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1.
Bioact Mater ; 19: 24-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35415312

RESUMO

Wound healing is a highly orchestrated process involving a variety of cells, including immune cells. Developing immunomodulatory biomaterials for regenerative engineering applications, such as bone regeneration, is an appealing strategy. Herein, inspired by the immunomodulatory effects of gastrodin (a bioactive component in traditional Chinese herbal medicine), a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane (gastrodin-PU) and nano-hydroxyapatite (n-HA) (gastrodin-PU/n-HA) composites were developed. RAW 264.7 macrophages, rat bone marrow mesenchymal stem cells (rBMSCs), and human umbilical vein endothelial cells (HUVECs) were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin (0.5%, 1%, and 2%) to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro. Results demonstrated that, compared with PU/n-HA, gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype, as evidenced by the higher expression level of pro-regenerative cytokines (CD206, Arg-1) and the lower expression of pro-inflammatory cytokines (iNOS). The expression levels of osteogenesis-related factors (BMP-2 and ALP) in the rBMSCs and angiogenesis-related factors (VEGF and BFGF) in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium. The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory (M1) phenotype to an anti-inflammatory and pro-healing (M2) phenotype were validated in a rat subcutaneous implantation model. And the 2% gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis. Additionally, 2% gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis. Thus, the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.

2.
Theranostics ; 12(12): 5434-5450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910788

RESUMO

Background: Acute kidney injury (AKI) is associated with damage to the nephrons and tubular epithelial cells (TECs), which can lead to chronic kidney disease and end-stage renal disease. Identifying new biomarkers before kidney dysfunction will offer crucial insight into preventive and therapeutic options for the treatment of AKI. Early growth response 1 (EGR1) has been found to be a pioneer transcription factor that can sequentially turn on/off key downstream genes to regulate whole-body regeneration processes in the leopard worm. Whether EGR1 modulates renal regeneration processes in AKI remains to be elucidated. Methods: AKI models of ischemia-reperfusion injury (IRI) and folic acid (FA) were developed to investigate the roles of EGR1 in kidney injury and regeneration. To further determine the function of EGR1, Egr1-/- mice were applied. Furthermore, RNA sequencing of renal TECs, Chromatin Immunoprecipitation (ChIP) assay, and Dual-luciferase reporter assay were carried out to investigate whether EGR1 affects the expression of SOX9. Results: EGR1 is highly expressed in the kidney after AKI both in humans and mice through analysis of the Gene Expression Omnibus (GEO) database. Furthermore, we verified that EGR1 rapidly up-regulates in the very early stage of IRI and nephrotoxic models of AKI, and validation studies confirmed the essential roles of EGR1 in renal tubular cell regeneration. Further experiments affirmed that genetic inhibition of Egr1 aggravates the severity of AKI in mouse models. Furthermore, our results revealed that EGR1 could increase SOX9 expression in renal TECs by directly binding to the promoter of the Sox9 gene, thus promoting SOX9+ cell proliferation by activating the Wnt/ß-catenin pathway. Conclusions: Together, our results demonstrated that rapid and transient induction of EGR1 plays a renoprotective role in AKI, which highlights the prospects of using EGR1 as a potential therapeutic target for the treatment of AKI.


Assuntos
Injúria Renal Aguda , Proteína 1 de Resposta de Crescimento Precoce , Túbulos Renais , Traumatismo por Reperfusão , Fatores de Transcrição SOX9 , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Animais , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células Epiteliais/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Regulação para Cima , Via de Sinalização Wnt
3.
Theranostics ; 12(12): 5470-5487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910794

