Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its ...cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.
Cancer is a destructive disease that causes high levels of morbidity and mortality. Doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, but its use places survivors at risk ...for cardiotoxicity. Many studies have demonstrated that multiple factors are involved in DOX-induced acute cardiotoxicity. Among them, oxidative stress and cell death predominate. In this review, we provide a comprehensive overview of the mechanisms underlying the source and effect of free radicals and dependent cell death pathways induced by DOX. Hence, we attempt to explain the cellular mechanisms of oxidative stress and cell death that elicit acute cardiotoxicity and provide new insights for researchers to discover potential therapeutic strategies to prevent or reverse doxorubicin-induced cardiotoxicity.
Assembly of micro-/nanocapsules holds great potential for catalysis, storage, and drug delivery due to their modifiable shell, high exposed surface area, and large accommodation space. Here, an ...ingenious one-step reaction strategy is presented to fabricate layered double hydroxide (LDH) microcapsules, which benefit from the oxyphilic and synergistic coordination of Ce species to stabilize the initial morphology of metal-organic frameworks (MOFs). Taking advantage of this unique superstructure, the as-prepared Ni-Fe-Ce-LDH microcapsules demonstrate excellent oxygen evolution reaction (OER) activity with an overpotential of 242 mV at 10 mA cm
−2
and long-term durability of at least 24 h. Density functional theory (DFT) results further confirm the electronic modulation induced by the Ce doping for both subtle 3D LDH architectures and superior OER performances. This work not only provides insight into the rare-earth (RE) doping mediated crystal growth and transformation process of MOFs but also represents a facile way to fabricate the desired microcapsule superstructure by virtue of the Lewis acid property and synergistic coordination of RE-ions.
A one-step synthesis has been developed to fabricate layered double hydroxide microcapsules
via
a Ce-doping strategy in metal-organic frameworks.
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
To clarify high‐risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI.
Approach and Results
...Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high‐risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3‐fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR‐6) with a concordance index of 0.824 (95% CI, 0.798–0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort.
Conclusions
Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR‐6 model provides an easy‐to‐use approach to assess the outcome of chronic DILI.
Interfacial solar vapor generation is an emerging technology that has the potential to alleviate the current global water crisis. However, water evaporation is an energy‐intensive phase‐change ...process and thus suffers from an inherently low evaporation yield. New stable and environmentally tolerant materials that can reduce energy requirements and accelerate water evaporation stand out from various studies. In this contribution, a piezoelectric ultrathin nanofilm is integrated into a solar evaporation membrane for simultaneous power generation and water activation. The resulting evaporator is used to continuously convert the wave energy in the ocean into electrical energy. It is found that the electrical energy generated by the evaporator can activate water in adjacent regions, facilitating water evaporation with an additional improvement of over 20% compared to an equivalent non‐piezoelectric evaporator. This paper presents the innovation of a promising membrane evaporation prototype based on the integration of wave‐triggered electricity and water activation.
A piezoelectric ultrathin nanofilm is integrated into a solar evaporation membrane, which triggers water activation nearby the electrical field generated through continuously converting wave energy in the ocean to electrical energy, thus facilitating water evaporation with an additional improvement of over 20% compared to an equivalent non‐piezoelectric evaporator.
Aging is an important risk factor for cardiovascular diseases, and aging‐related cardiac dysfunction serves as a major determinant of morbidity and mortality in elderly populations. Our previous ...study has identified fibronectin type III domain‐containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin‐induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno‐associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging‐related cardiac dysfunction. To verify the involvement of nucleotide‐binding oligomerization domain‐like receptor with a pyrin domain 3 (NLRP3) and AMP‐activated protein kinase α (AMPKα), Nlrp3 or Ampkα2 global knockout mice were used. Besides, young mice were injected with AAV9‐FNDC5 and maintained for 12 months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor‐α (TNF‐α) to examine the role of FNDC5 in vitro. We found that FNDC5 was downregulated in aging hearts. Cardiac‐specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging‐related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF‐α‐stimulated cardiomyocytes in vitro. Mechanistically, FNDC5 activated AMPKα through blocking the lysosomal degradation of glucagon‐like peptide‐1 receptor. More importantly, FNDC5 gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging‐related cardiac dysfunction by activating AMPKα, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.
