High Current Efficiency Red Perovskite Light-Emitting Diodes Meeting Rec. 2020 Standard.

Cesium lead iodide light-emitting diodes (LEDs) are attractive for displays due to their Rec. 2020 red standard compliance. However, achieving high current efficiencies (CEs), which is important for displays, is challenging because their emission spectrum is near the tail of the photopic luminosity function. Substituting some iodine with bromine can improve CEs by enlarging the bandgap, but defects easily form in iodine-bromine mixed perovskites. Here, we successfully reduced defect formation by adding organic ammonium salts and zwitterions. The organic ammonium salts do not form low-dimensional perovskites under the hydrogen bonding interaction of zwitterions. Instead, they passivate the cesium vacancy by forming new hydrogen bonds after perovskite crystallization. This approach leads to a red perovskite LED with a high CE of 12.8 cd A-1 and a peak external quantum efficiency of 20.3%, meeting the Rec. 2020 standard. It can be extended to large-area devices (2500 mm2) without a significant efficiency loss.

Nano-mechanical Immunoengineering: Nanoparticle Elasticity Reprograms Tumor-Associated Macrophages via Piezo1.

The mechanical properties of nanoparticles play a crucial role in regulating nanobiointeractions, influencing processes such as blood circulation, tumor accumulation/penetration, and internalization into cancer cells. Consequently, they have a significant impact on drug delivery and therapeutic efficacy. However, it remains unclear whether and how macrophages alter their biological function in response to nanoparticle elasticity. Here, we report on the nano-mechanical biological effects resulting from the interactions between elastic silica nanoparticles (SNs) and macrophages. The SNs with variational elasticity Young's moduli ranging from 81 to 837 MPa were synthesized, and it was demonstrated that M2 [tumor-associated macrophages (TAMs)] could be repolarized to M1 by the soft SNs. Additionally, our findings revealed that cell endocytosis, membrane tension, the curvature protein Baiap2, and the cytoskeleton were all influenced by the elasticity of SNs. Moreover, the mechanically sensitive protein Piezo1 on the cell membrane was activated, leading to calcium ion influx, activation of the NF-κB pathway, and the initiation of an inflammatory response. In vivo experiments demonstrated that the softest 81 MPa SNs enhanced tumor penetration and accumulation and repolarized TAMs in intratumoral hypoxic regions, ultimately resulting in a significant inhibition of tumor growth. Taken together, this study has established a cellular feedback mechanism in response to nanoparticle elasticity, which induces plasma membrane deformation and subsequent activation of mechanosensitive signals. This provides a distinctive "nano-mechanical immunoengineering" strategy for reprogramming TAMs to enhance cancer immunotherapy.

Green-synthesized lignin nanoparticles enhance Zea mays resilience to salt stress by improving antioxidant metabolism and mitigating ultrastructural damage.

Soil salinity poses a substantial threat to agricultural productivity, resulting in far-reaching consequences. Green-synthesized lignin nanoparticles (LNPs) have emerged as significant biopolymers which effectively promote sustainable crop production and enhance abiotic stress tolerance. However, the defensive role and underlying mechanisms of LNPs against salt stress in Zea mays remain unexplored. The present study aims to elucidate two aspects: firstly, the synthesis of lignin nanoparticles from alkali lignin, which were characterized using Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Fourier Infrared Spectroscopy (FT-IR) and Energy Dispersive X-Ray Spectroscopy (EDX). The results confirmed the purity and morphology of LNPs. Secondly, the utilization of LNPs (200 mg/L) in nano priming to alleviate the adverse effects of NaCl (150 mM) on Zea mays seedlings. LNPs significantly reduced the accumulation of Na+ (17/21%) and MDA levels (21/28%) in shoots/roots while increased lignin absorption (30/31%), resulting in improved photosynthetic performance and plant growth. Moreover, LNPs substantially improved plant biomass, antioxidant enzymatic activities and upregulated the expression of salt-tolerant genes (ZmNHX3 (1.52 & 2.81 FC), CBL (2.83 & 3.28 FC), ZmHKT1 (2.09 & 4.87 FC) and MAPK1 (3.50 & 2.39 FC) in both shoot and root tissues. Additionally, SEM and TEM observations of plant tissues confirmed the pivotal role of LNPs in mitigating NaCl-induced stress by reducing damages to guard cells, stomata and ultra-cellular structures. Overall, our findings highlight the efficacy of LNPs as a practical and cost-effective approach to alleviate NaCl-induced stress in Zea mays plants. These results offer a sustainable agri-environmental strategy for mitigating salt toxicity and enhancing crop production in saline environments.

AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.

AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.

Nanotechnology-enabled M2 macrophage polarization and ferroptosis inhibition for targeted inflammatory bowel disease treatment.

Transforming macrophages into the anti-inflammatory M2 phenotype could markedly strengthen inflammatory bowel disease (IBD) treatment, which is considered as a promising strategy. However, the high ferroptosis sensitivity of M2 macrophages, which decreases their activity, is a major stumbling block to this strategy. Therefore, promoting M2 polarization while simultaneously inhibiting ferroptosis to tackle this challenge is indispensable. Herein, a calcium­carbonate (CaCO3) mineralized liposome encapsulating a ferroptosis inhibitor (Fer-1) was developed (CaCO3@Lipo@Fer-1, CLF). The CaCO3 mineralized coating shields the liposomes to prevent the release of Fer-1 in circulation, while releasing Ca2+ in the acidic-inflammatory environment. This released Ca2+ promotes M2 polarization through the CaSR/AKT/ß-catenin pathway. The subsequently released Fer-1 effectively upregulates GSH and GPX4, scavenges reactive oxygen species, and inhibits ferroptosis in M2 macrophages. In vivo, CLF improved the targeting efficiency of IBD lesions (about 4.17-fold) through the epithelial enhanced permeability and retention (eEPR) effect and enhanced IBD therapy by increasing the M2/M1 macrophage ratio and inhibiting ferroptosis. We demonstrate that the synergistic regulation of macrophage polarization and ferroptosis sensitivity by this mineralized nanoinhibitor is a viable strategy for IBD therapy.

Spin coating epitaxial heterodimensional tin perovskites for light-emitting diodes.

Environmentally friendly tin (Sn) perovskites have received considerable attention due to their great potential for replacing their toxic lead counterparts in applications of photovoltaics and light-emitting diodes (LEDs). However, the device performance of Sn perovskites lags far behind that of lead perovskites, and the highest reported external quantum efficiencies of near-infrared Sn perovskite LEDs are below 10%. The poor performance stems mainly from the numerous defects within Sn perovskite crystallites and grain boundaries, leading to serious non-radiative recombination. Various epitaxy methods have been introduced to obtain high-quality perovskites, although their sophisticated processes limit the scalable fabrication of functional devices. Here we demonstrate that epitaxial heterodimensional Sn perovskite films can be fabricated using a spin-coating process, and efficient LEDs with an external quantum efficiency of 11.6% can be achieved based on these films. The film is composed of a two-dimensional perovskite layer and a three-dimensional perovskite layer, which is highly ordered and has a well-defined interface with minimal interfacial areas between the different dimensional perovskites. This unique nanostructure is formed through direct spin coating of the perovskite precursor solution with tryptophan and SnF2 additives onto indium tin oxide glass. We believe that our approach will provide new opportunities for further developing high-performance optoelectronic devices based on heterodimensional perovskites.

OsUGE2 Regulates Plant Growth through Affecting ROS Homeostasis and Iron Level in Rice.

