Association between the triglyceride glucose-body mass index and future cardiovascular disease risk in a population with Cardiovascular-Kidney-Metabolic syndrome stage 0-3: a nationwide prospective cohort study.

BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.

Repeat administration of human umbilical cord mesenchymal stem cells improves left ventricular diastolic function in mice with heart failure with preserved ejection fraction.

Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.v.), either once or repetitively, in a mouse model of HFpEF induced by a high-fat diet and NG-nitroarginine methyl ester hydrochloride. hucMSC treatment improved left ventricular diastolic dysfunction, reduced heart weight and pulmonary edema, and attenuated cardiac modeling (inflammation, interstitial fibrosis, and hypertrophy) in HFpEF mice. Repeat hucMSC administration had better outcomes than a single injection. In vitro, hucMSC culture supernatants reduced maladaptive remodeling in neonatal-rat cardiomyocytes. Ribonucleic acid sequencing and protein level analysis of left ventricle (LV) tissues suggested that hucMSCs activated the protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway to treat HFpEF. Inhibition of this pathway reversed the efficacy of hucMSC treatment. In conclusion, these findings indicated that hucMSCs could be a viable therapeutic option for HFpEF.

Therapeutic efficacy of ECs Foxp1 targeting Hif1α-Hk2 glycolysis signal to restrict angiogenesis.

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Two-pronged anti-cancer nanovaccines enpowered by exogenous/endogenous tumor-associated antigens.

Cancer vaccines based on single-source (exogenous or endogenous) tumor-associated antigens (TAAs) are often challenged by the insufficient T cell response and the immunosuppressive tumor microenvironment (TME). Herein, a dual TAAs-boosted nanovaccine based on cancer cell (4T1) membrane-cloaked, CO-immobilized Prussian blue nanoparticles (4T1-PB-CO NPs) is developed and coupled with anti-interleukin (IL)-10 therapy to maximize the efficacy of antitumor immunotherapy. 4T1 cell membrane not only endows NPs with tumor targeting ability, but also serves as exogenous TAAs to trigger CD4+ T cell response and M1-phenotype polarization of tumor-associated macrophages. Under near-infrared light irradiation, 4T1-PB-CO NPs release CO to induce immunogenic cell death (ICD) of tumor cells, thus generating endogenous TAAs to activate CD8+ T cell response. Meanwhile, ICD triggers release of damage-associated molecular patterns, which can promote DC maturation to amplify the antitumor T cell response. When combined with anti-IL-10 that reverses the immunosuppressive TME, 4T1-PB-CO NPs efficiently suppress the primary tumors and produce an abscopal effect to inhibit distant tumors in a breast tumor-bearing mouse model. Such a two-pronged cancer vaccine represents a promising paradigm for robust antitumor immunotherapy.

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Inhibition and transport mechanisms of the ABC transporter hMRP5.

Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.

Differences in Kondo Splitting of Surface Quantum Systems Induced by Two Distinct Magnetic Tips: A Joint Method of DFT and HEOM.

The interactions between a magnetic tip and local spin impurities initiate unconventional Kondo phenomena, such as asymmetric suppression or even splitting of the Kondo peak. However, a lack of realistic theoretical models and comprehensive explanations for this phenomenon persists due to the complexity of the interactions. This research employs a joint method of density functional theory (DFT) and hierarchical equation of motion (HEOM) to simulate and contrast the modulation of the spin state and Kondo behavior in the Fe/Cu(100) system with two distinct magnetic tips. A cobalt tip, possessing a larger magnetic moment, incites greater atomic displacement of the iron atom, more notable alterations in electronic structure, and enhanced charge transfer with the environment compared with the control process utilizing a nickel tip. Furthermore, the Kondo resonance undergoes asymmetric splitting as a result of the ferromagnetic correlation between the iron atom and the magnetic tip. The Co tip's higher spin polarization results in a wider spacing between the splitting peaks. This investigation underscores the precision of the DFT + HEOM approach in predicting complex quantum phenomena and explaining the underlying physical principles. This provides valuable theoretical support for developing more sophisticated quantum regulation experiments.

Enhancement of the function of mesenchymal stem cells by using a GMP-grade three-dimensional hypoxic large-scale production system.

Background: Efficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materials: We developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. Results: Inoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with 'cell cycle' and 'stroma/mesenchyme', with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-ß1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated ß-Galactosidase (SA-ß-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. Conclusion: The TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study.

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .

Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites.

Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP's structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.

Effects of Heat Treatment on the Microstructure and Mechanical Properties of a Dual-Phase High-Entropy Alloy Fabricated via Laser Beam Power Bed Fusion.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via laser beam power bed fusion (LB-PBF), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 °C for 1 h. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also influencing the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 h and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving LB-PBF and heat treatment.

A rapid and eco-friendly approach for the synthesis of low-silica SAPO-34 with excellent MTO catalytic performance.

A rapid and eco-friendly route has been developed for the synthesis of SAPO-34 with short crystallization time (1-3 h), low silica content (as low as 6.2 wt%) and excellent methanol-to-olefin (MTO) catalytic performance by utilization of a recycled mother liquid at elevated crystallization temperature.

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/).

A Comparative Study of Removal of Acid Red 27 by Adsorption on Four Different Chitosan Morphologies.

