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Forest fires are sudden, destructive, hazardous, and challenging to manage and rescue, earning them a place on UNESCO's list of the world's eight major natural disasters. Currently, amid global warming, all countries worldwide have entered a period of high forest fire incidence. Due to global warming, the frequency of forest fires has accelerated, the likelihood of large fires has increased, and the spatial and temporal dynamics of forest fires have shown different trends. Therefore, the impact of climate change on the spatiotemporal dynamics of forest fires has become a hot issue in the field of forest fire research in recent years. Therefore, it is of great significance and necessity to conduct a review of the research in this area. This review delves into the interactions and impacts between climate change and the spatiotemporal dynamics of forest fires. To address this issue, scholars have mainly adopted the following research methods: first, statistical analysis methods, second, the establishment of spatiotemporal prediction models for meteorology and forest fires, and third, the coupling of climate models with forest fire risk forecasting models. The statistical analysis method relies on the analysis of historical meteorological and fire-related data to study the effects of climate change and meteorological factors on fire occurrence. Meanwhile, forest fire prediction models utilize technical tools such as remote sensing. These models synthesize historical meteorological and fire-related data, incorporating key meteorological factors such as temperature, rainfall, relative humidity, and wind. The models revealed the spatial and temporal distribution patterns of fires, identified key drivers, and explored the interactions between climate change and forest fire dynamics, culminating in the construction of predictive models. With the deepening of the study, the coupling of climate models and fire risk ranking systems became a trend in the prediction of forest fire risk trends. Moreover, as the climate warms, the increased frequency of extreme weather events like heatwaves, droughts, snow and ice storms, and El Niño-Southern Oscillation (ENSO) has accelerated forest fire occurrences and raised the risk of major fires. This review offers valuable technical insights by comprehensively analyzing the spatial and temporal characteristics of forest fires, elucidating key meteorological drivers, and exploring potential mechanisms. These insights serve as a scientific foundation for preventive measures and effective forest fire management. In the face of a changing climate, this synthesis contributes to the development of informed strategies to mitigate the escalating threat of forest fires.
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Diabetes is one of the most prevalent diseases worldwide. The tissue regeneration of diabetes patients is known to be rather tricky as the result of vascular dysfunction, and this leads to various clinical complications including diabetic foot ulcers. The vascular endothelial cells, which compactly line the inner surface of blood vessels, are responsible for the growth and maintenance of blood vessels and play an essential role in tissue regeneration. Although the mechanical properties of cells are generally known to be regulated by physiological/pathological conditions, few studies have been performed to investigate vascular endothelial cellular mechanics under hyperglycemia and the biological functions related to tissue regeneration. In this study, we conduct a systematic investigation of this issue. The results suggested that the stiffness of human umbilical vein endothelial cells (HUVECs) can be significantly regulated by the glucose concentration, subsequently, leading to significant alterations in cell migration and proliferation capabilities that are closely related to tissue regeneration. The rearrangement of the cytoskeleton induced by hyperglycemia through Cdc42 was found to be one of the pathways for the alteration of the cell stiffness and the subsequent cell dysfunctions. Therefore, we suggested that the inhibition of Cdc42 might be a promising strategy to facilitate various tissue regeneration for diabetes patients.
