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Achilles tendinopathy (AT) is an injury caused by overuse of the Achilles tendon or sudden force on the Achilles tendon, with a considerable inflammatory infiltrate. As Achilles tendinopathy progresses, inflammation and inflammatory factors affect the remodeling of the extracellular matrix (ECM) of the tendon. Gastrodin(Gas), the main active ingredient of Astrodia has anti-inflammatory, antioxidant, and anti-apoptotic properties. The small intestinal submucosa (SIS) is a naturally decellularized extracellular matrix(dECM)material and has a high content of growth factors as well as good biocompatibility. However, the reparative effects of SIS and Gas on Achilles tendinopathy and their underlying mechanisms remain unknown. Here, it is found that SIS hydrogel loaded with gastrodin restored the mechanical strength of the Achilles tendon, facilitated ECM remodeling, and restored ordered collagen arrangement by promoting the translocation of protein synthesis. It also decreases the expression of inflammatory factors and reduces the infiltration of inflammatory cells by inhibiting the NF-κB signaling pathway. It is believed that through further research, Gas + SIS may be used in the future for the treatment of Achilles tendinopathy and other Achilles tendon injury disorders.
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A copper-catalyzed trifluoromethylation of benzene-linked 1,7-dienes with 1-trifluoromethyl-1,2-benziodoxole via a radical cascade cyclization process for the synthesis of mono- and bis-trifluoromethylated benzoxepines is developed. The selectivity depends on substituents on the double bond of the allyl group in 1,7-dienes. The large-scale operation and late-stage functionalization of bioactive molecules reveal the promising utility of this protocol.
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OBJECTIVE: This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle. METHODS: A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved. KEY FINDINGS: BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo. CONCLUSIONS: BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.
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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.
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The rocking-chair lithium-ion capacitors (RLICs), composed of a battery-type cathode and capacitive-type anode, alleviates the issue of increased internal resistance caused by electrolyte consumption during the cycling process of the lithium-ion capacitors (LICs). However, the poor conductivity of cathode materials and the mismatch between the cathode and anode are the key issues that hinder its commercial application. In this work, a modification simplification strategy is proposed to tailor the conductivity of the cathode and matching characteristic with the anode. The in situ grown lithium manganate (LMO) is featured with a three-dimensional conductive network constructed by reduced graphene oxide (rGO). The optimized LMO/rGO composite cathode demonstrates an excellent rate performance, lithium-ion diffusion rate, and cycling performance. After assembling an RLICs with activated carbon (AC), the RLICs exhibits an energy density of as high as 239.11 Wh/kg at a power density of 400 W/kg. Even at a power density of 200 kW/kg, its energy density can maintain at 39.9 Wh/kg. These excellent electrochemical performances are mainly attributed to the compounding of LMO with rGO, which not only improves the conductivity of the cathode but also realizes a better matching with the capacitive-type anode. This modification strategy provides a reference for the further development of energy storage devices suitable for actual production conditions and application scenarios.
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Background: Evidence regarding the potential health effects of Life's Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Objectives: The purpose of this study was to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality among individuals with T2D. Methods: We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results: During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted HRs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (95% CI: 0.53-0.59) for CVD, 0.57 (95% CI: 0.53-0.62) for heart disease, 0.53 (95% CI: 0.49-0.57) for stroke, and 0.73 (95% CI: 0.69-0.78) for total mortality (all P trend <0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17% to 42% lower risk of CVD, heart disease, stroke, and mortality. Conclusions: A higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D.
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Background: Taste and olfactory dysfunction are commonly associated with neurodegenerative diseases and cardiovascular risk factors, but their specific associations with stroke risk remain uncertain. Objectives: The purpose of this paper was to explore whether perceived taste and olfactory dysfunctions were associated with stroke risk. Methods: Included were 85,656 participants (mean age 51.0 ± 15.3 years) of the Kailuan study. Perceived olfactory and taste dysfunctions were assessed via a questionnaire at baseline (in 2014-2016). Incident stroke cases were confirmed by review of medical records. Cox proportional hazards models were used to investigate associations of perceived olfactory and taste dysfunctions with stroke risk, and mediation analysis was used to estimate the mediating effect of chronic disease statuses. Results: We documented 2,198 incident stroke cases during a mean of 5.6 years of follow-up. Perceived taste dysfunction was associated with a doubled risk of developing total stroke (adjusted HR: 2.03; 95% CI: 1.36-3.04; P < 0.001) even with adjustment of lifestyle factors, biomarkers (ie, blood lipids, blood glucose, blood pressure, and uric acid), and other potential confounders. However, perceived olfactory dysfunction (adjusted HR: 1.22; 95% CI: 0.79-1.90; P = 0.34) was not significantly associated with a high risk of total stroke. Similar results of both perceived taste and olfactory dysfunctions were observed for ischemic stroke. Presence of chronic diseases, including hypertension, diabetes, chronic kidney disease, and overweight/obesity, mediated 4% to 5% of the association of perceived taste dysfunction with both total stroke and ischemic stroke. Conclusions: In this large cohort study, perceived taste dysfunction was associated with a high risk of developing stroke.
