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Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC). Therefore, the development of innovative nanomedicines that can effectively disrupt the redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an oxidative stress amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme and a CaP mineralized layer, loaded with GSH inhibitor L-buthionine sulfoximine (BSO), and further surface-modified with hyaluronic acid that can target CD44, is introduced. In the acidic tumor microenvironment, Ca2+ is initially released, thereby leading to mitochondrial dysfunction and eventually triggering apoptosis. Additionally, BSO suppresses the synthesis of intracellular reduced GSH and further amplifies the level of oxidative stress in cancer cells. Furthermore, PdAg nanozyme can be activated by near-infrared light to induce photothermal and photodynamic effects, causing a burst of ROS and simultaneously promoting cell apoptosis via provoking immunogenic cell death. The high-performance therapeutic effects of PBCH, based on the synergistic effect of aforementioned multiple oxidative damage and photothermal ablation, are validated in TNBC cells and animal models, declaring its potential as a safe and effective anti-tumor agent. The proposed approach offers new perspectives for precise and efficient treatment of TNBC.
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Global warming and environmental pollutants both pose a threat to the behavior and physiology of animals, but research on the combined effects of the two is limited. Atrazine, a widely used herbicide, has toxic effects on organisms. In this study, the effects of environmental concentrations of atrazine exposure (100 µg/L) for seven days on the movement, metabolism and gene expression related to motility of Pelophylax nigromaculatus larvae (GS8) were investigated under global warming. The results showed that compared to the optimal growth temperature (18 °C), atrazine treatment under global warming (21 °C) significantly increased the average speed (about 11.2 times) and maximum acceleration (about 1.98 times) of P. nigromaculatus larvae, altered the relative abundance of 539 metabolites, including Formyl-5-hydroxykynurenamine, 2,4-Dihydroxybenzophenone, and FAPy-adenine, and changed the nucleotide metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and purine metabolism, as well as increased the gene expression of SPLA2 (about 6.46 times) and CHK (about 3.25 times). In summary, atrazine treatment under global warming caused metabolic disorders in amphibian larvae and increased the expression of some movement-related genes in the brain, resulting in abnormally active.
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Atrazina , Calentamiento Global , Herbicidas , Larva , Atrazina/toxicidad , Animales , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Larva/genética , Herbicidas/toxicidad , Ranidae/genética , Ranidae/metabolismo , Expresión Génica/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Movimiento/efectos de los fármacosRESUMEN
PURPOSE: To report the anatomic outcomes and retinal structure changes from lens-sparing vitrectomy (LSV) for eyes with Stage 3 or 4 familial exudative vitreoretinopathy (FEVR). METHODS: Overall, 133 consecutive eyes of 119 patients with Stage 3 (51 eyes) or 4 (82 eyes) FEVR who underwent LSV between January 2012 and May 2023 were retrospectively reviewed. RESULTS: One hundred twenty-nine eyes (97.0%) achieved traction relief through one LSV operation. The extent of retinal detachment improved in 98 eyes (73.7%), remained stable in 32 eyes (24.1%), and progressed in three eyes (2.3%). At long-term follow-up, 39 (29.3%) and 60 (45.1%) eyes had completely or partially reattached retina, respectively. The median change of venular angle was 3.6° (95% CI, 3.5-10.5; P < 0.001) and -9.9° (95% CI, -15.8 to -4.6; P < 0.001) for temporal and nasal vessels, respectively. The mean disk-fovea distance was 0.3 papillary diameter shorter (95% CI, -0.4 to -0.2; P < 0.001), and the mean temporal venular arcade distance was 0.02 papillary diameter larger (95% CI, -0.16 to 0.21; P = 0.361). CONCLUSION: These results suggest that LSV can relieve vitreoretinal traction and reattach the retina in late-stage FEVR eyes. Improvements in temporal and nasal venular angle and disk-fovea distance reflect positive retinal structure changes for patients.