BACKGROUND: The growth and development of rice (Oryza sativa L.) are affected by multiple factors, such as ROS homeostasis and utilization of iron. Here, we demonstrate that OsUGE2, a gene encoding a UDP-glucose 4-epimerase, controls growth and development by regulating reactive oxygen species (ROS) and iron (Fe) level in rice. Knockout of this gene resulted in impaired growth, such as dwarf phenotype, weakened root growth and pale yellow leaves. Biochemical analysis showed that loss of function of OsUGE2 significantly altered the proportion and content of UDP-Glucose (UDP-Glc) and UDP-Galactose (UDP-Gal). Cellular observation indicates that the impaired growth may result from decreased cell length. More importantly, RNA-sequencing analysis showed that knockout of OsUGE2 significantly influenced the expression of genes related to oxidoreductase process and iron ion homeostasis. Consistently, the content of ROS and Fe are significantly decreased in OsUGE2 knockout mutant. Furthermore, knockout mutants of OsUGE2 are insensitive to both Fe deficiency and hydrogen peroxide (H2O2) treatment, which further confirmed that OsUGE2 control rice growth possibly through Fe and H2O2 signal. Collectively, these results reveal a new pathway that OsUGE2 could affect growth and development via influencing ROS homeostasis and Fe level in rice.

Arginine-assembly as NO nano-donor prevents the negative feedback of macrophage repolarization by mitochondrial dysfunction for cancer immunotherapy.

Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy. However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization. The strategy is to first apply reversible tagging of hydrophobic terephthalaldehyde to create an arginine nano-assembly, and then load a toll-like receptor 7/8 agonist resiquimod (R848) (R848@Arg). Through this strategy, a high loading efficiency of 40 % for the arginine and repolarization characteristics for TAMs can be achieved. Upon the macrophage repolarization by R848, NO can be intracellularly generated from the released arginine by the upregulated inducible nitric oxide synthase. Mechanistically, NO effectively prevented the negative feedback of the repolarized macrophage by mitochondrial dysfunction via blocking oxidative phosphorylation. Notably, R848@Arg significantly increased the tumor inhibition ratio by 3.13-fold as compared to the free R848 by maintaining the M1-like phenotype infiltrating into tumor. The Arg-assembly as NO nano-donor provides a promising method for effective repolarization of macrophages.

Underactuated Humanoid Peeling Approach for Pickled Mustard Tuber Based on Metamorphic Constraints.

Pickled mustard tuber (PMT), also known as Brassica juncea var. tumida, is a conical tuberous vegetable with a scaly upper part and a coarse fiber skin covering the lower part. Due to its highly distorted and complex heterogeneous fiber network structure, traditional manual labor is still used for peeling and removing fibers from pickled mustard tuber, as there is currently no effective, fully automated method or equipment available. In this study, we designed an underactuated humanoid pickled mustard tuber peeling robot based on variable configuration constraints that emulate the human "insert-clamp-tear" process via probabilistic statistical design. Based on actual pickled mustard tuber morphological cluster analysis and statistical features, we constructed three different types of pickled mustard tuber peeling tool spectral profiles and analyzed the modular mechanical properties of three different tool configurations to optimize the variable configuration constraint effect and improve the robot's end effector trajectory. Finally, an ADAMS virtual prototype model of the pickled mustard tuber peeling robot was established, and simulation analysis of the "insert-clamp-tear" process was performed based on the three pickled mustard tuber statistical classification selection. The results showed that the pickled mustard tuber peeling robot had a meat loss rate of no more than 15% for each corresponding category of pickled mustard tuber, a theoretical peeling rate of up to 15 pieces per minute, and an average residual rate of only about 2% for old fibers. Based on reasonable meat loss, the efficiency of peeling was greatly improved, which laid the theoretical foundation for fully automated pickled mustard tuber peeling.

Breastmilk microbiome changes associated with lactational mastitis and treatment with dandelion extract.

