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1.
Polymers (Basel) ; 16(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39000732

RESUMEN

Most toughening methods for epoxy resins are usually used at the expense of other properties. Some polyhedral oligomeric silsesquioxanes (POSSs) with both a rigid Si-O-Si structure and flexible organic chain segments could be expected to be effective toughening agents. In this study, three reactive polyhedral oligomeric silsesquioxanes with a thiol group (OMPPS), a carboxyl group (OCOPS), and an epoxy group (OGCPS) were synthesized and characterized. They were utilized as modifiers to toughen 3-(oxiran-2-ylmethoxy)-N,N-bis(oxiran-2-ylmethyl)aniline (AFG-90MH)/4,4'-methylenebis(2-ethylaniline) (MOEA) (epoxy resin) with different molar ratios to obtain hybrid resins named OMPPS-EP-i, OCOPS-EP-j, and OGCPS-EP-k. The effects of the amount of modifier added and the length of the organic chain on the cage structure on various properties of the hybrid resins were investigated. The results show that all three modifiers show good compatibility with the epoxy resin. The hybrid resins have a low viscosity at 45~85 °C and can be cured at a low temperature (110 °C). The cured hybrid resins display improved toughness. Typically, the critical stress intensity factor (KIC) and impact strength of OGCPS-EP-0.6-C are 2.54 MPa∙m-1/2 and 19.33 kJ∙m-2, respectively, which increased by 58.75% and 22.48% compared with the pristine epoxy resin, respectively. In addition, the glass transition temperature and flexural strength of the hybrid resins are basically unchanged.

2.
Eur J Nutr ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700577

RESUMEN

PURPOSE: The aim of this study was to examine the associations between body composition and temporal eating patterns, including time of first eating occasion, time of last eating occasion, eating window, and eating jet lag (the variability in meal timing between weekdays and weekends). METHODS: A total of 131 participants were included in the study. Temporal eating pattern information was collected through consecutive 7-day eat timing questionnaires and photographic food records. Body composition was assessed by bioelectrical impedance analysis. Multiple linear regression models were used to evaluate the relationships of temporal eating patterns with body composition, and age was adjusted. Eating midpoint was additionally adjusted in the analysis of eating window. RESULTS: On weekdays, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with lower body fat percentage. On weekends, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with higher FFMI. Longer first eating occasion jet lag was associated with lower lean mass. CONCLUSION: Our study suggested that earlier and more regular eating patterns may have a benefit on body composition.

3.
Bioact Mater ; 36: 157-167, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38463554

RESUMEN

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

4.
Biochem Genet ; 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37672187

RESUMEN

Osteosarcoma is the most common type of primary malignant bone tumor. Due to the lack of selectivity and sensitivity of chemotherapy drugs to tumor cells, coupled with the use of large doses, chemotherapy drugs often have systemic toxicity. The use of modern sequencing technology to screen tumor markers in a large number of tumor samples is a common method for screening highly specific and selective anti-tumor drugs. This study aims to identify potential biomarkers using the latest reported gene expression signatures of oncogene-induced replication stress (ORS) in aggressive cancers, and potential anti-osteosarcoma drugs were screened in different drug databases. In this study, we obtained 89 osteosarcoma-related samples in the TARGET database, all of which included survival information. According to the median expression of each of six reported ORS gene markers (NAT10/DDX27/ZNF48/C8ORF33/MOCS3/MPP6), we divided 89 osteosarcoma gene expression datasets into a high expression group and a low expression group and then performed a differentially expressed gene (DEG) analysis. The coexisting genes of 6 groups of DEGs were used as replication stress-related genes (RSGs) of osteosarcoma. Then, key RSGs were screened using LASSO regression, a Cox risk proportional regression prognostic model and a tenfold cross-validation test. GSE21257 datasets collected from the Gene Expression Omnibus (GEO) database were used to verify the prognostic model. The final key RSGs selected were used in the L1000PWD and DGIdb databases to mine potential drugs. After further validation by the prognostic model, we identified seven genes associated with ORS in osteosarcoma as key RSGs, including transcription factor 7 like 2 (TCF7L2), solute carrier family 27 member 4 (SLC27A4), proprotein convertase subtilisin/kexin type 5 (PCSK5), nucleolar protein 6 (NOL6), coiled-coil-coil-coil-coil-helix domain containing 4 (CHCHD4), eukaryotic translation initiation factor 3 subunit B (EIF3B), and synthesis of cytochrome C oxidase 1 (SCO1). Then, we screened the seven key RSGs in two drug databases and found six potential anti-osteosarcoma drugs (D GIdb database: repaglinide, tacrolimus, sirolimus, cyclosporine, and hydrochlorothiazide; L1000PWD database: the small molecule VU-0365117-1). Seven RSGs (TCF7L2, SLC27A4, PCSK5, NOL6, CHCHD4, EIF3B, and SCO1) may be associated with the ORS gene signatures in osteosarcoma. Repaglinide, tacrolimus, sirolimus, cyclosporine, hydrochlorothiazide and the small molecule VU-0365117-1 are potential therapeutic drugs for osteosarcoma.