To investigate the relationship between structures and adsorption properties, four different morphologies of chitosan, with hydrogel (CSH), aerogel (CSA), powder (CSP), and electrospinning nanofiber (CSEN) characteristics, were employed as adsorbents for the removal of Acid Red 27. The structures and morphologies of the four chitosan adsorbents were characterized with SEM, XRD, ATR-FTIR, and BET methods. The adsorption behaviors and mechanisms of the four chitosan adsorbents were comparatively studied. All adsorption behaviors exhibited a good fit with the pseudo-second-order kinetic model (R2 > 0.99) and Langmuir isotherm model (R2 > 0.99). Comparing the adsorption rates and the maximum adsorption capacities, the order was CSH > CSA > CSP > CSEN. The maximum adsorption capacities of CSH, CSA, CSP, and CSEN were 2732.2 (4.523), 676.7 (1.119), 534.8 (0.885), and 215.5 (0.357) mg/g (mmol/g) at 20 °C, respectively. The crystallinities of CSH, CSA, CSP, and CSEN were calculated as 0.41%, 6.97%, 8.76%, and 39.77%, respectively. The crystallinity of the four chitosan adsorbents was the main factor impacting the adsorption rates and adsorption capacities, compared with the specific surface area. With the decrease in crystallinity, the adsorption rates and capacities of the four chitosan adsorbents increased gradually under the same experimental conditions. CSH with a low crystallinity and large specific surface area resulted in the highest adsorption rate and capacity.

Unraveling a Stable 16-Ring Aluminophosphate DNL-11 through Three-Dimensional Electron Diffraction for Atmospheric Water Harvesting.

Sorption-based atmospheric water harvesting (AWH) is a promising solution for addressing water scarcity. Developing cost-effective and stable water adsorbents with high water uptake capacity and a low-temperature regeneration requirement is a crucially important procedure. In this Communication, we present a novel and stable aluminophosphate (AlPO) molecular sieve (MS) named DNL-11 with 16-ring channels synthesized by using an affordable and commercialized organic structure directing agent (OSDA), whose crystallographic structure is elucidated by three-dimensional electron diffraction (3D ED). DNL-11 exhibits a significant water uptake capacity (189 mg/g) at a very low vapor pressure (5% relative humidity at 30 °C). In addition, most of the adsorbed water can be effortlessly removed by purging N2 at 25 °C under ambient pressure conditions. This may expand the possibility of AWH under extreme drought conditions.

H2-Promoted Benign Coke Strategy for Dimethyl Ether Carbonylation with Long-Term Stability and High Activity.

Zeolite-catalyzed dimethyl ether (DME) carbonylation provides a novel route to producing methyl acetate (MeOAc). Mordenite (MOR) has drawn significant interest because of its remarkable MeOAc selectivity in DME carbonylation, albeit with limited catalytic stability. Herein, novel MOR-based DME carbonylation catalysts, distinguished by long-term stability and high activity were successfully developed, based on an H2-promoted benign coke strategy. Both the H2 cofeeds and the presence of metal species with hydrogenation capability are demonstrated to be crucial for the regulation of coke depositions. The coke deposits can potentially cover the acid sites in the 12-MR main channels, thereby mitigating the occurrence of undesirable methanol-to-hydrocarbon side reactions. Meanwhile, the elimination of ultralarge coke species under the assistance of H2 and Cu species could ensure smooth mass transfer within the catalyst, contributing to its remarkable catalytic performance. The most highlighted DME carbonylation performance was achieved on coke-mediated CuZn-HMOR with a high MeOAc yield of 0.4-0.5 g·gcat-1·h-1 for over 520 h (over 50× enhancement versus HMOR), exhibiting promising industrial application potential. The current strategy is expected to inspire further research into zeolite-catalyzed reactions, which could be potentially improved by the presence of benign coke.

3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair.

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.

Single cell RNA-seq identifies a FOS/JUN-related monocyte signature associated with clinical response of heart failure patients with mesenchymal stem cell therapy.

Heart failure (HF) is a serious global health issue that demands innovative treatment approaches. In this study, we collected samples from 4 HF patients before and after MSC therapy and performed scRNA-seq. After the MSC therapy, the proportion of CD14+ monocytes decreased significantly in both the treatment response and non-response groups, with a more pronounced decrease in the treatment response group. The therapy-response and non-response group were clearly separated in the UMAP plot, while the CD14+ monocytes in the therapy-response group before and after MSC therapy were very similar, but there were significant differences in the non-response group. By further performing NMF analysis, we identified 11 subsets of CD14+ monocytes. More importantly, we identified a therapy-related CD14+ monocyte subpopulation. The predictive model based on CD14+ monocytes constructed by machine learning algorithms showed good performance. Moreover, genes such as FOS were highly enriched in the therapy-related CD14+ monocytes. The SCENIC analysis revealed potential regulatory factors for this treatment-responsive CD14+ monocytes, and FOS/JUN were identified as potential core indicators/regulators. Finally, HF patients were divided into three groups by NMF analysis, and the therapy-responsive CD14+ monocyte characteristics were differentially activated among the three groups. Together, this study identifies treatment-responsive CD14+ monocytes as a crucial biomarker for assessing the suitability of MSC therapy and determining which HF patients could benefit from it. This provides new clues for further investigating the therapeutic mechanisms of MSC therapy, offering beneficial insights for personalized treatment and improving prognosis in HF patients.