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In hypoxic and pseudohypoxic rodent models of pulmonary hypertension (PH), hypoxia-inducible factor (HIF) inhibition attenuates disease initiation. However, HIF activation alone, due to genetic alterations or use of inhibitors of prolyl hydroxylase domain (PHD) enzymes, has not been definitively shown to cause PH in humans, indicating the involvement of other mechanisms. Given the association between endothelial cell dysfunction and PH, the effects of pseudohypoxia and its underlying pathways were investigated in primary human lung endothelial cells. PHD2 silencing or inhibition, while activating HIF2α, induced apoptosis-resistance and IFN/STAT activation in endothelial cells, independent of HIF signaling. Mechanistically, PHD2 deficiency activated AKT and ERK, inhibited JNK, and reduced AIP1 (ASK1-interacting protein 1), all independent of HIF2α. Like PHD2, AIP1 silencing affected these same kinase pathways and produced a similar dysfunctional endothelial cell phenotype, which were partially reversed by AKT inhibition. Consistent with these in vitro findings, AIP1 protein levels in lung endothelial cells were decreased in Tie2-Cre/Phd2 knockout mice compared to wild-type controls. Lung vascular endothelial cells from patients with pulmonary arterial hypertension (PAH) showed IFN/STAT activation. Lung tissue from both SU5416/hypoxia PAH rats and PAH patients all showed AKT activation and dysregulated AIP1 expression. In conclusion, PHD2 deficiency in lung vascular endothelial cells drives an apoptosis-resistant and inflammatory phenotype, mediated by AKT activation and AIP1 loss independent of HIF signaling. Targeting these pathways, including PHD2, AKT, and AIP1, holds potential for developing new treatments for endothelial dysfunction in PH.
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Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.
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Regeneração Óssea , Colágeno , Células-Tronco Mesenquimais , Nanofios , Osteogênese , Alicerces Teciduais , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Nanofios/química , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Humanos , Colágeno/química , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Animais , Porphyromonas gingivalis/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Streptococcus mutans/fisiologia , Streptococcus mutans/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Pseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective. METHODS: 34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation. RESULTS: There was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5-99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation. CONCLUSIONS: This is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.
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Encéfalo , Radiômica , Humanos , Estudos de Viabilidade , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
We investigated the surface orthogonal patterning and bidirectional self-assembly of binary hairy nanoparticles (NPs) constructed by uniformly tethering a single NP with multiple V-shaped AB diblock copolymers using Brownian dynamics simulations in a poor solvent. At low concentration, the chain collapse and microphase separation of binary polymer brushes can lead to the patterning of the NP surface into A- and B-type orthogonal patches with various numbers of domains (valency), n = 1-6, that adopt spherical, linear, triangular, tetrahedral, square pyramidal, and pentagonal pyramidal configurations. There is a linear relationship between the valency and the average ratio of NP diameter to the polymers' unperturbed root-mean-square end-to-end distance for the corresponding valency. The linear slope depends on the grafting density and is independent of the interaction parameters between polymers. At high concentration, the orthogonal patch NPs serve as building blocks and exhibit directional attractions by overlapping the same type of domains, resulting in self-assembly into a series of fascinating architectures depending on the valency and polymer length. Notably, the 2-valent orthogonal patch NPs have the bidirectional bonding ability to form the two-dimensional (2D) square NP arrays by two distinct pathways. Simultaneously patching A and B blocks enables the one-step formation of 2D square arrays via bidirectional growth, whereas step-by-step patching causes the directional formation of 1D chains followed by 2D square arrays. Moreover, the gap between NPs in the 2D square arrays is related to the polymer length but independent of the NP diameter. These 2D square NP arrays are of significant value in practical applications such as integrated circuit manufacturing and nanotechnology.