5.
J Environ Manage ; 346: 118974, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37714088

RESUMEN

Quantifying the uncertainty of stormwater inflow is critical for improving the resilience of urban drainage systems (UDSs). However, the high computational complexity and time consumption obstruct the implementation of uncertainty-addressing methods for real-time control of UDSs. To address this issue, this study developed a machine learning-based surrogate model (MLSM) that maintains high-fidelity descriptions of drainage dynamics and meanwhile diminishes the computational complexity. With stormwater inflow and controls as inputs and system overflow as the output, MLSM is able to fast evaluate system performance, and therefore stochastic optimization becomes feasible. Thus, a real-time control strategy was built by combining MLSM with the stochastic model predictive control. This strategy used stochastic stormwater inflow scenarios as input and aimed to minimize the expected overflow under all scenarios. An ensemble of stormwater inflow scenarios was generated by assuming the forecast errors follow normal distributions. To downsize the ensemble, representative scenarios with their probabilities were selected using the simultaneous backward reduction method. The proposed control strategy was applied to a combined UDS of China. Results are as follows. (1) MLSM fit well with the original high-fidelity urban drainage model, while the computational time was reduced by 99.1%. (2) The proposed strategy consistently outperformed the classical deterministic model predictive control in both magnitude and duration dimensions of system resilience, when the consumed time compatible is with the real-time operation. It is indicated that the proposed control strategy could be used to inform the real-time operation of complex UDSs and thus enhance system resilience to uncertainty.

6.
Artículo en Inglés | MEDLINE | ID: mdl-37698961

RESUMEN

The imbalanced development between deep learning-based model design and motor imagery (MI) data acquisition raises concerns about the potential overfitting issue-models can identify training data well but fail to generalize test data. In this study, a Spatial Variation Generation (SVG) algorithm for MI data augmentation is proposed to alleviate the overfitting issue. In essence, SVG generates MI data using variations of electrode placement and brain spatial pattern, ultimately elevating the density of the raw sample vicinity. The proposed SVG prevents models from memorizing the training data by replacing the raw samples with the proper vicinal distribution. Moreover, SVG generates a uniform distribution and stabilizes the training process of models. In comparison studies involving five deep learning-based models across eight datasets, the proposed SVG algorithm exhibited a notable improvement of 0.021 in the area under the receiver operating characteristic curve (AUC). The improvement achieved by SVG outperforms other data augmentation algorithms. Further results from the ablation study verify the effectiveness of each component of SVG. Finally, the studies in the control group with varying numbers of samples show that the SVG algorithm consistently improves the AUC, with improvements ranging from approximately 0.02 to 0.15.


Asunto(s)
Algoritmos , Encéfalo , Humanos , Electrodos , Curva ROC
7.
Sci Total Environ ; 899: 165660, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37478924

RESUMEN

Tidal flats are of great importance to coastal residents and environments, which are recently facing unprecedented challenges due to massive urban expansions. While some case studies have been conducted in small areas, it is yet to come a picture to examine the issue at the nationwide level. To fill this void, it is necessary to reconsider whether the analytical and statistical methods used in the previous studies are still appropriate to the larger scales, which accordingly needs to be refined and updated. Aiming at this issue, this study implemented a justification for the conterminous United States, in which nearly 70 % of the counties by the seashore with intensified tidal flats in 1985 were selected to conduct a comprehensive assessment. Based on the 156 selected counties, this paper firstly analyzed the spatiotemporal change patterns of tidal flats and urban extents from 1985 to 2015, and then combined these results and implemented a series of correlation assessments between tidal flat loss and urban expansion. As a result, we found that urban expansions in the conterminous coastal United States have not only substantially squeezed the space of tidal flats, but also significantly affected the surrounding tidal flat environments during the three decades.