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This paper aims to realize a self-reference delamination inspection in CFRPs with diffuse ultrasonic waves. The static experiments are first conducted on samples with a machined defect of 0.5 mm in height which simulates an opening state delamination. The diffusivity decreases with delamination diameter (pristine, 6 mm, 12 mm) at a constant depth and increases with delamination depth (0.25 mm, 0.75 mm) at a given diameter. However, no clear pattern can be found for the dissipation coefficient because of the intrinsic absorption and manufacturing uncertainties. Both coefficients are insensitive to the delamination height under loading. In contrast, the corresponding maximum cross-correlation coefficient from coda wave interferometry shows a variation of 2.4-7 % in different samples. A sharp transition can be found due to the clapping effect when the delamination is fully closed. After then, the static loading is replaced by acoustic stressing pulse from PZT in a closed delamination sample. The low frequency pulse induced reverberation field is sampled by a high frequency diffuse wave semi-synchronously, which mimics a cyclic and low amplitude loading during service. All the dynamic cross-correlation coefficient curves present an ascending trend during voltage ramp-up due to the viscoelastic effect, no matter in the intact zone or delamination zone. When the voltage threshold of 250 V is reached, the clapping effect can be triggered. A descending trend has been found not only when the excitation is right above but also near the delamination. This can be applied as an indicator of the delamination existence regionally without scanning. Such nonlinear measurement system can be expanded to passive imaging and other deficiency inspection in CFRPs with less demanding facilities.
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OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with rising incidence worldwide. This study explored the anti-T2DM role of vitamin D, thereby providing novel therapeutic strategies. METHODS: C57BL/6 J mice and MIN6 cells were used to induce in vivo T2DM and damaged ß-cell models, respectively. Body weights, fasting blood glucose, and fasting insulin were measured in mice. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted on mice. Lipid indices (TG, TC, LDL-C, and HDL-C) were detected in mouse serum. Hematoxylin-eosin staining was used to evaluate pancreatic tissue injury. ELISA was used to assess insulin and oxidative stress (OS) markers (MDA, GSH, and SOD) in mice and MIN6 cells. Production of ROS was detected in islet ß-cells and MIN6 cells. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry, respectively. QRT-PCR and western blotting were used to detect pro-inflammatory factors (TNF-α and IL-6) and endoplasmic reticulum stress (ERS) markers (CHOP and GRP78), respectively. RESULTS: Vitamin D reduced body weights, fasting blood glucose, and insulin and ameliorated glucose tolerance and insulin sensitivity in T2DM mice. Besides, vitamin D decreased serum TG, TC, LDL-C, and increased HDL-C in T2DM mice. Vitamin D inhibited pancreatic histopathological injury, cell apoptosis, OS, and ß-cell decline in T2DM mice. Moreover, vitamin D alleviated cell death, insufficient insulin secretion, inflammation, OS, and ERS in damaged MIN6 cells. Notably, N-acetyl-L-cysteine (an OS inhibitor) enhanced these effects of vitamin D. CONCLUSIONS: Vitamin D relieved T2DM symptoms by alleviating OS-induced ß-cell impairment.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Mice , Animals , Diabetes Mellitus, Type 2/metabolism , Blood Glucose/metabolism , Vitamin D/pharmacology , Vitamin D/therapeutic use , Cholesterol, LDL , Mice, Inbred C57BL , Insulin , Insulin-Secreting Cells/metabolism , Oxidative Stress , Body WeightABSTRACT
Background: The aim of this study was to compare the characteristics of auditory P300 between non-clinical individuals with high and low schizotypal traits, and investigate the relationship between schizotypy and P300 under various oddball conditions. Methods: An extreme-group design was adopted. After screening 1,519 young adults using the Schizotypal Personality Questionnaire (SPQ), sixty-three participants were chosen and divided into two groups (schizotypy group: 31 participants; control group: 32 participants). Basic demographic information was assessed and matched between groups. Depression and anxiety indexes were evaluated and controlled. The P300 component was evoked by an auditory oddball paradigm with different frequencies and durations. Results: (1) The duration P300 amplitude at PZ site was significantly weaker in the schizotypy group than in the control group [F(1,54) = 7.455, p = 0.009, ηp2 = 0.121]. (2) In the schizotypy group, the latency of frequency P300 at PZ site under large-variant oddball condition was significantly correlated with total SPQ scores (rp = 0.451, p = 0.018) and disorganized dimension scores (rp = 0.381, p = 0.050). (3) In the control group, significantly negative correlations was found between the negative dimension score of SPQ and the frequency P300 amplitudes under small variant condition (PZ: rp = -0.393, p = 0.043; CPZ: rp = -0.406, p = 0.035). In addition, a significant negative relationship was found between disorganized dimension scores and the duration P300 latency at CPZ site under large-variant oddball condition (rp = -0.518, p = 0.006). Moreover, a significant negative association was found between the duration P300 amplitude at CPZ site under small-variant oddball condition and negative factor scores (rp = -0.410, p = 0.034). Conclusion: Individuals with high schizotypal traits were likely to have deficient attention and hypoactive working memory for processing auditory information, especially the duration of sounds. P300 effects were correlated with negative and disorganized schizotypy, rather than positive schizotypy. There were diverse patterns of relationship between schizotypal traits and P300 under different oddball conditions, suggesting that characteristics and parameters of target stimuli should be considered cautiously when implementing an auditory oddball paradigm for individuals with schizophrenia spectrum.