RESUMO

Rationale: Wound healing is among the most complicated physiological processes and requires the synchronization of various cell types with distinct roles to re-establish the condition of the original skin. Patients affected by peripheral neuropathies often experience failure to heal. Loss of Schwann cells (SCs), a crucial population of peripheral nervous system cells in skin, may contribute to chronic wounds. However, the role of SCs in wound healing are poorly understood. Methods: The activity of SCs was investigated by using a cell atlas of the wound healing process, which was generated by integrating single-cell RNA sequencing (scRNA-seq) libraries covering different states of mouse back skin. The results of in silico analysis were validated by in vitro cell culture and in vivo mouse model. Selective inhibitors and conditional RNAi by virus transfection were utilized to investigate the role of SCs in wound healing. Findings from mouse experiments were further verified in scRNA-seq analysis of diabetic patients. Results: Our in silico analysis revealed the heterogeneous cellular components of skin and the dynamic interactions of neural crest derived cells (NCs) with other cell types. We found that SCs dedifferentiated at an early stage of wound repair with upregulated Wnt signaling. We also identified dedifferentiated SC (dSC) defect in diabetic wounds in both mouse and human. Wnt inhibition at the wound site repressed SC dedifferentiation, leading to defective repair. Furthermore, dSCs derived TGF-ß3, which is context-dependent, promoted the migration of fibroblasts and keratinocytes. Moreover, TGF-ß3 supplementation enhanced the healing of chronic wounds in diabetic mice with impaired SCs. Conclusion: Our study thus advances the understanding of the roles of neural-derived cells in skin regeneration and suggests a potential therapeutic strategy for wound healing disorders.


Assuntos
Desdiferenciação Celular , Diabetes Mellitus Experimental , Doenças do Sistema Nervoso Periférico , Células de Schwann , Fator de Crescimento Transformador beta3 , Cicatrização , Animais , Desdiferenciação Celular/genética , Desdiferenciação Celular/fisiologia , Humanos , Camundongos , Doenças do Sistema Nervoso Periférico/genética , Células de Schwann/fisiologia , Pele/lesões , Pele/inervação , Fator de Crescimento Transformador beta3/genética , Cicatrização/genética , Cicatrização/fisiologia
4.
Mult Scler Relat Disord ; 66: 104070, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35914471

RESUMO

OBJECTIVES: This study aimed to explore the microstructural heterogeneity of different white matter (WM) tissues in relapsing-remitting multiple sclerosis (RRMS) patients by diffusion magnetic resonance imaging (dMRI) and its correlation with disability and cognitive status. MATERIALS AND METHODS: A total of 337 iron rim lesions (IRLs), 337 perilesional white matters of IRLs (IRLs-PLWMs), 330 non-iron rim lesions (non-IRLs), 330 non-IRLs-PLWMs, 42 normal-appearing white matters (NAWMs) in 42 RRMS patients, and 30 white matters in healthy controls (WMs in HCs) were enrolled in the lesion-wise analysis. Diffusion kurtosis imaging (DKI) parameters including kurtosis fractional anisotropy (KFA) and mean kurtosis (MK), and diffusion tensor imaging (DTI) parameters including fractional anisotropy (FA) and mean diffusivity (MD) were measured in the six types of tissues. Subgroup analysis was performed between non-IRLs with QSM hyperintense (non-IRLs-H) and non-IRLs with QSM isointense or hypointense (non-IRLs-I), as well as between non-IRLs-H-PLWMs and non-IRLs-I-PLWMs. Thirty-four out of forty-two patients were enrolled in patient-wise analysis. The relationships between these diffusion metrics of patients and their Kurtzke Expanded Disability Status Scale (EDSS) score and Symbol Digit Modalities Test (SDMT) score were analyzed separately by partial correlation analysis with age and disease duration (DD) as covariates. RESULTS: The KFA, FA, MK, and MD values were significantly different among the six types of tissues. The lowest KFA, FA, and MK values and the highest MD values were revealed in IRLs. There were significant differences in all the enrolled diffusion metrics between IRLs and non-IRLs, as well as between IRLs-PLWMs and non-IRLs-PLWMs (p < 0.05). There were no significant differences between NAWMs and WMs in HCs (p = 1.000 for all enrolled diffusion metrics). For all the enrolled diffusion metrics, no significant differences were found in the subgroup analysis. The FA, MK, and MD values of total lesions (including IRLs and non-IRLs) (r = -0.420, p = 0.017; r = -0.472, p = 0.006; r = -0.475, p = 0.006) and the MK values of IRLs (r = -0.438, p = 0.012) were correlated with the EDSS scores. There was no significant correlation between the diffusion parameter values and the SDMT scores. CONCLUSION: Our findings demonstrate that IRLs are more destructive than non-IRLs. Similarly, IRLs-PLWMs are more destructive than non-IRLs-PLWMs. Additionally, diffusion parameter values of MS lesions can reflect the disability degree. These findings contribute to a better understanding of the different evolution of MS lesions and the relationship between the disability level of patients and focal lesion damage degree.