Introduction: Dandelion (Pugongying) is one of the most frequently used Chinese herbs for treating lactational mastitis (LM). Pugongying granules, a patented medication primarily comprised of dandelion extract, have been approved by CFDA for LM treatment in China. The aims of this study were to investigate the etiology of LM and the mechanism by which Pugongying granules decrease LM symptoms, with a particular focus on the microbial communities found in breastmilk. Methods: Participants were recruited from a previously performed randomized controlled trial (Identifier: NCT03756324, ClinicalTrials.gov). Between 2019 and 2020, women diagnosed with unilateral LM at the Beijing University of Chinese Medicine Third Affiliated Hospital were enrolled. In total, 42 paired breastmilk samples from the healthy and affected breasts of the participants were collected. Additionally, 37 paired pre- and post-treatment breastmilk samples from the affected breast were collected from women who received a 3-day course of either Pugongying granules (20 women) or cefdinir (17 women). Clinical outcomes [e.g., body temperature, visual analogue scale (VAS) score for breast pain, the percentage of neutrophils (NE%)] were analyzed pre- and post-treatment, and the breastmilk samples were subjected to 16S rRNA gene sequencing to analyze the alpha and beta diversities and identify significant bacteria. Finally, the relationship between microorganisms and clinical outcomes was analyzed. Results: There was no significant difference in fever and pain between the Pugongying group and cefdinir group. The most prevalent bacterial genera in breastmilk were Streptococcus and Staphylococcus. Compared to healthy breastmilk, microbial diversity was reduced in affected breastmilk, and there was a higher relative abundance of Streptococcus. After Pugongying treatment, there was an increase in microbial diversity with significantly higher abundance of Corynebacterium. A negative correlation was found between Corynebacterium, VAS score, and NE%. Treatment with cefdinir did not affect microbial diversity. Taken together, our results show a correlation between LM and reduced microbial diversity, as well as an increased abundance of Streptococcus in affected breastmilk. Conclusion: Pugongying granules enhanced microbial diversity in breastmilk samples. Given the substantial variation in individual microbiomes, identifying specific species of Streptococcus and Corynebacterium associated with LM may provide additional insight into LM pathogenesis and treatment.

Construction and application on the training course of information literacy for clinical nurses.

DESIGN: A two-round Delphi survey was conducted to seek opinions from experts about the index system for the evaluation of training courses of clinical nursing staff's information literacy. Besides, a non-randomized controlled experimental study was adopted to check the application effect of the training courses. AIMS: This study intended to construct a training course of information literacy for clinical nurses, train nurses in order to improve their information literacy level and provide theoretical reference for the training of information literacy courses for clinical nurses. METHODS: Two rounds of Delphi study were conducted for the study among 26 clinical medical and nursing experts as well as educational experts from 5 different provinces and cities in China. From July 2022 to October 2022, a total of 84 clinical nurses from two hospitals were selected by the convenience sampling method, of which the nurses in one hospital were the control group and the nurses in the other hospital were the observation group. 42 nurses in the observation group were trained by the constructed information literacy training course. Questionnaire evaluation was used to compare the differences in the level of information literacy of nurses and the training effect between the two groups. RESULTS: The results of the Delphi consultation showed that the expert's judgment coefficient was 0.958, the expert's familiarity was 0.946, and the expert's authority coefficient was 0.952. Finally, a training course of information literacy for clinical nurses with 4 course categories and 45 specific course contents was formed. Among them, nursing information awareness included 7 courses, nursing information knowledge 15 courses, nursing information ability 19 courses, and nursing information ethics 4 courses. The results of the empirical study showed that the information literacy level of the nurses in the observation group after the training of the information literacy course was improved, and the scores in nursing information awareness, nursing information knowledge, nursing information ability, and information ethics were significantly higher than those in the control group after training (P < 0.05). CONCLUSIONS: The constructed information literacy training courses for clinical nurses were clearly targeted and systematic. Empirical research showed that the course contents were scientific and reasonable, which could provide reference for the training of clinical nurses' information literacy.

Psychological capital and alienation among patients with COVID-19 infection: the mediating role of social support.

