significant attention. Urban surface runoff is often the confluence of stormwater runoff from specific areas. However, the impact of precipitation on RDCs contamination in confluent stormwater runoff and receiving watersheds remains poorly understood. Herein, we investigated the profiles of RDCs and their transformation products in confluent stormwater runoff and receiving rivers affected by precipitation events. The results showed that 34 RDCs are ubiquitously present in confluent stormwater runoff and surface water, with mean concentrations of 1.03-2749 and 0.28-436 ng/L, respectively. The most dominant target compounds in each category were N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, 2-benzothiazolol, and 1,3-diphenylguanidine. Total RDCs concentrations in confluent stormwater runoff decreased spatially from industrial areas to business districts to college towns. A significant decrease in RDCs levels in surface water after rainfall was observed (P < 0.01), indicating that precipitation contributes to alleviating RDCs pollution in receiving watersheds. To our knowledge, this is the first report of N,N'-ditolyl-p-phenylenediamine quinone (DTPD-Q) levels in surface waters in China. The annual mass load of ∑RDCs reached 72,818 kg/y in confluent stormwater runoff, while 38,799 kg/y in surface water. The monitoring of confluent stormwater runoff is an efficient measure for predicting contamination loads from RDCs in rivers. Risk assessment suggested that most RDCs posed at least medium risks to aquatic organisms, especially 6PPD-quinone. The findings help to understand the environmental fate and risks of RDCs in the confluent stormwater runoff and receiving environments after precipitation events.
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Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.
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Alelos , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Oryza , Locos de Características Quantitativas , Sequências de Repetição em Tandem , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Sequências de Repetição em Tandem/genética , Mapeamento Cromossômico , Polimorfismo de Nucleotídeo Único , Fenótipo , Variação GenéticaRESUMO
Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.
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Background/purpose: Oral lichen planus (OLP) is a chronic inflammatory disease with unknown mechanisms of pathogenesis. Keratin 17 (KRT17) is a protein that regulates numerous cellular processes. This study aimed to explore the expression of KRT17 in OLP and its correlation with the severity of OLP. Materials and methods: RNA sequencing using epithelium from 5 OLP patients and 5 health control (HC) was performed, followed by functional analysis. The validation cohort of 20 OLP and 20 HC tissues were used to investigate positive area value of KRT17 by immunohistochemical analysis. Reticular, erosive and ulcerative (REU) scores were used for measuring the severity of OLP. Results: A total of 15493 genes were detected, of which 1492 genes were significantly up-regulated in OLP and 622 were down-regulated. The mRNA expression of KRT17 was elevated by 13.09-fold in OLP compared to that in HC. Pathway analysis demonstrated high KRT17 expression was associated with multiple biological processes. The median of percentage of KRT17 positive area value was 19.30 % in OLP and 0.01 % in HC (P < 0.001). Percentage of KRT17 positive area value was higher in erosive OLP patients (27.25 %) compared to that in non-erosive patients (15.02 %, P = 0.006). REU scores were positively correlated with percentage of KRT17 positive area value (r = 0.628, P = 0.003). Conclusion: The mRNA expression of KRT17 was elevated in OLP tissues compared to that in HC. KRT17 was positively correlated with the severity of OLP, indicating KRT17 might play a vital role in the pathogenesis of OLP.
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BACKGROUND: Third molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PURPOSE: The study purpose was to measure and compare differences in pain, swelling, trismus, wound healing, and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. STUDY DESIGN, SETTING, SAMPLE: This study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. PREDICTOR VARIABLE: The predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiological saline) side. MAIN OUTCOME VARIABLE: The primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening, were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. COVARIATES: The covariates included age, sex, and operation time. ANALYSES: The ShapiroâWilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P < .05. RESULTS: The study included 60 patients (mean age: 25.81 ± 4.91; 23 (38%) males, 37 (62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < .001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < .001), maximal incisional opening (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P < .001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P < .001), and swelling (6.86 ± 0.70 mm, 7.15 ± 0.80 mm, day 3, P = .006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ± 2.14, day 3, P < .001). CONCLUSION AND RELEVANCE: The application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative QOL.
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Road transportation is an important contributor to carbon emissions. China's car ownership is rapidly increasing, ranking first worldwide; however, there are limited data about carbon emission inventories. This study assesses carbon emissions from road transportation from the past to the future across China, using market survey, COPERT (Computer Programme to Calculate Emissions from Road Transport) model, and a combination method of principal component analysis and backpropagation neural network. From 2000 to 2020, the national carbon emissions from road transportation grew from 11.9 to 33.8 Mt CO2e, accounting for 0.47% of national total emissions by then. Trucks generally emit a higher proportion (77.3%) of total emissions than passenger cars (18.9%); however, the emission proportion of passenger cars (18.9-31.0%) has increased yearly. The carbon emissions at the prefecture level show an urban agglomeration trend, decreasing from the eastern coastal areas to central China. Future car ownership is expected to grow rapidly at 3.1% during 2021-2049, but only half of that growth rate during 2051-2060. Those vehicles are expected to contribute carbon emissions of 27.2-39.1 Mt CO2e under different scenarios in 2060. Scientifically reducing emissions and innovatively reducing the carbon emission coefficient, combined with a reasonable new energy vehicle growth scenario, are efficient methods for reducing national carbon levels. This study demonstrates that the uncertainty is within an acceptable range. This work details the carbon emission inventories associated with road transportation in China and provides basic data for developing a better carbon reduction policy for China's car industry.