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Purpose: Intestinal flora imbalance has been implicated in the activation of innate immunity in the kidneys. However, little is known about the potential links between lipopolysaccharide (LPS)-toll-like. receptor 4 (TLR4) signaling activated by intestinal barrier dysfunction and microalbuminuria in type 2 diabetes mellitus (T2DM). Patients and Methods: 61 patients with T2DM were stratified based on the absence (n=32) or presence (n=29) of microalbuminuria. There were also 28 control subjects. Urinary albumin excretion rate (UAER), serum levels of LPS, D-lactic acid (DLA), diamine oxidase (DAO), fasting blood glucose (FBG), interleukin-6 (IL-6), glycosylated hemoglobin A1 (HbA1c), and high-sensitivity C-reactive protein (hs-CRP), and TLR4 expression in peripheral blood mononuclear cells (PBMCs) were measured. Results: hs-CRP, IL-6, LPS, DLA, DAO, and TLR4 were markedly increased in subjects with T2DM compared to the controls (P < 0.05 for all). Moreover, LPS was positively correlated with FBG, HbA1c, hs-CRP, IL-6, UAER, DLA, DAO, and TLR4 (P < 0.05 for all). In addition, TLR4 was positively correlated with UAER, hs-CRP, FBG, DLA, HbA1c, and LPS (P < 0.05 for all). In regression analyses, TLR4, LPS, HbA1c, and hs-CRP were independently associated with UAER (P < 0.05 for all), while FBG, LPS, TLR4, and hs-CRP (P < 0.05 for all) were found to be risk factors for microalbuminuria in T2DM. Conclusion: Intestinal integrity is compromised in subjects with T2DM, and the activation of LPS-TLR4 signaling might play an important role in the development of microalbuminuria in T2DM.
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A highly stable interface for aqueous rechargeable Zn batteries is of importance to inhibit the growth of Zn dendrites and suppress the side reactions. In this work, we have developed a stable honeycomb-like ZnO passivation protective layer on the Zn surface, which is in situ generated with the assistance of a nonionic surfactant additive (polyethylene glycol tert-octylphenyl ether, denoted as PEGTE). The ZnO passivation layer can facilitate the uniform distribution of the electric field, guiding the uniform deposition of Zn2+ and inhibit the generation of dendrites. As a result, the symmetric cell using the electrolyte with PEGTE shows an excellent performance at high areal capacity, reflected by stable cycling for over 2400 h at 5 mAh/cm2 and 1300 h at 10 mAh/cm2. The full cell paired with V2O5 demonstrates a long lifespan for more than 600 cycles at a low negative/positive capacity ratio.
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Recent evidence has demonstrated that, when cultured on micro-patterned surfaces, living cells can move in a coordinated manner and form distinct migration patterns, including flowing chain, suspended propagating bridge, rotating vortex, etc. However, the fundamental question of exactly how and why cells migrate in these fashions remains elusive. Here, we present a theoretical investigation to show that the tight interplay between internal cellular activities, such as chemo-mechanical feedbacks and polarization, and external geometrical constraints are behind these intriguing experimental observations. In particular, on narrow strip patterns, strongly force-dependent cellular contractility and intercellular adhesion were found to be critical for reinforcing the leading edge of the migrating cell monolayer and eventually result in the formation of suspended cell bridges flying over nonadhesive regions. On the other hand, a weak force-contractility feedback led to the movement of cells like a flowing chain along the adhesive strip. Finally, we also showed that the random polarity forces generated in migrating cells are responsible for driving them into rotating vortices on strips with width above a threshold value (~10 times the size of the cell).
