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Background: Antioxidant therapy aimed at reducing excessive local oxidative stress is one of the most important strategies for promoting diabetic wound repair. The reversible transformation of Ce3+/Ce4+ in ceria (CeO2) can reduce excessive local oxidative stress. However, inducing angiogenesis, local anti-inflammatory effects, and other positive effects are challenging. Therefore, ideal dressings for chronic diabetic wound management must concurrently reduce excessive oxidative stress, promote angiogenesis, and have anti-inflammatory effects. Methods: In this study, Ce-doped borosilicate bioactive glasses (BGs) were prepared using the sol-gel method, and CeO2 nanocrystals (CeO2-NCs) were precipitated on the glass surface by heat treatment to obtain BG-xCe composite glass nanospheres. Subsequently, nanospheres were modified by amino group and combined with dopamine and acrylamide to obtain BG-xCe/polydopamine/polyacrylamide (PDA/PAM) composite hydrogel. Then, the morphology and properties of composite hydrogels were detected, and the properties to treat the diabetic wounds were also evaluated. Results: The results demonstrated that the BG-10Ce/PDA/PAM composite hydrogel possessed excellent tensile and adhesive properties. In vitro, the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) and fibroblasts (L929) were enhanced by reducing reactive oxygen species (ROS) levels in the conditioned medium. Animal experiments have shown that CeO2-NCs in hydrogels effectively scavenge ROS in diabetic wounds, and Sr dissolved from the glassy phase can modulate macrophage polarization to the M2 phenotype. Conclusions: The synergistic effect of both amorphous materials and nanocrystals provides the BG-10Ce/PDA/PAM composite hydrogel with great potential for diabetic wound healing.
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Carbon monoxide (CO) is a harmful gas with significant impacts on human health and the environment. Its timely detection, especially in the event of thermal runaway in automotive lithium batteries, is crucial to prevent casualties. This paper reviews the progress in the development of efficient, sensitive, and reliable CO sensors, focusing on electrochemical, optical, and resistive sensing materials. Low-dimensional materials have a large specific surface area, providing an abundant number of active sites, which has drawn extensive attention from researchers. According to the different sensor signals, we categorized these sensors into electrical and optical signal sensors. We hope that by systematically introducing the sensing mechanism and sensing performance of these two kinds of sensors, appropriate CO sensors can be developed in different application scenarios so as to realize early warning and monitoring to the maximum extent, reduce industrial losses, and ensure the life and health of personnel.
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OBJECTIVE: To apply machine learning models based on air conduction thresholds of pure-tone audiometry for automatic diagnosis of Meniere's disease (MD) and prediction of endolymphatic hydrops (EH). STUDY DESIGN: Retrospective study. SETTING: Tertiary medical center. METHODS: Gadolinium-enhanced magnetic resonance imaging sequences and pure-tone audiometry data were collected. Subsequently, basic and multiple analytical features were engineered based on the air conduction thresholds of pure-tone audiometry. Later, 5 classical machine learning models were trained to diagnose MD using the engineered features. The models demonstrating excellent performance were also selected to predict EH. The model's effectiveness in MD diagnosis was compared with experienced otolaryngologists. RESULTS: First, the winning light gradient boosting (LGB) machine learning model trained by multiple features demonstrates a remarkable performance on the diagnosis of MD, achieving an accuracy rate of 87%, sensitivity of 83%, specificity of 90%, and a robust area under the receiver operating characteristic curve of 0.95, which compares favorably with experienced clinicians. Second, the LGB model, with an accuracy of 78% on EH prediction, outperformed the other 3 machine learning models. Finally, a feature importance analysis reveals a pivotal role of the specific pure-tone audiometry features that are essential for both MD diagnosis and EH prediction. Highlighted features include standard deviation and mean of the whole-frequency hearing, the peak of the audiogram, and hearing at low frequencies, notably at 250 Hz. CONCLUSION: An efficient machine learning model based on pure-tone audiometry features was produced to diagnose MD, which also showed the potential to predict the subtypes of EH. The innovative approach demonstrated a game-changing strategy for MD screening and promising cost-effective benefits for the health care enterprise.