8.
Food Chem Toxicol ; 176: 113807, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37121429

RESUMEN

Cadmium (Cd), commonly found in diet and drinking water, is known to be harmful to the human liver. Nevertheless, the effects and mechanisms of gestational Cd exposure on fetal liver development remain unclear. Here, we reported that gestational Cd (150 mg/L) exposure obviously downregulated the expression of critical proteins including PCNA, Ki67 and VEGF-A in proliferation and angiogenesis in fetal livers, and lowered the estradiol concentration in fetal livers and placentae. Maternal estradiol supplement alleviated aforesaid impairments in fetal livers. Our data showed that the levels of pivotal estrogen synthases, such as CYP17A1 and 17ß-HSD, was markedly decreased in Cd-stimulated placentae but not fetal livers. Ground on ovariectomy (OVX), we found that maternal ovarian-derived estradiol had no major effects on Cd-impaired development in fetal liver. In addition, Cd exposure activated placental PERK signaling, and inhibited PERK activity could up-regulated the expressions of CYP17A1 and 17ß-HSD in placental trophoblasts. Collectively, gestational Cd exposure inhibited placenta-derived estrogen synthesis via activating PERK signaling, and therefore impaired fetal liver development. This study suggests a protective role for placenta-derived estradiol in fetal liver dysplasia shaped by toxicants, and provides a theoretical basis for toxicants to impede fetal liver development by disrupting the placenta-fetal-liver axis.


Asunto(s)
Cadmio , Trofoblastos , Embarazo , Femenino , Humanos , Cadmio/toxicidad , Cadmio/metabolismo , Trofoblastos/metabolismo , Placenta/metabolismo , Hígado/metabolismo , Estradiol , Estrógenos
9.
Orthop Surg ; 15(1): 111-117, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36394084

RESUMEN

OBJECTIVE: Previous studies on osteoporotic vertebral fractures are usually based on the neutral posture of spine; however, the fractures are usually associated with the flexion posture of spine. Therefore, we aimed to ascertain the relationship between vertebral compression fractures and thoracolumbar hyperflexion Cobb angles (TLHCobb) and determine the clinical cut-off of the TLHCobb angle. METHODS: In this retrospective case-control study, TLHCobbs were collected from 154 postmenopausal women (67.45 ± 6.68 years) with vertebral compression fractures (study group) and 310 postmenopausal women (66.57 ± 8.22 years) without vertebral compression fractures (control group) from June 2017 to July 2019. Demographic data, clinical data, and quantitative computed tomography (QCT) findings were compared between the groups. Chi-squared tests, unpaired t-tests, and Mann Whitney U were used to assess the group characteristics and proportions. Logistic regression was used to examine the association between vertebral compression fractures and TLHCobb. The cut-off of the TLHCobb was determined by ROC curve and Youden's index. RESULTS: Fracture prevalence was higher in the higher TLHCobb study group than that in the control group [OR = 2.81 (2.15-3.67)] after adjusting for age, BMI, and QCT findings. TLHCobbs at and >20.05° were associated with an increased fracture prevalence and ORs of 2.79 (1.82-4.27) and 4.83 (3.24-7.20), respectively. TLHCobb, disk height (semiquantitative grading score) and QCT values differed between the study and control groups (p < 0.001 for all three). There were no significant differences in body mass index (BMI), or coronal TLCobb between the two groups. CONCLUSION: There was an association between the prevalence of vertebral compression fractures and TLHCobbs in postmenopausal women, and a TLHCobb > 20.05° can be an indicator of vertebral fracture.


