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OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.
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Purpose: To observe the relationship between myopia progression and changes in retinal thickness during one year of follow-up among primary school children. Methods: The study included 1161 eyes of 708 myopic children, with 616 (53.06%) right eyes and 545 (46.94%) left eyes. The participants underwent a comprehensive ophthalmic examination, including visual acuity, axial length (AL), autorefraction, and optical coherence tomography (OCT) examination in 2016 and in 2017. An analysis was conducted on the differences in retinal thickness between different genders and between high myopia and nonhigh myopia. Furthermore, the study delved into the correlation between the progression of myopia and the changes of retinal thickness. Results: The average diopter was -1.83 ± 1.29D, average AL was 23.78 ± 0.94 mm, and average foveal thickness was 228.02 ± 23.00 µm. For the inner retina, the median value [the lower quartile value, the upper quartile value] of the foveal thickness was thicker in the high myopia group than the nonhigh myopia group (67 [64; 74] µm vs. 63 [56; 70] µm), while the parafoveal region and perifoveal region were thinner in the high myopia group than the nonhigh myopia group (106 [100; 123] µm vs. 124 [117; 130] µm; 95.0 [93; 102] µm vs. 104 [100; 108] µm). Among all the children with myopia, 67.53% (784/1161) of them have a diopter progression within one year. The AL progression was 95.43% (1108/1161). The retinal thickness of all children has slightly increased in various regions. As the AL of the eye increased and the diopter decreased, the progression degree of inner retinal thickness and full retinal thickness (exclusive of full fovea) decreased. Conclusion: For the school-age myopic children, the inner foveal retinal thickness were thicker in highly myopic students than in the nonhighly myopic students, while the parafoveal and perifoveal retina were thinner in highly myopic students. The inner and full retinal thicknesses of male students were thicker than that of females. The progression of myopia mainly affected the changes of the inner retinal thickness in the one-year follow-up.
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BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.
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Plasmonic color printing presents a sustainable solution for vibrant and durable color reproduction by leveraging the light-manipulating properties of nanostructures. However, the fabrication of plasmonic nanostructures has posed challenges, hindering widespread adoption. In this paper, we introduce plasmonic reflector arrays (PRAs) composed of three layersâAg nanoparticles (NPs), an Al2O3 spacer, and an Ag reflectorâdeposited via physical vapor deposition (PVD). By employing nanosecond and femtosecond laser writing techniques, we manipulate the surface morphology of silver nanoparticles on PRAs, resulting in a diverse range of structural colors that are both polarization-insensitive and polarization-sensitive. Furthermore, we demonstrate the versatility of nanosecond laser writing in creating intricate patterns on PRAs. Additionally, we propose a novel two-step method combining nanosecond and femtosecond laser processing to embed QR code patterns into PRAs, showcasing their potential for secure data encryption and transmission. This research underscores the promising applications of PRAs in advanced color printing and secure optical data encoding.
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Background: Osteosarcoma (OS) is an exceptionally aggressive bone neoplasm that predominantly impacts the paediatric and adolescent population, exhibiting unfavourable prognosis. The importance of RNA binding motif protein 14 (RBM14) in the aetiology of OS is not well understood, despite its established involvement in several other types of cancer. Methods: In this study, we conducted an analysis of the expression profiles of RBM14 in cancer tissues and cell lines. To achieve this, we will utilised data obtained from various databases including The Cancer Genome Atlas Program (TCGA) project, The Genotype-Tissue Expression (GTEx) Project, Gene Expression Omnibus (GEO) database, and cancer cell line encyclopedia (CCLE) data. Furthermore, this study also aims to examine the effects of RBM14 on the proliferation, migration, and invasive properties of OS cells using cell functional gain and loss studies. In this study, we carried out an in-depth investigation to explore possible molecular pathways that underlie the regulation of the malignant phenotype found in OS by RBM14. This investigation involved integrating data from RBM14 overexpression, RBM14 knockdown RNA-seq experiments, and an array comprising 6,096 perturbed genes obtained from the Genetic Perturbation Similarity Analysis Database (GPSAdb). This research offers an opportunity to build a robust conceptual framework for the potential advancement of novel therapeutic approaches that are especially aimed at attacking OS. Results: RBM14 plays an active role in OS by significantly contributing to the enhancement of cellular proliferation, migration, and invasion. At the molecular level, it is probable that RBM14 exerts control over the malignant characteristics of OS through its modulation of the Hippo signalling system. Conclusions: The above-mentioned findings underscore the significant importance of RBM14 as an intriguing target for therapy for the mitigation and management of OS. This particular protein holds an excellent opportunity for the development of novel and efficacious therapeutic approaches that possess the potential to yield favorable results for patients affected with OS.