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Herein we describe the discovery of a 2-aminopyridine scaffold as a potent and isoform selective inhibitor of the Nav1.8 sodium channel. Parallel library synthesis, guided by in silico predictions, rapidly transformed initial hits into a novel 2-aminopyridine lead class possessing good ADME and pharmacokinetic profiles that were able to display activity in a clinically translatable nonhuman primate capsaicin-sensitized thermode pharmacodynamic assay. Progress toward the lead identification, optimization, and in vivo efficacy of these compounds will be discussed.
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Magnetite (Fe3O4) has a large theoretical reversible capacity and rich Earth abundance, making it a promising anode material for LIBs. However, it suffers from drastic volume changes during the lithiation process, which lead to poor cycle stability and low-rate performance. Hence, there is an urgent need for a solution to address the issue of volume expansion. Taking inspiration from how glycophyte cells mitigate excessive water uptake/loss through their cell wall to preserve the structural integrity of cells, we designed Fe3O4@PMMA multi-core capsules by microemulsion polymerization as a kind of anode materials, also proposed a new evaluation method for real-time repair effect of the battery capacity. The Fe3O4@PMMA anode shows a high reversible specific capacity (858.0â mAh g-1 at 0.1â C after 300â cycles) and an excellent cycle stability (450.99â mAh g-1 at 0.5â C after 450â cycles). Furthermore, the LiNi0.8Co0.1Mn0.1O2/Fe3O4@PMMA pouch cells exhibit a stable capacity (200.6 mAh) and high-capacity retention rate (95.5 %) after 450â cycles at 0.5â C. Compared to the original battery, the capacity repair rate of this battery is as high as 93.4 %. This kind of bionic capsules provide an innovative solution for improving the electrochemical performance of Fe3O4 anodes to promote their industrial applications.
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BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Síndrome del Ovario Poliquístico , Vitamina D , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/sangre , Humanos , Femenino , Vitamina D/sangre , Polimorfismo de Nucleótido Simple , Testosterona/sangre , Predisposición Genética a la Enfermedad , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangreRESUMEN
Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.
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Regeneración Ósea , Hidrogeles , Osteogénesis , Factor A de Crecimiento Endotelial Vascular , Animales , Ratas , Regeneración Ósea/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Osteogénesis/efectos de los fármacos , Humanos , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones , Células Endoteliales de la Vena Umbilical Humana , Ratas Sprague-Dawley , Vidrio/química , Modelos Animales de Enfermedad , Silicatos/química , Silicatos/farmacología , Proliferación Celular/efectos de los fármacos , MasculinoRESUMEN
A 30-year-old man presented to otolaryngology department complaining of nasal congestion and runny nose for six months, with repeated fever, and shortness of breath.The weight loss in the past 20 days was about 5 kg. At first, he was diagnosed with respiratory infection and was treated with antibiotics, but it didn't work. Nasopharynx CT scan showed soft tissue thickening without bone destruction, with obvious inhomogeneous enhancement. Chest CT scan revealed multiple patchy clouding nodules and ground-glass opacity with poorly-defined border. Urine test showed urine microalbumin ≥ 150 mg per liter (reference range, 0-20), white-cell count of 11.0 cells per microliter (reference range, 0-5). Histology of nasopharynx biopsy showed small-medium-vessel necrotizing vasulitis.Although nasopharyngeal histopathology didn't reveal peri- and extravascular granulomatosis and antineutrophilic cytoplasmic antibodies (ANCA) was negtive, he had ENT signs, lung nodules, and kidney involvement and condition developed fast and biopsy showed small- and- medium-vessel vasculitis. Therefore, the patient met the classification criteria for GPA and his symptoms were disappeared 1 week after starting GPA treatment, the chest CT showed ground-glass opacity decreased and CRPãESR became normal. He was treated with rituximab combined with glucocorticoids for 4 weeks, after which he was discharged.
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Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.
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Cementos para Huesos , Durapatita , Microesferas , Osteogénesis , Polimetil Metacrilato , Estroncio , Cementos para Huesos/química , Polimetil Metacrilato/química , Osteogénesis/efectos de los fármacos , Porosidad , Estroncio/química , Animales , Ratones , Durapatita/química , Materiales Biocompatibles/química , Ensayo de Materiales , Proliferación Celular/efectos de los fármacos , Oseointegración/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Cerámica/química , Vidrio/química , Humanos , Sustitutos de Huesos/químicaRESUMEN
In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.