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OBJECTIVES: To investigate the association between venous outflow (VO) profiles and outcomes among acute ischemic stroke caused by anterior circulation large vessel occlusion (AIS-LVO) patients who had undergone endovascular treatment (EVT) in the late window of 6-24 h from stroke onset. METHODS: This was a post-hoc analysis of our preceding RESCUE-BT trial, with findings validated in an external cohort. Baseline computed tomographic angiography (CTA) was performed to assess VO using the Cortical Vein Opacification Score (COVES). The primary clinical outcome was functional independence at 90 days (modified Rankin Scale score of 0-2). The adjusted odd ratio (aOR) and confidence interval (CI) were obtained from multivariable logistic regressions. RESULTS: A total of 440 patients were included in the present study. After identifying the cutoff of COVES by marginal effects approach, enrolled patients were divided into the favorable VO group (COVES 4-6) and the poor VO (COVES 0-3) group. Multivariable logistic regression analysis showed that favorable VO (aOR 2.25; 95% CI 1.31-3.86; p = 0.003) was associated with functional independence. Similar results were detected in the external validation cohort. Among those with poor arterial collateralization, favorable VO was still an independent predictor of functional independence (aOR 2.09; 95% CI 1.06-4.10; p = 0.032). CONCLUSION: The robust VO profile indicated by COVES 4-6 could promote the frequency of functional independence among AIS-LVO patients receiving EVT in the late window, and the prognostic value of VO was independent of the arterial collateral status. CLINICAL RELEVANCE STATEMENT: The robust venous outflow profile was a valid predictor for functional independence among AIS-LVO patients receiving EVT in the late window (6-24 h) and the predictive role of venous outflow did not rely on the status of arterial collateral circulation.
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Interactions between dissolved organic matter (DOM) and surrounding environments are highly complex. Understanding DOM at the molecular level can contribute to the management of soil pollution and safeguarding agricultural fields. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) has enabled a molecular-level understanding of DOM. Accordingly, in this study, we investigated soil samples from 27 different regions of mainland China with various soil types and climatic characteristics. Based on the geographical features of the four typical climatic zones in mainland China (temperate monsoon, temperate continental, subtropical monsoon, and Qinghai-Tibet Plateau climates), we employed high-resolution mass spectrometry to determine the molecular diversity of DOM under different climatic conditions. The results indicated that lignin and tannin-like substances were the most active categories of DOM in the soils. Collectively, the composition and unsaturation of DOM molecules are influenced by sunlight, precipitation, temperature, and human activity. All climatic regions contained a substantial number of characteristic molecules, with CHO and CHON constituting over 80%, and DOM containing nitrogen and sulfur was relatively more abundant in the monsoon regions. The complex composition of DOM incorporates various active functional groups, such as -NO2 and -ONO2. Furthermore, soil DOM in the monsoon regions showed higher unsaturation and facilitated various (bio) biochemical reactions in the soil.
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Matéria Orgânica Dissolvida , Solo , Fazendas , Compostos Orgânicos/análise , Solo/química , ChinaRESUMO
BACKGROUND: Childbirth pain is a physiological phenomenon during the delivery process, the intense pain of childbirth could bring harmful effects to pregnant women and their babies. Assessment of childbirth pain is the first step in childbirth pain intervention. Some pain assessment scales have shortcomings such as interfering in the birthing process and affecting pain perception during delivery, while the Rating Scale of Pain Expression during Childbirth (ESVADOPA) could be used as an auxiliary scale to compensate for these shortcomings. The purpose of this study was to introduce the ESVADOPA and adapt it among Chinese pregnant women to check on the psychometric properties of the translated version of ESVADOPA. METHODS: A new translation model based on Brislin's classical back translation model was used to translate and cross-cultural adapt the ESVADOPA. During June 2021 and June 2022, pregnant women at Shandong Provincial Hospital Affiliated to Shandong First Medical University were invited. In the stage of translation and cross-culturally adaptation, 18 midwives and 30 pregnant women were invited to participate in the first round of pre-experiment. And in the second round of pre-experiment, 15 midwives and 20 pregnant women were invited to participate. The Chinese version of ESVADOPA was tested on a group of pregnant women (N = 487). Construct validity was evaluated by exploratory factor analysis, confirmatory factor analysis and criterion-related validity. Reliability was assessed by Cronbach's α coefficient, McDonald Omega, Spearman-Brown split-half reliability and Guttman split-half reliability. RESULTS: The item statistical analysis and construct validity resulted in six items and one factor that explained 61.064% of the total variance. Confirmatory factor analysis showed that the data fit the one-factor structure. Criterion-related validity indicated that the scale is significantly and positively correlated with the Numeric Rating Scale (NRS). Cronbach's α coefficient, McDonald Omega, Spearman-Brown split-half reliability, and Guttman split-half reliability of the Chinese version of ESVADOPA were 0.868, 0.896, 0.845, 0.842, respectively. CONCLUSION: The Chinese version of the ESVADOPA with good reliability and validity data could be used to assess the pain rating of pregnant women during childbirth without interfering in the birthing process.