BACKGROUND: COVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship. METHODS: The data were collected in China by the convenient sampling. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses. RESULTS: Psychological capital was significantly and negatively related to the COVID-19 patients' social alienation (p < .01). And social support partially mediated the correlation between psychological capital and patients' social alienation (p < .01). CONCLUSION: Psychological capital is critical to predicting COVID-19 patients' social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.

Nuclear translocation of OsMADS25 facilitated by OsNAR2.1 in reponse to nitrate signals promotes rice root growth by targeting OsMADS27 and OsARF7.

Nitrate is an important nitrogen source and signaling molecule that regulates plant growth and development. Although several components of the nitrate signaling pathway have been identified, the detailed mechanisms are still unclear. Our previous results showed that OsMADS25 can regulate root development in response to nitrate signals, but the mechanism is still unknown. Here, we try to answer two key questions: how does OsMADS25 move from the cytoplasm to the nucleus, and what are the direct target genes activated by OsMADS25 to regulate root growth after it moves to the nucleus in response to nitrate? Our results demonstrated that OsMADS25 moves from the cytoplasm to the nucleus in the presence of nitrate in an OsNAR2.1-dependent manner. Chromatin immunoprecipitation sequencing, chromatin immunoprecipitation qPCR, yeast one-hybrid, and luciferase experiments showed that OsMADS25 directly activates the expression of OsMADS27 and OsARF7, which are reported to be associated with root growth. Finally, OsMADS25-RNAi lines, the Osnar2.1 mutant, and OsMADS25-RNAi Osnar2.1 lines exhibited significantly reduced root growth compared with the wild type in response to nitrate supply, and expression of OsMADS27 and OsARF7 was significantly suppressed in these lines. Collectively, these results reveal a new mechanism by which OsMADS25 interacts with OsNAR2.1. This interaction is required for nuclear accumulation of OsMADS25, which promotes OsMADS27 and OsARF7 expression and root growth in a nitrate-dependent manner.

Supply chain resource scheduling optimization of e-commerce enterprises in international trade based on mobile edge computing.

The cross-border e-commerce supply chain network (CBESCN) has extensive geographical coverage, trade barriers and complexity of cross-border logistics issues, which makes its construction and development face many challenges. This article focuses on solving the operation optimisation problem of CBESCN under the background of the Internet of Things. A genetic algorithm constructed and solved the resource scheduling model of the supply chain of e-commerce enterprises in international trade. In addition, the mobile edge computing (MEC) optimisation scheme based on partial computation unloading is involved. The initial offload ratio is set and supply chain resources are allocated, then the remaining computing resources are distributed according to the server's computing power. Finally, the offload is optimised according to the resource allocation. The experimental results show that time delay and cost adjustment strategies can improve the CBE supply chain's comprehensive ability. The supply chain optimisation scheme proposed in this article can effectively use supply chain resources according to the requirements of computing tasks to reduce the total delay of task execution and the consumption of node computing.

OsUGE1 is directly targeted by OsGRF6 to regulate root hair length in rice.

KEY MESSAGE: Root hairs are required for water and nutrient acquisition in plants. Here, we report a novel mechanism that OsUGE1 is negatively controlled by OsGRF6 to regulate root hair elongation in rice. Root hairs are tubular outgrowths generated by the root epidermal cells. They effectively enlarge the soil-root contact area and play essential roles for nutrient and water absorption. Here, in this study, we demonstrated that the Oryza sativa UDP-glucose 4-epimerase 1-like (OsUGE1) negatively regulated root hair elongation and was directly targeted by Oryza sativa growth regulating factor 6 (OsGRF6). Knockout mutants of OsUGE1 using CRISPR-Cas9 technology showed longer root hairs than those of wild type. In contrast, overexpression lines of OsUGE1 displayed shorter root hair compared with those of wild type. GUS staining showed that it could specifically express in root hair. Subcellular localization analysis indicates that OsUGE1 is located in endoplasmic reticulum, nucleus and plasma membrane. More importantly, ChIP-qPCR, Yeast-one-hybrid and BiFC experiments revealed that OsGRF6 could bind to the promoter of OsUGE1. Furthermore, knockout mutants of OsGRF6 showed shorter root hair than those of wild type, and OsGRF6 dominantly expressed in root. In addition, the expression level of OsUGE1 is significantly downregulated in Osgrf6 mutant. Taken together, our study reveals a novel pathway that OsUGE1 is negatively controlled by OsGRF6 to regulate root hair elongation in rice.