6.
Microbiol Spectr ; : e0154222, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943267

RESUMO

Phytophthora nicotianae is an oomycete pathogen of global significance threatening many important crops. It is mainly controlled by chemosynthetic fungicides, which endangers ecosystem and human health; thus, there is an urgent need to explore alternatives for these fungicides. In this study, a new anti-oomycete aliphatic compound, 2E,4E-decadienoic acid (DDA), was obtained through coculture of Bacillus subtilis Tpb55 and Trichoderma asperellum HG1. Both in vitro and in vivo tests showed that DDA had a strong inhibitory effect against P. nicotianae. In addition, rhizosphere microbiome analysis showed that DDA reduced the relative abundance of Oomycota in rhizosphere soil. Transcriptome sequencing (RNA-Seq) analysis revealed that treatment of P. nicotianae with DDA resulted in significant downregulation of antioxidant activity and energy metabolism, including antioxidant enzymes and ATP generation, and upregulation of membrane-destabilizing activity, such as phospholipid synthesis and degradation. The metabolomic analysis results implied that the pathways influenced by DDA were mainly related to carbohydrate metabolism, energy metabolism, and the cell membrane. The biophysical tests further indicated that DDA produced oxidative stress on P. nicotianae, inhibited antioxidant enzyme and ATPase activity, and increased cell membrane permeability. Overall, DDA exerts inhibitory activity by acting on multiple targets in P. nicotianae, especially on the cell membrane and mitochondria, and can therefore serve as a novel environment-friendly agent for controlling crop oomycete disease. IMPORTANCE P. nicotianae is an oomycete pathogen that is destructive to crops. Although some oomycete inhibitors have been used during crop production, most are harmful to the ecology and lead to pathogen resistance. Alternatively, medium-chain fatty acids have been reported to exhibit antimicrobial activity in the medical field in previous studies; however, their potential as biocontrol agents has rarely been evaluated. Our in vivo and in vitro analyses revealed that the medium-chain fatty acid 2E,4E-decadienoic acid (DDA) displayed specific inhibitory activity against oomycetes. Further analysis indicated that DDA may acted on multiple targets in P. nicotianae, especially on the cell membrane and mitochondria. Our findings highlight the potential of DDA in controlling oomycete diseases. In conclusion, these results provide insights regarding the future use of green and environment-friendly anti-oomycete natural products for the prevention and control of crop oomycete diseases.

7.
Biomater Adv ; 137: 212822, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929237

RESUMO

The Boston Keratoprosthesis type I (B-KPro) is widely used in the world, but the lack of donor corneas limits its application. This study aims to prepare the acellular porcine cornea (APC) crosslinked with ultraviolet A (UVA)/riboflavin instead of donor corneas as the scaffold for B-KPro. Decellularization of freeze-thaw combined with biological enzymes resulted in approximately 5 ng/mg DNA residue, the a-Gal removal rate of 99%, and glycosaminoglycans retention at a high level of 46.66 ± 2.59 mg/mg. UVA/ riboflavin cross-linking was adopted to induce the formation of new chemical bonds between adjacent collagen chains in the corneal stroma to improve the mechanical properties and resistance to enzymatic hydrolysis. Through comprehensive analysis of the biomechanics, enzyme degradation, immunogenicity and histological structure of the APC crosslinked at different times, CL3 (irradiation conditions, 365 nm, 3 mW/cm, 80 min, both sides) was selected and transplanted into the rabbit cornea model through interlamellar keratoplasty and penetrating keratoplasty as the scaffold of the B-KPro. Compared with the native porcine cornea (NPC) and APC, the experiment of interlamellar pocket indicated that the structure of CL3 was homogeneous without degradation and vascularization in vivo at 12 weeks after surgery. Simultaneously, the results of transplantation of B-KPro showed complete epithelialization of CL3 within 1 week, and neovascularization of the cornea indicated rejection but could be controlled with immunosuppressants. At 3 months postoperatively, the lens of B-KPro remained transparent, and the structure of CL3 was compact and uniform, accompanied by the migration and proliferation of a large number of stromal cells without degradation, suggesting the CL3 could be a promising corneal substitute.