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Objective: To investigate the effect of arthroscopic triple release combined with rotator cuff repair in the treatment of rotator cuff injury combined with frozen shoulder and its influence on the range of motion and pain score of shoulder joint, and the levels of serum pain mediators. Methods: This was prospective study. A total of 132 patients with rotator cuff injury combined with frozen shoulder admitted to The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine from December 2020 to December 2022 were prospectively selected and divided into two groups according to the random number table method: control group (n=67) and observation group (n=65). Patients in the control group were treated with arthroscopic rotator cuff repair alone, while those in the observation group were treated with arthroscopic triple release combined with rotator cuff repair, and the surgical effects of the two groups were compared. Results: Three months after treatment, the external rotation, internal rotation, abduction, forward flexion, ß-endorphin(ß-EP), prostagranin E2 (PGE2) and substance P(SP)in the observation group were better than those in the control group (P<0.05), while the weight-bearing strength of the affected limb in internal rotation, external rotation and forward flexion was higher than that of the control group(P<0.05). Meanwhile, the Visual Analogue Scale (VAS) score of the observation group was lower than that of the control group at one month and three months after treatment, while the University of California at Los Angeles shoulder rating scale (UCLA) score and Constant-Murley Score (CMS) were higher than those of the control group (P< 0.05). Conclusion: Arthroscopic triple release combined with rotator cuff repair improves various effects for patients with rotator cuff injury combined with frozen shoulder, such as ameliorating the muscle strength of the affected limb and improving the level of pain mediators.
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BACKGROUND: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. METHODS: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. RESULTS: In cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P≤0.002) and were greater in the high-risk compared with the low-risk category (P≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P=0.0001) and REVEAL risk groups (log-rank: P<0.0001) each predicted transplant-free survival. The addition of cfDNA to REVEAL improved discrimination (area under the receiver operating characteristic curve, 0.72-0.78; P=0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P<0.05). cfDNA concentrations derived from erythrocyte progenitor cells, cardiac myocytes, and vascular endothelium were greater in patients with PAH with high-risk versus low-risk REVEAL scores (P≤0.02). CONCLUSIONS: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.
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Ácidos Nucleicos Livres , Hipertensão Arterial Pulmonar , Idoso , Biomarcadores , Ácidos Nucleicos Livres/genética , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/genética , Curva ROCRESUMO
NR2F2 is expressed in endothelial cells (ECs) and Nr2f2 knockout produces lethal cardiovascular defects. In humans, reduced NR2F2 expression is associated with cardiovascular diseases including congenital heart disease and atherosclerosis. Here, NR2F2 silencing in human primary ECs led to inflammation, endothelial-to-mesenchymal transition (EndMT), proliferation, hypermigration, apoptosis-resistance, and increased production of reactive oxygen species. These changes were associated with STAT and AKT activation along with increased production of DKK1. Co-silencing DKK1 and NR2F2 prevented NR2F2-loss-induced STAT and AKT activation and reversed EndMT. Serum DKK1 concentrations were elevated in patients with pulmonary arterial hypertension (PAH) and DKK1 was secreted by ECs in response to in vitro loss of either BMPR2 or CAV1, which are genetic defects associated with the development of PAH. In human primary ECs, NR2F2 suppressed DKK1, whereas its loss conversely induced DKK1 and disrupted endothelial homeostasis, promoting phenotypic abnormalities associated with pathologic vascular remodeling. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating chronic vascular diseases associated with EC dysfunction.NEW & NOTEWORTHY NR2F2 loss in the endothelial lining of blood vessels is associated with cardiovascular disease. Here, NR2F2-silenced human endothelial cells were inflammatory, proliferative, hypermigratory, and apoptosis-resistant with increased oxidant stress and endothelial-to-mesenchymal transition. DKK1 was induced in NR2F2-silenced endothelial cells, while co-silencing NR2F2 and DKK1 prevented NR2F2-loss-associated abnormalities in endothelial signaling and phenotype. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating vascular diseases associated with endothelial dysfunction.
