Neonatal heart tissue-derived EVs alleviate adult ischemic cardiac injury via regulating the function of macrophages and cardiac regeneration in murine models.

Previous studies confirmed the regenerative capacity of the mammalian neonatal heart. We recently found that adult heart tissue-derived EVs can protect the heart from myocardial ischemia-reperfusion (I/R). However, the role of EVs from neonatal heart tissue in cardiac healing post-ischemia remains unclear. In the present study, we revealed that intramyocardial administration of neonatal cardiac tissue-derived EVs (ncEVs) alleviated cardiac inflammation, mitigated reperfusion injury, and improved cardiac function in murine I/R models. In vitro, ncEVs inhibited M1 polarization of macrophages induced by LPS while up-regulated their phagocytic function via the miR-133a-3p-Ash1l signaling pathway. Moreover, the administration of ncEVs contributed to cardiac angiogenesis and improved cardiac function in murine myocardial infarction models. Collectively, these results suggested that neonatal heart-derived EVs can regulate the function of macrophages and contribute to cardiac regeneration and function recovery in murine cardiac ischemic models. Therefore, the derivatives in neonatal heart tissue-derived EVs might serve as a potential therapeutic strategy in ischemic diseases.

Amelioration of immunoglobulin A vasculitis by suppression of the pathological expansion of T follicular helper 17 cells.

The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.

Influence of metabolic syndrome on plaque features and clinical outcomes in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Currently, the influence of metabolic syndrome (Mets) on the plaque characteristics and prognosis of patients with acute coronary syndrome (ACS) is poorly understood. Thus, the study aimed to characterize the pancoronay plaques of ACS patients with Mets using optical coherence tomography (OCT) and to evaluate the cohort's prognosis. METHODS: Between February 2015 and September 2020, 745 ACS patients who underwent OCT imaging of the three coronary arteries were included, divided into Mets (n = 252) and non-Mets (n = 493) groups. The major adverse cardiovascular event (MACE) was a composite of cardiac death, non-fatal myocardial infarction (MI), and revascularization. RESULTS: Compared to the non-Mets group, the Mets group exhibited a higher proportion of females and cases of multivessel disease. In the Mets group, culprit lesions were found to have a greater degree of stenosis, thinner fibrous cap thickness and more thin-cap fibroatheroma (TCFA). Additionally, nonculprit lesions were more likely to exhibit plaque rupture, high-risk plaque characteristics, TCFA, macrophage infiltration, cholesterol crystals, and layered plaque. After a median follow-up of 2 years, 8.3% of patients experienced MACE, a rate that was higher in the Mets group, primarily attributed to non-fatal myocardial infarction and cardiac death. Multivariate analysis showed that Mets (aHR 1.73, p = 0.037), high-risk plaque (aHR 2.63, p < 0.001), age (aHR 1.03, p = 0.020), and left ventricular ejection fraction (aHR 0.96, p = 0.002) were independent predictors of MACE. CONCLUSIONS: The presence of Mets increased the vulnerability of the entire coronary tree and worsened the prognosis for patients with ACS.

Enhancing Photoreduction of Cr(VI) through a Multivalent Manganese(II)-Organic Framework Incorporating Anthracene Moieties.

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

Contrasting nitrogen transport patterns in subtropical basins revealed by combined multiple isotopic analyzes and hydrological simulations.

Although enhancing the knowledge of nitrogen (N) dynamics in aquatic systems is crucial for basin N management, there is still a lack of theories on the patterns of basin N sources and transport because of the intricate influence of human activities, climatic conditions, landscape patterns, and topography on the trajectory of basin N. To shed new light on the patterns of basin N sources and transport in the Chinese subtropical monsoon region, this study provides a comprehensive approach combining multiple isotopes and hydrological model based on monthly records of hydro-chemistry and isotopes (18O-NO3- /15N-NO-3 and 18O-H2O /2H-H2O) for river water, groundwater and rainfall in three basins over multiple years. Our observations of hydro-chemistry showed that fluvial N levels in highly urbanized basins (3.05 ± 1.42 mg·L-1) were the highest and were characterized by higher levels in the dry season. In the agricultural basin, fluvial N levels in February and March were approximately 1.9 times higher than those in the other months. The fluvial N load was higher in agricultural basins (0.624-0.728 T N km -2 y -1) than in urban basins (0.558 T N km -2 y -1), primarily because of variations in sewage treatment rates and fertilizer application. In highly urbanized basin, manure and sewage (46.9 %) were the dominant sources of fluvial N, which were discharged into rivers after treatment. In the plain agricultural basin, a substantial portion of diffused residential sewage leaches into aquifers and is stored. In the hilly agro-forest mixed basin, the high baseflow coefficient (75.8 %) and the key role of groundwater N, mainly from soil N (27.3 %), chemical fertilizers (20.2 %), manure and sewage (46.6 %), to fluvial N (26.5 %) indicated that a high proportion of the N sources leached into the aquifer and were then transported to rivers. For the first time, this study integrated multiple methods to substantiate the proposed typical patterns of N sources and transport within the basins. These findings have significant implications for tailored basin-specific N management strategies.