Assuntos
Córnea , Doenças da Córnea , Animais , Córnea/cirurgia , Doenças da Córnea/metabolismo , Reagentes de Ligações Cruzadas/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Próteses e Implantes , Coelhos , Riboflavina/farmacologia , Suínos , Raios Ultravioleta
8.
Cells ; 11(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35954164

RESUMO

Axotomy in the CNS activates retrograde signals that can trigger regeneration or cell death. Whether these outcomes use different injury signals is not known. Local protein synthesis in axon tips plays an important role in axon retraction and regeneration. Microarray and RNA-seq studies on cultured mammalian embryonic or early postnatal peripheral neurons showed that axon growth cones contain hundreds to thousands of mRNAs. In the lamprey, identified reticulospinal neurons vary in the probability that their axons will regenerate after axotomy. The bad regenerators undergo early severe axon retraction and very delayed apoptosis. We micro-aspirated axoplasms from 10 growing, 9 static and 5 retracting axon tips of spinal cord transected lampreys and performed single-cell RNA-seq, analyzing the results bioinformatically. Genes were identified that were upregulated selectively in growing (n = 38), static (20) or retracting tips (18). Among them, map3k2, csnk1e and gtf2h were expressed in growing tips, mapk8(1) was expressed in static tips and prkcq was expressed in retracting tips. Venn diagrams revealed more than 40 components of MAPK signaling pathways, including jnk and p38 isoforms, which were differentially distributed in growing, static and/or retracting tips. Real-time q-PCR and immunohistochemistry verified the colocalization of map3k2 and csnk1e in growing axon tips. Thus, differentially regulated MAPK and circadian rhythm signaling pathways may be involved in activating either programs for axon regeneration or axon retraction and apoptosis.


Assuntos
Axônios , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Lampreias/genética , Mamíferos , Regeneração Nervosa/genética , RNA-Seq , Transdução de Sinais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Transcriptoma/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-35954892

RESUMO

Wind erosion is crucial for assessing regional ecosystem services and sustainable development. The Agro-Pastoral Ecotone of northern China (APEC) is a typical region undergoing wind erosion and soil degradation. In this study, the National Wind Erosion Survey Model of China, the Integrated Wind Erosion Modeling System, and the regional versions of the Revised Wind Erosion Equation and Wind Erosion Prediction System were used to evaluate the regional potential wind erosion of the APEC during 2000 and 2012. The results showed that the potential wind erosion predicted by National Wind Erosion Survey Model of China (NWESMC), Revised Wind Erosion Equation (RWEQ), Wind Erosion Prediction System (WEPS), and Integrated Wind Erosion Modeling System (IWEMS) were significantly related to the observed wind erosion collected from published literature, but the observed data were generally smaller than the predicted values. The average potential wind erosions were 12.58, 25.87, 52.63, and 58.72 t hm-2 a-1 for NWESMC, RWEQ, WEPS, and IWEMS, respectively, while the spatial pattern and temporal trend of annual potential wind erosion were similar for different wind erosion models. Wind speed, soil moisture, and vegetation coverage were the dominant factors affecting regional wind erosion estimation. These results highlight that it is necessary to comprehensively calibrate and validate the selected wind erosion models. A long-term standard wind erosion monitoring network is urgently required. This study can serve as a useful reference for improving wind erosion models.