Asunto(s)
Enfermedades Óseas Metabólicas , Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Femenino , Humanos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/etiología , Estudios Retrospectivos , Posmenopausia , Estudios de Casos y Controles , Densidad Ósea , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología
10.
J Nippon Med Sch ; 90(6): 426-438, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38246614

RESUMEN

BACKGROUND: Copy number variation (CNV) is associated with progression of esophageal cancer (EC), a common gastrointestinal neoplasm. METHODS: Using sequencing data, CNV data, and clinical data of EC transcriptome samples obtained from public databases, we performed differential expression analysis on sequencing data. Differentially expressed CNV-driven lncRNAs were screened using the chi-square test, and CNV-driven lncRNA-associated miRNAs and mRNAs were predicted. Cytoscape software was then used to construct ceRNA networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate biological functions of mRNAs in the ceRNA network. Survival curves were plotted to explore correlations between lncRNAs in the ceRNA network and overall survival of CNV patients. Multiple databases were used to predict lncRNAs-related drugs. RESULTS: A dysregulated lncRNA-associated ceRNA network driven by CNV in EC, including 11 lncRNAs, 11 miRNAs and 159 mRNAs, was constructed. Downstream enrichment of mRNAs was related to biological processes such as extracellular matrix organization, indicating that these mRNAs mainly participate in intercellular exchange between tumor cells. Additionally, expression of all lncRNAs in the ceRNA network, except LINC00950, LINC01270 and MIR181A1HG, was correlated with patients' CNV. In addition, none of the 11 lncRNAs was significantly correlated with overall survival of CNV patients. CH5424802 and PD-033299CNV mainly affected the RTK signaling pathway and the cell cycle of tumor cells via RP11-180N14.1 and RP11-273 G15.2 in the ceRNA network. CONCLUSIONS: This study identified 11 CNV-driven lncRNAs that might affect EC development, 2 of which have promising effects if applied to drug treatment. These findings might assist in identifying novel treatments for EC.


Asunto(s)
Neoplasias Esofágicas , MicroARNs , ARN Largo no Codificante , Humanos , Variaciones en el Número de Copia de ADN/genética , ARN Endógeno Competitivo , ARN Largo no Codificante/genética , Neoplasias Esofágicas/genética , MicroARNs/genética
11.
Water Res ; 227: 119350, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36399841

RESUMEN

The active control of urban drainage systems (UDSs) is playing an increasingly important role in the world threatened by urban flooding and associated disasters caused by insufficient drainage capacity. However, little research has recognized the importance of the optimal use of in-pipe storage space. To address this issue, the use of the in-pipe storage capacity was optimized in this study. A novel approach, that is, dynamic programming with successive approximation considering the time lag of flow routing (DPSA-TL), was developed to determine the control policies, in addition to the commonly used passive, rule-based control (RBC), and evolutionary algorithm (EA) strategies. A real-life urban catchment considering flooding control and combined sewer overflow (CSO) reduction was used as the case study. First of all, the potential benefit of maximizing the use of in-pipe storage space was tested using the four control strategies in three storm events, including a 3-year, 2-hour design (46.5 mm), a 5-year, 2-hour design (56.0 mm) and a 7-h historical (152.5 mm) storm events. Results indicate that DPSA-TL performed best in all cases. Without compromising the goal of flooding control, it provided 16.5%, 12.6%, and 3.0% reductions in CSO volume for the three storm events when compared with the passive strategy. Due to the limited capacity of in-pipe storage, the relative improvement diminished as the total rainfall depth increased. Then, control strategies were further applicated to the real-time operation. DPSA-TL was found to be the best alternative for CSO control, with the CSO volume reduced by 14.7%, 11.4%, and 2.5% in the three storm events, respectively. The findings suggest that the performance of UDS can be significantly improved by optimizing the use of in-pipe storage capacity, and the proposed method is effective in the offline optimization and real-time control of UDSs.


Asunto(s)
Desastres , Inundaciones , Algoritmos
12.
Oxid Med Cell Longev ; 2022: 2240894, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388163

RESUMEN

Low back pain (LBP) seriously affects human quality of life. Intervertebral disc degeneration (IVDD) is the main pathological factor that leads to LBP, but the pathological mechanism underlying IVDD has not been fully elucidated. Neuropathic pain caused by IVDD is an important pathological factor affecting people's daily lives. Therefore, it is very important to identify therapeutic drugs to ameliorate IVDD and secondary neuropathic pain. Hydroxytyrosol (HT) is a natural compound derived from olive leaves and oil and has anti-inflammatory, antioxidant, and antitumor activities and other properties. In this study, TNF-α-stimulated human nucleus pulposus cells (HNPCs) were used to simulate the local inflammatory microenvironment observed in IVDD in vitro to explore the role of HT in alleviating various pathological processes associated with IVDD. A rat needle puncture model was used to further explore the role of HT in alleviating IVDD. Lipopolysaccharide (LPS) was used to stimulate microglia in vitro to comprehensively explore the role of HT in alleviating neuropathic pain, and a rat model involving chronic compression of the dorsal root ganglion (CCD) was established to simulate the neuropathic pain caused by IVDD. This study suggests that HT reduces the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and matrix metalloproteinase-13 (MMP-13); inhibits the production of mitochondrial reactive oxygen species (ROS); and maintains mitochondrial homeostasis. Thus, HT appears to reduce the rate of apoptosis and mitigate the loss of major intervertebral disc components by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Moreover, HT inhibited the secretion of COX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, and iNOS and activation of the NLRP3 inflammasome in microglia by inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinase (ERK) signaling pathways. In conclusion, HT plays a protective role against IVDD and secondary neuropathic pain by inhibiting the NF-κB, PI3K/AKT, and ERK signaling pathways.


