Modulation of anti-cardiac fibrosis immune responses by changing M2 macrophages into M1 macrophages.

BACKGROUND: Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported. METHODS: Here, we took glycogen synthetase kinase 3ß (GSK3ß) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment. RESULTS: NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF. CONCLUSION: Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF.

Square-planar Tetranuclear Cluster-based Alkaline Earth Metal-organic Frameworks with Enhanced Proton Conductivity.

Alkaline earth (AE) metal complexes have garnered significant interest in various functional fields due to their nontoxicity, low density, and low cost. However, there is a lack of systematic investigation into the structural characteristics and physical properties of AE-metal-organic frameworks (MOFs). In this research, we synthesized isostructural MOFs consisting of AE4(µ4-Cl) clusters bridged by benzo-(1,2;3,4;5,6)-tris(thiophene-2'-carboxylic acid) (BTTC3-) ligands. The resulting structure forms a truncated octahedral cage denoted as [AE4(m4-Cl)]6(BTTC)8, which further linked to a porous three-dimensional framework. Among the investigated AE ions (Ca, Sr, and Ba), the Ca4-MOF demonstrated good chemical stability in water compared to Sr4-MOF and Ba4-MOF. The N2 adsorption and solid-state UV-vis-NIR absorption behaviors were evaluated for all AE4-MOFs, showing similar trends among the different metal ions. Additionally, the proton conduction study revealed that the Ca4-MOF exhibited ultra-high proton conductivity, reaching 3.52×10-2 S cm-1 at 343 K and 98 % RH. Notably, the introduction of LiCl via guest exchange resulted in an improved proton conduction of up to 6.36×10-2 S cm-1 under similar conditions in the modified LiCl@Ca4-MOF. The findings shed light on the regulation of physical properties and proton conductivity of AE-MOFs, providing valuable insights for their potential applications in various fields.

Deep-learning-based real-time individualization for reduce-order haemodynamic model.

The reduced-order lumped parameter model (LPM) has great computational efficiency in real-time numerical simulations of haemodynamics but is limited by the accuracy of patient-specific computation. This study proposed a method to achieve the individual LPM modeling with high accuracy to improve the practical clinical applicability of LPM. Clinical data was collected from two medical centres comprising haemodynamic indicators from 323 individuals, including brachial artery pressure waveforms, cardiac output data, and internal carotid artery flow waveforms. The data were expanded to 5000 synthesised cases that all fell within the physiological range of each indicator. LPM of the human blood circulation system was established. A double-path neural network (DPNN) was designed to input the waveforms of each haemodynamic indicator and their key features and then output the individual parameters of the LPM, which was labelled using a conventional optimization algorithm. Clinically collected data from the other 100 cases were used as the test set to verify the accuracy of the individual LPM parameters predicted by DPNN. The results show that DPNN provided good convergence in the training process. In the test set, compared with clinical measurements, the mean differences between each haemodynamic indicator and the estimate calculated by the individual LPM based on the DPNN were about 10 %. Furthermore, DPNN prediction only takes 4 s for 100 cases. The DPNN proposed in this study permits real-time and accurate individualization of LPM's. When facing medical issues involving haemodynamics, it lays the foundation for patient-specific numerical simulation, which may be beneficial for potential clinical application.

Sustained AhR activity programs memory fate of early effector CD8+ T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.

Enhanced Alkaline Hydrogen Evolution Reaction via Electronic Structure Regulation: Activating PtRh with Rare Earth Tm Alloying.

Developing high-performance electrocatalysts for alkaline hydrogen evolution reaction (HER) is crucial for producing green hydrogen, yet it remains challenging due to the sluggish kinetics in alkaline environments. Pt is located near the peak of HER volcano plot, owing to its exceptional performance in hydrogen adsorption and desorption, and Rh plays an important role in H2O dissociation. Lanthanides (Ln) are commonly used to modulate the electronic structure of materials and further influence the adsorption/desorption of reactants, intermediates, and products, and noble metal-Ln alloys are recognized as effective platforms where Ln elements regulate the catalytic properties of noble metals. Here Pt1.5Rh1.5Tm alloy is synthesized using the sodium vapor reduction method. This alloy demonstrates superior catalytic activity, being 4.4 and 6.6 times more effective than Pt/C and Rh/C, respectively. Density Functional Theory (DFT) calculations reveal that the upshift of d-band center and the charge transfer induced by alloying promote adsorption and dissociation of H2O, making Pt1.5Rh1.5Tm alloy more favorable for the alkaline HER reaction, both kinetically and thermodynamically.