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Vitreorretinopatías Exudativas Familiares , Agudeza Visual , Vitrectomía , Humanos , Vitrectomía/métodos , Masculino , Vitreorretinopatías Exudativas Familiares/diagnóstico , Vitreorretinopatías Exudativas Familiares/cirugía , Estudios Retrospectivos , Femenino , Niño , Estudios de Seguimiento , Preescolar , Adolescente , Resultado del Tratamiento , Tomografía de Coherencia Óptica/métodos , Cristalino/cirugía , Retina/patología , Retina/diagnóstico por imagen , Retina/cirugía , Adulto , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/diagnóstico , Lactante , Adulto JovenRESUMEN
B-cell lymphoma/leukemia 11A (BCL11A) is highly expressed in B-cell non-Hodgkin lymphoma (B-NHL), blocks cell differentiation, and inhibits cell apoptosis. However, little is known about BCL11A in the proliferation, invasion, and migration of B-NHL cells. Here, we found increased expression of BCL11A in B-NHL patients and cell lines. Knockdown of BCL11A suppressed the proliferation, invasion, and migration of B-NHL cells in vitro and reduced tumor growth in vivo. RNA sequencing (RNA-seq) and KEGG pathway analysis demonstrated that BCL11A-targeted genes were significantly enriched in the PI3K/AKT signaling pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction (including COL4A1, COL4A2, FN1, SPP1), and SPP1 was the most significantly downregulated gene. qRTâPCR, western blotting, and immunohistochemistry revealed that silencing BCL11A reduced the expression level of SPP1 in Raji cells. Our study suggested that high level of BCL11A may promote B-NHL proliferation, invasion, and migration, and the BCL11A-SPP1 regulatory axis may play an important role in Burkitt's lymphoma.
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Linfoma de Células B , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Apoptosis , Proliferación Celular , Análisis de Secuencia de ARN , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Proteínas Represoras/metabolismoRESUMEN
PURPOSE: Whole-grain intake assessed through self-reported methods has been suggested to be inversely associated with the metabolic syndrome (MetS) risk in epidemiological studies. However, few studies have evaluated the association between whole-grain intake and MetS risk using objective biomarkers of whole-grain intake. The aim of this study was to examine the association between plasma 3-(3,5-Dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, and MetS risk in a Chinese population. METHODS: A case-control study of 667 MetS cases and 667 matched controls was conducted based on baseline data of the Tongji-Ezhou Cohort study. Plasma DHPPA concentrations were assessed by high-performance liquid chromatography-tandem mass spectrometry. The MetS was defined based on criteria set by the Joint Interim Statement. RESULTS: Plasma DHPPA was inversely associated with MetS risk. After adjustment for age, sex, body mass index, smoking status, alcohol drinking status, physical activity and education level, the odds ratios (ORs) for MetS across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.86 (0.58-1.26), 0.77 (0.52-1.15), and 0.59 (0.39-0.89), respectively. In addition, the cubic spline analysis revealed a potential nonlinear association between plasma DHPPA and MetS, with a steep reduction in the risk at the lower range of plasma DHPPA concentration. CONCLUSION: Our study revealed that individuals with higher DHPPA concentrations in plasma had lower odds of MetS compared to those with lower DHPPA concentrations in plasma. Our findings provided further evidence to support health benefits of whole grain consumption.