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X-ray images typically contain complex background information and abundant small objects, posing significant challenges for object detection in security tasks. Most existing object detection methods rely on complex networks and high computational costs, which poses a challenge to implement lightweight models. This article proposes Fine-YOLO to achieve rapid and accurate detection in the security domain. First, a low-parameter feature aggregation (LPFA) structure is designed for the backbone feature network of YOLOv7 to enhance its ability to learn more information with a lighter structure. Second, a high-density feature aggregation (HDFA) structure is proposed to solve the problem of loss of local details and deep location information caused by the necked feature fusion network in YOLOv7-Tiny-SiLU, connecting cross-level features through max-pooling. Third, the Normalized Wasserstein Distance (NWD) method is employed to alleviate the convergence complexity resulting from the extreme sensitivity of bounding box regression to small objects. The proposed Fine-YOLO model is evaluated on the EDS dataset, achieving a detection accuracy of 58.3% with only 16.1 M parameters. In addition, an auxiliary validation is performed on the NEU-DET dataset, the detection accuracy reaches 73.1%. Experimental results show that Fine-YOLO is not only suitable for security, but can also be extended to other inspection areas.
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To date, earlier diagnosis of Alzheimer's disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aß) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aß plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aß plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aß plaque formation.
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Maladie d'Alzheimer , Encéphale , Facteur de croissance du tissu conjonctif , Souris transgéniques , Maladie d'Alzheimer/imagerie diagnostique , Maladie d'Alzheimer/métabolisme , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , Facteur de croissance du tissu conjonctif/métabolisme , Animaux , Humains , Souris , Encéphale/imagerie diagnostique , Encéphale/métabolisme , Encéphale/anatomopathologie , Or/composition chimique , Barrière hémato-encéphalique/métabolisme , Barrière hémato-encéphalique/imagerie diagnostique , Plaque amyloïde/imagerie diagnostique , Plaque amyloïde/métabolisme , Nanoparticules métalliques/composition chimique , Modèles animaux de maladie humaine , Peptides bêta-amyloïdes/métabolisme , Femelle , Mâle , Imagerie multimodale/méthodes , Marqueurs biologiques/métabolisme , Imagerie optique/méthodesRÉSUMÉ
PURPOSE: This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. PATIENTS AND METHODS: This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. RESULTS: A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P < 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). CONCLUSIONS: This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.
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Imagerie par résonance magnétique , Traitement néoadjuvant , Tumeurs du pancréas , Tomographie par émission de positons , Humains , Tumeurs du pancréas/imagerie diagnostique , Tumeurs du pancréas/chirurgie , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/thérapie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Études rétrospectives , Radio-isotopes du gallium , Résultat thérapeutique , Imagerie multimodaleRÉSUMÉ
A novel photocatalytic palladium-induced 6-endo-selective alkyl Heck reaction of unactivated alkyl iodides and alkyl bromides has been described. This strategy facilitates the gentle and efficient synthesis of a variety of 5-phenyl-1,2,3,6-tetrahydropyridine derivatives. It demonstrates a broad substrate tolerance and excellent 6-endo selectivity. Unlike the high-temperature requirements of traditional alkyl Heck reactions, this transformation efficiently proceeds at room temperature and shows significant promise for industrial-scale applications. Mechanistic investigations reveal that this alkyl Heck reaction proceeds via a hybrid palladium-radical process.
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The Beijing-Tianjin-Hebei (BTH) is one of the key areas with PM2.5 air pollution in China. Driven by the PM2.5 target accessibility of the Interim Target-1 (IT-1) by World Health Organization (WHO) and China's carbon neutrality, this study explored and quantified the contribution of climate change and anthropogenic emission to future PM2.5 in the region. The experiments considered future climate change scenarios RCP8.5, RCP4.5, and RCP2.6 with the baseline (Base) and reduced emission (EIT1) inventories in 2030, and RCP4.5 climate scenario with 3 emission inventories in 2050, the additional strong control emission scenario called Best-Health-Effect (BHE). Under various climate scenarios, the future air quality research modelling system projected annual PM2.5 concentrations nearing 35 µg/m3 in 2030. However, considering only the effect of emission reduction, the annual PM2.5 concentrations under EIT1 emission scenario is about 35% less than under Base scenario in different key years. The future PM2.5 concentrations are highly related to anthropogenic emission from human activities, while climate change by 2030 or 2050 has little impact on future air quality over the BTH region. The BHE emission reduction is significantly required for China to meet the new PM2.5 guideline value of WHO in the future.