Exosomal U2AF2 derived from human bone marrow mesenchymal stem cells attenuates the intervertebral disc degeneration through circ_0036763/miR-583/ACAN axis.

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD.

Prevalence, Features, and Predictive Factors of Spontaneous Spinal Arthrodesis in Posttraumatic Thoracolumbar Kyphosis.

OBJECTIVE: Spontaneous spinal arthrodesis (SSA) is a phenomenon of spontaneous fusion, and SSA is not rare in posttraumatic thoracolumbar kyphosis (PTK). However, few reports have focused on SSA in patients with PTK. The objective of this study was to investigate the prevalence, features, and predictive factors of SSA in patients with PTK. METHODS: In this retrospective study, 70 patients with PTK were included. Data on the clinical and radiologic parameters were obtained and evaluated. According to whether there was SSA or not, patients were divided into an SSA group (n = 45) or a non-SSA group (n = 25). A binary logistic regression analysis was used to identify the predictive factors for SSA. RESULTS: The incidence of SSA in PTK was 64%. Among 45 patients with PTK with SSA, SSA was present as a solid bridging anterior osteophyte along the vertebral bodies in 11 patients, posterior contiguous bony growth through the facet joints bilaterally in 13 patients, bony formation in both anterior and posterior elements in 18 patients, and direct contiguous bony formation from the injured vertebral body to the adjacent one in 3 patients. Patients with longer disease duration, larger local Cobb angle, and anterior wall height loss (AWHL) ratio of injured vertebral body, and less kyphosis flexibility index were significantly more likely to develop SSA. The parameter of AWHL remained significant in binary logistic regression analysis. CONCLUSIONS: SSA in PTK was common, and the SSA sign presented in various patterns, which might have implications for surgical decisions. AWHL was the independent predictor for SSA.

Nanotexture and crystal phase regulation for synergistic enhancement in re-endothelialization on medical pure titanium surface.

Re-endothelialization has been recognized as a promising strategy to address the tissue hyperplasia and subsequent restenosis which are major complications associated with vascular implant/interventional titanium devices. However, the uncontrollable over-proliferation of smooth muscle cells (SMCs) limits the clinical application of numerous modified strategies. Herein, a novel modified strategy involving with a two-step anodic oxidation and annealing treatment was proposed to achieve rapid re-endothelialization function regulated by regular honeycomb nanotexture and specific anatase phase on the titanium surface. Theoretical calculation revealed that the presence of nanotexture reduced the polar component of surface energy, while the generation of anatase significantly enhanced the polar component and total surface energy. Meanwhile, the modified surface with regular nanotexture and anatase phase produced positive effect on the expression of CD31, VE-Cadherin and down-regulated α-SMA proteins expression, indicating excellent capacity of pro-endothelial regeneration and inhibition of SMCs proliferation and migration. One-month in vivo implantation in rabbit carotid arteries further confirmed that modified tube implant surface effectively accelerated confluent endothelial monolayer formation and promoted native-like endothelium tissue regeneration. By contrast, original titanium tube implant induced a disorganized tissue proliferation in the lumen with a high risk of restenosis. Collectively, this study opens us an alternative route to achieve the function that selectively promotes endothelial cells (ECs) growth and suppresses SMCs on the medical titanium surface, which has a great potential in facilitating re-endothelialization on the surface of blood-contacting titanium implant.

Integrative analysis reveals chemokines CCL2 and CXCL5 mediated shear stress-induced aortic dissection formation.

Background: Aortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. Methods: Gene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. Results: We identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. Conclusion: Through integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated "Endothelial-Monocyte-Neutrophil" axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

A comprehensive approach to prediction of fractional flow reserve from deep-learning-augmented model.

