Background:Macrophages play an important role in the development of cardiac fibrosis. However, the roles of different macrophage subtypes in cardiac fibroblast (CF) activation and cardiac fibrosis ...are unknown.Methods and Results:Bone marrow-derived macrophages (BMDMs) were treated with different stimuli to induce differentiation into M1, M2a, M2b, and M2c macrophage subtypes. CFs were co-cultured with different subtypes of macrophages or cultured with macrophage supernatants. Results revealed that M2b macrophages significantly suppressed the proliferation and migration of CFs, the expression of fibrosis-related proteins (collagen I COL-1 and α-smooth muscle actin α-SMA), and differentiation into cardiac myofibroblasts (MFs). The opposite effects were observed with M2a macrophages. A rat model of cardiac ischemia/reperfusion (I/R) injury was used to determine the effect of M2b macrophages transplantation. After cardiac I/R injury, transplantation of M2b macrophages improved cardiac function and reduced cardiac fibrosis. The effect of macrophage subtypes on p-ERK, ERK, p-p38, and p38 phosphorylation was examined by Western blotting. The results showed that M2b macrophages significantly inhibited the mitogen-activated protein kinase (MAPK) signaling pathway.Conclusions:These study results demonstrate for the first time that different subtypes of macrophages have different roles in regulating CF activation. M2b macrophages inhibit CF activation, and thus can be considered anti-fibrotic macrophages. M2a macrophages promote CF activation, and thus are pro-fibrotic macrophages.
As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in ...neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified
. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.
A novel and straightforward strategy for functionalized 1 H -indazoles is realized by the Rh( iii )-catalyzed double C–H activation and C–H/C–H cross coupling of readily available aldehyde ...phenylhydrazones. The reaction is scalable and various 1 H -indazoles could be afforded in moderate to high yields with good functional-group compatibility. Mechanism experiments and DFT calculations suggest the distinctive Rh( iii )-catalyzed C–H/C–H cross coupling reaction underwent a cascade C(aryl)–H bond metalation, C(aldhyde)–H bond insertion and reductive elimination process.
Solid-state batteries with high energy density and safety are promising next-generation battery systems. However, lithium oxide and lithium sulfide electrolytes suffer low ionic conductivity and poor ...electrochemical stability, respectively. Lithium halide solid electrolyte shows high conductivity and good compatibility with the pristine high-voltage cathode but limited applications due to the high price of rare metal. Zr-based lithium halides with low cost and high stability possess great potential. Herein, a small amount of In3+ is introduced in Li2ZrCl6 to synthesize Li2.25Zr0.75In0.25Cl6 electrolytes with a high room temperature Li-ion conductivity of 1.08 mS/cm. Solid-state batteries using Li2.25Zr0.75In0.25Cl6/Li5.5PS4.5Cl1.5 bilayer solid electrolytes combined with Li-In anode and pristine LiNi0.7Mn0.2Co0.1O2 cathode deliver high initial discharge capacities under different cut-off voltages. This work provides an effective strategy for enhancing the conductivity of Li2ZrCl6 electrolytes, promoting their applications in solid-state batteries.
Herein, a small amount of In3+ is introduced in Li2ZrCl6 to synthesize Li2.25Zr0.75In0.25Cl6 electrolytes with a high room temperature and Li-ion conductivity of 1.08 mS/cm. This work provides an effective strategy for enhancing the conductivity of Li2ZrCl6 electrolytes, promoting their applications in solid-state batteries. Display omitted
Monocytes or macrophages have been assessed as potential therapeutics to ameliorate myocardial ischemic diseases, but the results have been controversial. As regulatory macrophages, M2b macrophages ...could have enhanced protective effects. We tested the hypothesis that transplantation of M2b macrophages could ameliorate myocardial ischemia/reperfusion (I/R) injury. The potential mechanisms involved in it were investigated.
M2b macrophages were polarized by lipopolysaccharide (LPS) and the immune complex (IC) from bone marrow-derived macrophages (BMDMs) of C57BL/6 mice. They were identified based on surface marker expression and cytokine production. Myocardial I/R injury models were established with the same strain of mice. Once the ischemic area was identified, either 1×105 M2b macrophages (MT group) or the same volume of normal saline (CK group) was injected into the ischemic zone. Mice in the sham operation (SO) group underwent the operation without ligation of the coronary artery.
