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The urgent development of sodium ion batteries has stimulated the rapid innovation of sodium super ionic conductor-type Na3V2(PO4)3 materials with high energy density and ultra-high charge/discharge rates, where the bottlenecks are the activation of multi-electron reactions and the utilization of the third sodium ion. Herein, we design a trace topological doping strategy to introduce barium ions into crystal domains of Na3V2(PO4)3 to partially replace vanadium sites. Deep learning demonstrates that the violation of the inversion symmetry of vanadium by barium substitution can improve the structural stability and change the charge density distribution of vanadium, resulting in the re-distribution of surface electrons and supplying more possible migration paths for sodium ions. Simultaneously, the slight alteration of the crystal structure helps the positive shift of vanadium valence from +3 to +4, providing more multi-electron redox reactions. Among these candidates, NVBP-2 manifests a specific capacity of 65.1 mA h g-1 at 50C rate with superior charge-discharge capability and cycling performance. Moreover, it possesses decent long-term cycling stability with 81.2% capacity retention after 2000 cycles at 50C. In summary, the results indicate that trace topological doping of alkaline metal ions in combination with deep learning has a novel ability to achieve sodium ion storage regulation for sodium ion batteries, which exquisitely provides a new perspective for screening cathode materials with high electrochemical performance.
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In recent years, with the increasing global focus on environmental protection, the issue of microfiber release from denim during the washing process has gained attention. In this study, a programmable washing device simulating household drum washing was designed and developed, microfibers and indigo dyes released from denim washing were quantitatively detected, and we have also developed a novel method for estimating the release of microfibers during washing. The effects of washing time, washing temperature, and washing load on microfiber and indigo dye release from denim were explored. The results showed that the effect of washing load on microfiber and indigo dye release was greater than washing temperature and washing time. The research findings indicate that with an increase in washing time (35-95 min) and washing load (100-250 g), the shedding of microfibers and indigo dye significantly increases, reaching peak release levels of 343.6 µg/g fabric and 0.027 mg/L, respectively. However, there is a decreasing trend in the release of microfibers and indigo dye when the washing temperature exceeds 50 °C. Furthermore, our data suggests that an increase in washing load leads to a significant change in the number of microfibers (from 978 items/g fabric to 1997 items/g fabric) and their mass (from 156.87 µg/g fabric to 343.56 µg/g fabric). The influence of washing time, washing temperature, and washing load on microfiber length shows relatively small fluctuations within the range of 600-900 µm. This study provides new ideas and methods for estimating the release of microfiber and indigo dye in denim washing around the world.
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Índigo Carmim , TêxteisRESUMO
BACKGROUND: This study aimed to investigate the association between the serum-creatinine-to-cystatin C-to-waist-circumference (CCR/WC) ratio with lung function and severe airflow limitation (SAL). METHODS: The data were derived from the China Health and Retirement Longitudinal Study. Peak expiratory flow (PEF) was used as a measure of lung function parameter. Logistic and linear regression were utilized separately to evaluate the relationship between the CCR/WC ratio with PEF and SAL in baseline. Restricted cubic spline was used to explore potential non-linear associations between the CCR/WC ratio and SAL. Cox proportional-hazards models were used to assess the association between CCR/WC quartiles and the risk of new-onset SAL. RESULTS: A total of 6105 participants were included. This study revealed a positive association between the CCR/WC ratio and lung function (PEF: ß [partial coefficient]: 25.95, 95%CI: 12.72 to 39.18, p < 0.001; PEF/PEF prediction: ß = 0.08, 95%CI: 0.05 to 0.12, p < 0.001) and an inverse association relationship with SAL (OR [odds ratio]: 0.64, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.003). Subgroup analysis showed a significant association between the CCR/WC ratio and SAL in males (OR: 0.58, 95% CI: 0.37 to 0.90, p = 0.017) but not in females (p = 0.059). Cox regression analysis revealed a decreased risk of SAL in the quartiles (Q2-4) compared to the first quartile of the CCR/WC ratio (hazard ratios [HRs]: 0.49 to 0.73, all p < 0.05). CONCLUSIONS: This study highlights a positive association between the CCR/WC ratio and lung function, with a potential protective effect against SAL.