The underuse of invasive fractional flow reserve (FFR) in clinical practice has motivated research towards non-invasive prediction of FFR. Although the non-invasive derivation of FFR (FFRCT) using computational fluid dynamics (CFD) principles has become a common practice, its clinical application has been limited due to the considerable time required for computation of resulting changes in haemodynamic conditions. An alternative to CFD technology is incorporating a neural network into the computational process to reduce the time necessary for running an effective model. In this study we propose a cascade of data-driven and physic-based neural networks (DP-NN) for predicting FFR (DL-FFRCT). The first network of cascade network DP-NN includes geometric features, and the second network includes physical features. We compare the differences between data-driven neural network (D-NN) and DP-NN for predicting FFR. The training and testing datasets were obtained by solving the three-dimensional incompressible Navier-Stokes equations. Coronary flow and geometric features were used as inputs to train D-NN. In DP-NN the training process involves first training a D-NN to output resting ΔP as one input feature to the DP-NN. Secondly, the physics-based microcirculatory resistance as another input feature to the DP-NN. Using clinically measured FFR as the "gold standard", we validated the computational accuracy of DL-FFRCT in 77 patients. Compared to D-NN, DP-NN improved the prediction of ΔP (R2 = 0.87 vs. R2 = 0.92). Statistical analysis demonstrated that the diagnostic accuracy of DL-FFRCT was not inferior to FFRCT (85.71 % vs. 88.3 %) and the computational time was reduced by a factor of approximately 3000 (4.26 s vs. 3.5 h). DP-NN represents a near real-time, interpretable, and highly accurate deep-learning network, which contributes to the development of high-performance computational methods for haemodynamics. We anticipate that DP-NN will enable near real-time prediction of DL-FFRCT in personalized narrow blood vessels and provide guidance for cardiovascular disease treatments.

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.

Enhanced Alkaline Hydrogen Evolution Reaction through Lanthanide-Modified Rhodium Intermetallic Catalysts.

Design of highly efficient electrocatalysts for alkaline hydrogen evolution reaction (HER) is of paramount importance for water electrolysis, but still a considerable challenge because of the slow HER kinetics in alkaline environments. Alloying is recognized as an effective strategy to enhance the catalytic properties. Lanthanides (Ln) are recognized as an electronic and structural regulator, attributed to their unique 4f electron behavior and the phenomenon known as lanthanide contraction. Here, a new class of Rh3Ln intermetallics (IMs) are synthesized using the sodium vapor reduction method. The alloying process induced an upshift of the d-band center and electron transfer from Ln to Rh, resulting in optimized adsorption and dissociation energies for H2O molecules. Consequently, Rh3Tb IMs exhibited outstanding HER activity in both alkaline environments and seawater, displaying an overpotential of only 19 mV at 10 mA cm-2 and a Tafel slope of 22.2 mV dec-1. Remarkably, the current density of Rh3Tb IMs at 100 mV overpotential is 8.6 and 5.7 times higher than that of Rh/C and commercial Pt/C, respectively. This work introduces a novel approach to the rational design of HER electrocatalysis and sheds light on the role of lanthanides in electrocatalyst systems.

Paleo-marine redox environment fluctuation during the early Cambrian: Insight from iron isotope in the Tarim Basin, China.

The Ediacaran to Cambrian period is generally considered to be the vital transition in the history of marine redox environment and life evolution on earth. The ocean oxygenation levels during this transition period are still debated. Since iron is widely involved in biogeochemical cycles and undergoes redox cycling both in the seawater and sediments, it has become a significant proxy to reconstruct paleo-marine environment. In order to constrain the paleo-marine redox state in the early Cambrian, the iron isotope composition of bulk rock (δ56FeT) is interpreted combining with iron-speciation, redox sensitive elements and pyrite sulfur isotope (δ34Spy) of Yuertusi Formation in Tarim Block. The δ56FeT values varies from -0.39 ‰ to 0.48 ‰, with an average of 0.07 ‰, mainly controlled by pyrite mineral facies in this study. Based on the mechanism of pyrite generation in different redox condition, it is proposed that the marine environment of the lower Cambrian in the Tarim basin is dominated by anoxic with intermittent euxinic state. The dynamic evolution of redox environment can be divided into three intervals. The gradual decrease of δ56Fe in Interval I indicates the paleo-marine environment changed from anoxic ferruginous to euxinic, and the paleo-marine sulfate reservoir decreased to a limited level, which might be attributed to abundant burial of organic matter and pyrite. For Interval II, δ56Fe values first increase to evident positive because of partial oxidization then decreased to that of seawater (about 0 ‰) due to complete oxidization. In Interval III, the continuous decrease of δ56Fe values infers a sustaining oxidization. In summary, the paleo-marine environment of the lower Cambrian Yuertusi Formation evolved from anoxic ferruginous to euxinic and then oxidized continuous. Iron isotope statistics from geological historical periods indicate that seawater was relatively oxidized after the NOE event but did not reach the oxidation levels of present-day seawater.