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Antineoplásicos , Halogenación , Neoplasias , Polímeros , Humanos , Polímeros/química , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Animales , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Lithium-ion batteries (LIBs) are currently the predominant energy storage power source. However, the urgent issues of enhancing electrochemical performance, prolonging lifetime, preventing thermal runaway-caused fires, and intelligent application are obstacles to their applications. Herein, bio-inspired electrodes owning spatiotemporal management of self-healing, fast ion transport, fire-extinguishing, thermoresponsive switching, recycling, and flexibility are overviewed comprehensively, showing great promising potentials in practical application due to the significantly enhanced durability and thermal safety of LIBs. Taking advantage of the self-healing core-shell structures, binders, capsules, or liquid metal alloys, these electrodes can maintain the mechanical integrity during the lithiation-delithiation cycling. After the incorporation of fire-extinguishing binders, current collectors, or capsules, flame retardants can be released spatiotemporally during thermal runaway to ensure safety. Thermoresponsive switching electrodes are also constructed though adding thermally responsive components, which can rapidly switch LIB off under abnormal conditions and resume their functions quickly when normal operating conditions return. Finally, the challenges of bio-inspired electrode designs are presented to optimize the spatiotemporal management of LIBs. It is anticipated that the proposed electrodes with spatiotemporal management will not only promote industrial application, but also strengthen the fundamental research of bionics in energy storage.
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Grassland management affects soil respiration (Rs, consists of heterotrophic respiration and autotrophic respiration) through soil micro-ecological processes, such as hydrothermal, plant root, organic carbon decomposition and microbial activity. Flooding, an irregular phenomenon in grasslands, may strongly regulate the response of soil respiration and its components to grassland management, but the regulatory mechanism remains unclear. We conducted a 3-year experiment by grassland management (fencing and grazing) and flooding conditions (no flooding (NF), short-term flooding (STF) and long-term flooding (LTF)) to study their effects on Rs and its components in a meadow steppe in the Hui River basin of Hulunbuir. We found differences in the patterns of Rs and its components under grassland management and flooding conditions. In 2021-2023, the temporal trends of Rs, heterotrophic respiration (Rh) and autotrophic respiration (Ra) were generally consistent, with peaks occurring on days 190-220, and the peaks of grazing were higher than that of fencing. In NF, Rs of grazed grassland was significantly higher than that of fenced grassland in 2021-2022 (p < 0.05). In STF and LTF, there was no significant difference in Rs between fenced and grazed grassland (p > 0.05). The dependence of Rs on soil temperature (ST) decreased with increasing flooding duration, and the dependence of Rs on ST of grazed grassland was higher than fenced grassland under NF and STF, but there was no difference between fenced grassland and grazed grassland under LTF. In addition, Rh was more sensitive to ST than Ra. This may be due to the different pathways of ST effects on Rs under grazing in different flooding conditions. Our study indicates that the effect of flooding on Rs is the key to the rational use of grassland under future climate change. To reduce regional carbon emissions, we recommend grazing on flooding grassland and fencing on no-flooding grassland.
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Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.
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Cerio , Cobre , Macrófagos , Factor 2 Relacionado con NF-E2 , Cicatrización de Heridas , Factor 2 Relacionado con NF-E2/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratones , Cerio/química , Cerio/farmacología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Cobre/química , Cobre/farmacología , Células RAW 264.7 , Diabetes Mellitus Experimental/metabolismo , Radical Hidroxilo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Masculino , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
In this research, upconversion nanocrystals incorporated with MOR zeolite composites were synthesized using the desilicated MOR zeolite as a host for the in situ growth of NaREF4 (RE = Y, Gd) Yb/Er nanocrystals. The structure and morphology of the composites were studied with XRD, XPS, and TEM measurements, and the spectral studies indicated that the subsequent thermal treatment can effectively improve the upconversion emission intensity of Er3+. By using the NaYF4:Yb/Er@DSi1.0MOR-HT composite that holds the strongest upconversion emission, a probe of UCNC@DSiMOR/BPEI was constructed with the modification of branched poly ethylenimine for the detection of Cu2+. It was indicated that the integrated emission intensity of Er3+ shows a linear dependence with the logarithm value of the Cu2+ concentration ranging from 0.1 to 10 µM. This study offered a feasible method for the construction of UCNC@zeolite composites with enhanced upconversion emission, which may have a potential application as fluorescent probes for the detection of various metal ions by adjusting the doping luminescent center.
