5-Lipoxygenase (ALOX5) is an iron-containing and nonheme dioxygenase that catalyzes the peroxidation of polyunsaturated fatty acids such as arachidonic acid. ALOX5 is the rate-limiting enzyme for the ...biosynthesis of leukotrienes, a family of proinflammatory lipid mediators derived from arachidonic acid. ALOX5 also make great contributions to mediating lipid peroxidation. In recent years, it has been discovered that ALOX5 plays a central role in cell death including apoptosis, pyroptosis, and ferroptosis, a newly discovered type of cell death. According to the previous studies, ALOX5 can regulate cell death in two ways: one is inflammation and the other is lipid peroxidation. Meanwhile, it has been shown that ALOX5 activity is regulated by several factors including protein phosphorylation, ALOX5-interactng protein, redox state, and metal ions such as iron and calcium. In this review, we aim to summarize the knowledge on the emerging roles of ALOX5 protein phosphorylation in the regulation of cell death and inflammation in order to explore a potential target for human diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA ...methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.
Psoriasis is an immune-mediated systemic disease with associated comorbidities, including metabolic syndrome (MetS) which contributes substantially to premature mortality in patients with psoriasis. ...However, the pathological mechanisms underlying this comorbidity are unclear. Studies have shown that the pathological parameters of psoriasis mediate the development of MetS. We reviewed the potential mechanisms which mediate the association between psoriasis and MetS, including endoplasmic reticulum stress, pro-inflammatory cytokine releases, excess production of reactive oxygen species, alterations in adipocytokine levels and gut microbiota dysbiosis. Here, we highlight important research questions regarding this association and offer insights into MetS research and treatment.
Mitochondria are key regulators of cell fate through controlling ATP generation and releasing pro-apoptotic factors. Cardiac ischemia/reperfusion (I/R) injury to the coronary microcirculation has ...manifestations ranging in severity from reversible edema to interstitial hemorrhage. A number of mechanisms have been proposed to explain the cardiac microvascular I/R injury including edema, impaired vasomotion, coronary microembolization, and capillary destruction. In contrast to their role in cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. It is clear that abnormal mitochondrial signatures, including mitochondrial oxidative stress, mitochondrial fission, mitochondrial fusion, and mitophagy, play a substantial role in endothelial cell function. While the pathogenic role of each of these mitochondrial alterations in the endothelial cells I/R injury remains complex, profiling of mitochondrial oxidative stress and mitochondrial dynamics in endothelial cell dysfunction may offer promising potential targets in the search for novel diagnostics and therapeutics in cardiac microvascular I/R injury. The objective of this review is to discuss the role of mitochondrial oxidative stress on cardiac microvascular endothelial cells dysfunction. Mitochondrial dynamics, including mitochondrial fission and fusion, are critically discussed to understand their roles in endothelial cell survival. Finally, mitophagy, as a degradative mechanism for damaged mitochondria, is summarized to figure out its contribution to the progression of microvascular I/R injury.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper addresses the issue of two-dimensional (2-D) direction of arrival (DOA) estimation with coprime planar arrays (CPPAs) via sparse representation. Our work differs from the partial spectral ...search approach 25, which suppresses the phase ambiguity by searching the common peaks of two subarrays. We focus on the coprime property of CPPA, where the sparse array extension model with sum-difference coarray (SDCA) is derived for larger degrees of freedom (DOFs). Besides, to optimize the selection of regularization parameter, we also construct a new sparse representation algorithm by estimating the errors between the signal and noise parts. Further, an iterative scheme is presented to transform the 2-D grids searching to several times of 1-D searching, where the initial values are obtained by extracting one difference coarray from SDCA. So the proposed method can achieve aperture extension, high estimation performance, and low computational complexity. Besides, the sparse array extension model for multiple-input multiple-output radars is discussed and the Cramér-Rao bound for 2-D DOA estimation with CPPA is also derived in detail. Finally, simulation results demonstrate the effectiveness of proposed method compared to the state-of-the-art methods.