Asunto(s)
Degeneración del Disco Intervertebral , Neuralgia , Humanos , Ratas , Animales , Degeneración del Disco Intervertebral/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Ciclooxigenasa 2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Calidad de Vida , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Neuralgia/tratamiento farmacológico
13.
Front Oncol ; 12: 1036401, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408174

RESUMEN

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

14.
BMC Cancer ; 22(1): 1078, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36266614

RESUMEN

BACKGROUND: The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the clinicopathological features and prognostic determinants for patients with UMBTs? 2) Can a nomogram be developed for clinicians to predict the short and long-term outcomes for individuals with UMBTs? 3) Does surgery improve outcomes for UMBT patients who received radiotherapy or chemotherapy after balancing the confounding bias? METHODS: 400 UMBT patients were filtrated from the Surveillance, Epidemiology, and End Results database to assess the clinicopathological features, treatments, and factors affecting prognosis. The optimal cutoff values of continuous variables were identified by the x-tile software. Kaplan-Meier method and multivariate Cox proportional hazard modeling were performed to evaluate the independent prognostic factors. Nomogram was further developed by using R software with rms package. The surgical efficacy was further assessed for patients receiving radiotherapy or chemotherapy after performing propensity score matching. RESULTS: The enrolled cohort included 195 (48.8%) female and 205 (51.2%) male patients. The 2- and 5-year cancer-specific survival (CSS) and overall survival (OS) rate were 58.2 ± 3.0%, 46.8 ± 3.2%, and 46.5 ± 2.6%, 34.4 ± 2.5%, respectively. Nomogram was finally developed for CSS and OS according to the identified independent factors: age, tumor extent, primary tumor surgery, tumor size, and pathology grade. For UMBT patients who received radiotherapy or chemotherapy, surgical intervention was associated with better CSS (pr = 0.003, pc = 0.002) and OS (pr = 0.035, pc = 0.002), respectively. CONCLUSIONS: Nomogram was developed for individual UMBT patient to predict short and long-term CSS and OS rate, and more external patient cohorts are warranted for validation. Surgery improves outcomes for UMBT patients who received either radiotherapy or chemotherapy.


Asunto(s)
Neoplasias Óseas , Nomogramas , Humanos , Masculino , Femenino , Programa de VERF , Estadificación de Neoplasias , Pronóstico , Neoplasias Óseas/cirugía
15.
Chemosphere ; 307(Pt 1): 135668, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35835241

RESUMEN

Early-life exposure to environmental cadmium (Cd) is known to cause developmental disorders, yet the effect and mechanism of gestational exposure to Cd on the offspring's cognitive function remains unclear. Placenta as a well-established target organ for Cd-impaired fetal development, its role in estrogen regulation and offspring cognitive function is unknown. Our in vivo experiments found that gestational Cd exposure impaired cognitive function in adult male offspring, accompanied with lowered 17ß-estradiol (E2) level in the male fetal brain upon Cd exposure. Correspondingly, the expression of synapse-associated proteins including brain-derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95) and synapsin-1 were downregulated, which were reversed when supplemented with E2 hormone during gestation. Further observation showed placental estrogen synthesis inhibition and general control non-derepressible 2 (GCN2) signaling activation upon Cd exposure, whereas placental estrogen synthesis could be restored through inhibiting GCN2 activity. Based on ovariectomy (OVX) of pregnant mice, we confirmed that Cd exposure reduced E2 level in fetal brain via inhibiting placenta-derived estrogen synthesis. The aforementioned Cd-induced fetal brain injury and cognitive impairment in adult offspring were significantly alleviated when pregnant dams were supplemented with anti-stress agent N-Acetyl-l-cysteine. In summary, Cd disrupted placenta-derived estrogen synthesis via activating GCN2 signaling, and thereby caused cognitive impairment in adult offspring mice. Our findings suggest that placenta-derived estrogen may be an effect marker of environmental toxicants-evoked cognitive dysfunction in adult offspring and suggest that environmental toxicants may affect the fetal brain development via placenta-fetal-brain axis.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Cadmio , Acetilcisteína/farmacología , Animales , Encéfalo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cadmio/metabolismo , Cognición , Estradiol/metabolismo , Estrógenos/farmacología , Femenino , Masculino , Ratones , Placenta/metabolismo , Embarazo , Sinapsinas/metabolismo , Sinapsinas/farmacología
16.
Orthop Surg ; 14(5): 892-901, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35445546

