Chirality-Driven Orbital Angular Momentum and Circular Dichroism in CoSi.

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

Status of self-medication and the relevant factors regarding drug efficacy and safety as important considerations among adolescents aged 12-18 in China: a cross-sectional study.

The objective of this study was to investigate self-medication behavior among Chinese adolescents aged 12-18 years and explore the factors associated with whether adolescents prioritize drug efficacy or safety when engaging in self-medication behavior. In 2021, a questionnaire investigation was conducted in the Chinese mainland using a multi-stage sampling approach. After a statistical description, logistic regression was used to analyze the factors associated with considering drug efficacy and safety. The self-medication rate among Chinese adolescents aged 12-18 years was 96.61%. Of these, 65.84% considered drug safety to be essential, while 58.72% prioritized drug efficacy. Regression analysis showed that individuals with better healthcare were more likely to consider drug efficacy an important factor. Additionally, those with a healthier family lifestyle were more likely to prioritize efficacy. When individuals engage in self-medication, those residing in urban areas and possessing advanced preventive health literacy and ample family health resources tend to prioritize drug safety to a greater extent. Conversely, those with higher monthly household incomes and only children exhibit a decreased inclination towards prioritizing safety during self-medication. Self-medication is a frequently observed practice among Chinese adolescents aged 12-18. Several factors, such as demographic and sociological characteristics, health literacy, and family health status, have been found to be associated with the extent to which adolescents prioritize medication safety and efficacy when engaging in self-medication practices. Higher levels of health literacy and better family health status were positively correlated with considering both the efficacy and safety of drugs as important factors when self-medicating.

Research and experimental verification on the mechanisms of cellular senescence in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high heterogeneity, poor prognosis, and a low 10-year survival rate of less than 50%. Although cellular senescence displays extensive effects on cancer, the comprehensions of cellular senescence-related characteristics in TNBC patients remains obscure. Method: Single-cell RNA sequencing (scRNA-seq) data were analyzed by Seurat package. Scores for cellular senescence-related pathways were computed by single-sample gene set enrichment analysis (ssGSEA). Subsequently, unsupervised consensus clustering was performed for molecular cluster identification. Immune scores of patients in The Cancer Genome Atlas (TCGA) dataset and associated immune cell scores were calculated using Estimation of STromal and Immune cells in MAlignantTumours using Expression data (ESTIMATE) and Microenvironment Cell Populations-counter (MCP-counter), Tumor Immune Estimation Resource (TIMER) and Estimating the Proportion of Immune and Cancer cells (EPIC) methods, respectively. Immunotherapy scores were assessed using TIDE. Furthermore, feature genes were identified by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses; these were used to construct a risk model. Additionally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and transwell assay were conducted for in vitro validation of hub genes. Result: TNBC was classified into three subtypes based on cellular senescence-related pathways as clusters 1, 2, and 3. Specifically, cluster 1 showed the best prognosis, followed by cluster 2 and cluster 3. The levels of gene expression in cluster 2 were the lowest, whereas these were the highest in cluster 3. Moreover, clusters 1 and 3 showed a high degree of immune infiltration. TIDE scores were higher for cluster 3, suggesting that immune escape was more likely in patients with the cluster 3 subtype who were less likely to benefit from immunotherapy. Next, the TNBC risk model was constructed and validated. RT-qPCR revealed that prognostic risk genes (MMP28, ACP5 and KRT6A) were up-regulated while protective genes (CT83) were down-regulated in TNBC cell lines, validating the results of the bioinformatics analysis. Meanwhile, cellular experiments revealed that ACP5 could promote the migration and invasion abilities in two TNBC cell lines. Finally, we evaluated the validity of prognostic models for assessing TME characteristics and TNBC chemotherapy response. Conclusion: In conclusion, these findings help to assess the efficacy of targeted therapies in patients with different molecular subtypes, have practical applications for subtype-specific treatment of TNBC patients, and provide information on prognostic factors, as well as guidance for the revelation of the molecular mechanisms by which senescence-associated genes influence TNBC progression.

Enzyme-Empowered "Two Birds with One Stone" Strategy for Amplifying Tumor Apoptosis and Metabolic Clearance.

Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel "two birds with one stone" technique for amplifying enzyme-mediated tumor apoptosis and enzyme-promoted metabolic clearance is proposed and achieved using GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G). Re@ReP-G reduces ATP production while increasing H2O2 concentrations in the tumor microenvironment through GOx-induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti-apoptotic Bcl-2 proteins, the upregulation of pro-apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser-induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, H2O2 catalyzes the conversion of rhenium nanoclusters in Re@ReP-G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP-G-based "two birds with one stone" therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.

Longitudinal volumetric changes in amygdala subregions in frontotemporal dementia.

