circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.

JMJD3 Is Required for Acute Pancreatitis and Pancreatitis-Associated Lung Injury.

Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.

Small-molecule-based targeted therapy in liver cancer.

Liver cancer is one of the most prevalent malignant tumors worldwide. According to the Barcelona Clinic Liver Cancer staging criteria, clinical guidelines provide tutorials to clinical management of liver cancer at their individual stages. However, most patients diagnosed with liver cancer are at advanced stage; therefore, many researchers conduct investigations on targeted therapy, aiming to improve the overall survival of these patients. To date, small-molecule-based targeted therapies are highly recommended (first line: sorafenib and lenvatinib; second line: regorafenib and cabozantinib) by current the clinical guidelines of the American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network. Herein, we summarize the small-molecule-based targeted therapies in liver cancer, including the approved and preclinical therapies as well as the therapies under clinical trials, and introduce their history of discovery, clinical trials, indications, and molecular mechanisms. For drug resistance, the revealed mechanisms of action and the combination therapies are also discussed. In fact, the known small-molecule-based therapies still have limited clinical benefits to liver cancer patients. Therefore, we analyze the current status and give our ideas for the urgent issues and future directions in this field, suggesting clues for novel techniques in liver cancer treatment.

Repair Engineering of Crystal Structure in van der Waals Materials by Probe Electron Beam.

The advancement of electronic technology has led to increasing research on performance and stability. Continuous electrical pulse stimulation can cause crystal structure changes, affecting performance and accelerating aging. Controlled repair of these defects is crucial. In this study, we investigated crystal structure changes in van der Waals (vdW) InSe crystals under continuous electric pulses by using electron beam lithography (EBL) and spherical aberration corrected transmission electron microscopy (Cs-TEM). Results show that electrical pulses induce amorphous regions in the InSe lattice, increasing the device resistance. We used Cs-STEM probe scanning for precise repair, abbreviated SPRT, to optimize device performance. SPRT is related to electric fields induced by the electron beam and can be applied to other 2D materials like α-In2Se3 and CrSe2, offering a potential approach to extend device lifespan.

Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

SGK1 contributes to ferroptosis in coronary heart disease through the NEDD4L/NF-κB pathway.

The prevalence of coronary heart disease (CHD) has increased significantly with the aging population worldwide. It is unclear whether ferroptosis occurs during CHD. Hence, we aimed to investigate the potential mechanisms associated with ferroptosis in CHD. Bioinformatics was used to characterize differentially expressed genes (DEGs) in CHD-related datasets (GSE21610 and GSE66360). There were 76 and 689 DEGs in the GSE21610 and GSE66360, respectively, and they predominantly associated with immune and inflammatory responses. DDX3Y, EIF1AY, KDM5D, RPS4Y1, SGK1, USP9Y, and NSG1 were intersecting DEGs of GSE21610 and GSE66360. Their expression pattern in circulating endothelial cells (ECs) derived from healthy individuals and CHD patients are consistent with the results of bioinformatics analysis, especially SGK1. In vitro, SGK1 knockdown alleviated the Erastin-induced downregulation of SLC7A11, GPX4, GSH, and GSSG, as well as the upregulation of lipid peroxidation, Fe accumulation, and mitochondrial damage in mouse aortic ECs (MAECs). Notably, SGK1 may interact with NEDD4L according to the String database. Moreover, SGK1 promoted NEDD4L and p-P65 expression in MAECs. Interestingly, the effect of SGK1 knockdown on ferroptosis in MAECs was rescued by overexpression of NEDD4L or PMA (NF-κB pathway activator). In vivo, SGK1 knockdown facilitated the recovery of body weight, blood lipids, and aortic tissue structure in CHD animal models. Furthermore, SGK1 knockdown alleviated Fe accumulation in the aorta and inactivated the NEDD4L-NF-κB pathway. In conclusion, SGK1 contributes to EC ferroptosis by regulating the NEDD4L-NF-κB pathway. SGK1 could be recognized as a therapeutic target related to ferroptosis in CHD.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Novel humanized monoclonal antibodies against ROR1 for cancer therapy.

BACKGROUND: Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) contributes to cancer cell proliferation, survival and migration, playing crucial roles in tumor development. ROR1 has been proposed as a potential therapeutic target for cancer treatment. This study aimed to develop novel humanized ROR1 monoclonal antibodies and investigate their anti-tumor effects. METHODS: ROR1 expression in tumor tissues and cell lines was analyzed by immunohistochemistry and flow cytometry. Antibodies from mouse hybridomas were humanized by the complementarity-determining region (CDR) grafting technique. Surface plasmon resonance spectroscopy, ELISA assay and flow cytometry were employed to characterize humanized antibodies. In vitro cellular assay and in vivo mouse experiment were conducted to comprehensively evaluate anti-tumor activity of these antibodies. RESULTS: ROR1 exhibited dramatically higher expression in lung adenocarcinoma, liver cancer and breast cancer, and targeting ROR1 by short-hairpin RNAs significantly inhibited proliferation and migration of cancer cells. Two humanized ROR1 monoclonal antibodies were successfully developed, named h1B8 and h6D4, with high specificity and affinity to ROR1 protein. Moreover, these two antibodies effectively suppressed tumor growth in the lung cancer xenograft mouse model, c-Myc/Alb-cre liver cancer transgenic mouse model and MMTV-PyMT breast cancer mouse model. CONCLUSIONS: Two humanized monoclonal antibodies targeting ROR1, h1B8 and h6D4, were successfully developed and exhibited remarkable anti-tumor activity in vivo.

Advances in spatial transcriptomics and its applications in cancer research.

Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and illustration of gene expression in the spatial context of tissues. Compared with the traditional transcriptomics technologies, spatial transcriptomics technologies not only detect gene expression levels in cells, but also inform the spatial location of genes within tissues, cell composition of biological tissues, and interaction between cells. Here we summarize the development of spatial transcriptomics technologies, spatial transcriptomics tools and its application in cancer research. We also discuss the limitations and challenges of current spatial transcriptomics approaches, as well as future development and prospects.

Simultaneously Producing H2 and H2O2 by Photocatalytic Water Splitting: Recent Progress and Future.

The solar-driven overall water splitting (2H2O→2H2 + O2) is considered as one of the most promising strategies for reducing carbon emissions and meeting energy demands. However, due to the sluggish performance and high H2 cost, there is still a big gap for the current photocatalytic systems to meet the requirements for practical sustainable H2 production. Economic feasibility can be attained through simultaneously generating products of greater value than O2, such as hydrogen peroxide (H2O2, 2H2O→H2 + H2O2). Compared with overall water splitting, this approach is more kinetically feasible and generates more high-value products of H2 and H2O2. In several years, there has been an increasing surge in exploring the possibility and substantial progress has been achieved. In this review, a concise overview of the importance and underlying principles of PIWS is first provided. Next, the reported typical photocatalysts for PIWS are discussed, including commonly used semiconductors and cocatalysts, essential design features of these photocatalysts, and connections between their structures and activities, as well as the selected approaches for enhancing their stability. Then, the techniques used to quantify H2O2 and the operando characterization techniques that can be employed to gain a thorough understanding of the reaction mechanisms are summarized. Finally, the current existing challenges and the direction needing improvement are presented. This review aims to provide a thorough summary of the most recent research developments in PIWS and sets the stage for future advancements and discoveries in this emerging area.

Study on the Commercial Metalized Plastic Current Collector PET-Cu and PP-Cu Toward High-Energy Lithium-Ion Battery.

Commercial metalized plastic current collector (MPCC) is receiving widespread attention from the business and academic communities, due to its properties of excellent electrical conductivity and low mass density. However, the application of MPCC on the side of copper is rarely studied. Herein, sandwich-like polyethylene terephthalate-based (PET) and polypropylene-based (PP) copper (Cu) current collectors via magnetron sputtering and electroplating are fabricated. Most importantly, the electrical performance, mechanical safety quality, and revealed the corresponding failure mechanism for the MPCC cells are first systematically evaluated. First, during the 45 °C electrical cycling tests, PET-Cu CC (82.67%) and PP-Cu CC (82.32%) cells both have comparable capacity retention with the traditional Cu CC (Tra-Cu CC) cell (84.55%) after 500 cycles. The slight reduction in the cycling performance is induced by the crack of the Cu layer around the embedded SiO2 particle for PET-Cu CC cell and the detachment of Cu layer for PP-Cu CC cell. Second, during the nail-penetration test, MPCC cells maintain no fire and explosion for more than 5 min, since the heat-shrinkable function of polymeric film can interrupt the continuous Joule heat released by internal short-circuit. This work provides important guidance for the large-scale application of MPCC in the field of lithium-ion batteries.

An angel or a devil? Current view on the role of CD8+ T cells in the pathogenesis of myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4+ T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8+ T cells also play a critical role in the pathogenesis and treatment of MG. MAIN BODY: Herein, we review the literature on CD8+ T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3+CD8+CD20+ T, and CXCR5+ CD8+ T cells. CONCLUSIONS: Further studies on CD8+ T cells in MG are necessary to determine, among others, the real pattern of the Vß gene usage of autoantigen-specific CD8+ cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8+ cells from MG/EAMG, and the subset of autoantigen-specific CD8+ cells (Tc1, Tc17, and IL-17+IFN-γ+CD8+ T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5+ CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.

Highly stable coherent nanoprecipitates via diffusion-dominated solute uptake and interstitial ordering.

Lightweight design strategies and advanced energy applications call for high-strength Al alloys that can serve in the 300‒400 °C temperature range. However, the present commercial high-strength Al alloys are limited to low-temperature applications of less than ~150 °C, because it is challenging to achieve coherent nanoprecipitates with both high thermal stability (preferentially associated with slow-diffusing solutes) and large volume fraction (mostly derived from high-solubility and fast-diffusing solutes). Here we demonstrate an interstitial solute stabilizing strategy to produce high-density, highly stable coherent nanoprecipitates (termed the V phase) in Sc-added Al-Cu-Mg-Ag alloys, enabling the Al alloys to reach an unprecedented creep resistance as well as exceptional tensile strength (~100 MPa) at 400 °C. The formation of the V phase, assembling slow-diffusing Sc and fast-diffusing Cu atoms, is triggered by coherent ledge-aided in situ phase transformation, with diffusion-dominated Sc uptake and self-organization into the interstitial ordering of early-precipitated Ω phase. We envisage that the ledge-mediated interaction between slow- and fast-diffusing atoms may pave the way for the stabilization of coherent nanoprecipitates towards advanced 400 °C-level light alloys, which could be readily adapted to large-scale industrial production.

Prognostic effect of the TyG index on patients with severe aortic stenosis following transcatheter aortic valve replacement: a retrospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. METHODS: This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell's C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01-7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16-7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42-5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell's C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P < 0.001; NRI: 0.32, P < 0.001; Cardiovascular mortality, IDI: 0.043, P < 0.001; NRI: 0.37, P < 0.001; MACE, IDI: 0.092, P < 0.001; NRI: 0.32, P < 0.001). CONCLUSIONS: In patients with severe AS receiving TAVR, there was a positive linear relationship between TyG index and poor prognosis, with 8.4 as the optimal bivariate cutoff value. Our findings suggest TyG index holds potential value for risk stratification and guiding therapeutic decisions in patients after TAVR.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Neuronal Hyperactivity in the Hippocampus during the Early Stage of Streptozotocin-Induced Type 1 Diabetes in Mice.

INTRODUCTION: Cognitive dysfunction due to reduced neuronal transmission in the brain is a major emerging complication in diabetes. However, recent neuroimaging studies have demonstrated non-linear changes including hyperactivity in the hippocampus during the early stage of diabetes. This study aimed to determine the changes in neuronal activity at a single-cell level in hippocampal CA1 pyramidal neurons in the early stage of streptozotocin-induced type 1 diabetes in mice. METHODS: Whole-cell patch-clamp recordings from acute brain slices were performed in mice over 4 consecutive weeks following the induction of hyperglycaemia using streptozotocin. In addition, microdialysate was collected from CA1 area while the mice were in an arousal state. The concentrations of glutamate and GABA in the microdialysate were then measured using ultra-performance liquid chromatography with mass spectrometry. RESULTS: CA1 neurons in streptozotocin-induced diabetic mice exhibited higher membrane potentials (p = 0.0052), higher frequency of action potentials (p = 0.0052), and higher frequency of spontaneous excitatory post-synaptic currents (p = 0.037) compared with controls during the second week after hyperglycaemia was established. No changes in electrophysiological parameters were observed during the first, the third, and the fourth week. Moreover, the diabetic mice had higher extracellular glutamate concentration in CA1 area compared with controls (p = 0.021) during the second week after the initiation of diabetes. No change in the extracellular GABA concentration was observed. CONCLUSION: Our study demonstrated a temporary state of neuronal hyperactivity at the single-cell level in the hippocampal CA1 region during the early stage of diabetes. This neuronal hyperactivity might be related to altered glutamate metabolism and provide clues for future brain-target intervention.

T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

Ru-Doped NiFe-MIL-53 with Facilitated Reconstruction and Active Hydrogen Supplement for Enhanced Nitrate Reduction.

The Electrochemical reduction of nitrate to ammonia (NH3) is a process of great significance to energy utilization and environmental protection. However, it suffers from sluggish multielectron/proton-involved steps involving coupling reactions between different reaction intermediates and active hydrogen species (Hads) produced by water decomposition. In this study, a Ru-doped NiFe-MIL-53 (NiFeRu-MIL-53) supported on Ni foam (NF) has been designed for the nitrate reduction reaction (NO3RR). The NiFeRu-MIL-53 exhibits excellent NO3RR activity with a maximum Faradaic efficiency (FE) of 100% at -0.4 V vs. RHE for NH3 and a maximum NH3 yield of 62.39 mg h-1 cm-2 at -0.7 V vs. RHE in alkaline media. This excellent performance for the NO3RR is attributed to a strong synergistic effect between Ru and reconstructed NiFe(OH)2. Additionally, the doped Ru facilitates water dissociation, leading to an appropriate supply of Hads required for N species hydrogenation during NO3RR, thereby further enhancing its performance. Furthermore, in situ Raman analysis reveals that incorporating Ru facilitates the reconstruction of MOFs and promotes the formation of hydroxide active species during the NO3RR process. This work provides a valuable strategy for designing electrocatalysts to improve the efficiency of the reduction of electrochemical nitrate to ammonia.

Trends in statin use for the primary prevention of atherosclerotic cardiovascular disease among US adults by demographic characteristics, 1999-2020.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Statins, which are effective in preventing ASCVD, are underused, particularly for primary prevention. This study examined trends in statin use for primary ASCVD prevention from 1999 to 2020, focusing on demographic variations. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, the present study includes individuals aged 18 years and older who had a greater than 10% risk of ASCVD over 10 years, and excluded patients with existing ASCVD. Subgroup analyses by demographic categories were performed. We calculated the changes in statin usage and used linear and quadratic tests to assess the linear and nonlinear trends in those changes. RESULTS: A total of 10,037 participants were included. Statin usage increased from 16.16% in 1999 to 36.24% in 2010, and 41.74% in 2020 (quadratic P-value < 0.001). In the 18-44 years age group, statin usage increased from 2.52% in 1999 to 8.14% in 2020 (linear P-value = 0.322), showing no significant linear trend. In the "never-married" group, statin usage increased from 19.16% in 1999 to 30.05% in 2020 (linear P-value = 0.256). CONCLUSION: Statin usage has shown a positive trend among populations requiring primary prevention for ASCVD. Currently, health policies are proving effective. However, the overall statin usage rate remains less than 50%. Additionally, young and never-married individuals should also receive special attention regarding statin usage as primary treatment for ASCVD.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.