Assuntos
Ecossistema , Vento , China , Conservação dos Recursos Naturais , Solo
10.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35955949

RESUMO

Leaf morphology is one of the important traits related to ideal plant architecture and is an important factor determining rice stress resistance, which directly affects yield. Wax layers form a barrier to protect plants from different environmental stresses. However, the regulatory effect of wax synthesis genes on leaf morphology and salt tolerance is not well-understood. In this study, we identified a rice mutant, leaf tip rumpled 1 (ltr1), in a mutant library of the classic japonica variety Nipponbare. Phenotypic investigation of NPB and ltr1 suggested that ltr1 showed rumpled leaf with uneven distribution of bulliform cells and sclerenchyma cells, and disordered vascular bundles. A decrease in seed-setting rate in ltr1 led to decreased per-plant grain yield. Moreover, ltr1 was sensitive to salt stress, and LTR1 was strongly induced by salt stress. Map-based cloning of LTR1 showed that there was a 2-bp deletion in the eighth exon of LOC_Os02g40784 in ltr1, resulting in a frameshift mutation and early termination of transcription. Subsequently, the candidate gene was confirmed using complementation, overexpression, and knockout analysis of LOC_Os02g40784. Functional analysis of LTR1 showed that it was a wax synthesis gene and constitutively expressed in entire tissues with higher relative expression level in leaves and panicles. Moreover, overexpression of LTR1 enhanced yield in rice and LTR1 positively regulates salt stress by affecting water and ion homeostasis. These results lay a theoretical foundation for exploring the molecular mechanism of leaf morphogenesis and stress response, providing a new potential strategy for stress-tolerance breeding.


Assuntos
Oryza , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Melhoramento Vegetal , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Tolerância ao Sal/genética
11.
Front Bioeng Biotechnol ; 10: 885130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957638

RESUMO

Background: The relationship between maxillary sinus pneumatization and respiratory-induced fluid mechanics remains unclear. The purpose of this study was to simulate and measure the respiratory-induced mechanical stimulation at the sinus floor under different respiratory conditions and to investigate its potential effect on the elevated sinus following sinus-lifting procedures. Methods: The nasal airway together with the bilateral maxillary sinuses of the selected patient was segmented and digitally modeled from a computed tomographic image. The sinus floors of the models were elevated by simulated sinus augmentations using computer-aided design. The numerical simulations of sinus fluid motion under different respiratory conditions were performed using a computational fluid dynamics (CFD) algorithm. Sinus wall shear stress and static pressure on the pre-surgical and altered sinus floors were examined and quantitatively compared. Results: Streamlines with minimum airflow velocity were visualized in the sinus. The sinus floor pressure and the wall shear stress increased with the elevated inlet flow rate, but the magnitude of these mechanical stimulations remained at a negligible level. The surgical technique and elevated height had no significant influence on the wall pressure and the fluid mechanics. Conclusion: This study shows that respiratory-induced mechanical stimulation in the sinus floor is negligible before and after sinus augmentation.

12.
Clin Breast Cancer ; 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961861

RESUMO

BACKGROUND: Few studies have concerned the prognosis of metaplastic breast cancer (MpBC), a rare and diverse malignancy. A prognostic index estimating the MpBC survival would be attractive in clinical practice. PATIENTS AND METHODS: We retrospectively analyzed MpBC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors were identified and the final nomogram was developed to predict the 1-, 3-, or 5-year overall survival (OS). Calibration curves were provided to internally validate the performance of the nomogram and discriminative ability was appraised by concordance index (C-index). RESULTS: A total of 1017 MpBC patients diagnosed between 2010 and 2015 were assigned into 3:1 as training set (n = 763) and SEER validation set (n = 254). An external validation was performed by an individual set of 94 MpBC patients from National Cancer Center in China from 2010 to 2018. The nomogram finally consisted of 7 independent prognostic factors and presented a good accuracy for predicting the OS with the C-index of 0.77 (95% CI: 0.751-0.786). Interestingly, the nomogram based on the western (including 92.5% non-Asian) SEER validation population (C-index of nomogram: 0.76, 95% CI: 0.737-0.796) also has an optimal discrimination in Asian population (C-index of nomogram: 0.70). The calibration plots of the nomogram predictions were also accurate and corresponded closely with the actual survival rates. CONCLUSION: This novel nomogram was accurate enough to predict the OS by using readily available clinicopathologic factors in MpBC general population, which could provide individualized recommendations for patients and clinical decisions for physicians.