Protocol for Bulk-ATAC sequencing in head and neck squamous cell carcinoma.

The transposase-accessible chromatin using sequencing (ATAC-seq) offers a simplified approach to detect chromatin changes in cancer cells after genetic intervention and drug treatment. Here, we present an optimized ATAC-seq protocol to elucidate chromatin accessibility changes at the epigenetic level in head and neck squamous cell carcinoma cells. We describe steps for cell lysate preparation, transposition, and tagmentation, followed by library amplification and purification. We then detail next-generation sequencing and data analysis. For complete details on the use and execution of this protocol, please refer to Buenrostro et al.,1 Chen et al.,2.

Mesenchymal Stem Cell Therapy in Kidney Diseases: Potential and Challenges.

Kidney disease (KD) is a life-threatening disease characterized by high morbidity and mortality in clinical settings, which can be caused by many reasons, and the incidence increases with age. However, supportive therapy and kidney transplantation still have limitations in alleviating KD progression. Recently, mesenchymal stem cells (MSCs) have shown great potential in repairing injury through their multidirectional differentiation and self-renewal ability. Of note, MSCs serve as a safe and effective therapeutic strategy for treating KD in preclinical and clinical trials. Functionally, MSCs ameliorate KD progression by regulating the immune response, renal tubular cell apoptosis, tubular epithelial-mesenchymal transition, oxidative stress, angiogenesis, and so on. In addition, MSCs exhibit remarkable efficacy in both acute kidney injury (AKI) and chronic kidney disease (CKD) through paracrine mechanisms. In this review, we outline the biological characteristics of MSCs, discuss the efficacy and mechanisms of MSCs-based therapy for KD, summarize the completed and ongoing clinical trials, as well as analyze limitations and new strategies, aiming to provide new ideas and approaches for the preclinical experiments and clinical trials of MSCs transplantation for KD.

The relationship between components of hypoglycemia worries and avoiding hypoglycemia behavior in type 2 diabetes mellitus with hypoglycemia: a network analysis.

BACKGROUND: The fear of hypoglycemia in type 2 diabetes mellitus (T2DM) patients with hypoglycemia has seriously affected their quality of life. They are always afraid of hypoglycemia and often take excessive action to avoid it. Yet, researchers have investigated the relationship between hypoglycemia worries and excessive avoiding hypoglycemia behavior using total scores on self-report measures. However, network analysis studies of hypoglycemia worries and excessive avoiding hypoglycemia behavior in T2DM patients with hypoglycemia are lacking. PURPOSE: The present study investigated the network structure of hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia and aimed to identify bridge items to help them correctly treat hypoglycemia and properly deal with hypoglycemia fear. METHODS: A total of 283 T2DM patients with hypoglycemia were enrolled in our study. Hypoglycemia worries and avoiding hypoglycemia behavior were evaluated with the Hypoglycemia Fear Scale. Network analyses were used for the statistical analysis. RESULTS: B9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influences in the present network. In the community of hypoglycemia worries, W17 "I worry about hypoglycemia during sleep" has the highest bridge expected influence. And in the community of avoiding hypoglycemia behavior, B9 "Had to stay at home for fear of hypoglycemia" has the highest bridge expected influence. CONCLUSION: Complex patterns of associations existed in the relationship between hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia. From the perspective of network analysis, B9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influence, indicating their highest importance in the network. W17 "I worry about hypoglycemia during sleep" aspect of hypoglycemia worries and B9 "Had to stay at home for fear of hypoglycemia" aspect of avoiding hypoglycemia behavior have the highest bridge expected influence, indicating they have the strongest connections with each community. These results have important implications for clinical practice, which provided potential targets for interventions to reduce hypoglycemia fear and improve the quality of life in T2DM patients with hypoglycemia.