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Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.
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To investigate the effects of microplastics (MPs) on hydrolysis, acidification and microbial characteristics during waste activated sludge (WAS) anaerobic fermentation process, five different kinds of MPs were added into the WAS fermentation system and results indicated that, compared to the control group, the addition of polyvinyl chloride (PVC)-MPs exhibited the least inhibition on volatile fatty acids (VFAs), reducing them by 13.49 %. Conversely, polyethylene (PE)-MPs resulted in the greatest inhibition, with a reduction of 29.57 %. MPs, while accelerated the dissolution of WAS that evidenced by an increase of lactate dehydrogenase (LDH) release, concurrently inhibited the activities of relevant hydrolytic enzymes (α-Glucosidase, protease). For microbial mechanisms, MPs addition affected the proliferation of key microorganisms (norank_f_Bacteroidetes_vadinHA17, Ottowia, and Propioniclava) and reduced the abundance of genes associated with hydrolysis and acidification (pfkb, gpmI, ilvE, and aces). Additionally, MPs decreased the levels of key hydrolytic and acidogenic enzymes to inhibit hydrolysis and acidification processes. This research provides a basis for understanding and unveils impact mechanisms of the impact of MPs on sludge anaerobic fermentation.
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Fermentation , Microplastiques , Élimination des déchets liquides , Anaérobiose , Élimination des déchets liquides/méthodes , Microplastiques/toxicité , Eaux d'égout/microbiologie , Voies et réseaux métaboliques , Polluants chimiques de l'eau , Acides gras volatils/métabolisme , Microbiote/effets des médicaments et des substances chimiques , BioréacteursRÉSUMÉ
Researches on the advanced nitrogen (N) removal of municipal tailwater always overlooked the value of refractory degradable dissolved organic matter (R-DOM). In this study, a novel electric field coupled ironcarbon biofilter (E-ICBF) was utilized to explore the performance and microbial changes with polyethylene glycol (PEG) as the representative R-DOM. Results demonstrated that the removal efficiencies of E-ICBF for nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), and total nitrogen (TN) improved by 28.76 %, 12.96 %, and 28.45 %, compared to quartz sand biofilter (SBF). Moreover, removal efficiencies of NO3--N and TN in E-ICBF with R-DOM went up by 12.11 % and 14.02 % compared to methanol. Additionally, both PEG and the electric field reduced the microbial richness and diversity. However, PEG promoted the increase of denitrifying bacteria abundance including unclassified_f_Comamonadaceae, Thauera, and unclassified_f_Gallionellaceae. The electric field improved the abundances of genes related to N removal (hao, nasC, nasA, nifH, nifD, nifK) and PEG further enhanced the effect. The abundances of key enzymes [EC:1.7.5.1], [EC:1.7.2.1], [EC:1.7.2.4], and [EC:1.7.2.5] decreased due to the addition of PEG and the electric field mitigated the negative influence. Additionally, the electric field changed relationships between microorganisms and pollutant removal, and improved interspecific relationships between denitrifying bacterial genera and other genera in E-ICBF.
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Carbone , Azote , Élimination des déchets liquides , Azote/métabolisme , Élimination des déchets liquides/méthodes , Filtration/méthodes , Fer , Dénitrification , Bactéries/métabolisme , Polluants chimiques de l'eau/analyse , Dépollution biologique de l'environnementRÉSUMÉ
Amyloid-ß (Aß) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aß aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer's disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aß42, we developed an Aß42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aß-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aß42 misfolding, accelerating Aß42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aß clearance exhibited by this Aß42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
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Maladie d'Alzheimer , Peptides bêta-amyloïdes , Cérium , Nanocomposites , Espèces réactives de l'oxygène , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/métabolisme , Animaux , Espèces réactives de l'oxygène/métabolisme , Peptides bêta-amyloïdes/métabolisme , Nanocomposites/composition chimique , Souris , Cérium/composition chimique , Cérium/pharmacologie , Souris transgéniques , Silice/composition chimique , Fragments peptidiques/composition chimique , Fragments peptidiques/pharmacologie , Humains , Encéphale/métabolisme , Nanoparticules/composition chimique , Glycoprotéines/composition chimique , Glycoprotéines/pharmacologie , Glycoprotéines/métabolisme , Modèles animaux de maladie humaine , Protéines viralesRÉSUMÉ
There has been a plethora of studies on urbanization and older adults, and more recent ones on how older adults adapt to this process with their cognitive competence. Yet it has been unclear about the relationship between them, like how the level and rate of urbanization affect the cognitive function among older adults. This study sourced, formed, and analyzed a set of geospatial big datasets from different sources, such as the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data, and the NPP/VIIRS nighttime light (NTL) data. Results showed a generally negative linear association between the rate of urbanization and cognitive performance among older adults in China. The "U" shaped non-linear relationship between urbanization level and cognitive function, as well as the tipping point, were identified. At the same time, it should be noted that mediators such as education, physical activity, social activity, and community elderly service might be able to mitigate these negative associations. Furthermore, older adults living in eastern regions or urban areas appeared to have better cognitive function than those living in mid-western regions or rural areas in China. The findings also pointed to the importance of focusing on older adults with poor cognitive health status in rapidly urbanizing areas.