13.
ESC Heart Fail ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950517

RESUMO

AIMS: The present study aimed to evaluate the prognostic value of atrial strain and strain rate (SR) parameters derived from cardiac magnetic resonance (CMR) feature tracking (FT) in patients with ischaemic and non-ischaemic dilated cardiomyopathy with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation. METHODS AND RESULTS: A total of 300 patients who underwent CMR with left ventricular ejection fraction (LVEF) ≤ 40% and ischaemic or non-ischaemic dilated cardiomyopathy were analysed in this retrospective study. Major adverse cardiac events (MACEs) include cardiovascular death, heart transplantation, and rehospitalization for worsening HF. Ninety-four patients had MACEs during median follow-up of 3.84 years. Multivariate Cox regression models adjusted for common clinical and CMR risk factors detected a significant association between LA-εs and MACE in ischaemic (HR = 0.94/%; P = 0.002), non-ischaemic dilated cardiomyopathy (HR = 0.88/%; P = 0.001), or all included patients (HR = 0.87; P < 0.001). LA-εs provided incremental prognostic value over conventional outcome predictors (Uno C statistical comparison model: from 0.776 to 0.801, P < 0.0001; net reclassification improvement: 0.075, 95% CI: 0.0262-0.1301). Kaplan-Meier analysis revealed that the risk of MACE occurrence increased significantly with lower tertiles of left atrial reservoir strain (LA-εs) (log-rank P < 0.0001). Patients in the worst LA-εs tertile faced a significantly increased risk of MACEs irrespective of late gadolinium enhancement (LGE) (log-rank P < 0.0001). CONCLUSIONS: LA-εs derived from CMR FT has a significant prognostic impact on patients with ischaemic or non-ischaemic dilated cardiomyopathy, incremental to common clinical and CMR risk-factors.

14.
J Prosthodont ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950785

RESUMO

PURPOSE: To compare and evaluate density changes in alveolar bones and biomechanical responses including stress/strain distributions around customized root implants (CRIs), traditional implants, and natural teeth. MATERIALS AND METHODS: A three-dimensional finite element model of the maxillary dentition defect, CRI models, traditional restored implant models, and natural teeth with periodontal tissue models were established. The chewing load of the central incisor, the traditional implant, and the CRI was 100N, and the load direction was inclined by 11° in the sagittal plane. According to the bone remodeling numerical algorithm, the bone mineral density and distribution were calculated and predicted. In addition, animal experiments were performed to verify the feasibility of the implant design. The results of the simulation calculations were compared with animal experimental data in vivo to verify their validity. RESULTS: No significant differences in bone mineral density and stress/strain distribution were found between the CRI and traditional implant models. The animal experimental results (X-ray images and histological staining) were consistent with the numerical simulated results. CONCLUSIONS: CRIs were more similar to traditional implants than to natural teeth in terms of biomechanical and biological evaluation. Considering the convenience of clinical application, this biomechanical evaluation provides basic theoretical support for further applications of CRI. This article is protected by copyright. All rights reserved.

15.
Front Immunol ; 13: 920253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911687

RESUMO

Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.