We found a significant decrease in serum cardiac troponin I (cTnI) level, the infarct area, apoptosis index, and nuclear factor-κB (NF-κB) signaling activation in the MT group after 2h of reperfusion; the changes were induced by I/R. In addition, the injury resulted in significantly up-regulated expression of A20 and continued to be improved by the transplanted M2b macrophages.
The administration of M2b macrophages significantly attenuated myocardial I/R injury. A20 may be part of the protective mechanism through limiting NF-κB signaling-mediated apoptosis.
Abstract Background The triglyceride-glucose (TyG) index and its combination with obesity indicators can predict cardiovascular diseases (CVD). However, there is limited research on the relationship ...between changes in the triglyceride glucose-waist height ratio (TyG-WHtR) and CVD. Our study aims to investigate the relationship between the change in the TyG-WHtR and the risk of CVD. Methods Participants were from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reporting heart disease and stroke. Participants were divided into three groups based on changes in TyG-WHtR using K-means cluster analysis. Multivariable binary logistic regression analysis was used to examine the association between different groups (based on the change of TyG-WHtR) and CVD. A restricted cubic spline (RCS) regression model was used to explore the potential nonlinear association of the cumulative TyG-WHtR and CVD events. Results During follow-up between 2015 and 2020, 623 (18.8%) of 3312 participants developed CVD. After adjusting for various potential confounders, compared to the participants with consistently low and stable TyG-WHtR, the risk of CVD was significantly higher in participants with moderate and increasing TyG-WHtR (OR 1.28, 95%CI 1.01–1.63) and participants with high TyG-WHtR with a slowly increasing trend (OR 1.58, 95%CI 1.16–2.15). Higher levels of cumulative TyG-WHtR were independently associated with a higher risk of CVD events (per SD, OR 1.27, 95%CI 1.12–1.43). Conclusions For middle-aged and older adults, changes in the TyG-WHtR are independently associated with the risk of CVD. Maintaining a favorable TyG index, effective weight management, and a reasonable waist circumference contribute to preventing CVD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
DBF4 zinc finger (DBF4) is a critical component involved in DNA replication and cell proliferation. It acts as a positive regulator of the cell division cycle 7 kinase. In this study, our ...investigation encompassed the impact of DBF4 on hepatocellular carcinoma (HCC) progression and delved into the potential mechanisms. We utilized open-access databases like TCGA and GEO to analyze the association between DBF4 and 33 different tumor types. We also conducted immunohistochemistry experiments to validate the expression of DBF4 in HCC, STAD, COAD, READ, PAAD, and LGG. Furthermore, we employed lentiviral transduction to knockdown DBF4 in HLF and SMMC cells, as well as to overexpress DBF4 in Huh7 cells. Subsequently, we evaluated the impact of DBF4 on proliferation, migration, and invasion of hepatocellular carcinoma cells. RNA sequencing and KEGG pathway enrichment analysis were also conducted to identify potential pathways, which were further validated through WB experiments. Finally, pathway inhibitor was utilized in rescue experiments to confirm whether DBF4 exerts its effects on tumor cells via the implicated pathway. Our findings revealed that DBF4 exhibited significant expression levels in nearly all examined tumors, which were further substantiated by the results of immunohistochemistry analysis. High DBF4 expression was correlated with poor overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), disease-free interval (DFI), relapse-free interval (RFI) in majority of tumor types, particularly in patients with HCC. In vitro experiments demonstrated that inhibition of DBF4 impaired the proliferative, migratory, and invasive abilities of HCC cells, whereas overexpression of DBF4 promoted these phenotypes. Sequencing results indicated that DBF4 may induce these changes through the ERBB signaling pathway. Further experimental validation revealed that DBF4 activates the ERBB signaling pathway, leading to alterations in the JNK/STAT, MAPK, and PI3K/AKT signaling pathways, thereby impacting the proliferative, migratory, and invasive abilities of tumor cells. Lastly, treatment of Huh7 cells overexpressing DBF4 with the ERBB2 inhibitor dacomitinib demonstrated the ability of ERBB2 inhibition to reverse the promoting effect of DBF4 overexpression on the proliferative, migratory, and invasive abilities of HCC cells. DBF4 plays a pivotal oncogenic role in HCC by promoting the ERBB signaling pathway and activating its downstream PI3K/AKT, JNK/STAT3, and MAPK signaling pathways. DBF4 may serve as a prognostic biomarker for patients with HCC.