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Cognition , Urbanisation , Humains , Chine/épidémiologie , Sujet âgé , Mâle , Femelle , Études longitudinales , Sujet âgé de 80 ans ou plus , Analyse spatiale , Population rurale/statistiques et données numériques , Adulte d'âge moyen , Population urbaineRÉSUMÉ
Incorporation of a polar filler such as silica into a nonpolar rubber matrix is challenging and energy consuming due to their large difference in polarity. Epoxidation of carbon-carbon double bonds in unsaturated rubber, especially for rubber with low unsaturation such as butyl rubber, is an effective method to introduce polar functional groups to the rubber macromolecules for better filler dispersion. Although different epoxidation reagents including hydrogen peroxide (H2O2), peracid, and meta-chloroperoxybenzoic acid (mCPBA) have been previously reported, these reagents have different drawbacks. In this article, a metal-free epoxidation reagent, dimethyl dioxirane (DMDO), generated from acetone and Oxone is explored for efficient epoxidation of rubber with low unsaturation. The effects of the addition manner of the reactant Oxone and buffer sodium bicarbonate (NaHCO3) and reaction temperature on the epoxide formation are studied. Compared to peracid, a faster and more efficient epoxidation without the generation of a ring-opened product is achieved when DMDO is used as the epoxidation reagent. Furthermore, it is found that the epoxidation using DMDO is not sensitive to the water concentration in the rubber solution up to 20 wt %. The addition of quaternary ammonium salt as a phase transfer catalyst not only improves the conversion but also further increases the water tolerance to 25 wt %. The reaction conditions for preparation of epoxidized butyl rubber with different percentages of epoxide group are optimized by Design of Experiments (DoE). At the end, improved dispersion of silica in the matrix of epoxidized butyl rubber is achieved, as revealed by the rubber process analyzer (RPA) and atomic force microscopy (AFM).
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Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.
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Mouvement cellulaire , Dynamines , Cellules endothéliales de la veine ombilicale humaine , Sous-unité alpha du facteur-1 induit par l'hypoxie , Souris de lignée C57BL , Dynamique mitochondriale , Quinazolinones , Espèces réactives de l'oxygène , Néovascularisation rétinienne , Facteur de croissance endothéliale vasculaire de type A , Dynamique mitochondriale/effets des médicaments et des substances chimiques , Animaux , Sous-unité alpha du facteur-1 induit par l'hypoxie/métabolisme , Humains , Espèces réactives de l'oxygène/métabolisme , Dynamines/métabolisme , Dynamines/antagonistes et inhibiteurs , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Quinazolinones/pharmacologie , Néovascularisation rétinienne/métabolisme , Néovascularisation rétinienne/anatomopathologie , Néovascularisation rétinienne/traitement médicamenteux , Mouvement cellulaire/effets des médicaments et des substances chimiques , Souris , Prolifération cellulaire/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Mitochondries/effets des médicaments et des substances chimiques ,RÉSUMÉ
Importance: Treatments are needed to slow progression of or reduce incidence of myopia. Objective: To evaluate the efficacy and safety of daily 650-nm low-level red light (LLRL) for myopia treatment. Design, Setting, and Participants: Single-masked, randomized clinical trial at 1 site in China. Baseline measurements were completed from August to September 2021. Participants were children aged 6 to 12 years with spherical equivalent error (SER) of -6 diopters (D) to 3 D. Data were analyzed from March to July 2023. Interventions: Irradiation daily with 650-nm LLRL for 3 minutes twice daily 4 or more hours apart or no intervention. Main Outcomes and Measures: Primary outcomes were changes in cycloplegia SER and axial length (AL) at 6- and 12-month follow-up visits. Safety was assessed on masked fundus photograph evaluations. Results: A total of 336 children were randomly allocated into the LLRL group or control group