Assuntos
Neoplasias Laríngeas , Receptor Notch1 , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Imunidade/genética , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirurgia , Mutação , Recidiva Local de Neoplasia/patologia , Receptor Notch1/genética , Receptor Notch1/imunologia
16.
Huan Jing Ke Xue ; 43(8): 4387-4393, 2022 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-35971735

RESUMO

The pollution of micro/nanoplastics in the natural environment is becoming increasingly serious, but the potential effects of nanoplastics on crops remain unclear. In the present study, the effects of polystyrene nanoplastics (PS-NPs) with a particle size of 80 nm on the chlorophyll content, antioxidant enzyme activity, and nutritional quality of Allium sativum L. were explored via hydroponic culture. The results showed that the chlorophyll contents in leaves of A. sativum treated with PS-NPs were significantly lower than those in the control, indicating that the synthesis of chlorophyll was inhibited. The superoxide dismutase (SOD), ascorbate peroxidase (APX) activities, and proline contents in leaves of A. sativum initially increased but then decreased with the increase in ρ(PS-NPs). The activity of guaiacol peroxidase (POD) increased with the increase in ρ(PS-NPs) for 10 days of treatment; however, it was inhibited for 20 days of treatment. The malondialdehyde (MDA) content increased with the rise in ρ(PS-NPs). When ρ(PS-NPs) increased to 100 mg·L-1, the MDA content in leaves of A. sativum increased by 43.24% and 89.70% for 10 and 20-day treatments, respectively, compared with those in the control. Meanwhile, the contents of soluble protein, soluble sugar, and vitamin C were higher than those in the control for 10-day treatments; however, the vitamin C content decreased by 26.53% after 20 days of treatment. These results indicated that PS-NPs had a significant oxidative stress on A. sativum, and a high concentration of PS-NPs stress would have deleterious effects on the nutritional quality of A. sativum.


Assuntos
Alho , Poliestirenos , Antioxidantes/metabolismo , Ácido Ascórbico , Clorofila , Alho/metabolismo , Microplásticos
17.
J Prosthodont Res ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35934782

RESUMO

PURPOSE: This study aimed to evaluate the influence of subcrestal implant placement depth on bone remodeling using time-dependent finite element analysis (FEA) with a bone-remodeling algorithm over 12 months. METHODS: Seven models of different subcrestal implant placement depths (0, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm) were analyzed using FEA to evaluate the biomechanical responses in the bone and implant, including von Mises equivalent stress, strain energy density (SED), and overloading elements. SED was used as a mechanical stimulus to simulate cortical and cancellous bone remodeling over the first 12 months after final prosthesis delivery. RESULTS: The highest increase in cortical bone density was observed at Depth 1.5, whereas the lowest increase was observed at Depth 3.0. In contrast, the highest increase in bone density was observed at Depth 3.0 in the cancellous bone, whereas the lowest increase was observed at Depth 0. The highest peak von Mises stress in the cortical bone occurred at Depth 2.5 (107.24 MPa), while that in the cancellous bone was at Depth 2.5 (34.55 MPa). Notably, the maximum von Mises stress values in the cancellous bone exceeded the natural limit of the bony material, as indicated by the overloading elements observed at the depths of 2.0, 2.5, and 3.0 mm. CONCLUSION: Greater bone density apposition is observed with deeper implant placement. An implant depth of more than 1.5 mm exhibited a higher maximum von Mises stress and greater overloading elements.

18.
J Clin Lab Anal ; : e24659, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35971777

RESUMO

OBJECTIVE: To evaluate the consistency between the results of Sysmex UF-5000 system and Atellica® UAS 800 Urine Sediment Analyzer. METHODS: A total of 636 random urine samples were collected from inpatients and outpatients from March to September 2021. Urine was collected for analysis by the Sysmex UF-5000, Atellica UAS 800 systems, and manual microscopic examination. The results of manual microscopy as the gold standard, the coincidence rate and false-negative rate of Sysmex UF-5000 and Atellica UAS 800 systems in the detection of red blood cells, white blood cells, and casts were calculated. RESULTS: The coincidence rates of red blood cells, white blood cells, and cast, crystals, and other sediment components for the Sysmex UF-5000 system were 85.37%, 87.89%, 91.67%, 88.36%, and 71.86%. The false-negative rates were 28.47%, 3.75%, 68.97%, 37.25%, and 30.63%. The coincidence rates of red blood cells, white blood cells, and cast, crystals, and other sediment components for the Atellica UAS 800 system were 85.06%, 90.25%, 59.12%, 91.67%, and 67.45% and the false-negative rates were 60.42%, 21.25%, 36.21%, 19.64%, and 35.80%. CONCLUSION: Two instruments are superior in the detection of red blood cells and white blood cells. The Atellica UAS 800 system with image review has a good coincidence rate in the identification of crystals and casts. The identification of various sediment components in urine by both instruments meets the laboratory requirements. Two instruments with different methodologies have their own characteristics, and we should reasonably use them according to the conditions of the laboratory.