Electrochemical Potential-Driven Shift of Frontier Orbitals in M-N-C Single-Atom Catalysts Leading to Inverted Adsorption Energies.

Electronic structure is essential to understanding the catalytic mechanism of metal single-atom catalysts (SACs), especially under electrochemical conditions. This study delves into the nuanced modulation of "frontier orbitals" in SACs on nitrogen-doped graphene (N-C) substrates by electrochemical potentials. We observe shifts in Fermi level and changes of d-orbital occupation with alterations in electrochemical potentials, emphasizing a synergy between the discretized atomic orbitals of metals and the continuous bands of the N-C based environment. Using O2 and CO2 as model adsorbates, we highlight the direct consequences of these shifts on adsorption energies, unveiling an intriguing inversion of adsorption energies on Co/N-C SAC under negative electrochemical potentials. Such insights are attributed to the role of the dxz and dz2 orbitals, pivotal for stabilizing the π* orbitals of O2. Through this exploration, our work offers insights on the interplay between electronic structures and adsorption behaviors in SACs, paving the way for enhanced catalyst design strategies in electrochemical processes.

Identification of disulfidptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer.

Introduction: Breast cancer (BC) is now the most common type of cancer in women. Disulfidptosis is a new regulation of cell death (RCD). RCD dysregulation is causally linked to cancer. However, the comprehensive relationship between disulfidptosis and BC remains unknown. This study aimed to explore the predictive value of disulfidptosis-related genes (DRGs) in BC and their relationship with the TME. Methods: This study obtained 11 disulfidptosis genes (DGs) from previous research by Gan et al. RNA sequencing data of BC were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) databases. First, we examined the effect of DG gene mutations and copy number changes on the overall survival of breast cancer samples. We then used the expression profile data of 11 DGs and survival data for consensus clustering, and BC patients were divided into two clusters. Survival analysis, gene set variation analysis (GSVA) and ss GSEA were used to compare the differences between them. Subsequently, DRGs were identified between the clusters used to perform Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a prognosis model. Finally, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. CCK-8 and a colony assay obtained by knocking down genes and gene sequencing were used to validate the model. Result: Two DG clusters were identified based on the expression of 11DGs. Then, 225 DRGs were identified between them. RS, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-RS shows a better prognosis and higher immunotherapy response than high-RS. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. CCK-8 and colony assay obtained by knocking down genes have demonstrated that the knockdown of high-risk genes in the RS model significantly inhibited cell proliferation. Discussion: This study elucidates the potential relationship between disulfidptosis-related genes and breast cancer and provides new guidance for treating breast cancer.

Low-dose exercise protects the heart against established myocardial infarction via IGF-1-upregulated CTRP9 in male mice.

Regular exercise is recommended as an important component of therapy for cardiovascular diseases in clinical practice. However, there are still major challenges in prescribing an optimized exercise regimen to individual patients with established cardiac disease. Here, we tested the effects of different exercise doses on cardiac function in mice with established myocardial infarction (MI). Exercise was introduced to mice with MI after 4 weeks of surgery. Low-dose exercise (15 min/day for 8 weeks) improved mortality and cardiac function by increasing 44.39% of ejection fractions while inhibiting fibrosis by decreasing 37.74% of distant region. Unlike higher doses of exercise, low-dose exercise consecutively upregulated cardiac expression of C1q complement/tumor necrosis factor-associated protein 9 (CTRP9) during exercise (>1.5-fold). Cardiac-specific knockdown of CTRP9 abolished the protective effects of low-dose exercise against established MI, while cardiac-specific overexpression of CTRP9 protected the heart against established MI. Mechanistically, low-dose exercise upregulated the transcription factor nuclear receptor subfamily 2 group F member 2 by increasing circulating insulin-like growth factor 1 (IGF-1), therefore, upregulating cardiac CTRP9 expression. These results suggest that low-dose exercise protects the heart against established MI via IGF-1-upregulated CTRP9 and may contribute to the development of optimized exercise prescriptions for patients with MI.