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Hipertensão Arterial Pulmonar , Doenças Vasculares , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Endoteliais/metabolismo , Doenças Vasculares/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Pulmonar Primária Familiar/metabolismo , Inflamação/patologia , Fator II de Transcrição COUP/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
We review here the neuronal mechanisms that cause seizures in focal epileptic disorders and, specifically, those involving limbic structures that are known to be implicated in human mesial temporal lobe epilepsy. In both epileptic patients and animal models, the initiation of focal seizures - which are most often characterized by a low-voltage fast onset EEG pattern - is presumably dependent on the synchronous firing of GABA-releasing interneurons that, by activating post-synaptic GABAA receptors, cause large increases in extracellular [K+] through the activation of the co-transporter KCC2. A similar mechanism may contribute to seizure maintenance; accordingly, inhibiting KCC2 activity transforms seizure activity into a continuous pattern of short-lasting epileptiform discharges. It has also been found that interactions between different areas of the limbic system modulate seizure occurrence by controlling extracellular [K+] homeostasis. In line with this view, low-frequency electrical or optogenetic activation of limbic networks restrain seizure generation, an effect that may also involve the activation of GABAB receptors and activity-dependent changes in epileptiform synchronization. Overall, these findings highlight the paradoxical role of GABAA signaling in both focal seizure generation and maintenance, emphasize the efficacy of low-frequency activation in abating seizures, and provide experimental evidence explaining the poor efficacy of antiepileptic drugs designed to augment GABAergic function in controlling seizures in focal epileptic disorders.
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Epilepsias Parciais , Simportadores , Animais , Humanos , Ligantes , Convulsões , Receptores de GABA-A , Ácido gama-AminobutíricoRESUMO
PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.
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Órgãos em Risco , Radiocirurgia , Humanos , Feminino , Dosagem Radioterapêutica , Órgãos em Risco/efeitos da radiação , Estudos de Viabilidade , Planejamento da Radioterapia Assistida por Computador/métodos , Radiocirurgia/métodosRESUMO
PURPOSE: Ethos CBCT-based adaptive radiotherapy (ART) system can generate an online adaptive plan by re-optimizing the initial reference plan based on the patient anatomy at the treatment. The optimization process is fully automated without any room for human intervention. Due to the change in anatomy, the ART plan can be significantly different from the initial plan in terms of plan parameters such as the aperture shapes and number of monitor units (MUs). In this study, we investigated the feasibility of using calculation-based patient specific QA for ART plans in conjunction with measurement-based and calculation-based QA for initial plans to establish an action level for the online ART patient-specific QA. METHODS: A cohort of 98 cases treated on CBCT-based ART system were collected for this study. We performed measurement-based QA using ArcCheck and calculation-based QA using Mobius for both the initial plan and the ART plan for analysis. For online the ART plan, Mobius calculation was conducted prior to the delivery, while ArcCheck measurement was delivered on the same day after the treatment. We first investigated the modulation factors (MFs) and MU numbers of the initial plans and ART plans, respectively. The γ passing rates of initial and ART plan QA were analyzed. Then action limits were derived for QA calculation and measurement for both initial and online ART plans, respectively, from 30 randomly selected patient cases, and were evaluated using the other 68 patient cases. RESULTS: The difference in MF between initial plan and ART-plan was 12.9% ± 12.7% which demonstrates their significant difference in plan parameters. Based on the patient QA results, pre-treatment calculation and measurement results are generally well aligned with ArcCheck measurement results for online ART plans, illustrating their feasibility as an indicator of failure in online ART QA measurements. Furthermore, using 30 randomly selected patient cases, the γ analysis action limit derived for initial plans and ART plans are 89.6% and 90.4% in ArcCheck QA (2%/2 mm) and are 92.4% and 93.6% in Mobius QA(3%/2 mm), respectively. According to the calculated action limits, the ArcCheck measurements for all the initial and ART plans passed QA successfully while the Mobius calculation action limits flagged seven and four failure cases respectively for initial plans and ART plans, respectively. CONCLUSION: An ART plan can be substantially different from the initial plan, and therefore a separate session of ART plan QA is needed to ensure treatment safety and quality. The pre-treatment QA calculation via Mobius can serve as a reliable indicator of failure in online ART plan QA. However, given that Ethos ART system is still relatively new, ArcCheck measurement of initial plan is still in practice. It may be skipped as we gain more experience and have better understanding of the system.