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Background: Anemia in children is still an important public problem in China and can have a profound impact on the physical and mental health of children. The purpose of this study was to explore the risk factors for anemia among Chinese children aged 3-7 years old and to provide some basis for the prevention and control of anemia. Methods: A matched case-control study was conducted and 1104 children (552 cases and 552 controls) were recruited in this study. Cases were children who were diagnosed with anemia by the doctor of physical examination and checked by one deputy chief physician of pediatrics, and controls were healthy children without anemia. Data were collected using a self-designed structured questionnaire. Univariable and multivariable analyses were used to identify independent determinants of anemia. P values less than 0.05 were used to declare statistical significance. Results: In the multivariable analyses, maternal anemia before or during pregnancy and lactation (OR = 2.14, 95% CI: 1.10â¼4.15; OR = 2.86, 95% CI: 1.66â¼4.94; OR = 2.51, 95% CI: 1.13â¼5.60), gestational weeks (OR = 0.72, 95% CI: 0.53â¼0.96), having G6PD deficiency or thalassemia (OR = 8.12, 95% CI: 2.00â¼33.04; OR = 36.25, 95% CI: 10.40â¼126.43), having cold and cough in previous two weeks (OR = 1.56, 95% CI: 1.04â¼2.34), family income (OR = 0.80, 95% CI: 0.65â¼0.97), and being a picky eater (OR = 1.80, 95% CI: 1.20â¼2.71) were determinants of anemia in children aged 3-7 years old. Conclusions: Some of the identified factors are modifiable and could be targeted to reduce childhood anemia. More emphasis should be given by the concerned bodies to intervene in the anemia problem by improving the maternal health education, screening for disease-related anemia, requesting medical services in a timely manner, improving the economic status of households, promoting dietary habits, and improving sanitation and hygiene practices.
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Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
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Neoplasias , Fototerapia , Linhagem Celular Tumoral , Fototerapia/métodos , Imunoterapia/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Raios Infravermelhos , Neoplasias/tratamento farmacológicoRESUMO
Traditional immunohistochemistry (IHC) has already become an essential method of diagnosis and therapy in cancer management. However, this antibody-based technique is limited to detecting a single marker per tissue section. Since immunotherapy has revolutionized the antineoplastic therapy, developing new immunohistochemistry strategies to detect multiple markers simultaneously to better understand tumor environment and predict or assess response to immunotherapy is necessary and urgent. Multiplex immunohistochemistry (mIHC)/multiplex immunofluorescence (mIF), such as multiplex chromogenic IHC and multiplex fluorescent immunohistochemistry (mfIHC), is a new and emerging technology to label multiple biomarkers in a single pathological section. The mfIHC shows a higher performance in cancer immunotherapy. This review summarizes the technologies, which are applied for mfIHC, and discusses how they are employed for immunotherapy research.
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Neoplasias , Humanos , Imunofluorescência , Imuno-Histoquímica , Biomarcadores , Imunoterapia , Biomarcadores TumoraisRESUMO
BACKGROUND AND OBJECTIVES: Melasma is a refractory skin disease due to its complex pathogenesis and difficult treatment. Studies have found that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) could serve as a novel cell-free therapeutic strategy in regenerative and esthetic medicine. It could potentially treat melasma, but the skin barrier is a challenge. In this study, we aim to explore the safety and efficacy of hUCMSC-Exos in the treatment of melasma and the means to promote its percutaneous penetration. MATERIALS AND METHODS: In the animal study about the effect of penetration, percutaneous penetration of PKH67-labeled hUCMSC-Exos was studied under microneedles, 1565 nm nonablative fractional laser (NAFL), and a plasma named Peninsula Blue Aurora Shumin Master (PBASM) treatments, observed by confocal laser scanning microscopy. In the clinical application study, 60 patients with melasma treated in our department were divided into four groups. NAFL combined with normal saline treatment was used for Group A. Microneedles, NAFL, and PBASM combined with hUCMSC-Exos treatments were used for Groups B, C, and D, respectively. Each patient received four treatments at 1-month intervals. Assessments were done using the degree of pain posttreatment, melasma area and severity score, improvement rate, physician global assessment score, satisfaction, and complications. RESULTS: In the animal study about the effect of penetration, hUCMSC-Exos can penetrate the deep dermis under microneedles, NAFL, and PBASM treatments. In the clinical application study, compared with Group A, Groups B, C, and D showed significantly improved therapeutic effect and patient satisfaction (p < 0.05), and there was no significant difference among Groups B, C, and D.(p > 0.05). Patients in Group B reported higher pain levels than those in the other three groups (p < 0.05); the treatment experience of patients in Group D was better. CONCLUSION: hUCMSC-Exos can improve the symptoms of melasma safely and effectively. Compared with microneedles, NAFL and PBASM can also achieve a good effect toward promoting penetration. These findings are worthy of exploration and clinical application.