•The reason for poor compatibility between Li6.5Sb0.5Ge0.5S5I electrolyte and cathode was revealed.•Introducing Li3InCl6 alleviates the (electro)chemical instability between the cathode materials and ...Li6.5Sb0.5Ge0.5S5I and improves battery performance.•The improved solid-state lithium battery provides excellent capacity and rate performance over a wide temperature range.
Sb-based lithium sulfide electrolytes are promising for all-solid-state lithium battery applications due to their ultrahigh Li-ion conductivity (10−2 S/cm) which is even comparable to current liquid electrolytes. However, the poor electrochemical stability between this electrolyte and high voltage layered structure cathode makes it difficult to achieve excellent battery performances. Herein, Li6.5Sb0.5Ge0.5S5I electrolyte with ionic conductivity up to 10 m S/cm is successfully synthesized and the electrochemical failure mechanism of the corresponding battery using bare LiNi0.6Mn0.2Co0.2O2 cathode and Li-In anode is revealed. Furthermore, Li3InCl6 electrolyte is introduced both as an ionic additive in the cathode mixture and as an isolating layer to avoid side reactions. The designed configuration delivers a high discharge capacity of 162.7 mAh/g at 0.5C and sustains 74.5% of the capacity after 200 cycles at room temperature. Moreover, it also can reversibly cycle from -20 to 60 °C with superior battery performances. This work provides a general design strategy for utilizing highly conductive sulfide electrolytes with low stability in all-solid-state batteries.
Introducing the Li3InCl6 electrolyte as an ionic additive in the cathode mixture and as an isolation layer to evade side reactions, an all-solid-state lithium battery with excellent electrochemical performance has been fabricated.
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The thermal management problems of traction drive systems for high-speed trains are of great importance for the operation reliability of high-speed trains. The thermal performance of transformer and ...traction rectifier are mainly affected by the aerodynamic performance of pantograph. Nine bowheads with different sawtooth structures on the lower surface are proposed and a CFD numerical model is built with Transition SST turbulence model. The influence of the number and height of sawteeth on the aerodynamic characteristics of the bowhead flow field are investigated. The results show that compared with the rectangular bowhead, the aerodynamic drag of the 5w3h-shaped bowhead is reduced by 8.6%, 8.7%, and 9.9% at train speeds of 250 km/h, 300 km/h, and 350 km/h, respectively. The promotion of aerodynamic performance of pantograph is beneficial to improve the thermal characteristics of traction drive systems for high-speed trains.
Abstract
Background
Transcatheter aortic valve replacement (TAVR) is a growing less invasive surrogate for high-risk patients with aortic valve disease. Although the number of TAVR procedures is ...growing rapidly, TAVR prosthesis surgical explantation are rare procedures but increasing in frequency.
Case presentation
We herein presented a case of 68-year-old male who underwent quaternate TAVR bioprostheses implantation. Three months later, his symptoms deteriorated due to aggravated paravalvular leakage and severe mitral regurgitation. A challenging surgical explantation procedure was therefore performed. During the surgery, lethal penetrations of aortic wall due to migration of these devices were found and four bioprostheses were integrally explanted. The native calcified aortic leaflet was removed and replaced with a 23 mm. The impaired segment of ascending aorta was replaced with a Dacron graft afterwards.
Conclusions
In summary, we presented a surgical case of explantation of four TAVR Bioprostheses, which is so far the maximum number of surgical-explant devices ever reported. This extreme individual case aggregates our technical experiences with this unique category of patients and raise the concern of the best initial valve strategy for relatively younger patients with severe aortic valve stenosis.
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