Subject(s)
Cell Movement , FeedbackABSTRACT
This study was to preview the risk of 30-day mortality in sepsis patients using sentiment analysis. The clinical data of patients and nursing notes were collected from the Medical Information Mart for Intensive Care (MIMIC-III) database. The factors influencing 30-day mortality were analyzed using the Cox regression model. And, the prognostic index (PI) was estimated. The receiver operating characteristic (ROC) curve was used to determine the PI cut-off point and assess the prediction ability of the model. In total, 1844 of 3560 patients were eligible for the study, with a 30-day mortality of 37.58%. Multivariate Cox analysis showed that sentiment polarity scores, sentiment subjectivity scores, simplified acute physiology score (SAPS)-II, age, and intensive care unit (ICU) types were all associated with the risk of 30-day mortality (P < 0.05). In the preview of 30-day mortality, the area under the curve (AUC) of ROC was 0.78 (95%CI: 0.74-0.81,P < 0.001) when the cut-off point of PI was 0.467. The documented notes from nurses were described for the first time. Sentiment scores measured in nursing notes are associated with the risk of 30-day mortality in sepsis patients and may improve the preview of 30-day mortality.
Subject(s)
Sepsis , Critical Care , Humans , Intensive Care Units , Prognosis , ROC Curve , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate clinicians' compliance with the 2018 Surviving Sepsis Campaign (SSC) update "1-hour sepsis Bundle therapy" (1-hour Bundle) when treating patients with Sepsis 3 in the intensive care unit (ICU), and to analyze its impact on patient outcomes. METHODS: A multicenter, prospective observational cohort study was conducted. A total of 153 ICU patients in Ziyang First People's Hospital, Ziyang People's Hospital and Yanjiang District People's Hospital who were diagnosed of sepsis by the definition and diagnostic criteria of Sepsis 3 from January 2019 to December 2020 were selected. Among them, 95 patients who had completed 1-hour Bundle were divided into the Bundle compliance group. 58 patients who did not complete the Bundle within 1 hours were classified as the Bundle non-compliance group. The distribution of pathogenic bacteria and infected sites, 1-hour Bundle compliance and 28-day survival in the 3 hospitals were analyzed. Univariate analysis was used to analyze the risk factors affecting the prognostic between the two groups of sepsis patients. Cox regression model was used to draw a 28-day survival curve to evaluate the survival of the patients in the two groups. RESULTS: Among 153 sepsis patients in 3 hospitals, the detection rate of pathogenic bacteria was 61.44% (94/153), and Gram-negative bacteria accounted for 79.79% (75/94). The top 3 infection sites were respiratory system, gastrointestinal tract and urinary system, accounted for 32.0%, 28.1% and 18.3%, respectively. In the 3 hospitals, 62.09% (95/153) of patients fully implemented the 1-hour Bundle. The poorly implemented indicators in the 1-hour Bundle were 1-hour blood microbial culture [77.78% (119/153)] and 1-hour antimicrobial application [79.74% (122/153)]. There was no significant difference in the baseline indicators between Bundle compliance and non-compliance groups. Univariate analysis showed that the main prognostic indicators: 28-day survival rate in the Bundle compliance group was significantly higher than that in the Bundle non-compliance group [80.00% (76/95) vs. 62.06% (36/58), χ2 = 6.447, P = 0.014]. Secondary evaluation indicators: mean arterial pressure (MAP) at 6 hours and 24 hours in the Bundle compliance group were significantly higher than those in the Bundle non-compliance group [mmHg (1 mmHg = 0.133 kPa): 78.22±11.25 vs. 69.86±14.04, 79.78±11.45 vs. 75.35±12.90]. However, the median length of in hospital stay in the Bundle compliance group was significantly longer than that in the Bundle non-compliance group [days: 13 (17) vs. 6 (11)], with statistically significant differences (all P < 0.05). Bivariate Logistic regression analysis showed that 6 hours and 24 hours MAP were risk factors affecting the prognosis of patients with sepsis [odds ratio (OR), 95% confidence interval (95%CI): 1.064 (0.994-1.102), 1.032 (1.003-1.063), both P < 0.05]. CONCLUSIONS: The 1-hour Bundle compliance rate of ICU patients with sepsis in 3 hospitals of Ziyang City was 62.09%, and the compliance is still to be improved, especially for the 2 aspects of empirical antimicrobial use and microbial culture retention before antimicrobial use. The 28-day survival rate in the Bundle compliance group was significantly higher than that in the Bundle non-compliance group, suggesting that the 1-hour Bundle regimen can improve the prognosis of patients with sepsis.