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Exossomos , Melanose , Células-Tronco Mesenquimais , Animais , Humanos , Pele , Melanose/terapia , Células-TroncoRESUMO
Circulating biomarkers play important roles in diagnosis of malignant tumors. N-glycosylation is an important post-translation patter and obviously affect biological behaviors of malignant tumor cells. However, the role of N-glycosylation sites in early diagnosis of tumors still remains further investigation. In this study, plasma from 20 lung adenocarcinoma (LUAD), which were all classified as stage I, as well as 20 normal controls (NL) were labeled and screened by mass spectrometry (MS). Total 39 differential N-glycosylation sites were detected in LUAD, 17 were up-regulated and 22 were down-regulated. In all differential sites, ITGB3-680 showed highest potential in LUAD which showed 99.2% AUC, 95.0% SP and 95.0% SN. Besides, APOB-1523 (AUC: 89.0%, SP: 95.0%, SN: 70.0%), APOB-2982 (AUC: 86.8%, SP: 95.0%, SN: 45.0%) and LPAL2-101 (AUC: 81.1%, SP: 95.0%, SN: 47.4%) also acted as candidate biomarkers in LUAD. Combination analysis was then performed by random forest model, all samples were divided into training group (16 cases) and testing group (4 cases) and conducted by feature selection, machine learning, integrated model of classifier and model evaluation. And the results indicated that combination of differential sites could reach 100% AUC in both training and testing group. Taken together, our study revealed multiple N-glycosylation sites which could be applied as candidate biomarkers for early diagnosis diagnosis of LUAD.
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Background: Ferroptosis is an iron-dependent form of cell death. In this study, we identified ferroptosis-related long noncoding RNAs (FRlncRNAs) to investigate their association with hepatocellular carcinoma (HCC) in prognosis, tumor immune environment, and genome instability. Methods: Transcriptome profile data of HCC were retrieved from a public database. FRlncRNAs were identified by co-expression analysis. Patients were randomly divided into training and test cohorts. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were performed to construct a risk model. Patients were divided into high- and low-risk groups based on the risk model. AUC and C index were used to assess the risk model. Survival analysis, immune status, and genome instability were compared between the two groups. Results: Sixteen FRlncRNAs were identified and used to construct an FRlncRNA signature for the risk model. The Kaplan-Meier analysis revealed that patients in the high-risk group had poorer overall survival than patients in the low-risk group. The area under curve of the risk model was 0.879, 0.809, and 0.757 in the training cohort and 0.635, 0.688, and 0.739 in the test cohort at 1, 2, and 3 years, respectively. The risk model was an independent prognostic predictor and showed excellent prediction of prognosis compared with clinicopathological features. For the differentially expressed ferroptosis-related genes, many enriched metabolic pathways were identified in the functional enrichment analysis. Immune cells such as CD8+ T cells, macrophages M1, natural killer cells, and B cells, which may be associated with antitumor immune responses, differed between the high- and low-risk groups. Genome instability based on the risk model was also explored. A total of 61 genes were differently mutated between the two risk groups, and among them, TP53, HECW2, TRIM66, MCTP2, and KIAA1551 had the most significant mutation frequency differences. Conclusion: The FRlncRNA signature is closely related with overall survival, tumor immune environment, and genome instability in HCC.