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Síndrome Metabólico , Granos Enteros , Biomarcadores , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Síndrome Metabólico/epidemiología , Ácidos Fenilpirúvicos , Resorcinoles , Secale/química , Triticum/químicaRESUMEN
OBJECTIVE: To assess the bi-directional associations of epilepsy with dementia and Alzheimer's disease (AD). METHODS: We searched PubMed, Embase and the Cochrane Library for longitudinal studies assessing the associations of epilepsy with dementia and AD up to 4 August 2021. Two authors independently extracted study characteristics, exposures, outcomes and covariates. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random effects model. RESULTS: From 8,545 articles identified in the initial research, 27 publications describing 20 longitudinal studies were included in the final analyses. There were 10 studies on epilepsy predicting risk of dementia, 5 studies on epilepsy predicting risk of AD, 11 studies on dementia predicting risk of epilepsy, and 6 studies on AD predicting risk of epilepsy. Baseline epilepsy was associated with higher risk of dementia (pooled HR 2.00; 95% CI 1.73-2.33) and AD (pooled HR 1.81; 95% CI 1.19-2.75). The pooled HRs for epilepsy associated with baseline dementia and AD were 2.91 (95% CI) 2.11-4.01) and 3.11 (95% CI 2.47-3.90), respectively. These positive associations persisted in sensitivity and subgroup analyses. CONCLUSIONS: Our findings suggested positive and bi-directional associations of epilepsy with dementia and AD. However, these associations should be carefully interpreted due to the presence of substantial heterogeneity, and they need to be verified in additional high-quality studies.
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Enfermedad de Alzheimer , Demencia , Epilepsia , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Demencia/diagnóstico , Demencia/epidemiología , Demencia/etiología , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/epidemiología , Humanos , Estudios LongitudinalesRESUMEN
AIMS/HYPOTHESIS: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma ß-amyloid (Aß) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aß40 and Aß42 with risk of type 2 diabetes. METHODS: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aß40 and Aß42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aß40 and Aß42 concentrations with the likelihood of type 2 diabetes. RESULTS: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aß concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aß40 and 2.01 (95% CI 1.50, 2.69) for plasma Aß42. Each 30 ng/l increment of plasma Aß40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aß42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aß40 and Aß42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aß40 and Aß42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aß40 and 2.88 (95% CI 1.44, 5.75) for plasma Aß42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aß40 and each 5 ng/l increment in plasma Aß42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively. CONCLUSIONS/INTERPRETATION: Our findings suggest positive associations of plasma Aß40 and Aß42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aß in linking type 2 diabetes and Alzheimer's disease.
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Péptidos beta-Amiloides/sangre , Diabetes Mellitus Tipo 2/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUD: Chromium has been suggested playing a role in alleviating diabetes, insulin resistance and lipid anomalies, but the effect on metabolic syndrome (MetS) in humans remains controversial. METHODS: We conducted a matched case-control study in a Chinese population, involving 2141 MetS cases and 2141 healthy controls, which were 1:1 matched by age (±2 years) and sex. Plasma chromium was measured by inductively coupled plasma mass spectrometry. RESULTS: Plasma chromium levels were lower in MetS group than in control group (mean: 4.36 µg/L and 4.66 µg/L, respectively, P < 0.001), and progressively decreased with the number of MetS components (P for trend < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence intervals) for MetS across increasing quartiles of plasma chromium levels were 1 (reference), 0.84 (0.67-1.05), 0.76 (0.61-0.95), and 0.62 (0.49-0.78), respectively (P for trend < 0.001). For the components of MetS (high waist circumference, high triglycerides and high blood glucose), the odds ratios (95% confidence intervals) of the highest quartiles were 0.77 (0.61-0.95), 0.67 (0.55-0.80), and 0.53 (0.44-0.64), respectively (P for trend < 0.05). CONCLUSIONS: Our results indicated that plasma chromium levels were inversely associated with MetS in Chinese adults. The association may be explained by the relations between plasma chromium levels and high waist circumference, and the triglycerides and blood glucose levels.
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Síndrome Metabólico , Adulto , Glucemia , Índice de Masa Corporal , Estudios de Casos y Controles , China/epidemiología , Cromo , Estudios Transversales , Humanos , Síndrome Metabólico/epidemiología , Factores de Riesgo , Triglicéridos , Circunferencia de la CinturaRESUMEN
ABSTRACT: Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.