19.
Ecotoxicol Environ Saf ; 242: 113910, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35917712

RESUMO

The accumulation of potentially harmful substances in tea garden soils and tea leaves, especially persistent organic pollutants (POPs), is a special concern for tea consumers worldwide. However, their potential health and ecological risks in tea gardens have rarely been investigated. This study proposed measures to improve the degradation ability of POPs by the tea rhizosphere and to reduce the human health risks caused by POPs after tea consumption. In this study, the binding energy values of six types of POPs and the degraded protein were used to reflect the degradation ability and calculated using molecular dynamic simulations. The main root secretions (i.e., catechin, glucose, arginine, and oxalic acid) were selected and applied with a combination of tea fertilizer and trace element combination (i.e., urea, straw, and copper element), leading to an improved degradation ability (49.59 %) of POPs. To investigate the mechanisms of the factors that affect the degradation ability, molecular docking, tensor singular value decomposition methods, multivariate correlation analysis and 2D-QSAR model were used. The results showed that the solvation energy and solvent accessible surface area are the main forces, and the molecular weight, boiling point, and topological radius of the POPs were the key molecular features affecting their degradation ability. Based on the three key characteristics, a diet avoidance scheme (i.e., avoiding lysine, maslinic acid, ethanol, perfluorocaproic acid, and cholesterol with tea), which can reduce the binding ability of POP residues to aromatic hydrocarbon receptors by 506.13 %. This work will provide theoretical strategies to improve the quality and safety of tea production and reduce the potential risks of harmful substance residues in tea garden soils and tea leaves.

20.
Front Oncol ; 12: 853815, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912262

RESUMO

Purpose: The aim of this study is to evaluate the utility of magnetization transfer (MT) imaging in the study of normal uterus and common uterine lesions. Methods: This prospective study enrolled 160 consecutive patients with suspected uterine lesions. MT ratio (MTR) map was obtained by pelvic MT imaging on a 3.0T MRI scanner. Patients confirmed by pathology were divided into microscopic lesion group and lesion group, according to whether the maximum diameter of the lesion was less than 5 mm. After evaluating and eliminating patients with poor image quality by a three-point Likert scale, MTR values of lesions and normal endometrium, myometrium, and cervix were independently measured on the MTR map by two radiologists. Inter-reader agreement was evaluated. MTR values were compared among different uterine lesions and normal uterine structures using the Mann-Whitney U test with Bonferroni correction. Receiver operating characteristic curve was performed. The correlations between age and MTR values were explored by Pearson correlation analyses. Results: A total of 96 patients with 121 uterine lesions in the lesion group and 41 patients in the microscopic lesion group were measured. The MTR values among normal endometrium, myometrium, and cervix were statistical significant differences (P < 0.05). There were significant differences between endometrial cancer and normal endometrium and between cervical cancer and normal cervix (both P ≤ 0.001). Area under the curve (AUC) for diagnosing endometrial and cervical cancer were 0.73 and 0.86. Myometrial lesions had significantly higher MTR values than endometrial lesions and cervical cancer (both P < 0.001), and the AUC for differentiating myometrial lesions from them were 0.89 and 0.94. MTR values of endometrial cancer were significantly higher than those of cervical cancer (P = 0.02). There was a critical correlation between age and MTR values in endometrial cancer (r = 0.81, P = 0.04). Conclusions: MTR values showed significant differences among normal uterine structures. It was valuable for diagnosing and differentiating uterine cancer. MTR values could differentiate myometrial lesions from endometrial or cervical lesions.

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