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Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-ß/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.
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BACKGROUND: Achieving long-term clinical remission in Crohn's disease (CD) with antitumor necrosis factor α (anti-TNF-α) agents remains challenging. AIMS: This study aims to establish a prediction model based on patients' clinical characteristics using a machine-learning approach to predict the long-term efficacy of infliximab (IFX). METHODS: Three cohorts comprising 746 patients with CD were included from 3 inflammatory bowel disease (IBD) centers between June 2013 and January 2022. Clinical records were collected from baseline, 14-, 30-, and 52-week post-IFX treatment. Three machine-learning approaches were employed to develop predictive models based on 23 baseline predictors. The SHapley Additive exPlanations (SHAP) algorithm was used to dissect underlying predictors, and latent class mixed model (LCMM) was applied for trajectory analysis of the longitudinal change of blood routine tests along with long-term IFX therapy. RESULTS: The XGBoost model exhibited the best discrimination between long-term responders and nonresponders. In the internal training and testing set, the model achieved an AUC of 0.91 (95% CI, 0.86-0.95) and 0.71 (95% CI, 0.66-0.87), respectively. Moreover, it achieved a moderate predictive performance in the independent external cohort, with an AUC of 0.68 (95% CI, 0.59-0.77). The SHAP algorithm revealed disease-relevant laboratory measurements, notably hemoglobin (HB), white blood cells (WBC), erythrocyte sedimentation rate (ESR), albumin (ALB), and platelets (PLT), alongside age at diagnosis and the Montreal classification, as the most influential predictors. Furthermore, 2 distinct patient clusters based on dynamic laboratory tests were identified for monitoring the long-term remission. CONCLUSIONS: The established prediction model demonstrated remarkable discriminatory power in distinguishing long-term responders from nonresponders to IFX therapy. The identification of distinct patient clusters further emphasizes the need for tailored therapeutic approaches in CD management.
The study developed a machine-learning model using clinical data to predict long-term efficacy of IFX in Crohn's disease. The XGBoost model demonstrated strong discriminatory power, revealing influential predictors and distinct patient clusters, emphasizing the importance of tailored therapeutic approaches in CD management.
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Background: This study examines whether clot patterns at large artery occlusion sites, as observed using digital subtraction angiography (DSA) and computed tomography angiography (CTA), can reliably indicate intracranial atherosclerotic stenosis (ICAS) in acute ischemic stroke (AIS) patients. Methods: We conducted a retrospective analysis of patients treated with stent retriever thrombectomy for intracranial occlusions at our institute since 2017, with follow-up assessments conducted at 3 months. The patients were grouped based on the initial angiography clot topographies (i.e., cut-off or tapered signs). We assessed the potential of these topographies in predicting ICAS, including a clinical outcome analysis based on clot pattern, age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and onset-to-door time. Results: Among 131 patients (with a mean age of 66.6 years), the clot pattern emerged as a significant predictor of ICAS. The DSA-based model had a predictive area under the curve (AUC) of 0.745, with 55.1% sensitivity and 94.0% specificity. A multivariate model including age, onset-to-door time, TOAST classification as large artery atherosclerosis (LAA), and the presence of the tapered sign in clot patterns had an AUC of 0.916. In patients over 65 years of age with an onset-to-door time of >5 h and exhibiting a tapered sign in the clot pattern, the AUC reached 0.897. The predictive ability of the tapered sign was similar in DSA and CTA, showing 73.4% agreement between modalities. Conclusion: The clot pattern with the tapered sign as observed using DSA is significantly associated with ICAS. Incorporating this clot pattern with age, TOAST classification as LAA, and onset-to-door time enhances the prediction of ICAS. The clot pattern identified by CTA is also a reliable predictor, highlighting the importance of assessing clot patterns in ICAS identification.
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The international food trade is beneficial for enhancing global food security but also raises issues such as global cropland redistribution, land use efficiency, and environmental problems. While current studies have examined the impacts of the international food trade on these issues, its long-term effects on global cropland use efficiency remain unclear, especially when considering different crops and countries. Utilizing the international trade theory and the principle of virtual cropland, this study explores the relationship between international food trade and global cropland use efficiency from 2000 to 2022. The results illustrate that the global crop trade surged by 142%, outpacing the 102% increase in virtual cropland trade, which was attributed to crop yield enhancements. By 2022, the global virtual cropland trade encompassed 10.7% of the total croplands, with China emerging as the foremost importer, particularly due to soybean imports. Notably, the global crop trade led to substantial cropland savings and higher cropland use efficiency, totaling 1244.9 million hectares (Mha) between 2000 and 2020. These gains were largely attributed to the superior yields of major crop-exporting countries. Despite these gains, socio-economically vulnerable countries face significant challenges, potentially compromising their food security amidst the complexities of the global trade dynamics.