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Antígeno B7-H1 , Neoplasias Óseas , Condrosarcoma , Inhibidores de Puntos de Control Inmunológico , Receptor de Muerte Celular Programada 1 , Humanos , Condrosarcoma/terapia , Condrosarcoma/patología , Condrosarcoma/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Neoplasias Óseas/metabolismo , Neoplasias Óseas/inmunología , Neoplasias Óseas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodosRESUMEN
Ultrasonic nondestructive testing (NDT) usually utilizes conventional bulk piezoelectric transducers as transceivers. However, the complicated preparation and assembly process of bulk piezoelectric ceramics limits the development of NDT probes toward miniaturization and high frequency. In this paper, a 4.4 mm × 4.4 mm aluminum nitride (AlN) piezoelectric micromachined ultrasonic transducer (PMUT) array is designed, fabricated, characterized, and packaged for ultrasonic pulse-echo NDT of solids for the first time. The PMUT array is prepared based on the cavity silicon-on-insulator (CSOI) process and packaged using polyurethane (PU) material with acoustic properties similar to water. The fabricated PMUT array resonates at 2.183 MHz in air and at around 1.25 MHz after PU encapsulation. The bandwidth of the packaged PMUT receiver (244 kHz) is wider than that of a bulk piezoelectric transducer (179 kHz), which is good for axis resolution improvement. In this work, a hybrid ultrasonic NDT probe is designed using two packaged PMUT receivers and one 1.25 MHz bulk transmitter. The bulk transmitter radiates an ultrasonic wave into the sample, and the defect echo is received by two PMUT receivers. The 2D position of the defect could be figured out by time-of-flight (TOF) difference, and a 30 mm × 65 mm detection area is acquired. This work demonstrates the feasibility of applying AlN PMUTs to ultrasonic NDT of solids and paves the way toward a miniaturized NDT probe using AlN PMUT technology.
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Lead (Pb) is present in aquatic environments with a continuous or pulse form due to the regular or irregular discharge of wastewater. These two modes of exposure result in different toxicological effects on aquatic animals. To compare the effects of Pb exposure mode on the swimming behavior of amphibian larvae, this study proposed a combination method to examine the brain-gut axis (gut bacteria, histopathology, metabolomics, and ethology) in order to evaluate the ecotoxic differences in Pelophylax nigromaculatus tadpoles (Gs 21-28) when exposed to continuous (CE100) versus pulse exposure (PE100) of environmental concentrations of Pb (100 µg/L). The results showed that: 1) CE100 significantly decreased the movement distance and swimming activity of the tadpoles compared to PE100 and the control, while there were no significant differences between the control group and PE100. 2) At the phyla level, compared to PE100, CE100 treatment significantly decreased the abundance of Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes and increased the abundance of Fusobacteria in the gut. At the genus level, compared to PE100, CE100 significantly increased the abundance of U114 and decreased the abundance of Anaerorhabdus, Exiguobacterium and Microbacterium. 3) Compared to PE100, CE100 changed the metabolites of the brain-gut axis pathway, such as quinolinic acid, L-valine, L-dopa, L-histidine, urocanic acid, L-threonine, γ-aminobutyric acid (GABA), L-glutamate (Glu), acetylcholine (Ach), L-tyrosine (Tyr), L-tryptophan (Trp), and levodopa (DOPA). 4) CE100 and PE100 played a repressive role in the histidine metabolism and tyrosine metabolism pathways and played a promoting role in the purine metabolism and pyrimidine metabolism pathways. This study provides a method for evaluating the toxic effects of heavy metal exposure via two different exposure modes (pulse versus continuous) which tadpoles may encounter in the natural environment from a combined study examining the brain-gut axis.
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Eje Cerebro-Intestino , Microbioma Gastrointestinal , Animales , Larva , Plomo , Natación , Bacterias , FirmicutesRESUMEN
Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.