FNDC5 is downregulated in aging hearts, and cardiac‐specific overexpression of FNDC5 or irisin infusion attenuates aging‐related inflammation, cardiac remodeling, and dysfunction. Mechanistically, FNDC5 activates AMPKα through blocking the lysosomal degradation of GLP‐1R.
Electrocatalytic water splitting (2H2O → 2H2 + O2) is a very promising avenue to effectively and environmentally friendly produce highly pure hydrogen (H2) and oxygen (O2) at a large scale. Different ...materials have been developed to enhance the efficiency for water splitting. Among them, chalcogenides with unique atomic arrangement and high electronic transport show interesting catalytic properties in various electrochemical reactions, such as the hydrogen evolution reaction, oxygen evolution reaction, and overall water splitting, while the control of their morphology and structure is of vital importance to their catalytic performance. Herein, the general synthetic methods are summarized to prepare metal chalcogenides and different strategies are designed to improve their catalytic performance for water splitting. The remaining challenges in the research and development of metal chalcogenides and possible directions for future research are also summarized.
Herein, the general synthetic methods and different strategies for preparing metal chalcogenides are summarized to improve their catalytic performance in the hydrogen evolution reaction and oxygen evolution reaction. The challenges of built metal chalcogenides catalysts are summarized to enhance and develop future promising applications.
The rational design of heterogeneous catalysts is crucial for achieving optimal physicochemical properties and high electrochemical activity. However, the development of new amorphous–crystalline ...heterostructures is significantly more challenging than that of the existing crystalline–crystalline heterostructures. To overcome these issues, a coordination‐assisted strategy that can help fabricate an amorphous NiO/crystalline NiCeOx (a‐NiO/c‐NiCeOx) heterostructure is reported herein. The coordination geometry of the organic ligands plays a pivotal role in permitting the formation of coordination polymers with high Ni contents. This consequently provides an opportunity for enabling the supersaturation of Ni in the NiCeOx structure during annealing, leading to the endogenous spillover of Ni from the depths of NiCeOx to its surface. The resulting heterostructure, featuring strongly coupled amorphous NiO and crystalline NiCeOx, exhibits harmonious interactions in addition to low overpotentials and high catalytic stability in the oxygen evolution reaction (OER). Theoretical calculations prove that the amorphous–crystalline interfaces facilitate charge transfer, which plays a critical role in regulating the local electron density of the Ni sites, thereby promoting the adsorption of oxygen‐based intermediates on the Ni sites and lowering the dissociation‐related energy barriers. Overall, this study underscores the potential of coordinating different metal ions at the molecular level to advance amorphous–crystalline heterostructure design.
An innovative coordination‐assisted strategy can be exploited to construct amorphous–crystalline heterostructures from heterometallic coordination polymers with high Ni contents. The favorable amorphous–crystalline interface and Ce–O–Ni interactions generated in the heterostructures derived from the coordination polymers facilitate charge transfer, thereby amplifying the electronic delocalization of Ni atoms and improving the activity for the oxygen evolution reaction.
Interfacial solar steam generation has been proved to be effective for desalination and water purification applications and a large number of smartly designed structures have been reported to reduce ...the heat conduction loss into bulk water by introducing thermally insulating porous foams. Actually, directly using air as the thermal insulation layer should be one of the most efficient ways to reduce the heat loss into bulk water. To this end, we present a bridge-arched hollow and self-floating integrative solar absorber/water evaporator prepared by a one-step hydrothermal reaction. The fully integrative water evaporator can achieve ∼92.9% water evaporation efficiency and 1.476 kg m
−2
h
−1
water evaporation rate under just 1 sun illumination. Such a high efficiency is caused by the unique bridge-arched raised upper surface, hollow interior, and tailored bilayer structure consisting of hydrophilic porous melamine foam for water transportation and a reduced graphene oxide layer for photothermal conversion. These features not only provide broadband solar absorption (∼95%), efficient light-to-heat conversion and a high water evaporation rate, but also suppress the heat loss at the same time. Owing to the simplicity of fabrication and recyclability, this novel composite structure is an ideal material for commercial, portable solar thermal conversion applications to obtain clean water
via
seawater desalination and wastewater purification.
A bridge-arched integrated evaporator that introduces air as the thermal insulation layer exhibits high-efficiency solar steam generation.
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