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The yield behavior of aluminum alloy 5754-H111 under different stress conditions for three kinds of plastic work is studied using an anisotropic Drucker model. It is found that when the plastic work is 30 MPa, the anisotropic Drucker model has the most accurate prediction. Comparing the Hill48 and Yld91 models with the Drucker model, the results show that both the anisotropic Drucker and Yld91 models can accurately predict the yield behavior of the alloy. Cylinder drawing finite element analysis is performed under the AFR, but it is not possible to accurately predict the position and height of earing appearance. The anisotropic Drucker model is used to predict the earing behavior under the non-AFR, which can accurately predict the earing phenomenon. Numerical simulation is conducted using three different combinations of yield functions: the anisotropic yield function and the anisotropic plastic potential function (AYAPP), the anisotropic yield function and the isotropic plastic potential function (AYIPP), and the isotropic yield function and the anisotropic plastic potential function (IYAPP). It is concluded that the influence of the plastic potential function on predicting earing behavior is more critical than that of the yield function.
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The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.
Subject(s)
Apoptosis , Calcium , Cellular Senescence , Pilocarpine , Animals , Pilocarpine/pharmacology , Guinea Pigs , Apoptosis/drug effects , Calcium/metabolism , Cellular Senescence/drug effects , Ciliary Body/metabolism , Male , Cells, Cultured , Reactive Oxygen Species/metabolismABSTRACT
Background: Tendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. Methods: The biomimetic scaffold was designed based on the "tissue-inducing biomaterials" theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatinmp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-ß3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment. Results: The hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance. Conclusion: The hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon. The translational potential of this article: The novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.
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The fascinating scent of rose (Rosa genus) flowers has captivated human senses for centuries, making them one of the most popular and widely used floral fragrances. Despite much progress over the last decade, many biochemical pathways responsible for rose scents remain unclear. We analyzed the floral scent compositions from various rose varieties and selected the modern cultivar Rosa hybrida 'Double Delight' as a model system to unravel the formation of rose dominant volatile terpenes, which contribute substantially to the rose fragrance. Key genes involved in rose terpene biosynthesis were functionally characterized. Cytosolic geranyl diphosphate (GPP) generated by geranyl/farnesyl diphosphate synthase (G/FPPS1) catalysis, played a pivotal role in rose scent production, and terpene synthases (TPSs) in roses play an important role in the formation of most volatile terpenes, but not for geraniol, citral or ß-citronellol. Subsequently, a series of enzymes, including geraniol dehydrogenase (GeDH), geranial reductase (GER), 12-oxophytodienoate reductase (OPR) and citronellal reductase (CAR), were characterized as involved in the transformation of geraniol to ß-citronellol in roses through three successive steps. Interestingly, the ß-citronellol biosynthesis pathway appears to be conserved in other horticultural plants like Lagerstroemia caudata and Paeonia lactiflora. Our findings provide valuable insights into the biosynthesis of rose volatile terpenoid compounds and offer essential gene resources for future breeding and molecular modification efforts.
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The short-video application TikTok shows great potential for disseminating health information. We assessed the content, sources, and quality of information in videos related to nonalcoholic fatty liver disease (NAFLD) on TikTok. Our study aims to identify upload sources, content, and characteristic information for NAFLD videos on TikTok and further evaluate factors related to video quality. We investigated the top 100 videos related to NAFLD on TikTok and analyzed the upload sources, content, and characteristics of these videos. Evaluate video quality using the DISCERN tool and Global Quality Score (GQS). In addition, the correlation between video quality and video characteristics is further studied. In terms of video sources, the majority of NAFLD videos on TikTok (85/100, 85%) were posted by doctors, ensuring the professionalism of the content, and among the video content, disease knowledge was the most dominant video content, accounting for 57% (57/100) of all videos, and the average DISCERN and GQS scores of all 100 videos were 39.59 (SD 3.31) and 2.99 (SD 0.95), respectively. DISCERN and GQS data show that videos related to NAFLD do not have high-quality scores on TikTok, mainly fair (68/100, 68%) and moderate (49/100, 49%). In general, the quality of NAFLD video information from professional content and professional sources was higher than that of nonprofessional sources and nonprofessional content, the video quality of general surgeons was better than that of other department physicians, and the video quality of junior physicians was better than that of senior physicians. In terms of video correlation, durations, the number of fans, and the total number of works were negatively correlated with DISCERN scores (Râ <â 0, Pâ <â .05), while likes, comments, collections, shares, and days since upload were not significantly correlated with DISCERN and GQS scores (Pâ >â .05). The medical information on TikTok is not rigorous enough to guide patients to make accurate judgments, platforms should monitor and guide publishers to help promote and disseminate quality content.