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Radioterapia de Intensidade Modulada , Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Garantia da Qualidade dos Cuidados de Saúde , Dosagem RadioterapêuticaRESUMO
Stabilization/solidification (S/S) with ordinary portland cement (OPC)-based binders is a suitable method to remediate heavy metal (HM)-contaminated soil and reuse resources of industrial wastes. In industrial wastes, alkaline wastes such as red mud (RM), soda residue (SR), pulverized fly ash (PFA), and alkalinity granulated blast furnace slag (GGBS) can immobilize HM ions (Pb2+, Zn2+, Cd2+, Cr3+, and Cu2+) by precipitation. However, some HM ions (such as AsO43-) would redissolve within the strong alkali environment. In this case, PFA, GGBS, metakaolin (MK), and incinerated sewage sludge ash (ISSA) which have low pH, can be used to immobilize HM ions or added to the OPC-based binders to adjust the pH in the soil products. Moreover, the calcium silicate hydrate (CSH), calcium aluminum silicate hydrate (CASH), ettringite (AFt), and calcium monosulfoalumiante hydrates (AFm) generated during the pozzolanic reaction can also immobilize HM ions by adsorption on the surface, ion exchange, and encapsulation. SR and GGBS can be used to immobilize the HMs (such as CrO42- and AsO43-), which are mainly affected by AFt and AFm. For those not affected by AFt and AFm but related to immobilization by precipitating (such as Mn2+), other wastes except SR and GGBS are suitable for treating contaminated soil. Nevertheless, the formation of AFt is also instrumental for soil product strength. There are several factors affecting soil product strength. In the future, the influence of different hydration products on the S/S effects, competitive adsorption of HM ions, effects on long-term HM stabilization, and novel materials are worth being explored by researchers.
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Resíduos Industriais , Metais Pesados , Cálcio , Metais Pesados/química , Cinza de Carvão , SoloRESUMO
Treatment with mineralocorticoid receptor (MR) antagonists beginning at the outset of disease, or early thereafter, prevents pulmonary vascular remodeling in preclinical models of pulmonary arterial hypertension (PAH). However, the efficacy of MR blockade in established disease, a more clinically relevant condition, remains unknown. Therefore, we investigated the effectiveness of two MR antagonists, eplerenone (EPL) and spironolactone (SPL), after the development of severe right ventricular (RV) dysfunction in the rat SU5416-hypoxia (SuHx) PAH model. Cardiac magnetic resonance imaging (MRI) in SuHx rats at the end of week 5, before study treatment, confirmed features of established disease including reduced RV ejection fraction and RV hypertrophy, pronounced septal flattening with impaired left ventricular filling and reduced cardiac index. Five weeks of treatment with either EPL or SPL improved left ventricular filling and prevented the further decline in cardiac index compared with placebo. Interventricular septal displacement was reduced by EPL whereas SPL effects were similar, but not significant. Although MR antagonists did not significantly reduce pulmonary artery pressure or vessel remodeling in SuHx rats with established disease, animals with higher drug levels had lower pulmonary pressures. Consistent with effects on cardiac function, EPL treatment tended to suppress MR and proinflammatory gene induction in the RV. In conclusion, MR antagonist treatment led to modest, but consistent beneficial effects on interventricular dependence after the onset of significant RV dysfunction in the SuHx PAH model. These results suggest that measures of RV structure and/or function may be useful endpoints in clinical trials of MR antagonists in patients with PAH.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Disfunção Ventricular Direita , Animais , Modelos Animais de Doenças , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Indóis , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pirróis , Ratos , Disfunção Ventricular Direita/tratamento farmacológicoRESUMO
Methylene and methyl tricyclic isoquinolinones were selectively prepared using a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a base- and temperature-controlled Heck reaction catalyzed by palladium(0). Exo- to endo-double-bond migration in isoquinolinones was achieved with 93-99% yields by treatment of the Heck products with Cs2CO3 in dimethyl sulfoxide (DMSO) at 150 °C. A probable mechanism for Cs2CO3-promoted olefin isomerization was proposed and examined using D-isotope labeling experiments. Finally, yuanamide, a 13-methyl-8-oxoprotoberberine alkaloid, was synthesized using the palladium-catalyzed aza-Wacker/Heck/migration sequence.
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Amidas , Paládio , Catálise , Isomerismo , Estrutura MolecularRESUMO
Tandem Diels-Alder reactions of masked porphyrindienes (i.e., sulfolenoporphyrins) with benzoquinones and stilbenes, followed by aromatization, have been developed to load porphyrin with mixed annulation units (i.e., terphenyl and naphthoquinone), furnishing the low-symmetry π-extended porphyrins (DxAy) with push-pull skeletons. All low-symmetrical chromophores display panchromatic absorption spectra, which look like a spectral combination of symmetrical congeners (D4/A4) in a certain ratio. Among them, tD2A2 with trans-arrangement of push/pull units possesses the largest maximum centered at 766 nm with the onset around 900 nm. The fusion of the electron-deficient naphthoquinone moiety on the porphyrin core results in the approximately quantitative regulation of the Eox1 and HOMOs (i.e., 0.10-0.13 V increase for the Eox1 and 0.14-0.16 eV decrease for the HOMOs per naphthoquinone unit). In brief, this work provides a new way to construct low-symmetry π-extended porphyrins with tunable properties resorting to the ratios and locations of the annulated push-pull units.