Guest-dependent dynamics having both crystal contraction and expansion upon inclusion of various guests is uncovered in a 3D covalent organic framework (COF) prepared with a facile and scalable ...method. A molecular-level understanding of how the framework adjusts the node geometry and molecular configuration to perform significant contraction and large amplitude expansion are resolved through synchrotron in-house powder X-ray diffraction (PXRD) and Rietveld refinements. We found that the COF adopts a contracted phase at ambient conditions upon capturing moisture and is also adaptive upon inclusion of organic solvents, which is highlighted by a large crystal expansion (as large as 50% crystallographic volume increment and a 3-fold channel size enlargement). With this new knowledge of the structural adaptability, the diverse responses and coherent switchability are thereby presented to pave the way to rational design and deliberate control of dynamic COFs.
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IJS, KILJ, NUK, PNG, UL, UM
X-Ray single-crystal diffraction has been the most straightforward and important technique in structural determination of crystalline materials for understanding their structure-property ...relationships. This powerful tool can be used to directly visualize the precise and detailed structural information of porous coordination polymers or metal-organic frameworks at different states, which are unique for their flexible host frameworks compared with conventional adsorbents. With a series of selected recent examples, this review gives a brief overview of single-crystal X-ray diffraction studies and single-crystal to single-crystal transformations of porous coordination polymers under various chemical and physical stimuli such as solvent and gas sorption/desorption/exchange, chemical reaction and temperature change.
FUN14 domain-containing protein 1 (Fundc1)-dependent mitophagy, mainly activated by ischemic/hypoxic preconditioning, benefits acute myocardial reperfusion injury and chronic metabolic syndrome via ...sustaining mitochondrial homeostasis. Mitochondrial fission plays a pathogenic role in ischemic acute kidney injury (AKI) through perturbation of mitochondrial quality and activation of mitochondrial apoptosis. The aim of our study was to explore the role of Fundc1 mitophagy in ischemia preconditioning (IPC)-mediated renoprotection. Proximal tubule-specific Fundc1 knockout (Fundc1PTKO) mice were subjected to ischemia reperfusion injury (IRI) and IPC prior to assessment of renal function, mitophagy, mitochondrial quality control, and Drp1-related mitochondrial fission. Following exposure to IPC, Fundc1 mitophagy was activated through post-transcriptional phosphorylation at Ser17. Interestingly, IRI-mediated renal injury, inflammation, and tubule cell death were mitigated by IPC whereas proximal tubule-specific Fundc1 knockout (Fundc1PTKO) mice abolished IPC-offered renoprotection. Mechanistically, IRI-evoked mitochondrial damage was improved by IPC whereas Fundc1 deficiency provoked mitochondrial abnormality, manifested by impaired mitochondrial quality and hyperactivated Drp1-dependent mitochondrial fission. Interestingly, Fundc1 deficiency-associated mitochondrial dysfunction was reversed by pharmacological inhibition of mitochondrial fission. In vivo, Fundc1 deletion-caused renal injury, severe pro-inflammatory response, and tubule cell death could be nullified by way of knockout Drp1 on Fundc1PTKO background. Finally, we also revealed that IPC triggered Fundc1 mitophagy activation through UNC-51-like kinase 1 (Ulk1) and Ulk1 ablation interrupted IPC-mediated Fundc1 activation and thus attenuated IPC-induced renoprotection. Fundc1 mitophagy, primarily driven by IPC, confers resistance to AKI through reconciliation of mitochondrial fission, implicating the therapeutic potential of targeting mitochondrial homeostasis for AKI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed ...functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients' survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT-DNA-PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN-ATM-CHK2 signal and ATR-CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.
The slow redox kinetics of polysulfides and the difficulties in decomposition of Li
S during the charge and discharge processes are two serious obstacles to the practical application of ...lithium-sulfur batteries. Herein, we construct the Fe-Co diatomic catalytic materials supported by hollow carbon spheres to achieve high-efficiency catalysis for the conversion of polysulfides and the decomposition of Li
S simultaneously. The Fe atom center is beneficial to accelerate the discharge reaction process, and the Co atom center is favorable for charging process. Theoretical calculations combined with experiments reveal that this excellent bifunctional catalytic activity originates from the diatomic synergy between Fe and Co atom. As a result, the assembled cells exhibit the high rate performance (the discharge specific capacity achieves 688 mAh g
at 5 C) and the excellent cycle stability (the capacity decay rate is 0.018% for 1000 cycles at 1 C).
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