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Carbono , Meios de Transporte , Emissões de Veículos , China , Emissões de Veículos/análise , Carbono/análise , Poluentes Atmosféricos/análise , Monitoramento AmbientalRESUMO
Species categorical authentication of accelerants has traditionally relied on fire debris analysis. To explore a novel method for identifying the accelerants species, four commonly used accelerants for arson were loaded onto different substrates and ignited at different locations. The entire combustion process was recorded and flame characteristics were analyzed. The results showed that the probability density function (PDF) of flame apex angle counts within a certain period after ignition can be used to distinguish accelerant species, and this method is not affected by accelerant loading amount, ignition location, and substrate, demonstrating strong stability and universality, while the temporal variation of flame area and the value obtained by dividing half of the flame width by the flame height (tangent of flame cone angle) can effectively differentiate gasoline and diesel. The utilization of flame characteristics for identifying accelerants species holds significant implications for arson investigation.
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OBJECTIVE: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association. METHODS: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman-infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD. RESULTS: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41-2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67-1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37-0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns. CONCLUSIONS: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring.
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Dermatite Atópica , Suplementos Nutricionais , Primeiro Trimestre da Gravidez , Deficiência de Vitamina D , Vitamina D , Humanos , Feminino , Dermatite Atópica/epidemiologia , Dermatite Atópica/sangue , Gravidez , Vitamina D/análogos & derivados , Vitamina D/sangue , Estudos Prospectivos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Adulto , Lactente , Primeiro Trimestre da Gravidez/sangue , China/epidemiologia , Recém-Nascido , Coorte de Nascimento , Fenômenos Fisiológicos da Nutrição Materna , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Fatores de Risco , Masculino , IncidênciaRESUMO
Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention.
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Administração Intranasal , Transtorno do Espectro Autista , Ocitocina , Humanos , Ocitocina/administração & dosagem , Ocitocina/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Masculino , Feminino , Criança , Análise por Conglomerados , Resultado do Tratamento , Estudos Cross-Over , Pré-EscolarRESUMO
Acidic bacterial biofilms-associated enamel white spot lesions (WSLs) are one of the hallmarks of early caries, causing demineralization and decomposition of dental hard tissues. Therefore, to effectively prevent and treat WSLs, it is important to inhibit the activity of cariogenic bacteria while promoting the remineralization of demineralized enamel. Amorphous calcium phosphate (ACP) favors hard tissue remineralization due to its biological activity and ability to release large amounts of Ca2+ and PO4 3-. However, ACP-based biomineralization technology is not effective due to its lack of antimicrobial properties. Here, carboxymethyl chitosan (CMCS) was employed as a reducing agent and stabilizer, and dual-functional nanohybrids CMCS/AuNPs/ACP with biofilm resistance and mineralization properties were successfully synthesized. The addition of AuNPs enhances the antimicrobial activity and participates in regulating the formation of hydroxyapatite (HAp). The nanohybrids exhibited significant destructive effects against cariogenic bacteria and their biofilms and showed bactericidal activity under bacteria-induced acidic conditions. More importantly, this nanohybrids showed superior results in promoting the remineralization of demineralized enamel, compared to fluoride and CMCS/ACP in vitro. The CMCS/AuNPs/ACP nanohybrids not only reverse the cariogenic microenvironment at the microbial level, but also promote self-repairing of enamel WSLs regarding the microstructure. The present work offers a theoretical and experimental basis for using the CMCS/AuNPs/ACP nanohybrids as a potential dual-functional agent for the clinical treatment of enamel WSLs.
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The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.
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Quitosana , Portadores de Fármacos , Liberação Controlada de Fármacos , Fluoruracila , Microesferas , Dióxido de Silício , Fluoruracila/química , Quitosana/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Porosidade , Tamanho da Partícula , Preparações de Ação Retardada/química , Sistemas de Liberação de MedicamentosRESUMO
Heavy metal Cu2+ emitted in industry and residues of glyphosate pesticides are pervasive in ecosystems, accumulated in water bodies and organisms' overtime, constituting hazard to human and ecological balance. The development of rapid, highly selective, reversibility and sensitive biosensor in vivo detection for Cu2+ and glyphosate was imminent. A novel dual-recognition fluorescence biosensor MPH was successfully synthesized based on triphenylamine, which demonstrated remarkable ratiometric fluorescence quenching toward Cu2+, while MPH-Cu2+ (1:1) ensemble exhibited ratiometric fluorescence restoration for glyphosate, both with observable color changes in daylight and UV lamp. The biosensor exhibited rapid, outstanding selectivity, anti-interference, and multiple cycles reversibility through "turn-off-on" fluorescence towards Cu2+ and glyphosate, respectively. Surprisingly, the clearly binding mechanisms of MPH to Cu2+ and MPH-Cu2+ ensemble to glyphosate were determined, respectively, based on the Job's plot, FT-IR, ESI-HRMS, 1H NMR titration and theoretical calculations of dynamics and thermodynamics. In addition, biosensor MPH demonstrated successful detection of Cu2+ and glyphosate across diverse environmental samples including tap water, extraction solutions of traditional Chinese medicine honeysuckle and soil samples. In the meantime, fluorescence imaging of Cu2+ and glyphosate at both micro and macro scales in various living organisms, such as rice roots, MCF-7 cells, zebrafish, and mice, were successfully achieved. Overall, this work was expected to become a promising and versatile fluorescence biosensor for rapid and reversible detection of Cu2+ and glyphosate both in vitro and vivo.