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Neoplasias de la Mama , Oro , Hipertermia Inducida , Receptor ErbB-2 , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Humanos , Ratones , Animales , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Hipertermia Inducida/métodos , Oro/química , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Plata/química , Línea Celular Tumoral , Modelos Animales de Enfermedad , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Combinada/métodos , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND: The prevalence of muscle atrophy in patients suffering from chronic kidney disease (CKD) presents a significant challenge to healthcare providers, necessitating innovative approaches to management and care. Against this backdrop, this study embarks on a comprehensive review of literature concerning the application of exercise interventions in the nursing care of these patients. Such interventions are critical in addressing the debilitating effects of the condition, which include progressive loss of muscle mass and strength, adversely affecting patient mobility, quality of life, and overall survival. This review aims to identify the specific exercise modalities, contents, outcome indicators, and application effects associated with this intervention, in the context of the complex interplay of metabolic, inflammatory, and hormonal factors contributing to muscle wasting in CKD patients. By examining the efficacy of various exercise interventions, this study seeks to elucidate optimal strategies for mitigating the impact of CKD-induced muscle atrophy, thereby informing clinical practices and improving patient outcomes. METHODS: According to the method of a scoping review, nine databases (Cochrane, PubMed, EMBASE, Web of Science, ProQuest, Ovid, CNKI, Wanfang Data, and VIP) were searched until September 28, 2023. The included literature was screened, summarized, and analyzed. RESULTS: A total of 20 pieces of literature were included. Some types include aerobic exercise, resistance exercise, and aerobic combined resistance exercise. The exercise intensity primarily falls within the mild to moderate range, with a recommended frequency of 2 - 3 times a week, lasting 30 - 60 min each time. The types of outcomes encompassed in this study include body composition, functional testing, strength measurements, laboratory examinations, cardiopulmonary function assessments, and patient-reported outcomes. To varying degrees, exercise intervention positively impacts the subjects' physical activity ability, body composition, and skeletal muscle status. Currently, resistance training is the primary type of intervention used for preventing and treating CKD patients induced by muscle atrophy. CONCLUSION: Exercise intervention can improve muscle strength, physical function, and quality of life in patients with CKD muscle atrophy. Therefore, patients should be fully informed of the effect of exercise intervention in the treatment of chronic kidney disease-induced muscle atrophy in future, so as to promote the standardized implementation of exercise intervention.
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Importance: Anti-vascular endothelial growth factor (VEGF) treatment through intravitreal or subretinal administrations has been proven effective for VEGF-driven pediatric vitreoretinal diseases but are not feasible for advanced cases, such as shallow traction retinal detachments or peripheral circumferential retinal detachments which adhere to the lens. Intra-anterior chamber injection (IAcI) of anti-VEGF may be a viable alternative in such cases but needs evaluation. Objective: To investigate the effects and safety of IAcI of anti-VEGF to treat VEGF-driven pediatric vitreoretinal diseases. Design, Setting, and Participants: This was a retrospective observational case series study conducted at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine in China. The study included 14 eyes of 13 children diagnosed with vitreoretinal disease exhibiting elevated vascular activity between January and August 2023. Intervention: IAcI with ranibizumab. Main Outcomes and Measures: Retinal vascular abnormalities, vitreous hemorrhage resolution, and complications 1 month and 3 months after injection. Results: Of 13 patients included in this study, 12 were male. The mean age was 4.6 years (range, 1 month to 9 years). Six patients were diagnosed with familial exudative vitreoretinopathy, 4 with morning glory syndrome, 1 with retinopathy of prematurity, and 2 with chronic retinal detachments of unknown causes. At 1-month postoperative follow-up, vascular activity had decreased in 14 of 14 eyes. At 3-month follow-up, vascular activity had resolved in 7 of 14 eyes, persisted in 6 of 14 eyes, and reactivated in 1 of 14 eyes. On final observation, no complications were reported. Conclusions and Relevance: These findings support the possibility of treatment using IAcI with ranibizumab to decrease retinal vascular abnormalities in familial exudative vitreoretinopathy or retinopathy of prematurity or related conditions, but further studies are needed to understand more precise benefits and risks. This approach might be considered in cases where intravitreal or subretinal injection are not feasible, recognizing the limitations of these findings and that longer-term outcomes still need to be monitored.