The involvement of CaMKKI in activating AMPKα in yesso scallop Patinopecten yessoensis under high temperature stress.

Calcium/calmodulin dependent protein kinase kinase (CaMKK), a highly conserved protein kinase, is involved in the downstream processes of various biological activities by phosphorylating and activating 5'-AMP-activated protein kinase (AMPK) in response to the increase of cytosolic-free calcium (Ca2+). In the present study, a CaMKKI was identified from Yesso scallop Patinopecten yessoensis. Its mRNA was ubiquitously expressed in haemocytes and all tested tissues with the highest expression level in mantle. The expression level of PyCaMKKI mRNA in adductor muscle was significantly upregulated at 1, 3 and 6 h after high temperature treatment (25 °C), which was 3.43-fold (p < 0.05), 5.25-fold (p < 0.05), and 5.70-fold (p < 0.05) of that in blank group, respectively. At 3 h after high temperature treatment (25 °C), the protein level of PyAMPKα, as well as the phosphorylation level of PyAMPKα at Thr170 in adductor muscle, and the positive co-localized fluorescence signals of PyCaMKKI and PyAMPKα in haemocyte all increased significantly (p < 0.05) compared to blank group (18 °C). The pull-down assay showed that rPyCaMKKI and rPyAMPKα could bind each other in vitro. After PyCaMKKI was silenced by siRNA, the mRNA and protein levels of PyCaMKKI and PyAMPKα, and the phosphorylation level of PyAMPKα at Thr170 in adductor muscle were significantly down-regulated (p < 0.05) compared with the negative control group receiving an injection of siRNA-NC. These results collectively suggested that PyCaMKKI was involved in the activation of PyAMPKα in response to high temperature stress and would be helpful for understanding the function of PyCaMKKI-PyAMPKα pathway in maintaining energy homeostasis under high temperature stress in scallops.

High Stability and Corrosion-Resistant Gas of Recyclable and Versatile Manganese-Doped Lead-Free Double Perovskite Crystals toward Novel Functional Fabric and Photoelectric Device.

Lead-free halide perovskites possess excellent photoelectric properties, making them widely used in the photoelectric fields. Herein, lead-free double perovskite crystals (PCs) doped with manganese (Cs2NaInCl6:Mn2+) are successfully prepared by the more energy-efficient crystallization method. The crystals emit bright orange-red light under the ultraviolet (UV) lamp, showing unique optical properties. They have the highest photoluminescence quantum yield of 42.91%. The white light-emitting diodes (LEDs) are fabricated using these perovskite crystals, which show a color rendering index of 92 and external quantum efficiency (EQE) as high as 16.3%. Furtherly, perovskite-modified fiber paper made of aramid chopped fibers (ACFs) and polyphenylene sulfide (PPS) exhibited fluorescent properties under different conditions. This paper combines fiber composite technology with PPS fiber filter bags, which are widely used in environmental protection, for the first time and demonstrates functional fiber filter bags with fluorescent characteristics. This filter bag provides an idea for the automatic detection of industrial filtration. Meanwhile, after being exposed to industrial waste gas for 60 h, the filter bag can maintain superior fluorescence performance. In this study, lead-free double perovskites are synthesized using an efficient method for preparing high-performance LEDs and high-stability fluorescent fibers. Concurrently, the application of perovskites in environmental protection is expanded.

Classification of multiple primary lung cancer in patients with multifocal lung cancer: assessment of a machine learning approach using multidimensional genomic data.

Background: Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. Methods: A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. Results: We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). Conclusion: These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction.

Background: Treatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs. Materials and methods: hUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server. Result: 3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs. Conclusion: Clinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as "division of labor" mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

PyLKB1 regulates glucose transport via activating PyAMPKα in Yesso Scallop Patinopecten yessoensis under high temperature stress.