Amygdala atrophy has been found in frontotemporal dementia (FTD), yet the specific changes of its subregions across different FTD phenotypes remain unclear. The aim of this study was to investigate the volumetric alterations of the amygdala subregions in FTD phenotypes and how they evolve with disease progression. Patients clinically diagnosed with behavioral variant FTD (bvFTD) (n = 20), semantic dementia (SD) (n = 20), primary nonfluent aphasia (PNFA) (n = 20), Alzheimer's disease (AD) (n = 20), and 20 matched healthy controls underwent whole brain structural MRI. The patient groups were followed up annually for up to 3.5 years. Amygdala nuclei were segmented using FreeSurfer, corrected by total intracranial volumes, and grouped into the basolateral, superficial, and centromedial subregions. Linear mixed effects models were applied to identify changes in amygdala subregional volumes over time. At baseline, bvFTD, SD, and AD displayed global amygdala volume reduction, whereas amygdala volume appeared to be preserved in PNFA. Asymmetrical amygdala atrophy (left > right) was most pronounced in SD. Longitudinally, SD and PNFA showed greater rates of annual decline in the right basolateral and superficial subregions compared to bvFTD and AD. The findings provide comprehensive insights into the differential impact of FTD pathology on amygdala subregions, revealing distinct atrophy patterns that evolve over disease progression. The characterization of amygdala subregional involvement in FTD and their potential role as biomarkers carry substantial clinical implications.

Identification of potential biomarkers and therapeutic targets related to post-traumatic stress disorder due to traumatic brain injury.

BACKGROUND: Post-traumatic stress disorder (PTSD), a disease state that has an unclear pathogenesis, imposes a substantial burden on individuals and society. Traumatic brain injury (TBI) is one of the most significant triggers of PTSD. Identifying biomarkers associated with TBI-related PTSD will help researchers to uncover the underlying mechanism that drives disease development. Furthermore, it remains to be confirmed whether different types of traumas share a common mechanism of action. METHODS: For this study, we screened the eligible data sets from the Gene Expression Omnibus (GEO) database, obtained differentially expressed genes (DEGs) through analysis, conducted functional enrichment analysis on the DEGs in order to understand their molecular mechanisms, constructed a PPI network, used various algorithms to obtain hub genes, and finally evaluated, validated, and analyzed the diagnostic performance of the hub genes. RESULTS: A total of 430 upregulated and 992 down-regulated differentially expressed genes were extracted from the TBI data set. A total of 1919 upregulated and 851 down-regulated differentially expressed genes were extracted from the PTSD data set. Functional enrichment analysis revealed that the differentially expressed genes had biological functions linked to molecular regulation, cell signaling transduction, cell metabolic regulation, and immune response. After constructing a PPI network and introducing algorithm analysis, the upregulated hub genes were identified as VNN1, SERPINB2, and ETFDH, and the down-regulated hub genes were identified as FLT3LG, DYRK1A, DCN, and FKBP8. In addition, by comparing the data with patients with other types of trauma, it was revealed that PTSD showed different molecular processes that are under the influence of different trauma characteristics and responses. CONCLUSIONS: By exploring the role of different types of traumas during the pathogenesis of PTSD, its possible molecular mechanisms have been revealed, providing vital information for understanding the complex pathways associated with TBI-related PTSD. The data in this study has important implications for the design and development of new diagnostic and therapeutic methods needed to treat and manage PTSD.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury.

PURPOSE: Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis. METHODS: Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization. RESULTS: Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. CONCLUSION: This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

High-Performance Single-Crystal Lithium-Rich Layered Oxides Cathode Materials via Na2WO4-Assisted Sintering.

Single-crystal lithium-rich layered oxides (LLOs) with excellent mechanical properties can enhance their crystal structure stability. However, the conventional methods for preparing single-crystal LLOs, require large amounts of molten salt additives, involve complicated washing steps, and increase the difficulty of large-scale production. In this study, a sodium tungstate (Na2WO4)-assisted sintering method is proposed to fabricate high-performance single-crystal LLOs cathode materials without large amounts of additives and additional washing steps. During the sintering process, Na2WO4 promotes particle growth and forms a protective coating on the surface of LLOs particles, effectively suppressing the side reactions at the cathode/electrolyte interface. Additionally, trace amounts of Na and W atoms are doped into the LLOs lattice via gradient doping. Experimental results and theoretical calculations indicate that Na and W doping stabilizes the crystal structure and enhances the Li+ ions diffusion rate. The prepared single-crystal LLOs exhibit outstanding capacity retention of 82.7% (compared to 65.0%, after 200 cycles at 1 C) and a low voltage decay rate of 0.76 mV per cycle (compared to 1.80 mV per cycle). This strategy provides a novel pathway for designing the next-generation high-performance cathode materials for Lithium-ion batteries (LIBs).

Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease.

We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRß)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2'-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.

EEGProgress: A fast and lightweight progressive convolution architecture for EEG classification.

Because of the intricate topological structure and connection of the human brain, extracting deep spatial features from electroencephalograph (EEG) signals is a challenging and time-consuming task. The extraction of topological spatial information plays a crucial role in EEG classification, and the architecture of the spatial convolution greatly affects the performance and complexity of convolutional neural network (CNN) based EEG classification models. In this study, a progressive convolution CNN architecture named EEGProgress is proposed, aiming to efficiently extract the topological spatial information of EEG signals from multi-scale levels (electrode, brain region, hemisphere, global) with superior speed. To achieve this, the raw EEG data is permuted using the empirical topological permutation rule, integrating the EEG data with numerous topological properties. Subsequently, the spatial features are extracted by a progressive feature extractor including prior, electrode, region, and hemisphere convolution blocks, progressively extracting the deep spatial features with reduced parameters and speed. Finally, the comparison and ablation experiments under both cross-subject and within-subject scenarios are conducted on a public dataset to verify the performance of the proposed EEGProgress and the effectiveness of the topological permutation. The results demonstrate the superior feature extraction ability of the proposed EEGProgress, with an average increase of 4.02% compared to other CNN-based EEG classification models under both cross-subject and within-subject scenarios. Furthermore, with the obtained average testing time, FLOPs, and parameters, the proposed EEGProgress outperforms other comparison models in terms of model complexity.

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis.

BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.

Spatial Variation Generation Algorithm for Motor Imagery Data Augmentation: Increasing the Density of Sample Vicinity.

The imbalanced development between deep learning-based model design and motor imagery (MI) data acquisition raises concerns about the potential overfitting issue-models can identify training data well but fail to generalize test data. In this study, a Spatial Variation Generation (SVG) algorithm for MI data augmentation is proposed to alleviate the overfitting issue. In essence, SVG generates MI data using variations of electrode placement and brain spatial pattern, ultimately elevating the density of the raw sample vicinity. The proposed SVG prevents models from memorizing the training data by replacing the raw samples with the proper vicinal distribution. Moreover, SVG generates a uniform distribution and stabilizes the training process of models. In comparison studies involving five deep learning-based models across eight datasets, the proposed SVG algorithm exhibited a notable improvement of 0.021 in the area under the receiver operating characteristic curve (AUC). The improvement achieved by SVG outperforms other data augmentation algorithms. Further results from the ablation study verify the effectiveness of each component of SVG. Finally, the studies in the control group with varying numbers of samples show that the SVG algorithm consistently improves the AUC, with improvements ranging from approximately 0.02 to 0.15.

Progress in Electrochemical Immunosensors with Alkaline Phosphatase as the Signal Label.

Electrochemical immunosensors have shown great potential in clinical diagnosis, food safety, environmental protection, and other fields. The feasible and innovative combination of enzyme catalysis and other signal-amplified elements has yielded exciting progress in the development of electrochemical immunosensors. Alkaline phosphatase (ALP) is one of the most popularly used enzyme reporters in bioassays. It has been widely utilized to design electrochemical immunosensors owing to its significant advantages (e.g., high catalytic activity, high turnover number, and excellent substrate specificity). In this work, we summarized the achievements of electrochemical immunosensors with ALP as the signal reporter. We mainly focused on detection principles and signal amplification strategies and briefly discussed the challenges regarding how to further improve the performance of ALP-based immunoassays.

Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy.

Background: The negative impact of long COVID on social life and human health is increasingly prominent, and the elevated risk of cardiovascular disease in patients recovering from COVID-19 has also been fully confirmed. However, the pathogenesis of long COVID-related inflammatory cardiomyopathy is still unclear. Here, we explore potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy. Methods: Datasets that met the study requirements were identified in Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were obtained by the algorithm. Then, functional enrichment analysis was performed to explore the basic molecular mechanisms and biological processes associated with DEGs. A protein-protein interaction (PPI) network was constructed and analyzed to identify hub genes among the common DEGs. Finally, a third dataset was introduced for validation. Results: Ultimately, 3,098 upregulated DEGs and 1965 downregulated DEGs were extracted from the inflammatory cardiomyopathy dataset. A total of 89 upregulated DEGs and 217 downregulated DEGs were extracted from the dataset of convalescent COVID patients. Enrichment analysis and construction of the PPI network confirmed VEGFA, FOXO1, CXCR4, and SMAD4 as upregulated hub genes and KRAS and TXN as downregulated hub genes. The separate dataset of patients with COVID-19 infection used for verification led to speculation that long COVID-associated inflammatory cardiomyopathy is mainly attributable to the immune-mediated response and inflammation rather than to direct infection of cells by the virus. Conclusion: Screening of potential biomarkers and therapeutic targets sheds new light on the pathogenesis of long COVID-associated inflammatory cardiomyopathy as well as potential therapeutic approaches. Further clinical studies are needed to explore these possibilities in light of the increasingly severe negative impacts of long COVID.