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Non-alcoholic Fatty Liver Disease , Video Recording , Humans , Cross-Sectional Studies , Information Dissemination/methodsABSTRACT
Decellularized scaffolds retain the main bioactive substances of the extracellular matrix, which can better promote cell proliferation and matrix reconstruction at the defect site, and have great potential for morphological and functional restoration in patients with tissue defects. Due to the safety of the material source of allogeneic decellularized scaffolds, there is a great limitation in their clinical application, so the preparation and evaluation of xenodermal acellular scaffolds have attracted much attention. In terms of skin tissue structure and function, porcine skin has a high degree of similarity to human skin and has the advantages of sufficient quantity and no ethical issues. However, there is a risk of immune rejection after xenodermal acellular scaffold transplantation. To address the above problems, this paper focuses on porcine dermal decellularized scaffolds prepared using two common decellularization preparation methods and compares the decellularization efficiency, retention of active components of the extracellular matrix, structural characterization of the decellularized scaffolds, and the effect of porcine dermal decellularized scaffolds on mouse Raw264.7 macrophages, so as to make a functional evaluation of the active components and immune effects of porcine dermal decellularized scaffolds, and to provide a reference for filling trauma-induced defects in humans.
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Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.
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Neoplasms , Humans , Neoplasms/diagnosis , Neoplasms/therapy , Neoplasms/diagnostic imaging , Neoplasms/genetics , Nanoparticles/therapeutic use , Nanoparticles/chemistry , Nanotechnology/trends , Nanomedicine/trends , Drug Delivery SystemsABSTRACT
Na5YSi4O12 (NYSO) is demonstrated as a promising electrolyte with high ionic conductivity and low activation energy for practical use in solid Na-ion batteries. Solid-state NMR was employed to identify the six types of coordination of Na+ ions and migration pathway, which is vital to master working mechanism and enhance performance. The assignment of each sodium site is clearly determined from high-quality 23Na NMR spectra by the aid of Density Functional Theory calculation. Well-resolved 23Na exchangespectroscopy and electrochemical tracer exchange spectra provide the first experimental evidence to show the existence of ionic exchange between sodium at Na5 and Na6 sites, revealing that Na transport route is possibly along three-dimensional chain of open channel-Na4-open channel. Variable-temperature NMR relaxometry is developed to evaluate Na jump rates and self-diffusion coefficient to probe the sodium-ion dynamics in NYSO. Furthermore, NYSO works well as a dual ion conductor in Na and Li metal batteries with Na3V2(PO4)3 and LiFePO4 as cathodes, respectively.
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Pancreatic adenocarcinoma (PAAD) is a prevalent and highly malignant gastrointestinal tumor. Therefore, exploring the mechanisms of drug resistance and immune pathways in PAAD is crucial for clinical treatment. In this study, a total of 497 differentially expressed genes (DEGs) were identified between normal and PAAD samples, and which were enriched to 117 GO terms and 7 functional pathways. Subsequently, 5 overall survival-related DEGs (ESRP1, KRT6A, H2BC11, H2BC4 and KLK) was generated using Cox hazards regression analysis in TCGA dataset. Furthermore, the weighted gene co-expression network analysis revealed a strong association between ESRP1 and PAAD among 5 survival-related DEGs. Patients were divided into two clusters based on ESRP1 expression levels, and low ESRP1 expression existed stronger immune infiltration and higher expression of immunomodulatory targets than high ESRP1 expression by single-sample gene set enrichment analysis, which indicated that low ESRP1 expression was associated with longer survival compared to high ESRP1 expression. Finally, our study also found that immune cells distribution and immunomodulatory targets gene expression in the GEO dataset were similar to the TCGA cohort. Overall, our findings suggest that ESRP1 may play a role in influencing immune contexture and regulating immune function of PAAD patients by integrating data from various databases. SIGNIFICANCE: Utilizing TCGA and GEO datasets, this study uncovers the significant impact of epithelial splicing regulatory protein 1 (ESRP1) on PAAD. ESRP1 emerges as a key regulator of immune function, influencing tumor microenvironment and immune cell infiltration. Cluster analysis shows that low ESRP1 expression correlates with enhanced immune activity, predicting better prognosis. This discovery suggests that ESRP1 can serve as a potential biomarker for the prognosis of PAAD, offering new insights into personalized immunotherapy by influencing immune regulation and tumor progression.