Dynamic changes of inulin utilization associated with longitudinal development of gut microbiota.

Inulin is a typical kind of fermentable polysaccharide and has emerged as a promising dietary supplement due to its multiple health-promoting effects. This study aimed to unveil the dynamic change pattern of inulin utilizability as a fermentation substrate during gut microbiota development and illuminate its potential association with gut microbiota in Chinese Jinhua native pig models via longitudinal analyses. Herein, fresh feces were collected at one week pre- and post-weaning as well as 3rd month post-weaning, respectively. Targeted metabolomics and in vitro simulated fermentation revealed increasing concentrations of fecal short-chain fatty acids (SCFAs) and elevating utilizability of inulin as a fermentation substrate. Microbiomic analyses demonstrated the conspicuous longitudinal alteration in gut microbial composition and a significant rise in microbial community diversity during gut microbiota development. Furthermore, gut microbial functional analyses showed a remarkable increase in the relative abundances of carbohydrate metabolism pathways, including pentose phosphate pathway, galactose metabolism pathway, butanoate metabolism pathway as well as fructose and mannose metabolism pathway. Notably, relative abundances of bacterial genera Bifidobacterium, Roseburia, Faecalibacterium and Enterococcus displayed significantly positive correlations with the production of microbial fermentation-derived SCFAs. Collectively, these findings offer novel insights into understanding inulin utilizability variations from the perspective of gut microbiota development.

Icariside II preconditioning evokes robust neuroprotection against ischaemic stroke, by targeting Nrf2 and the OXPHOS/NF-κB/ferroptosis pathway.

BACKGROUND AND PURPOSE: Astrocytic nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a potential therapeutic target of ischaemic preconditioning (IPC). Icariside II (ICS II) is a naturally occurring flavonoid derived from Herba Epimedii with Nrf2 induction potency. This study was designed to clarify if exposure to ICS II mimicks IPC neuroprotection and if Nrf2 from astrocytes contributes to ICS II preconditioning against ischaemic stroke. EXPERIMENTAL APPROACH: Mice with transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischaemia and primary astrocytes challenged with oxygen-glucose deprivation (OGD) were used to explore the neuroprotective effect of ICS II preconditioning. Additionally, Nrf2-deficient mice were pretreated with ICS II to determine whether ICS II exerts its neuroprotection by activating Nrf2. KEY RESULTS: ICS II pretreatment mitigated cerebral injury in the mouse model of ischaemic stroke along with improving long-term recovery. Furthermore, proteomics screening identified Nrf2 as a crucial gene evoked by ICS II treatment and required for the anti-oxidative effect and anti-inflammatory effect of ICS II. Also, ICS II directly bound to Nrf2 and reinforced the transcriptional activity of Nrf2 after MCAO. Moreover, ICS II pretreatment exerted cytoprotective effects on astrocyte cultures following lethal OGD exposure, by promoting Nrf2 nuclear translocation and activating the OXPHOS/NF-κB/ferroptosis axis, while neuroprotection was decreased in Nrf2-deficient mice and Nrf2 siRNA blocked effects of ICS II. CONCLUSION AND IMPLICATIONS: ICS II preconditioning provides robust neuroprotection against ischaemic stroke via the astrocytic Nrf2-mediated OXPHOS/NF-κB/ferroptosis axis. Thus, ICS II could be a promising Nrf2 activator to treat ischaemic stroke.