Subject(s)
Sepsis , Shock, Septic , Humans , Intensive Care Units , Prognosis , Prospective Studies , Sepsis/diagnosis , Sepsis/therapyABSTRACT
Bone regeneration and repair has become one of the major clinical challenges worldwide and it involves multiple processes including inflammation, angiogenesis and osteogenesis. In this study, we synthesized strontium Laminarin polysaccharide (LP-Sr), a novel polysaccharide-metal complex that should have therapeutic effects on modulating osteogenesis and angiogenesis. The structure and composition of the as-fabricated LP-Sr were analyzed by EDS, XRD, FITR, 1H NMR, HPLC, etc. The results indicate that we successfully synthesized this novel polysaccharide complex. Moreover, we evaluated the biomedical potential of this complex in promoting osteogenesis and angiogenesis by cell proliferation assay, ALP staining, immunofluorescent staining of CD31 and reverse transcription polymerase chain reaction (RT-PCR). The biological experiment results show that LP-Sr can effectively promote proliferation and increase the expression of VEGF and EGFL6 in HUVECs and significantly up-regulate the expression of Col1α1 and OCN in MC3T3-E1. Besides, it is suggested that LP-Sr has positive effects on the suppression of pro-inflammatory factor IL6 in both HUVECs and MC3T3-E1. Moreover, the osteogenic and angiogenic markers, i.e. alkaline phosphatase (ALP) and CD31, exhibited high expression in LP-Sr group. Hence, we believe that LP-Sr should be a promising and novel polysaccharide complex in modulating osteogenesis-angiogenesis for bone regeneration.
Subject(s)
Bone Regeneration/drug effects , Glucans/chemistry , Neovascularization, Physiologic/drug effects , Osteogenesis/drug effects , Polysaccharides/pharmacology , Strontium/pharmacology , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Fluorescence , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice , Molecular Weight , Monosaccharides/analysis , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Proton Magnetic Resonance Spectroscopy , Reference Standards , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Temperature , Thermogravimetry , X-Ray DiffractionABSTRACT
Sodium (Na) metal is considered as a promising anode candidate for large-scale energy storage systems because of its high theoretical capacity and low electrochemical redox potential. However, Na anode suffers from a few challenges, such as the dendrite growth and severe parasitic reactions with electrolytes, which greatly hinder its practical applications. In this work, we demonstrate that an organosulfur compound additive (tetramethylthiuram disulfide) provides a facile and promising approach to overcome the above challenges in carbonate-based electrolytes. This unique organosulfur additive can in situ form a stable interfacial protection layer rich in organic sulfide salts on the sodium metal surface during cycling, leading to a stable stripping/plating cycling. Additionally, a cycling Coulombic efficiency of 94.25% is achieved, and the full battery using Prussian Blue as a cathode delivers a reversible capacity of 86.2 mAh g-1 with a capacity retention of 80% after 600 cycles at 4 C.