RESUMEN

OBJECTIVE: To compare the efficacy and safety of retaining the posterior longitudinal ligament (PLL) with resecting the PLL in inside-out percutaneous endoscopic transforaminal discectomy (PETD) surgery for lumbar disc herniation (LDH). METHOD: A total of 135 patients with symptomatic LDH who were treated by inside-out PETD surgery from January 2015 to January 2017were included in this retrospective analysis. There were 38 males and 30 females in the PLL resection group (mean age = 52.40 ± 8.73 years) and 35 males and 32 females in the PLL retention group (mean age = 53.50 ± 9.24 years). The visual analogue scale (VAS) score, Oswestry disability index (ODI), and modified MacNab criteria were used to evaluate clinical outcomes. Operation time, blood loss, recurrence of LDH, and complications were recorded. Three months after surgery, magnetic resonance imaging was performed to confirm that nerve root compression was relieved. RESULTS: The VAS and ODI scores improved significantly immediately after surgery, at 1 month after surgery, at 3 months after surgery, and at last follow-up compared with those before surgery (P < 0.01). The scores also improved significantly between immediately after surgery and 1 month after surgery in the two groups (P < 0.001). Multivariate analysis indicated that age ≥ 50 years (odds ratio (OR) = 6.33, 95% confidence interval (CI): 1.64-21.98, P = 0.014), pain duration ≥6 months (OR = 4.68, 95% CI: 1.29-6.51, P = 0.025), pre-ODI score ≥ 40% (OR = 5.97, 95% CI: 2.41-14.86, P = 0.003) were all associated with poor functional outcomes. There was no significant difference in the excellent/good ratio between the two groups and the mean operation time of the retention group was 71.5% of that of the resection group (82.7 ± 18.5 min vs 115.6 ± 24.6 min, P < 0.01). In the patients, no serious complications, such as dural tear, wound infection, or persistent nerve root injury, were observed during the follow-up period. There was no significant difference in the complication rate between the two groups (6/68 vs 6/67, P = 0.979). Although the recurrence rate was higher in retention group, there was no significant difference between the two groups (1/68 vs 2/67, P = 0.551). CONCLUSION: The PLL is recommended to be retained for inside-out PETD surgery.


Asunto(s)
Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Adulto , Discectomía/métodos , Discectomía Percutánea/métodos , Endoscopía/métodos , Femenino , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Ligamentos Longitudinales/cirugía , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
17.
Ecotoxicol Environ Saf ; 233: 113313, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35182801

RESUMEN

BACKGROUND: A few studies have reported phthalate exposure as a risk factor for depressive symptoms, but the results have been inconsistent. Whether chronic inflammation mediates the relationship between phthalates (PAEs) and depressive symptoms remains unclear. In this study, we establish mediating models of inflammatory factors and explore the mediating role of chronic inflammation in the association between PAEs exposure and depressive symptoms. METHODS: The sample included 989 participants from the Study on Health and Environment of the Elderly in Lu'an City, Anhui Province. Geriatric depression scale (GDS-30) was used to screen depressive symptoms of the elderly. The levels of seven kinds of PAEs in urine samples and four inflammatory factors in serum of the elderly were measured. To establish the mediating effect of inflammatory factors to explore the potential effect of PAEs exposure on the increased odds of depressive symptoms. RESULTS: Adjusted for multiple variables, the highest tertiles of Mono (2-ethylhexyl) phthalate (MEHP) (95%CI = 1.051-2.112), Mono benzyl phthalate (MBzP) (95%CI = 1.016-2.082) and Mono butyl phthalate (MBP) (95%CI = 1.102-2.262) were positively correlated with depressive symptoms. The mediating effect of IL-6 and generalized inflammation factor between MEHP exposure and depressive symptoms were 15.96% (95%CI=0.0288-0.1971) and 14.25% (95%CI = 0.0167-0.1899). CONCLUSIONS: High levels of MEHP, MBzP and MBP increased the odds of depressive symptoms in the elderly, and chronic inflammation had a partial mediating effect on the increased odds of depressive symptoms due to MEHP exposure.