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Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , RNA Longo não Codificante , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Prognóstico , Ubiquitina-Proteína LigasesRESUMO
The main strategy of tissue repair and regeneration focuses on the application of mesenchymal stem cells and cell-based nanoparticles, but there are still multiple challenges that may have negative impacts on human safety and therapeutic efficacy. Cell-free nanotechnology can effectively overcome these obstacles and limitations. Mesenchymal stem cell (MSC)-derived natural small extracellular vesicles (sEVs) represent ideal nanotherapeutics due to their low immunogenicity and lack of tumorigenicity. Here, sEVs harvested from Wharton's jelly mesenchymal stem cells (WJMSCs) were identified. In vitro results showed that WJMSC-sEVs efficiently entered chondrocytes in the osteoarthritis (OA) model, further promoted chondrocyte migration and proliferation and modulated immune reactivity. In vivo, WJMSC-sEVs notably promoted chondrogenesis, which was consistent with the effect of WJMSCs. RNA sequencing results revealed that sEV-microRNA-regulated biocircuits can significantly contribute to the treatment of OA, such as by promoting the activation of the calcium signaling pathway, ECM-receptor interaction pathway and NOTCH signaling pathway. In particular, let-7e-5p, which is found in WJMSC-sEVs, was shown to be a potential core molecule for promoting cartilage regeneration by regulating the levels of STAT3 and IGF1R. Our findings suggest that WJMSC-sEV-induced chondrogenesis is a promising innovative and feasible cell-free nanotherapy for OA treatment.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Nanopartículas , Geleia de Wharton , Cartilagem , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismoRESUMO
Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
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Imunoconjugados , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial , Receptores ErbB/metabolismo , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Due to the high absorption rate of traditional autologous fat grafting, cell-assisted lipotransfer (CAL) and platelet-rich plasma (PRP)-assisted lipotransfer were developed. The purpose of this article was to evaluate the efficacy and safety of CAL and PRP in promoting the survival of autologous fat grafting through systematic review and meta-analysis. We searched Pubmed, Cochrane Library, Web of Science, and EMBASE for clinical studies on CAL and PRP-assisted lipotransfer published from January 2010 to January 2020. Then a meta-analysis was performed to assess the efficacy of CAL and PRP-assisted lipotransfer through data analysis of fat survival rate. We also assessed the incidence of complications and multiple operations to analyze their safety. A total of 36 studies (1697 patients) were included in this review. Regardless of the recipient area, CAL and PRP-assisted lipotransfer significantly improved the fat survival rate (CAL vs non-CAL: 71% vs 48%, P < 0.0001; PRP vs non-PRP: 70% vs 40%, P < 0.0001; CAL vs PRP: 71% vs 70%, P = 0.7175). However, in large-volume fat grafting, such as breast reconstruction, both increased the incidence of complications and did not decrease the frequency of multiple operations after lipotransfer. Further prospective studies are needed to evaluate the clinical benefits of CAL and PRP-assisted lipotransfer.
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Tecido Adiposo/transplante , Plasma Rico em Plaquetas/metabolismo , Adolescente , Adulto , Humanos , Adulto JovemRESUMO
In the last few decades, antibody-based diagnostic and therapeutic applications have been well established in medicine and have revolutionized cancer managements by improving tumor detection and treatment. Antibodies are unique medical elements due to their powerful properties of being able to recognize specific antigens and their therapeutic mechanisms such as blocking specific pathways, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. Furthermore, modification techniques have paved the way for improving antibody properties and to develop new classes of antibody-conjugate-based diagnostic and therapeutic agents. These techniques allow arming antibodies with various effector molecules. However, these techniques are utilizing the most frequently used amino acid residues for bioconjugation, such as cysteine and lysine. These bioconjugation approaches generate heterogeneous products with different functional and safety profiles. This is mainly due to the abundance of lysine and cysteine side chains. To overcome these limitations, different site-direct conjugation methods have been applied to arm the antibodies with therapeutic or diagnostics molecules to generate unified antibody conjugates with tailored properties. This review summarizes some of the enzyme-based site-specific conjugation approaches.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.