in a 1:1 ratio. The control group contained 86 female patients (51.2%), and the treatment group contained 90 female patients (53.6%). The mean (SD) age, SER, and AL were 9.0 (1.9) years, -1.3 (1.5) D, and 23.8 (1.0) mm for all patients. A total of 161 (95.8%) in the LLRL group and 159 (94.6%) in the control group returned for the 6-month follow-up. A total of 157 (93.5%) in the LLRL group and 152 (90.5%) in the control group returned for the 12-month follow-up. Mean (SD) changes in SER were 0.15 (0.16) D and -0.26 (0.21) D for the LLRL group and the control group, respectively (difference, -0.41 D; 95% CI, -0.48 to -0.34 D; P < .001), at 6 months and 0.24 (0.27) D and -0.65 (0.33) D for the LLRL group and the control group, respectively (difference, -0.89 D; 95% CI, -0.95 to -0.83 D; P < .001), at 12 months. Mean (SD) changes in AL were -0.06 (0.08) mm and 0.13 (0.12) mm for the LLRL group and control group, respectively (difference, 0.19 mm; 95% CI, 0.16 to 0.22 mm; P < .001), at 6 months and -0.11 (0.10) mm and 0.26 (0.16) mm for the LLRL group and control group, respectively (difference, 0.37 mm; 95% CI, 0.34 to 0.40 mm; P < .001). Masked fundus photograph review did not identify retinal changes in either group. Conclusions and relevance: These findings suggest daily use of 650-nm LLRL for 1 year can slow progression of SER and AL without safety concerns identified. Confirmation of these findings at independent sites seems warranted, as well as determining whether these effects can be sustained with or without continued treatment and whether LLRL has any effect on pathological myopia. Trial Registration: ChiCTR2200058963.
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Longueur axiale de l'oeil , Myopie , Réfraction oculaire , Acuité visuelle , Humains , Femelle , Mâle , Enfant , Longueur axiale de l'oeil/imagerie diagnostique , Myopie/physiopathologie , Myopie/thérapie , Réfraction oculaire/physiologie , Méthode en simple aveugle , Acuité visuelle/physiologie , Photothérapie de faible intensité/méthodes , Résultat thérapeutique , Études de suivi ,RÉSUMÉ
Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g-1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.
Sujet(s)
Carbone , Charbon de bois , Graphite , Biomasse , SuieRÉSUMÉ
Inflammation-induced osteoclast proliferation is a crucial contributor to impaired bone metabolism. Kurarinone (KR), a flavonoid extracted from the Radix Sophorae Flavescentis, exhibits notable anti-inflammatory properties. Nevertheless, the precise influence of KR on osteoclast formation remains unclear. This study's objective was to assess the impact of KR on osteoclast activity in vitro and unravel its underlying mechanism. Initially, a target network for KR-osteoclastogenesis-osteoporosis was constructed using network pharmacology. Subsequently, the intersecting targets were identified through the Venny platform and a PPI network was created using Cytoscape 3.9.1. Key targets within the network were identified employing topological algorithms. GO enrichment and KEGG pathway analysis were then performed on these targets to explore their specific functions and pathways. Additionally, molecular docking of potential core targets of KR was conducted, and the results were validated through cell experiments. A total of 83 target genes overlapped between KR and osteoclastogenesis-osteoporosis targets. Enrichment analysis revealed their role in inflammatory response, protein tyrosine kinase activity, osteoclast differentiation, and MAPK and NF-κB signaling pathways. PPI analysis and molecular docking demonstrate that key targets MAPK14 and MAPK8 exhibit more stable binding with KR compared to other proteins. In vitro experiments demonstrate that KR effectively inhibits osteoclast differentiation and bone resorption without cellular toxicity. It suppresses key osteoclast genes (NFATc1, c-Fos, TRAP, MMP9, Ctsk, Atp6v2), hinders IκB-α degradation, and inhibits ERK and JNK phosphorylation, while not affecting p38 phosphorylation. The results indicate that KR may inhibit osteoclast maturation and bone resorption by blocking NF-κB and MAPK signaling pathways, suggesting its potential as a natural therapeutic agent for osteoporosis.