Liver kinase B1 (LKB1) is a classical serine/threonine protein kinase and plays an important role in maintaining energy homeostasis through phosphorylate AMP-activated protein kinase α subunit (AMPKα). In this study, a homologous molecule of LKB1 with a typical serine/threonine kinase domain and two nuclear localization sequences (NLSs) was identified in Yesso Scallop Patinopecten yessoensis (PyLKB1). The mRNA transcripts of PyLKB1 were found to be expressed in haemocytes and all the examined tissues, including gill, mantle, gonad, adductor muscle and hepatopancreas, with the highest expression level in hepatopancreas. PyLKB1 was mainly located in cytoplasm and nucleus of scallop haemocytes. At 3 h after high temperature stress treatment (25 °C), the mRNA transcripts of PyLKB1, PyAMPKα, and PyGLUT1 in hepatopancreas, the phosphorylation level of PyAMPKα at Thr170 in hepatopancreas, the positive fluorescence signals of PyLKB1 in haemocytes, glucose analogue 2-NBDG content in haemocytes, and glucose content in hepatopancreas, haemocytes and serum all increased significantly (p < 0.05) compared to blank group (15 °C). However, there was no significant difference at the protein level of PyLKB1 and PyAMPKα. After PyLKB1 was knockdown by siRNA, the mRNA expression level of PyGLUT1, and the glucose content in hepatopancreas and serum were significantly down-regulated (p < 0.05) compared with the negative control group receiving an injection of siRNA-NC. However, there were no significant difference in PyGLUT1 expression, glucose content and glucose analogue 2-NBDG content in haemocytes. These results collectively suggested that PyLKB1-PyAMPKα pathway was activated to promote glucose transport by regulating PyGLUT1 in response to high temperature stress. These results would be helpful for understanding the function of PyLKB1-PyAMPKα pathway in regulating glucose metabolism and maintaining energy homeostasis under high temperature stress in scallops.

Molecular Dynamics Simulation of the Adsorption and Diffusion of C8 Aromatic Isomers in MIL-47(V).

The separation of C8 aromatic isomers (oX: o-xylene, pX: p-xylene, mX: m-xylene, and EB: ethylbenzene) remains an enormous challenge in industrial production due to their similar molecular structures and physical properties. Porous materials with suitable pore structures and selective recognition sites to discriminate the slight structural differences of isomers are imminently needed. In this paper, MIL-47(V) with a three-dimensional (3D) grid structure of 10.5 × 10.5 Å2 and a one-dimensional (1D) diamond channel was selected as the adsorbent. However, the mechanism of the adsorption and separation of C8 aromatic isomers in porous materials still needs to be understood. Given the importance of C8 aromatic isomers' confinement in MIL-47(V) for adsorption and diffusion applications, it is important to understand C8 aromatic isomers' behavior in MIL-47(V). Here, we demonstrated from a simulation perspective that metal-organic frameworks MIL-47(V) with one-dimensional (1D) diamond channels can identify C8 aromatic isomers. Molecular dynamics (MD) simulations have shown that organic ligands with guest response sites of MIL-47(V) can effectively distinguish between C8 aromatic isomers by adaptation to the shape of a specific isomer. MIL-47(V) has high adsorption and an excellent separation sequence between C8 aromatic isomers: oX > pX ≈ mX > EB. Significant differences exist in π-π superposition interactions between C8 aromatic isomers and between C8 aromatic isomers and the skeletons. This phenomenon is mainly caused by the unique pore structure and guest response characteristics of MIL-47(V). This work is identified as a supplementary instruction to experimental research and is expected to provide profound insights into research on developing C8 aromatic isomers' adsorption and separation and theoretical support.

Extracellular vesicles from normal tissues orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis.

Extracellular vesicles (EVs) exist throughout our bodies. We recently revealed the important role of intracardiac EVs induced by myocardial ischemia/reperfusion on cardiac injury and dysfunction. However, the role of EVs isolated from normal tissues remains unclear. Here we found that EVs, derived from murine heart, lung, liver and kidney have similar effects on macrophages and regulate the inflammation, chemotaxis, and phagocytosis of macrophages. Interestingly, EV-treated macrophages showed LPS resistance with reduced expressions of inflammatory cytokines and enhanced phagocytic activity. Furthermore, we demonstrated that the protein content in EVs contributed to the activation of inflammation, while the RNA component mainly limited the excessive inflammatory response of macrophages to LPS. The enrichment of miRNAs, including miR-148a-3p, miR-1a-3p and miR-143-3p was confirmed in tissue EVs. These EV-enriched miRNAs contributed to the inflammation remission in LPS induced macrophages through multiple pathways, including STAT3, P65 and SAPK/JNK. Moreover, administration of both EVs and EV-educated macrophages attenuated septic injury and cytokine storm in murine CLP models. Taken together, the present study disclosed that EVs from normal tissues can orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis. Therefore, tissue derived EVs or their derivatives may serve as potential therapeutic strategies in inflammatory diseases.

Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus.

PURPOSE: The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. METHODS: We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. RESULTS: We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. CONCLUSION: Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

Extracellular vesicles derived from different tissues attenuate cardiac dysfunction in murine MI models.

BACKGROUND: Extracellular vesicles (EVs) derived from various cell sources exert cardioprotective effects during cardiac ischemic injury. Our previous study confirmed that EVs derived from ischemic-reperfusion injured heart tissue aggravated cardiac inflammation and dysfunction. However, the role of EVs derived from normal cardiac tissue in myocardial ischemic injury remains elusive. RESULTS: In the present study, normal heart-derived EVs (cEVs) and kidney-derived EVs (nEVs) were isolated and intramyocardially injected into mice after myocardial infarction (MI). We demonstrated that administration of both cEVs and nEVs significantly improved cardiac function, reduced the scar size, and alleviated inflammatory infiltration into the heart. In addition, cardiomyocyte apoptosis was inhibited, whereas angiogenesis was enhanced in the hearts receiving cEVs or nEVs treatment. Moreover, intramyocardial injection of cEVs displayed much better cardiac protective efficacy than nEVs in murine MI models. RNA-seq and protein-protein interaction (PPI) network analysis revealed the protective mRNA clusters in both cEVs and nEVs. These mRNAs were involved in multiple signaling pathways, which may synergistically orchestrate to prevent the heart from further damage post MI. CONCLUSIONS: Collectively, our results indicated that EVs derived from normal heart tissue may represent a promising strategy for cardiac protection in ischemic heart diseases.

TIGIT reverses IFN-α-promoted Th1-like Tregs via in-sequence effects dependent on STAT4.

OBJECTIVES: The induction direction of interferon (IFN)-α in T-cell phenotype and function varies depending on the activation state of the cell and the time of stimulation. To assess the effects of elevated IFN-α on regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) patients, we investigated the differentiation of Th1-like Tregs under in-sequence and out-of-sequence conditions and the reversal effect of activating TIGIT on immune suppression. METHODS: Phenotypes and activation levels of Tregs from SLE patients and healthy controls were analyzed using flow cytometry. In vitro culture conditions based on the sequence of TCR activation and IFN-α stimulation simulated in-sequence or out-of-sequence effects. CD4+T cells and Tregs were cultured under the above conditions with or without TIGIT agonist. Expression of related characteristic markers and phosphorylation levels of AKT, mTOR, and STATs were detected using flow cytometry and ELISA. RESULTS: The frequency of Th1-like Tregs and activation levels of Tregs increased, but TIGIT expression in Tregs decreased in SLE patients. IFN-α promoted the conversation of Tregs to Th1-like Tregs while reducing immunosuppressive function under in-sequence conditions. The STAT4 pathway, but not the STAT1 pathway, was crucial for the IFN-α-mediated in-sequence effects. Reactivation of TIGIT reversed Th1 polarization of Tregs by suppressing AKT/mTOR and STAT4 signaling. CONCLUSIONS: Our findings suggest that IFN-α mediated in-sequence effects on Tregs may be responsible for the expansion of Th1-like Tregs in SLE. TIGIT can restore immune suppression damage in Tregs and represents a potential therapeutic target for SLE.

A Multifunctional Co-Based Metal-Organic Framework as a Platform for Proton Conduction and Ni trophenols Reduction.

The design and development of proton conduction materials for clean energy-related applications is obviously important and highly desired but challenging. An ultrastable cobalt-based metal-organic framework Co-MOF, formulated as [Co2(btzip)2(µ2-OH2)] (namely, LCUH-103, H2btzip = 4, 6-bis(triazol-1-yl)-isophthalic acid) had been successfully synthesized via the hydrothermal method. LCUH-103 exhibits a three-dimensional framework and a one-dimensional microporous channel structure with scu topology based on the binuclear metallic cluster {Co2}. LCUH-103 indicated excellent chemical and thermal stability; peculiarly, it can retain its entire framework in acid and alkali solutions with different pH values for 24 h. The excellent stability is a prerequisite for studying its proton conductivity, and its proton conductivity σ can reach up to 1.25 × 10-3 S·cm-1 at 80 °C and 100% relative humidity (RH). In order to enhance its proton conductivity, the proton-conducting material Im@LCUH-103 had been prepared by encapsulating imidazole molecules into the channels of LCUH-103. Im@LCUH-103 indicated an excellent proton conductivity of 3.18 × 10-2 S·cm-1 at 80 °C and 100% RH, which is 1 order of magnitude higher than that of original LCUH-103. The proton conduction mechanism was systematically studied by various detection means and theoretical calculations. Meanwhile, LCUH-103 is also an excellent carrier for palladium nanoparticles (Pd NPs) via a wetness impregnation strategy, and the nitrophenols (4/3/2-NP) reduction in aqueous solution by Pd@LCUH-103 indicated an outstanding conversion efficiency, high rate constant (k), and exceptional cycling stability. Specifically, the k value of 4-NP reduction by Pd@LCUH-103 is superior to many other reported catalysts, and its k value is as high as 1.34 min-1 and the cycling stability can reach up to 6 cycles. Notably, its turnover frequency (TOF) value is nearly 196.88 times more than that of Pd/C (wt 5%) in the reaction, indicating its excellent stability and catalytic activity.

