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The development of noble-metal-free heterogeneous catalysts that can realize the aerobic oxidation of C–H bonds at low temperature is a profound challenge in the catalysis community. Here we report the synthesis of a mesoporous Mn 0.5 Ce 0.5 O x solid solution that is highly active for the selective oxidation of hydrocarbons under mild conditions (100–120 °C). Notably, the catalytic performance achieved in the oxidation of cyclohexane to cyclohexanone/cyclohexanol (100 °C, conversion: 17.7%) is superior to those by the state-of-art commercial catalysts (140–160 °C, conversion: 3-5%). The high activity can be attributed to the formation of a Mn 0.5 Ce 0.5 O x solid solution with an ultrahigh manganese doping concentration in the CeO 2 cubic fluorite lattice, leading to maximum active surface oxygens for the activation of C–H bonds and highly reducible Mn 4+ ions for the rapid migration of oxygen vacancies from the bulk to the surface. Precious metal free catalysts for aerobic oxidation of hydrocarbons are industrially useful materials. Here, the authors report a mesoporous maganese-cerium oxide solid solution that is highly active for the selective oxidation of C-H bonds in hydrocarbons under mild conditions.

Empagliflozin (EMPA) is an SGLT-2 inhibitor that can control hyperglycemia. Clinical trials have indicated its cardio-protective effects against cardiac remodeling in diabetes or non-diabetes patients. However, the underlying molecular mechanisms of EMPA's cardio-protective effects remain elusive. We evaluated whether the EMPA attenuated the pressure-overload-induced cardiac hypertrophy by inhibiting the Wnt/β-catenin pathway. Furthermore, the effects of the EMPA on a mouse model of transverse aortic constriction (TAC) induced cardiac hypertrophy was also evaluated. Mice were administrated with 0.5% CMC-Na as a vehicle or EMPA (10 mg/kg/day, daily, throughout the study) by intragastric gavage. The echocardiography and histologic morphological analyses revealed that EMPA attenuated TAC-induced cardiac hypertrophy. Moreover, it also ameliorated TAC-induced cardiac fibrosis and decreased the cell size of the cardiomyocytes in isolated adult cardiomyocytes. Molecular mechanism analysis revealed that the EMPA reduced the TAC-induced enhanced expression of the Wnt/β-catenin pathway . For assessments, isolated neonatal rat cardiomyocytes (NRCMs) were treated with Angiotensin II (AngII) and EMPA; the results showed that in the absence of EMPA, the expression of the Wnt/β-catenin pathway was enhanced. In the trans-genetic heterozygous β-catenin deletion mice, EMPA attenuated TAC-induced cardiac remodeling by reducing the Wnt/β-catenin pathway. In addition, molecular docking analysis indicated that EMPA interacts with FZD4 to inhibit the TAC and AngII induced Wnt/β-catenin pathway in cardiomyocytes. Our study illustrated that EMPA might directly interact with FZD4 to inhibit the TAC and AngII-induced activation of the Wnt/β-catenin pathway to attenuate the adverse cardiac remodeling.

Increasing the efficiency of visible‐light‐driven water splitting systems will require improvements in the charge separation characteristics and redox reaction kinetics associated with narrow‐bandgap photocatalysts. Although the traditional approach of loading a single cocatalyst on selective facets provides reaction sites and reduces the reaction overpotential, pronounced surface charge carrier recombination still results in limited efficiency increases. The present study demonstrates a significant improvement in the hydrogen evolution activity of the layered single‐crystal photocatalyst Y2Ti2O5S2. Increased performance is obtained through sequential loading of Pt cocatalysts using a two‐step process followed by photodeposition of Cr2O3 nanolayers. The stepwise deposition of Pt involved an impregnation‐reduction pretreatment with subsequent photodeposition and produced numerous hydrogen production sites while promoting electron capture. The Cr2O3 shells formed on Pt nanoparticles further promoted electron transfer from the Pt to the water and inhibited surface carrier recombination. Importantly, it is also possible to construct a Z‐scheme overall water splitting system using the optimized Y2Ti2O5S2 in combination with surface‐modified BiVO4 in the presence of [Fe(CN)6]3−/4−, yielding a solar‐to‐hydrogen energy conversion efficiency of 0.19%. This work provides insights into precise surface modifications of narrow‐bandgap photocatalysts as a means of improving the solar water splitting process. Fine engineering of the surface modification for single‐crystal Y2Ti2O5S2 nanosheets promotes the electron transfer, inhibits the surface carrier recombination, and enhances the H2 evolution activity, enabling the construction of a Z‐scheme overall water splitting system with a solar‐to‐hydrogen energy conversion efficiency of 0.19% using a long‐wavelength photoresponsive oxysulfide.

Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI. Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice. Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung. In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI.

Gestational diabetes mellitus (GDM), a prevalent prenatal metabolic disorder characterized by hyperglycemia occurring in approximately 9.2% of pregnancies globally, imposes significant cardiovascular risks on offspring, including developmental cardiac hypertrophy and long-term functional impairment. Despite its clinical importance, the molecular mechanisms governing GDM-induced cardiac malformations remain elusive. This study aimed to delineate the regulatory role of the Wnt/β-catenin/Tcf7l2 signaling pathway in mediating pathological cardiac remodeling in GDM-exposed offspring through experimental manipulation using a clinically relevant murine model. We established a clinically relevant GDM mouse model exhibiting key metabolic features including hyperinsulinemia and impaired glucose tolerance, which faithfully recapitulates human GDM pathology. Cardiomyocyte-specific β-catenin knockout and cardiomyocyte-specific overexpression of constitutively active β-catenin were employed for genetic manipulation. Pharmacological intervention was performed using saxagliptin, a clinically approved DPP-4 inhibitor. Cardiac phenotypes were evaluated by histopathological analysis, echocardiography, and molecular assessments of Wnt/β-catenin pathway activity and hypertrophic markers. Histopathological and echocardiographic analyses revealed pronounced cardiac hypertrophy in GDM-exposed offspring, concomitant with activation of the Wnt/β-catenin/Tcf7l2 pathway in myocardial tissues. Functional studies demonstrated that cardiomyocyte-specific β-catenin ablation attenuated GDM-induced hypertrophic remodeling, whereas constitutive β-catenin overexpression exacerbated cardiac dysfunction. Importantly, pharmacological intervention with saxagliptin significantly ameliorated cardiac hypertrophy in GDM-offspring. This therapeutic effect was paralleled by marked suppression of Wnt/β-catenin signaling activity and reduced expression of ANP. Collectively, these findings provide compelling evidence that dysregulation of the Wnt/β-catenin/Tcf7l2 pathway constitutes a critical mediator in GDM-induced cardiac hypertrophy, and highlight saxagliptin as a potential therapeutic strategy to mitigate adverse cardiac outcomes in GDM offspring.

Increasing the efficiency of visible-light-driven water splitting systems will require improvements in the charge separation characteristics and redox reaction kinetics associated with narrow-bandgap photocatalysts. Although the traditional approach of loading a single cocatalyst on selective facets provides reaction sites and reduces the reaction overpotential, pronounced surface charge carrier recombination still results in limited efficiency increases. The present study demonstrates a significant improvement in the hydrogen evolution activity of the layered single-crystal photocatalyst Y Ti O S . Increased performance is obtained through sequential loading of Pt cocatalysts using a two-step process followed by photodeposition of Cr O nanolayers. The stepwise deposition of Pt involved an impregnation-reduction pretreatment with subsequent photodeposition and produced numerous hydrogen production sites while promoting electron capture. The Cr O shells formed on Pt nanoparticles further promoted electron transfer from the Pt to the water and inhibited surface carrier recombination. Importantly, it is also possible to construct a Z-scheme overall water splitting system using the optimized Y Ti O S in combination with surface-modified BiVO in the presence of [Fe(CN) ] , yielding a solar-to-hydrogen energy conversion efficiency of 0.19%. This work provides insights into precise surface modifications of narrow-bandgap photocatalysts as a means of improving the solar water splitting process.

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.

Background Gut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear. Results Here, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2. Conclusions Together, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA. 2VpFEiBoi5zKv8qdp_bZN4 Video Abstract

Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor, containing GBM stem cells (GSCs) that contribute to therapeutic resistance and relapse. Exposing potential GSC vulnerabilities may provide therapeutic strategies against GBM. Here, we interrogated the role of adenosine-to-inosine (A-to-I) RNA editing mediated by adenosine deaminase acting on RNA 1 (ADAR1) in GSCs and found that both ADAR1 and global RNA editomes were elevated in GSCs compared with normal neural stem cells. ADAR1 inactivation or blocking of the upstream JAK/STAT pathway through TYK2 inhibition impaired GSC self-renewal and stemness. Downstream of ADAR1, RNA editing of the 3'-UTR of GM2A, a key ganglioside catabolism activator, proved to be critical, as interference with ganglioside catabolism and disruption of ADAR1 showed a similar functional impact on GSCs. These findings reveal that RNA editing links ganglioside catabolism to GSC self-renewal and stemness, exposing a potential vulnerability of GBM for therapeutic intervention.

Glioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear. Here, we find that classical (CL) and mesenchymal (MES) GSCs are enriched in reactive immune region and high CL-MES signature informs poor prognosis in GBM. Through integrated analyses of GSCs RNA sequencing and single-cell RNA sequencing datasets, we identify specific GSCs targets, including MEOX2 for the CL GSCs and SRGN for the MES GSCs. MEOX2-NOTCH and SRGN-NFκB axes play important roles in promoting proliferation and maintaining stemness and subtype signatures of CL and MES GSCs, respectively. In the tumor microenvironment, MEOX2 and SRGN mediate the resistance of CL and MES GSCs to macrophage phagocytosis. Using genetic and pharmacologic approaches, we identify FDA-approved drugs targeting MEOX2 and SRGN. Combined CL and MES GSCs targeting demonstrates enhanced efficacy, both in vitro and in vivo. Our results highlighted a therapeutic strategy for the elimination of heterogeneous GSCs populations through combinatorial targeting of MEOX2 and SRGN in GSCs. The molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.