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Enzima de Conversão de Angiotensina 2/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vasopressinas/imunologia , Internalização do Vírus , COVID-19/imunologia , COVID-19/virologia , Linhagem Celular , Humanos , Ligação ProteicaRESUMO
Radiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Lesões por Radiação , Diferenciação Celular , Humanos , Imunomodulação , Lesões por Radiação/terapiaRESUMO
BACKGROUND: Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. METHODS: In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. RESULTS: We noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity, and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated. CONCLUSIONS: Altogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.
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Cicatriz Hipertrófica , Animais , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/prevenção & controle , Meios de Cultivo Condicionados/farmacologia , Fibroblastos/patologia , Hidrogéis , Polissacarídeos , Coelhos , Células-Tronco/patologiaRESUMO
Phospholipase A2 (PLA2) may be a vital biomarker for the prediction and diagnosis of some diseases. Consequently, it is of great significance to quantitatively detect PLA2 in biologic samples. Herein, on the basis of the principle of luminescence resonance energy transfer (LRET) between upconversion nanoparticles (UCNPs) and SYBR Green I (SG), we proposed a technology for the highly sensitive detection of PLA2 amount. Therein, as an energy receptor, SG will be quantitatively loaded into liposomes firstly. Then, due to the hydrolysis of liposomes under the catalysis of PLA2, SG will be released and inserted into the double-stranded DNA (dsDNA) on the surface of UCNPs, which triggers the LRET because of the shortening of effective spatial distance between UCNPs and SG. Under exciting of NIR light, UCNPs emit luminescence at 476 nm, which makes SG emit fluorescence at 522 nm through LRET. Under optimal conditions, the emission intensity ratio (I522 nm/I476 nm) increased linearly with the PLA2 amount in the range of 20 U/L to 400 U/L, and the limit of detection (LOD) reached 15 U/L. Here, after comparing with the clinical standard method, it is found that the biosensor is expected to provide a convenient and sensitive assay for the detection of PLA2 in actual serum samples. Furthermore, such biosensor can also be used to test the inhibitor of PLA2.
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Transferência Ressonante de Energia de Fluorescência , Nanopartículas , Benzotiazóis , Diaminas , Compostos Orgânicos , Fosfolipases , QuinolinasRESUMO
High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.
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Aclimatação/genética , Cromatina/metabolismo , Etnicidade/genética , Redes Reguladoras de Genes , Modelos Genéticos , Altitude , Doença da Altitude/etnologia , Doença da Altitude/genética , Doença da Altitude/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular/genética , Células Cultivadas , Cromatina/genética , Sequenciamento de Cromatina por Imunoprecipitação , Resistência à Doença/genética , Feminino , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Oxigênio/metabolismo , Polimorfismo de Nucleotídeo Único , Gravidez , Cultura Primária de Células , RNA-Seq , Elementos Reguladores de Transcrição/genética , Seleção Genética , Tibet/etnologia , Fatores de Transcrição/metabolismo , Sequenciamento Completo do GenomaRESUMO
The cycling of phosphorus (P), iron (Fe) and sulfur (S) in sediments has been previously investigated, but its impacts on the formation of black-odorous waterbodies remains unclear. Here, high-resolution (i.e., 2 mm for P and Fe, and 0.042 mm for S of 2D presentation) simultaneous measurements of P, Fe, and S profiles in river sediments based on the diffusive gradients in thin-films (DGT) technique were conducted in the Pearl River Delta region, South China. Similar distribution trends and significant positive correlations (R = 0.67-0.93, p < 0.01) were observed between Fe and P. Considering the high diffusion fluxes of Fe and P together, it revealed that P release was promoted by the Fe reduction. The two-dimensional labile S profiles showed that their concentrations in sediments were higher by factors of 1.6-20 than those in overlying water. The minor diffusion fluxes of S and the accumulation of acid volatile sulfide indicated that S2- combining with Fe2+ occurred prior to diffusion. Furthermore, the formation mechanisms of black-odorous waterbodies were explored: (i) oxygen depletion by COD and NH4+âN and large amounts of sulfate input were the main exogenous driving factors. (ii) Reduction of Fe and S to form ferrous sulfide accompanied with P release in sediments were the dominant endogenous causes. These observations together with mechanism analysis can provide a basis for the governance of black-odorous rivers.