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Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.
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[This corrects the article DOI: 10.1016/j.gendis.2022.07.001.].
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Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Azidas , Desoxiglucosa , Animales , Ratones , Aminopropionitrilo/efectos adversos , Aneurisma de la Aorta Torácica/genética , Aneurisma de la Aorta Torácica/inducido químicamente , Aneurisma de la Aorta Torácica/metabolismo , Desoxiglucosa/análogos & derivados , Modelos Animales de Enfermedad , Factor de Crecimiento Nervioso/genética , Factor de Crecimiento Nervioso/efectos adversos , Semaforina-3A/genéticaRESUMEN
Cardiomyocyte apoptosis is an important cause of trauma-induced secondary cardiac injury (TISCI), in which the endoplasmic reticulum stress (ERS)-mediated apoptosis signaling pathway is known to be first activated, but the mechanism remains unclear. In this study, rat models of traumatic injury are established by using the Noble-Collip trauma device. The expression of glucose-regulating protein 78 (GRP78, a molecular chaperone of the cardiomyocyte ER), acetylation modification of GRP78 and apoptosis of cardiomyocytes are determined. The results show that ERS-induced GRP78 elevation does not induce cardiomyocyte apoptosis in the early stage of trauma. However, with prolonged ERS, the GRP78 acetylation level is elevated, and the apoptosis of cardiomyocytes also increases significantly. In addition, in the early stage of trauma, the expression of histone acetyl-transferase (HAT) P300 is increased and that of histone deacetylase 6 (HDAC6) is decreased in cardiomyocytes. Inhibition of HDAC function could induce the apoptosis of traumatic cardiomyocytes by increasing the acetylation level of GRP78. Our present study demonstrates for the first time that post-traumatic protracted ERS can promote cardiomyocyte apoptosis by increasing the acetylation level of GRP78, which may provide an experimental basis for seeking early molecular events of TISCI.
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Lesiones Cardíacas , Miocitos Cardíacos , Animales , Ratas , Acetilación , Apoptosis , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
ConspectusSulfur-based cathode materials have become a research hot spot as one of the most promising candidates for next-generation, high-energy lithium batteries. However, the insulating nature of elemental sulfur or organosulfides has become the biggest challenge that leads to dramatic degradation and hinders their practical application. The disadvantage is more obvious for all-solid-state battery systems, which require both high electronic and ionic migration at the same sites to realize a complete electrochemical reaction. In addition to adding conductive components into the cathode composites, another effective way to realize high-reversibility sulfur-based cathodes is by optimizing the inherent nature of sulfur-based materials to make them "conductive". Inorganic polysulfide materials including polysulfide molecules, selenium-sulfur solid solutions, and (lithium) metal polysulfides are promising, as they have different structures that can make them intrinsically conductive or becoming conductive during lithiation. They all contain at least one -S-S- bridged bond, which is the intrinsic structural characteristic and the source of the chemical properties of these polysulfide compounds. For example, by balancing the conductivity and reversible capacity, researchers in the US National Aeronautics and Space Administration (NASA) have shown that 500 Wh/kg solid-state Li-Se/S batteries can power cars and even electric aircraft.We have long been focusing on the inorganic polysulfide component, reported the selenium-sulfur solid solutions, the first sulfur-rich phosphorus polysulfide molecules, and followed the research of metal polysulfide components. The proposed Account summarizes our current knowledge of the fundamental aspects of inorganic polysulfides in energy storage systems based on state-of-the-art publications on this topic. Both fast electron and ion migrations within the electrode materials are vital to achieving high-energy batteries. We begin by illustrating effective approaches to enhance the electronic/ionic conductivity of sulfur-based electrode materials. We then present some basic observations and properties (especially the intrinsic high conductivities) of the inorganic polysulfide electrode materials. The key chemical and structural factors dictating their conductive and electrochemical behaviors will be discussed. Finally, we show the advantages and broad applications of inorganic polysulfides in energy storage areas. The proposed Account will provide an insightful perspective on the current knowledge of inorganic polysulfide materials, as well as their future research directions and development potential, serving as a keynote reference for researchers in the field of energy storage.
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Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-ß (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC.