Rechargeable all-solid-state lithium metal batteries (ASSLMBs) utilizing inorganic solid-state electrolytes (SSEs) are promising for electric vehicles and large-scale grid energy storage. However, the Li dendrite growth in SSEs still constrains the practical utility of ASSLMBs. To achieve a high dendrite-suppression capability, SSEs must be chemically stable with Li, possess fast Li transfer kinetics, and exhibit high interface energy. Herein, a class of low-cost, eco-friendly, and sustainable oxyhalide-nitride solid electrolytes (ONSEs), denoted as LixNyIz-qLiOH (where x = 3y + z, 0 ≤ q ≤ 0.75), is designed to fulfill all the requirements. As-prepared ONSEs demonstrate chemically stable against Li and high interface energy (>43.08 meV Å-2), effectively restraining Li dendrite growth and the self-degradation at electrode interfaces. Furthermore, improved thermodynamic oxidation stability of ONSEs (>3 V vs Li+/Li, 0.45 V for pure Li3N), arising from the increased ionicity of LiâN bonds, contributes to the stability in ASSLMBs. As a proof-of-concept, the optimized ONSEs possess high ionic conductivity of 0.52 mS cm-1 and achieve long-term cycling of Li||Li symmetric cell for over 500 h. When coupled with the Li3InCl6 SSE for high-voltage cathodes, the bilayer oxyhalide-nitride/Li3InCl6 electrolyte imparts 90% capacity retention over 500 cycles for Li||1 mAh cm-2 LiCoO2 cells.
BACKGROUND & AIMS: Our previous study has demonstrated that Telomeric repeat-binding factor 2-interacting protein 1(Terf2ip), played an important role in hepatic ischemia reperfusion injury. This study is aimed to explore the function and mechanism of Terf2ip in non-alcoholic steatohepatitis (NASH). METHODS: The expression of Terf2ip was detected in liver tissue samples obtained from patients diagnosed with NASH. Mice NASH models were constructed by fed with high-fat diet (HFD) or methionine/choline deficient diet (MCD) in Terf2ip knockout and wild type (WT) mice. To further investigate the role of Terf2ip in NASH, adeno-associated viruses (AAV)-Terf2ip was administrated to mice. RESULTS: We observed a significant down-regulation of Terf2ip levels in the livers of NASH patients and mice NASH models. Terf2ip deficiency was associated with an exacerbation of hepatic steatosis in mice under HFD or MCD. Additionally, Terf2ip deficiency impaired lipophagy and fatty acid oxidation (FAO) in NASH models. Mechanically, we discovered that Terf2ip bound to the promoter region of Sirt1 to regulate Sirt1/AMPK pathway activation. As a result, Terf2ip deficiency was shown to inhibit lipophagy through the AMPK pathway, while the activation of Sirt1 alleviated steatohepatitis in the livers of mice. Finally, re-expression of Terf2ip in hepatocyes alleviated liver steatosis, inflammation, and restored lipophagy. CONCLUSIONS: These results revealed that Terf2ip played a protective role in the progression of NASH through regulating lipophagy and FAO by binding to Sirt1 promoter. Our findings provided a potential therapeutic target for the treatment of NASH.
Photosynthesis of H2O2 from earth-abundant O2 and H2O molecules offers an eco-friendly route for solar-to-chemical conversion. The persistent challenge is to tune the photo-/thermo- dynamics of a photocatalyst toward efficient electron-hole separation while maintaining an effective driving force for charge transfer. Such a case is achieved here by way of a synergetic strategy of sub-band-assisted Z-Scheme for effective H2O2 photosynthesis via direct O2 reduction and H2O oxidation without a sacrificial agent. The optimized SnS2/g-C3N4 heterojunction shows a high reactivity of 623.0 µmol g-1 h-1 for H2O2 production under visible-light irradiation (λ > 400 nm) in pure water, ≈6 times higher than pristine g-C3N4 (100.5 µmol g-1 h-1). Photodynamic characterizations and theoretical calculations reveal that the enhanced photoactivity is due to a markedly promoted lifetime of trapped active electrons (204.9 ps in the sub-band and >2.0 ns in a shallow band) and highly improved O2 activation, as a result of the formation of a suitable sub-band and catalytic sites along with a low Gibbs-free energy for charge transfer. Moreover, the Z-Scheme heterojunction creates and sustains a large driving force for O2 and H2O conversion to high value-added H2O2.
Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes. Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.
Antifungal Agents , Needles , Tinea Pedis , Tinea Pedis/drug therapy , Animals , Hydrogen-Ion Concentration , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/administration & dosage , Matrix Metalloproteinases/metabolism , Humans , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Guinea Pigs , Gelatin/chemistry , Methacrylates/chemistry
Introduction: The risk of ketosis is assessed by monitoring changes in plasma metabolites and cow behavior during the peripartum period. However, little is known about changes in the fecal bile acid and microbiota of cows before parturition. Therefore, this study clarified the bile acid profile and screened potential warning biomarkers in heifers 7 days before calving. Methods: Ninety healthy cows were tracked in the transition period, and plasma and feces were collected 7 days before calving, on calving day, and 7 days after calving. The cows were divided into ketosis and healthy groups based on the blood ß-hydroxybutyric acid levels from day 7 after calving. The levels of serum biochemical indices were measured at three time points using commercial kits. Ten cows in the ketosis group (KET-7) and 10 healthy cows (HEA-7) were randomly selected 7 days before calving for metabolome and 16S rRNA amplicon sequencing. Results: No significant differences in serum energy-related indices were observed 7 days before calving. The major bile acids in the feces of the KET-7 group were non-conjugated secondary bile acids (UnconSBA). Differential bile acids were primarily derived from UnconSBA. The potential ketosis warning metabolite in feces for 7 days before delivery was isodeoxycholic acid. The abundance of Rikenellaaceae-RC9-gut-group in the KET-7 group increased, whereas the abundance of Oscillospiraceae UCG-010 bacteria significantly decreased. Lactobacillus and Prevotella-9 in feces were potential warning biomarkers for ketosis in dairy cows 7 days before calving. The variation in differential bile acids in the plasma, consistent with the feces, was mainly derived from UnconSBA. Lithocholic acid in the plasma was a potential ketosis warning metabolite 7 days before delivery. Conclusion: Ketotic cows experienced bile acid metabolism disorders 7 days before calving, and the gut microbiota was closely related to bile acid metabolism disorders. Future studies should investigate the relationship between secondary bile acids and the development of ketosis.
The rapid transition of agricultural systems substantially affects residential and industrial land use systems in rural areas, often generating spatiotemporal trade-offs between residential and industrial functions and producing considerable ecological impacts, which has thus far not been well understood. We conduct an indicator-based assessment of transitioning agriculture systems, and then links the transitioning agricultural systems to trade-offs between residential and industrial functions from 2005 to 2020 by using a case study-the metropolitan suburbs of Beijing, China. Also, the associated ecological impacts of the trade-offs are characterized based on the calculation of the ecological quality index (EQI) and ecological contribution rate. The results show that trade-offs between residential and industrial functions in the metropolitan suburbs have gradually adapted to the different agricultural systems in transition, which can be characterized by increasing industrial function as well as declining residential function, together with the diversification of land use into a mixed pattern. Additionally, along with the transitioning process comes a U shape of the ecological quality curve, which indicates that relentless industrial sprawl into regions where the agricultural system has a low capacity for technology, as well as decay in rural areas attributed to a rural exodus and industrial decline in semi-subsistence agricultural areas, even cause ecological degradation. In general, trade-offs between residential and industrial functions (especially for the non-agricultural production function) in rural areas could partially and temporally generate unfavorable ecological impacts, but it seems to be a favorable phenomenon to promote ecological quality in the long term. Therefore, to achieve rural sustainable planning, it is necessary for land use management to observe the trade-offs between residential and industrial functions while avoiding negative impacts, such as low-density land use patterns, disordered land use functions, and eco-environmental deterioration. Such effective strategies can contribute to the feasible implementation of policies aiming to achieve the compatible development of liveable residences, highly efficient industrial production, and eco-friendly operations in rural areas.
Agriculture , China , Industry , Conservation of Natural Resources , Rural Population , Ecology
Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.
Emulsions , Glycolipids , Glycoproteins , Lecithins , Lipid Droplets , Lecithins/chemistry , Glycolipids/chemistry , Lipid Droplets/chemistry , Glycoproteins/chemistry , Glycoproteins/analysis , Humans , Glycine max/chemistry , Milk, Human/chemistry , Chemical Phenomena , Particle Size , Ultrasonic Waves , Sonication
Background: Tillage practices can substantially affect soil properties depending on crop stage. The interaction between tillage and crop growth on arbuscular mycorrhizal fungi (AMF) communities remains unclear. We investigated the interactions between four tillage treatments (CT: conventional tillage, RT: reduced tillage, NT: no tillage with mulch, and SS: subsoiling with mulch), maintained for 25 years, and two wheat growth stages (elongation stage and grain filling stage) on AMF diversity and community composition. Results: The AMF community composition strongly changed during wheat growth, mainly because of changes in the relative abundance of dominant genera Claroideoglomus, Funneliformi, Rhizophagu, Entrophospora, and Glomus. Co-occurrence network analysis revealed that the grain filling stage had a more complex network than the elongation stage. Redundancy analysis results showed that keystone genera respond mainly to changes in soil organic carbon during elongation stage, whereas the total nitrogen content affected the keystone genera during grain filling. Compared with CT, the treatments with mulch, i.e., NT and SS, significantly changed the AMF community composition. The change of AMF communities under different tillage practices depended on wheat biomass and soil nutrients. NT significantly increased the relative abundances of Glomus and Septoglomus, while RT significantly increased the relative abundance of Claroideoglomus. Conclusion: Our findings indicate that the relative abundance of dominant genera changed during wheat growth stages. Proper tillage practices (e.g., NT and SS) benefit the long-term sustainable development of the Loess Plateau cropping systems.
OBJECTIVE: To investigate whether postoperative administration of Shensong Yangxin capsules (SSYX) and dronedarone for atrial fibrillation (AF) can reduce the recurrence of paroxysmal AF after radiofrequency ablation, thus providing a more optimal choice of antiarrhythmic medication during the blank period. METHODS: We included 120 patients with paroxysmal AF who underwent radiofrequency ablation at our hospital between July 2020 and July 2022. They underwent routine circumferential pulmonary vein ablation and, subsequently, left and right atrial pressure monitoring to assess sinoatrial node recovery time under burst 400/300 ms stimulation. Postoperatively, the patients were randomly divided into 2 groups (60 patients each). The control group was administered dronedarone orally for 3 months and the study group was treated with SSYX combined with dronedarone. This study aimed to compare differences in clinical efficacy of the treatment between the 2 groups. RESULTS: The left and right atrial pressures in both groups were higher than those in the preoperative period (Pâ <â .05), with no statistically significant differences between the 2 groups (Pâ >â .05). Sinoatrial node recovery time under burst 400/300 ms stimulation showed no statistical difference between the 2 groups (Pâ >â .05). At 3 months and 1 year postoperatively, the AFEQT scale scores for both groups were lower than those before treatment (Pâ <â .05), with the study group scoring lower than the control group at 3 months (Pâ <â .05). However, no statistically significant difference was observed between the 2 groups at 1 year postoperatively (Pâ >â .05). At 3 months postoperatively, the sinus rhythm maintenance rate and heart rate were higher in the intervention group than in the control group (Pâ <â .05); however, these differences between the 2 groups were not statistically significant at 1 year postoperatively (Pâ >â .05). CONCLUSION SUBSECTIONS: The combination of SSYX and dronedarone could effectively reduce the early recurrence of paroxysmal AF after radiofrequency ablation, increase heart rate, and improve the quality of life.
Anti-Arrhythmia Agents , Atrial Fibrillation , Catheter Ablation , Dronedarone , Drugs, Chinese Herbal , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/surgery , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Male , Female , Middle Aged , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/administration & dosage , Dronedarone/therapeutic use , Dronedarone/administration & dosage , Catheter Ablation/methods , Treatment Outcome , Recurrence , Aged , Drug Therapy, Combination , Capsules
BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.
Rheum , Rheum/genetics , Plant Breeding , Anthraquinones , Chromosomes , Genome Size , Evolution, Molecular
BACKGROUND: A major risk factor for neurodegenerative disorders is old age. Nutritional interventions that delay aging, such as calorie restriction (CR) and intermittent fasting (IF), as well as pharmaceuticals that affect the pathways linking nutrition and aging processes, have been developed in recent decades and have been shown to alleviate the effects of aging on the brain. SUMMARY: CR is accomplished by alternating periods of ad libitum feeding and fasting. In animal models, IF has been shown to increase lifespan and slow the progression and severity of age-related pathologies such as cardiovascular and neurodegenerative diseases and cancer. According to recent research, dietary changes can help older people with dementia retain brain function. However, the mechanisms underlying the neuroprotective effect of IF on the aging brain and related questions in this area of study (i.e., the potential of IF to treat neurodegenerative disorders) remain to be examined. KEY MESSAGES: This review addresses the hypothesis that IF may have translational potential in protecting the aged brain while summarizing the research supporting the putative neuroprotective mechanisms of IF in animal models. Additionally, given the emerging understanding of the connection between aging and dementia, our investigations may offer a fresh perspective on the use of dietary interventions for enhancing brain function and preventing dementia in elderly individuals. Finally, the absence of guidelines regarding the application of IF in patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge of the long-term effects of IF on dementia before it can be widely prescribed. In conclusion, IF may be an ancillary intervention for preserving memory and cognition in elderly individuals.
Tensile-compression fatigue deformation tests were conducted on AZ31 magnesium alloy at room temperature. Electron backscatter diffraction (EBSD) scanning electron microscopy was used to scan the microstructure near the fatigue fracture surface. It was found that lamellar {10-11}-{10-12} secondary twins (STs) appeared inside primary {10-11} contraction twins (CTs), with a morphology similar to the previously discovered {10-12}-{10-12} STs. However, through detailed misorientation calibration, it was determined that this type of secondary twin is {10-11}-{10-12} ST. Through calculation and analysis, it was found that the matrix was under compressive stress in the normal direction (ND) during fatigue deformation, which was beneficial for the activation of primary {10-11} CTs. The local strain accommodation was evaluated based on the geometric compatibility parameter (m') combined with the Schmid factor (SF) of the slip system, leading us to propose and discuss the possible formation mechanism of this secondary twin. The analysis results indicate that when the local strain caused by basal slip at the twin boundaries cannot be well transmitted, {10-11}-{10-12} STs are activated to coordinate the strain, and different loading directions lead to different formation mechanisms. Moreover, from the microstructure characterization near the entire fracture surface, we surmise that the presence of such secondary twins is not common.
The integration of one-selector-one-resistor crossbar arrays requires the selectors featured with high nonlinearity and bipolarity to prevent leakage currents and any crosstalk among distinct cells. However, a selector with sufficient nonlinearity especially in the frame of device miniaturization remains scarce, restricting the advance of high-density storage devices. Herein, a high-performance memory selector is reported by constructing a graphene/hBN/WSe2 heterostructure. Within the temperature range of 300-80 K, the nonlinearity of this selector varies from ≈103 - ≈104 under forward bias, and increases from ≈300 - ≈105 under reverse bias, the highest reported nonlinearity among 2D selectors. This improvement is ascribed to direct tunneling at low bias and Fowler-Nordheim tunneling at high bias. The tunneling current versus voltage curves exhibit excellent bipolarity behavior because of the comparable hole and electron tunneling barriers, and the charge transport polarity can be effectively tuned from N-type or P-type to bipolar by simply changing source-drain bias. In addition, the conceptual memory selector exhibits no sign of deterioration after 70 000 switching cycles, paving the way for assembling 2D selectors into modern memory devices.
Replacing expensive silver with inexpensive copper for the metallization of silicon wafer solar cells can lead to significant reductions in material costs associated with cell production, but the susceptibility of the Cu material to oxidation remains a challenging issue to solve. In this study, we investigate copper metallization of Indium Tin Oxide surfaces to define copper grid electrodes for heterojunction cells. We propose a novel laser-induced selective metallization (LISM) method to fabricate large-scale copper electrodes for heterojunction solar cells at low cost. This study includes a comprehensive evaluation of the morphological characteristics and electrical properties of the electrodes. The effects of laser parameters on the morphology, composition, size, and conductivity of copper electrodes are investigated. The goal of establishing the process window is to obtain the optimal laser parameters for manufacturing highly conductive copper electrodes. These optimized parameters will then be employed to fabricate high-performance electrodes for solar cells. Furthermore, a detailed analysis of the mechanism underlying laser selective metallization is provided. The resulting Cu electrodes exhibit high conductivity and low resistivity of 1.98 × 10-5Ω.cm, demonstrating the potential of this method for efficient and cost-effective solar electrode production.
Aiming to provide a basis for the application of Gynura divaricata (L.) DC polysaccharide (GDP) in functional foods, the hypoglycemic effects of GDP, and action mechanisms, were investigated. Results showed that GDP effectively inhibited α-glucosidase and remarkably increased the glucose absorption, glycogen content, and pyruvate kinase and hexokinase activities of insulin-resistant HepG2 cells, indicating its potent in vitro hypoglycemic effect. In streptozotocin-induced type 2 diabetes mice, GDP significantly improved various glycolipid metabolism-related indices in serum and liver, e.g., fasting blood glucose, oral glucose tolerance, glycosylated serum protein content, serum insulin level, antioxidant enzyme activities, TG, TC, LDL-C, and HDL-C levels, and hepatic glycogen content, and recovered the structure of gut microbiota to the normal level. It was also found that GDP significantly affected the expression of related genes in the PI3K/Akt, AMPK, and GS/GSK-3ß signaling pathways. Therefore, GDP regulates blood glucose possibly by directly inhibiting α-glucosidase, exerting antioxidant activity, and regulating intestinal microbiota.
Blood Glucose , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Hypoglycemic Agents , Polysaccharides , Animals , Gastrointestinal Microbiome/drug effects , Mice , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/administration & dosage , Male , Humans , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/microbiology , Asteraceae/chemistry , alpha-Glucosidases/metabolism , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Hep G2 Cells , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Insulin/metabolism , Insulin/blood , Liver/metabolism , Liver/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism
BACKGROUND: To assess the associations of replacing sedentary behavior with different types of physical activity with mortality among the US adults of varying diabetes statuses. METHODS: This prospective cohort study included 21,637 participants (mean age, 48.5 y) from the National Health and Nutrition Examination Survey 2007-2018. Physical activity including leisure-time moderate-vigorous-intensity activity (MVPA), walking/bicycling, worktime MVPA, and sedentary behavior. We conducted an isotemporal substitution analysis using Cox regression to estimate the associations between replacements and mortality risks. RESULTS: We found significant protective associations between replacing 30 minutes per day sedentary behavior with 3 types of physical activity and all-cause, cardiovascular disease (CVD) mortality risk (except worktime MVPA for CVD mortality) among total participants, with hazard ratio (HR; 95% confidence interval [CI]) ranging from 0.86 (0.77-0.95) to 0.96 (0.94-0.98). Among participants with diagnosed diabetes, replacing sedentary behavior with leisure-time MVPA was associated with a lower all-cause mortality risk (HR 0.81, 95% CI, 0.70-0.94), which was also observed in other subgroups, with HRs (95% CI) ranging from 0.87 (0.80-0.94) to 0.89 (0.81-0.99). Among those with prediabetes/undiagnosed diabetes, replacing sedentary behavior with walking/bicycling was associated with lower CVD mortality risk, and replacement to work-time MVPA was associated with lower all-cause and CVD mortality risk, with HRs (95% CI) ranging from 0.72 (0.63-0.83) to 0.96 (0.92-0.99). CONCLUSIONS: Replacing sedentary behaviors with 30 minutes per day leisure-time MVPA was associated with lower all-cause mortality, regardless of diabetes statuses. Among people with prediabetes/undiagnosed diabetes, walking/bicycling was additionally associated with lower CVD mortality, and worktime MVPA was associated with lower all-cause and CVD mortality.
The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.
Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.
This paper presents a novel and efficient method for certifying primary organs involved in secondary metabolite synthesis. As the most important secondary metabolite in Parispolyphylla var. yunnanensis (Franch.) Hand. -Mzt. (PPY), Paris saponin (PS) has a variety of pharmacological activities and PPY is in increasing demand. This study established leaf, rhizome, and stem-vascular-bundle 13C6-Glucose feeding and non-feeding four treatments to precisely certify the primary organs involved in Paris saponins VII (PS VII) synthesis. By combining liquid chromatography-mass spectrometry (LC-MS), the 13C/12C ratios of leaf, rhizome, stem, and root in different treatments were quickly and accurately calculated, and four types of PS isotopic ion peak(M-) ratios were found: (M+1) -/M-, (M+2) -/M-, (M+3) -/M- and (M+4) -/M-. The results showed that the ratio of 13C/12C in the rhizomes of the stem-vascular-bundle and rhizome feeding treatments was significantly higher than that in the non-feeding treatment. Compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves increased significantly under leaf and stem-vascular-bundle feeding treatments. Simultaneously, compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves under rhizome treatment showed no significant difference. Furthermore, the ratio of PS VII molecules (M+2) -/M- in the stem, root, and rhizome showed no differences among the four treatments. Compared to the non-feeding treatment, the ratio of the Paris saponin II (PS II) molecule (M+2) -/M- in leaves under leaf feeding treatment showed no significant difference, and the (M+3) -/M- ratio of PS II molecules in leaves under leaf feeding treatment were lower. The data confirmed that the primary organ for the synthesizing of PS VII is the leaves. It lays the foundation for future identification of the primary organs and pathways involved in the synthesis of secondary metabolites in medicinal plants.
Liquid Chromatography-Mass Spectrometry , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Chromatography, Liquid , Plant Leaves
Soft and stretchable conductors with high electrical conductivity and tissue-like mechanical properties are crucial for both on-skin and implantable electronic devices. Liquid metal-based conductors hold great promise due to their metallic conductivity and minimal stiffness. However, the surface oxidation of liquid metal particles in polymeric matrices poses a challenge in forming a continuous pathway for highly conductive elastic composites. Here, it is reported a printable composite material based on liquid metal and conducting polymer that undergoes a self-assembly process, achieving high conductivity (2089 S cm-1) in the bottom surface while maintaining an insulated top surface, high stretchability (>800%), and a modulus akin to human skin tissue. This material is further applied to fabricate skin-interfaced strain sensors and electromyogram sensors through 3D printing.