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A novel electroporation system was developed to introduce transient membrane pores to cells in a spatially and temporally controlled manner, allowing us to achieve fast electrotransfection and live cell staining as well as to systematically interrogate the dynamics of the cell membrane. Specifically, using this platform, we showed that both reversible and irreversible electroporation could be induced in the cell population, with nano-sized membrane pores in the former case being able to self-reseal in ~10 min. In addition, green fluorescent protein(GFP)-vinculin plasmid and 543 phalloidin have been delivered successively into fibroblast cells, which enables us to monitor the distinct roles of vinculin and F-actin in cell adhesion and migration as well as their possible interplay during these processes. Compared to conventional bulk electroporation and staining methods, the new system offers advantages such as low-voltage operation, cellular level manipulation and testing, fast and adjustable transfection/staining and real-time monitoring; the new system therefore could be useful in different biophysical studies in the future.
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Sodium metal anode (SMA) is one of the most favored choices for the next-generation rechargeable battery technologies owing to its low cost and natural abundance. However, the poor reversibility resulted from dendrite growth and formation of unstable solid electrolyte interphase has significantly hindered the practical application of SMAs. Herein, we report that a nucleation buffer layer comprising elaborately designed core-shell C@Sb nanoparticles (NPs) enables the homogeneous electrochemical deposition of sodium metal for long-term cycling. These C@Sb NPs can increase active sites for initial sodium nucleation through Sb-Na alloy cores and keep these cores stable through carbon shells. The assembled cells with this nucleation layer can deliver continuously repeated sodium plating/stripping cycles for nearly 6000 h at a high areal capacity of 4 mA h cm-2 with an average Coulombic efficiency 99.7%. This ingenious structure design of alloy-based nucleation agent opens up a promising avenue to stabilize sodium metal with targeted properties.
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Leukemia is a commonly seen disease caused by abnormal differentiation of hematopoietic stem cells and blasting in bone marrow. Despite drugs are used to treat the disease clinically, the influence of these drugs on leukemia cells' biomechanical properties, which are closely related to complications like leukostasis or infiltration, is still unclear. Due to non-adherent and viscoelastic nature of leukemia cells, accurate measurement of their elastic modulus is still a challenging issue. In this study, we adopted rate-jump method together with optical tweezers indentation to accurately measure elastic modulus of leukemia cells K562 after phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRA), Cytoxan (CTX), and Dexamethasone (DEX) treatment, respectively. We found that compared to control sample, K562â¯cells treated by PMA showed nearly a threefold increase in elastic modulus. Transwell experiment results suggested that the K562â¯cells treated with PMA have the lowest migration capability. Besides, it was shown that the cytoskeleton protein gene α-tubulin and vimentin have a significant increase in expression after PMA treatment by qPCR. The results indicate that PMA has a significant influence on protein expression, stiffness, and migration ability of the leukemia cell K562, and may also play an important role in the leukostasis in leukemia.
Subject(s)
Antineoplastic Agents/pharmacology , Biomechanical Phenomena/drug effects , Cell Movement/drug effects , Leukemia/drug therapy , Cyclophosphamide/pharmacology , Dexamethasone/pharmacology , Elastic Modulus/drug effects , Humans , K562 Cells , Leukemia/pathology , Tetradecanoylphorbol Acetate/pharmacology , Tretinoin/pharmacologyABSTRACT
Metal polyphosphides are regarded as the ideal anode candidates for sodium storage because of their high theoretical capacity, reasonable potential, and abundant resource alternative. However, most of them suffer from irreversibility problems, as reflected by their low reversible capacity, inferior Coulombic efficiency (CE), low rate capability, and poor cycling stability. In this work, we systematically compare the electrochemical behavior of a variety of polyphosphides bulks, discovering that the CuP2 bulks have higher initial reversible capacity (416 mAh g-1 at 0.1 A g-1) and CE (74%) compared to the FeP2, CoP3, and NiP2 bulks, which is related to the unique crystal structure of CuP2. The CuP2 electrode is optimized by the rational design of encapsulating CuP2 nanoparticles into three-dimensional graphene networks (CuP2@GNs), leading to excellent electrochemical performance. In the carbonate electrolyte, the CuP2@GNs electrode can deliver the reversible capacities of up to 804, 736, 685, 621, and 508 mAh g-1 at 0.1, 0.5, 1, 2, and 5 A g-1, respectively, along with a first CE of 66%. The reversible capacity can be up to 737 mAh g-1 at 0.1 A g-1 with a first CE of 83% in the ether electrolyte. These excellent performance demonstrates that CuP2@GNs could be a promising anode material for sodium-ion batteries.