Ternary Rare Earth Alloy Pt3-xIrxSc Nanoparticles Modulate Negatively Charged Pt via Charge Transfer To Facilitate pH-Universal Hydrogen Evolution.

Rare earth (RE) elements possess electronic configurations that can provide additional pathways for tailoring the electronic structures of active elements through alloying, making it an important area of exploration in electrocatalysis. However, the large negative redox potential between RE and Pt has hindered the development of RE nanoalloys. In this study, a solid-phase synthesis strategy was employed to synthesize ternary Pt3-xIrxSc nanoparticles (NPs). By leveraging the electronegativity difference between Pt (2.28), Ir (2.20), and Sc (1.36), a charge-balance strategy was implemented to stabilize and enhance the catalytic performance of the alloy. The electron transfer from Sc to Pt/Ir results in the latter being negatively charged, and the Ir modifies the electron density of Pt, enabling favorable adsorption of active H species during the hydrogen evolution reaction (HER). Pt2IrSc exhibits enhanced HER activity at all pH values, achieving low overpotentials at 10 mA cm-2 of only 13, 18, and 25 mV in 0.5 M H2SO4, 1 M PBS, and 1 M KOH, respectively. This electrocatalyst also exhibits robust electrocatalytic stability even after 20,000 cycles. This work represents an application of the charge balance strategy to RE nanoalloys, and it is expected to inspire the design and synthesis of highly reactive RE nanoalloys.

Forkhead box O6 (FoxO6) promotes cardiac pathological remodeling and dysfunction by activating Kif15-TGF-ß1 under aggravated afterload.

Pathological cardiac hypertrophy exhibits complex and abnormal gene expression patterns and progresses to heart failure. Forkhead box protein O6 (FoxO6) is a key transcription factor involved in many biological processes. This study aimed to explore the role of FoxO6 in cardiac hypertrophy. Three groups of mice were established: wild-type, FoxO6 knockout, and FoxO6-overexpressing. The mice received daily administration of angiotensin-II (Ang-II) or saline for 4 weeks, after which they were examined for cardiac hypertrophy, fibrosis, and function. Elevated cardiac expression of FoxO6 was observed in Ang-II-treated mice. FoxO6 deficiency attenuated contractile dysfunction and cardiac remodeling, including cardiomyocyte hypertrophy and fibroblast proliferation and differentiation. Conversely, FoxO6 overexpression aggravated the cardiomyopathy and heart dysfunction. Further studies identified kinesin family member 15 (Kif15) as downstream molecule of FoxO6. Kif15 inhibition attenuated the aggravating effect of FoxO6 overexpression. In vitro, FoxO6 overexpression increased Kif15 expression in cardiomyocytes and elevated the concentration of transforming growth factor-ß1 (TGF-ß1) in the medium where fibroblasts were grown, exhibiting increased proliferation and differentiation, while FoxO6 knockdown attenuated this effect. Cardiac-derived FoxO6 promoted pathological cardiac remodeling induced by aggravated afterload largely by activating the Kif15/TGF-ß1 axis. This result further complements the mechanisms of communication among different cells in the heart, providing novel therapeutic targets for heart failure.

Boosting reactivity of water-gas shift reaction by synergistic function over CeO2-x/CoO1-x/Co dual interfacial structures.

Dual-interfacial structure within catalysts is capable of mitigating the detrimentally completive adsorption during the catalysis process, but its construction strategy and mechanism understanding remain vastly lacking. Here, a highly active dual-interfaces of CeO2-x/CoO1-x/Co is constructed using the pronounced interfacial interaction from surrounding small CeO2-x islets, which shows high activity in catalyzing the water-gas shift reaction. Kinetic evidence and in-situ characterization results revealed that CeO2-x modulates the oxidized state of Co species and consequently generates the dual active CeO2-x/CoO1-x/Co interface during the WGS reaction. A synergistic redox mechanism comprised of independent contribution from dual functional interfaces, including CeO2-x/CoO1-x and CoO1-x/Co, is authenticated by experimental and theoretical results, where the CeO2-x/CoO1-x interface alleviates the CO poison effect, and the CoO1-x/Co interface promotes the H2 formation. The results may provide guidance for fabricating dual-interfacial structures within catalysts and shed light on the mechanism over multi-component catalyst systems.