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Desprendimiento de Retina , Retinopatía de la Prematuridad , Recién Nacido , Humanos , Masculino , Niño , Preescolar , Femenino , Ranibizumab , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Desprendimiento de Retina/etiología , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/tratamiento farmacológico , Vitreorretinopatías Exudativas Familiares/complicaciones , Vitreorretinopatías Exudativas Familiares/tratamiento farmacológico , Inyección Intracameral , China , Estudios Retrospectivos , Inyecciones Intravítreas , BevacizumabRESUMEN
Evaluating and understanding the effect of manufacturing processes on the creep performance in superalloys poses a significant challenge due to the intricate composition involved. This study presents a machine-learning strategy capable of evaluating the effect of the heat treatment process on the creep performance of superalloys and predicting creep rupture life with high accuracy. This approach integrates classification and regression models with domain-specific knowledge. The physical constraints lead to significantly enhanced prediction accuracy of the classification and regression models. Moreover, the heat treatment process is evaluated as the most important descriptor by integrating machine learning with superalloy creep theory. The heat treatment design of Waspaloy alloy is used as the experimental validation. The improved heat treatment leads to a significant enhancement in creep performance (5.5 times higher than the previous study). The research provides novel insights for enhancing the precision of predicting creep rupture life in superalloys, with the potential to broaden its applicability to the study of the effects of heat treatment processes on other properties. Furthermore, it offers auxiliary support for the utilization of machine learning in the design of heat treatment processes of superalloys.
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Brake wear particles (BWPs) are considered one of the most significant non-exhaust particle emission sources from motor vehicles. Previous studies have primarily focused on BWPs from conventional fuel vehicles (CFVs), with limited research available on BWPs from new energy vehicles (NEVs). We developed an independent BWP emission testing system applicable to NEVs and conducted BWP emission tests on representative NEVs and CFVs under various testing cycles via a chassis dynamometer. The BWP emission characteristics of the NEVs equipped with regenerative braking system significantly differed from those of gasoline vehicles. For transient emission characteristics, gasoline vehicles exhibited higher peak concentrations during brake events than brake drag events, while those with regenerative braking exhibited the opposite feature. Under continuous braking, the concentration of ultrafine particles emitted by NEVs was reduced by more than 3 orders of magnitude compared to gasoline vehicles. In terms of single-particle morphology, BWPs could be mainly divided into three categories: carbonaceous particles, iron-rich particles, and mixed metal particles. We obtained realistic emission characteristics of BWPs from NEVs, which could provide data support and a scientific basis for the formulation of relevant emission standards and control measures in the future.
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Purpose: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP). Methods: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed. Results: The mean follow-up was 17.6 months. After the 3rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 (p < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR. Conclusion: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation.
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Sustained deep emission reduction in road transportation is encountering bottleneck. The Intelligent Transportation-Speed Guidance System (ITSGS) is anticipated to overcome this challenge and facilitate the achievement of low-carbon and clean transportation. Here, we compiled vehicle emission datasets collected from real-world road experiments and identified the mapping relationships between four pollutants (CO2, CO, NOx, and THC) and their influencing factors through machine learning. We developed random forest models for each pollutant and achieved strong predictive performance, with an R2 exceeding 0.85 on the test dataset for all models. The environmental benefits of ITSGS at the urban scale were quantified by combining emission models with large-scale real trajectory data from Zibo, Shandong Province. Based on temporal and spatial analyses, we found that ITSGS has varying degrees of emission reduction potential during the morning peak, flat peak, and evening peak hours. Values can range from 5.71 %-8.16 % for CO2 emissions, 13.63 %-16.25 % for NOx emissions, 13.69 %-16.45 % for CO emissions, and 4.84-7.07 % for THC emissions, respectively. Additionally, ITSGS can significantly expand the area of low transient emission zones. The best time for achieving maximum environmental benefits from ITSGS is during the workday flat peak. ITSGS limits high-speed and aggressive driving behavior, thereby smoothing the driving trajectory, reducing the frequency of speed switches, and lowering road traffic emissions. The results of the ITSGS environmental benefits evaluation will provide new insights and solutions for sustainable road traffic emission reduction. SYNOPSIS: Large-scale deployment of Intelligent Transportation - Speed Guidance System is a sustainable solution to help achieve low-carbon and clean transportation.