Asunto(s)
Contaminantes Ambientales , Ácidos Ftálicos , Anciano , Depresión/inducido químicamente , Dibutil Ftalato , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/orina , Humanos , Inflamación/inducido químicamente , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/orina
18.
Eur Spine J ; 31(4): 935-942, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35039964

RESUMEN

PURPOSE: The Fremantle back awareness questionnaire (FreBAQ) was recently developed as simple and quick tool to assess back-specific body perception in Low back pain (LBP) patients. The aim of the present study was to translate and cross-culturally adapt the Fremantle back awareness questionnaire (FreBAQ) into a Simplified Chinese version (FreBAQ-C), and evaluate the reliability and validity of the FreBAQ-C in patients with non-specific Chronic Low back pain (CLBP). METHODS: The FreBAQ was translated into Chinese according to established methods. Internal consistency was assessed according to Cronbach's alpha. Test-retest reliability was estimated by Intraclass correlation coefficient (ICC). Construct validity was evaluated by correlations between the FreBAQ-C and Visual analogue scale (VAS), Roland-Morris disability questionnaire (RDQ), Pain catastrophizing scale (PCS), Tampa scale for kinesiophobia (TSK) as well as Hospital anxiety and depression scale (HADS). RESULTS: A total of 105 participants (38 males and 67 females) were included in this study with the mean age of 54.1 ± 15.6 years, mean duration of LBP of 6.8 ± 4.6 years. The FreBAQ-C total scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach's alpha = 0.833). ICC of test-retest reliability was good (0.897, 95% confidence interval: 0.852-0.929). The limits of agreement (LOA) ranged from - 5.8 to 6.3. The Standard error of measurement (SEM) and Minimum detectable change (MDC) were 2.16 and 5.99. Construct validity was confirmed by significant correlation of The FreBAQ-C and VAS during motion (r = 0.274, p = 0.005) and rest (r = 0.243, p = 0.012), RDQ (r = 0.377, p < 0.001), PCS (r = 0.439, p < 0.001), and TSK(r = 0.311, p = 0.001). CONCLUSIONS: The FreBAQ-C was demonstrated to have acceptable reliability and validity for patients with non-specific CLBP in Chinese mainland. It will allow evaluating body preception of the back in the Chinese population with CLBP.


Asunto(s)
Dolor de la Región Lumbar , Adulto , Anciano , China , Comparación Transcultural , Evaluación de la Discapacidad , Femenino , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/epidemiología , Masculino , Persona de Mediana Edad , Psicometría/métodos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
19.
Bioact Mater ; 12: 292-302, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35087969

RESUMEN

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.

20.
IEEE Trans Cybern ; 52(9): 9290-9301, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33170793

RESUMEN

In this article, a dynamic-neighborhood-based switching PSO (DNSPSO) algorithm is proposed, where a new velocity updating mechanism is designed to adjust the personal best position and the global best position according to a distance-based dynamic neighborhood to make full use of the population evolution information among the entire swarm. In addition, a novel switching learning strategy is introduced to adaptively select the acceleration coefficients and update the velocity model according to the searching state at each iteration, thereby contributing to a thorough search of the problem space. Furthermore, the differential evolution algorithm is successfully hybridized with the particle swarm optimization (PSO) algorithm to alleviate premature convergence. A series of commonly used benchmark functions (including unimodal, multimodal, and rotated multimodal cases) is utilized to comprehensively evaluate the performance of the DNSPSO algorithm. The experimental results demonstrate that the developed DNSPSO algorithm outperforms a number of existing PSO algorithms in terms of the solution accuracy and convergence performance, especially for complicated multimodal optimization problems.

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