Function and clinical application of exosome-how to improve tumor immunotherapy?

In recent years, immunotherapy has been increasingly used in clinical practice to treat tumors. However, immunotherapy's efficacy varies between tumor types and patient populations, and long-term drug resistance often occurs during treatment. Therefore, it is essential to explore the molecular mechanisms of immunotherapy to improve its efficacy. In this review, we focus on the significance of tumor-derived exosomes in the clinical treatment of tumors and how modifying these exosomes may enhance immune effectiveness. Specifically, we discuss exosome components, such as RNA, lipids, and proteins, and the role of membrane molecules on exosome surfaces. Additionally, we highlight the importance of engineered exosomes for tumor immunotherapy. Our goal is to propose new strategies to improve the efficacy of tumor immunotherapy.

Highly efficient zinc electrode prepared by electro-deposition in a salt-induced pre-phase separation region solution.

Efficient electrode design is crucial for the electrochemical reduction of CO2 to produce valuable chemicals. The solution used for the preparation of electrodes can affect their overall properties, which in turn determine the reaction efficiency. In this work, we report that transition metal salts could induce the change of two-phase ionic liquid/ethanol mixture into miscible one phase. Pre-phase separation region near the phase boundary of the ternary system was observed. Zinc nanoparticles were electro-deposited along the fibres of carbon paper (CP) substrate uniformly in the salt-induced pre-phase separation region solution. The as-prepared Zn(1)/CP electrode exhibits super-wettability to the electrolyte, rendering very high catalytic performance for CO2 electro-reduction, and the Faradaic efficiency towards CO is 97.6% with a current density of 340 mA cm-2, which is the best result to date in an H-type cell.

The involvement of AMP-activated protein kinase α in regulating glycolysis in Yesso scallop Patinopecten yessoensis under high temperature stress.

AMP-activated protein kinase α subunit (AMPKα), the central regulatory molecule of energy metabolism, plays an important role in maintaining energy homeostasis and helping cells to resist the influence of various adverse factors. In the present study, an AMPKα was identified from Yesso scallop Patinopecten yessoensis (PyAMPKα). The open reading frame (ORF) of PyAMPKα was of 1599 bp encoding a putative polypeptide of 533 amino acid residues with a typical KD domain, a α-AID domain and a α-CTD domain. The deduced amino acid sequence of PyAMPKα shared 59.89-74.78% identities with AMPKαs from other species. The mRNA transcripts of PyAMPKα were found to be expressed in haemocytes and all the examined tissues, including gill, mantle, gonad, adductor muscle and hepatopancreas, with the highest expression level in adductor muscle. PyAMPKα was mainly located in cytoplasm of scallop haemocytes. At 3 h after high temperature stress treatment (25 °C), the mRNA transcripts of PyAMPKα, the phosphorylation level of PyAMPKα at Thr170 and the lactic acid (LD) content in adductor muscle all increased significantly, while the glycogen content decreased significantly. The activity of pyruvate kinase (PyPK) and the relative mRNA expression level of phosphofructokinase (PyPFK) were significantly up-regulated at 3 h after high temperature stress treatment (25 °C). Furthermore, the PyAMPKα activator AICAR could effectively upregulate the phosphorylation level of PyAMPKα, and increase activities of PyPFK and pyruvate kinase (PyPK). Meanwhile the glycogen content also declined under AICAR treatment. These results collectively suggested that PyAMPKα was involved in the high temperature stress response of scallops by enhancing glycolysis pathway of glycogen. These results would be helpful for understanding the functions of PyAMPKα in maintaining energy homeostasis under high temperature stress in scallops.