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More attention has been paid to ubiquitous microplastics (MPs). As a major food producer, the situation of MPs in China's farmland is of even greater concern. Spatial distributions, characteristics, and compositions of MPs in five types of agricultural lands with representative crops were investigated by collecting 477 soil samples from 109 cities in 31 administrative regions of mainland China. To better control MPs in farmland, nearly 400 field questionnaires were obtained, and meteorological conditions, soil properties, and other statistics were collected to quantify potential sources and determine influencing factors. The average abundances of MPs was 2462 ± 3767 items/kg in the agricultural soils, and MP abundance in the greenhouses, farmlands with film mulching, and blank farmlands from four integrated physical geographic regions were determined. The contributions of agricultural films, livestock and poultry manures, irrigation water, and air deposition to MPs in farmlands have been calculated. Influencing factors, such as recovery method, plowing frequency, meteorological conditions, and part of soil properties, were significantly correlated with the abundances of MPs in the agricultural soils (p < 0.05), while mulching age mainly affected MPs in the greenhouses (p < 0.05). This study provides basic scientific data for decision-making and further analysis.
Assuntos
Microplásticos , Poluentes do Solo , Solo , Plásticos , Fazendas , Poluentes do Solo/análise , ChinaRESUMO
BACKGROUND: Recurrence of pelvic organ prolapse (POP) after transvaginal mesh (TVM) implantation pelvic floor reconstruction surgery remains an unresolved problem in clinical practice. In this retrospective observational study, clinical and pelvic floor ultrasound (PFUS) parameters were analyzed in order to identify high-risk factors of POP recurrence. METHODS: The clinical and PFUS data from September 2013 to November 2019 of patients who underwent TVM were retrospectively analyzed. The patients with prolapse recurrence on postoperative follow-up diagnosed by PFUS were selected as case group, the clinical and PFUS parameters of them were compared with the control group in which the patients had no sign of prolapse recurrence. Univariate and multivariate regression analyses were performed based on age, BMI, gravidity, parity, surgical history (non-POP hysterectomy and incontinence-or-POP surgery), preoperative POP stage, follow-up in years, levator avulsion and hiatal area (HA) on Valsalva. RESULTS: Altogether 102 patients entered the study and the median interval between PFUS and TVM surgery was 2.5 years. Univariate analysis showed that levator avulsion and HA were significantly different between case group and control; multivariate regression analysis showed that only HA was related to prolapse recurrence after TVM (OR = 1.202, 95% CI 1.100-1.313, P < 0.001). The area under the ROC curve was 0.775 (95% CI 0.684-0.867, P < 0.001). CONCLUSIONS: Hiatal area on Valsalva was related to prolapse recurrence after TVM surgery and it is an important parameter for postoperative follow-up of TVM surgery.
Assuntos
Diafragma da Pelve , Prolapso de Órgão Pélvico , Feminino , Humanos , Diafragma da Pelve/diagnóstico por imagem , Prolapso de Órgão Pélvico/diagnóstico por imagem , Prolapso de Órgão Pélvico/etiologia , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , UltrassonografiaRESUMO
We present an adaptive optics (AO) system for a 1.94-µm laser source. Our system consists of a home-made Shack-Hartmann wavefront sensor and silver-coated bimorph deformable mirror operating in a closed-loop control scheme. The wavefront sensor used an uncooled vapor phase deposition PbSe focal-plane array for the actual light sensing. An effect of thermal afterimage was found to be reducing the centroid detection precision significantly. The effect was analyzed in detail and finally has been dealt with by updating the background calibration. System stability was increased by reduction of control modes. The system functionality and stability were demonstrated by improved focal spot quality. By replacing some of the used optics, the range of the demonstrated mid-IR AOS could be extended to cover the spectral range of 1-5 µm. To the best of our knowledge, it is the first AO system built specifically for mid-IR laser wavefront correction.