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The arbitrary disposal of used brake pads from motor vehicles has resulted in severe heavy metal pollution and resource wastage, highlighting the urgent need to explore the significant untapped potential of these discarded materials. In this study, The in-situ growth of highly dispersed Fe2O3 nanocrystals was achieved by simple oxidation annealing of brake pad debris(BPD). Interestingly, Cu remained unoxidized and acted as a "valence state transformation bridge of Fe2O3" to construct the "triple Fe-C-Cu sites". The Fenton degradation experiment of pollutants was conducted under constant temperature conditions at 40 °C, a stirring rate of 1300 rpm, a pH value of 3, a catalyst dosage of 0.5 g/L, pollutant dosage ranging from 50 to 400 mg/L, and H2O2 dosage of 0.25 g/L. Experimental results showed that BPD treated at 300 °C for 2 h exhibited optimal Fenton-like oxidation activity, achieving rapid degradation of over 90 % of refractory antibiotics, such as tetracycline and ciprofloxacin, in organic wastewater within 10 min. This remarkable performance was mainly attributed to the synergistic effect of "Fe-C-Cu triple sites", where the electron-donating role of C in the Fe-C and Cu-C interfaces facilitated the conversion of the Fe(III) to Fe(II) and Cu(II) to Cu(I). In addition, the ability of Cu2+ to accept electrons at the Fe-Cu interface promoted the transition from Fe (II) to Fe (III). This "balance of electron gain and loss" accelerated the interfacial electron transfer and the recycle of dual Fenton sites, Fe(II)/Fe(III) and Cu(I)/Cu(II), to generate more ·OH from H2O2. Therefore, this strategy of functionalizing BPD as Fenton-like catalysts without the addition of external Fe provides intriguing prospects for understanding the construction of Fe-based Fenton catalysts and resource utilization of Fe-containing solid waste materials.
Asunto(s)
Contaminantes Ambientales , Hierro , Hierro/química , Peróxido de Hidrógeno/química , Automóviles , Oxidación-Reducción , Compuestos Férricos/química , Compuestos Ferrosos , CatálisisRESUMEN
Adherence to healthy dietary patterns is associated with a reduced risk of kidney dysfunction. Nevertheless, the age-related mechanisms that underpin the relationship between diet and kidney function remain undetermined. This study aimed to investigate the mediating role of serum α-Klotho, an anti-aging protein, in the link between a healthy diet and kidney function. A cross-sectional study was conducted on a cohort of 12,817 individuals aged between 40 and 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. For each participant, the Healthy Eating Index 2015 (HEI-2015) score was calculated as a measure of a healthy dietary pattern. Creatinine-based estimated glomerular filtration rate (eGFR) was used to assess kidney function. Multivariable regression models were used to analyze the association between the standardized HEI-2015 score and eGFR after adjusting for potential confounders. Causal mediation analysis was performed to assess whether serum α-Klotho influenced this association. The mean (±SD) eGFR of all individuals was 86.8 ± 19.8 mL/min per 1.73 m2. A high standardized HEI-2015 score was associated with a high eGFR (ß [95% CI], 0.94 [0.64-1.23]; p < 0.001). The mediation analysis revealed that serum α-Klotho accounted for 5.6-10.5% of the association of standardized overall HEI-2015 score, total fruits, whole fruits, greens and beans, and whole grain with eGFR in the NHANES. According to the results from the subgroup analysis, serum α-Klotho exerted a mediating effect in the participants aged 60-79 years and in males. A healthy diet may promote kidney function by up-regulating serum anti-aging α-Klotho. This novel pathway suggests important implications for dietary recommendations and kidney health.