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BACKGROUND AND AIMS: Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. METHODS: VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. RESULTS: Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. CONCLUSIONS: Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis.
Subject(s)
Apoptosis , Atherosclerosis/metabolism , Myocytes, Smooth Muscle/cytology , Palmitates/pharmacology , Reactive Oxygen Species/metabolism , Toll-Like Receptor 4/metabolism , Tumor Suppressor Protein p53/metabolism , Caspase 3/metabolism , Caspase 9/metabolism , Cell Survival , Enzyme Inhibitors/pharmacology , Humans , In Situ Nick-End Labeling , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/drug effects , NADPH Oxidases/antagonists & inhibitors , Oxidative Stress , RNA, Messenger/metabolismABSTRACT
The expression levels of the protein tyrosine kinase Ack1 has been reported to be dysregulated in various cancers and involve in oncogenesis and progression. However, the expression and role of Ack1 in osteosarcoma remains unknown. In this study, we found that Ack1 were evidently upregulated in human osteosarcoma tissues and cell lines. In addition, the clinical data showed that high expression level of Ack1 is closely associated with clinical stage and positive distant metastasis, and negatively correlated with overall survival. Then, bioinformatics prediction and luciferase reporter assay indicated Ack1 as a direct target of miR-24, and Ack1 could be downregulated by miR-24 at both the mRNA and protein expression levels. Moreover, Ack1 expression levels were inversely correlated with that of miR-24 in osteosarcoma tissues. Furthermore, functional assay showed that miR-24 significantly suppressed osteosarcoma progression partially mediated by inhibiting Ack1 expression. Finally, western bolt assay revealed that miR-24 regulate AKT/MMPs pathway via Ack1 in osteosarcoma cells. In conclusion, our study demonstrated the suppression of miR-24 on osteosarcoma metastasis by targeting Ack1 via AKT/MMPs pathways, providing a novel strategy for the diagnosis and treatment of osteosarcoma patients.
Subject(s)
Bone Neoplasms/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , MicroRNAs/genetics , Osteosarcoma/genetics , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Animals , Bone Neoplasms/metabolism , Bone Neoplasms/mortality , Bone Neoplasms/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Nude , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , Molecular Mimicry , Oligoribonucleotides/genetics , Oligoribonucleotides/metabolism , Osteosarcoma/metabolism , Osteosarcoma/mortality , Osteosarcoma/pathology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Survival Analysis , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The aim of this study was to evaluate the reliability of open reduction and minimally invasive plate osteosynthesis (MIPO) for anterior ring fracture combined with pubic symphysis separation and to explore the operative techniques and therapeutic efficacy. MATERIAL AND METHODS: We used minimally invasive plate osteosynthesis (MIPO) to treat anterior ring fracture combined with pubic symphysis separation. RESULTS: During postoperative follow-up, all patients recovered well, with no fat liquefaction, infection, femoral nerve or iliac blood vessels injury, deep vein thrombosis, heterotopic ossification, or any and other complications. CONCLUSIONS: The MIS or MIPPO for anterior ring fracture combined with pubic symphysis separation has the advantages of short operation time and less blood loss. This clinical operation is safe and feasible, with therapeutic efficacy.