Anion-Cation Dual-Ion Multisite Doping Stabilizes the Crystal Structure of Li-Rich Layered Oxides.

Li-rich layered oxide (LLOs) cathode materials are gaining increasing attention as lithium-ion batteries (LIBs) pursue greater energy density. However, LLOs still suffer from severe capacity fading and voltage decay due to their unstable crystal structure. Hence, the anion-cation dual-ion multisite doping strategy based on Mg and S atoms is used to stabilize the crystal structures of LLOs. Mg substitutes Li atoms in the Li and transition-metal (TM) layers, while S atoms occupy tetrahedral interstitial sites and lattice O sites, all of which contribute to the crystal structure stability of LLOs. Theoretical calculations show that Mg/S dual-ion multisite doping successfully reduces the energy levels of the TM 3d-O 2p and isolated O 2p orbitals, which effectively stabilizes the lattice oxygen. Therefore, multisite-doped samples exhibit promising electrochemical performance. This strategy provides a new approach to enhance the crystal structure stability of LLOs for the design of high-energy-density Li-ion batteries.

The PI3K-Akt-mTOR pathway mediates renal pericyte-myofibroblast transition by enhancing glycolysis through HKII.

BACKGROUND: Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-ß1 (TGF-ß1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. METHODS: Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRß + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-ß1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. RESULTS: An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-ß1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-ß1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. CONCLUSIONS: The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Family functioning and nicotine dependence among smoking fathers: a cross-sectional study.

BACKGROUND: Nicotine dependence is a significant public health issue, and understanding the factors associated with nicotine dependence in this population is crucial for developing effective interventions. This study examined the association between family functioning and nicotine dependence levels of smoking fathers based on the McMaster model of family functioning (MMFF), providing evidence for future interventions. METHODS: In this study, we selected fathers of first- to fifth-grade students from 10 pilot elementary schools in Qingdao whose families smoked. We used the Fagerstrom test to assess nicotine dependence and the Family Assessment Device to evaluate family functioning. We performed univariate analysis to compare differences among those with different levels of nicotine dependence, and we used an ordinal logistic regression analysis to investigate the influences related to nicotine dependence. RESULTS: This study included 874 smokers, with 78.5% having mild nicotine dependence, 11.7% having moderate dependence, and 9.84% having severe dependence. Univariate analysis showed that smokers with severe dependence had lower education levels, higher prevalence of chronic diseases, more frequent alcohol consumption, and poorer family functioning compared to those with mild to moderate dependence. Ordinal logistic regression analysis showed that poorer general functioning scores (OR = 1.087, 95% CI: 1.008-1.173, P = 0.030), poorer behavioral control (OR = 1.124, 95% CI: 1.026-1.232, P = 0.012), more quit attempts, frequent alcohol consumption, and longer smoking duration may be associated with a higher likelihood of developing severe nicotine dependence. The older age of starting smoking and higher education level may be associated with a lower likelihood of developing severe nicotine dependence. However, it is important to note that the cross-sectional nature of this study precludes the determination of causal relationships. CONCLUSIONS: This study finds that heavy nicotine dependence in smoking fathers is associated with risky behaviors and demographics such as longer smoking duration and frequent alcohol consumption. Targeted smoking cessation interventions are crucial for this group, taking these specific factors into consideration. Family functioning, particularly general functioning and behavioral control, may also be linked to nicotine dependence, indicating the need for further research in this area.

Understanding influencing attributes of COVID-19 vaccine preference and willingness-to-pay among Chinese and American middle-aged and elderly adults: A discrete choice experiment and propensity score matching study.

Background and objective: COVID-19 has imposed burdens on public health systems globally. Owing to the urgency of vaccination, this study aimed at comparing the differences in preference and willingness to pay of COVID-19 vaccine among Chinese and American middle-aged and elderly adults. Methods: A cross-sectional survey containing demographic questions, rating their acceptance of COVID-19 vaccination with and without recommendations from friends, family members or employers (the social cues referred to in our study), and a discrete choice experiment understanding COVID-19 vaccine preference and willingness to pay was conducted to collect data. Propensity score matching was utilized to adjust confounding factors of baseline characteristics and the relative importance of respondents' preference for each attribute and its level was estimated using a conditional logit model. Then, willingness to pay was calculated. Results: In total, 3,494 (2,311 and 1,183 from China and the United States, respectively) completed the questionnaire, among which 3,444 questionnaires were effective. After propensity score matching, 1,604 respondents with 802 from the US and 802 from China were included. Under the influence of the social cues, Chinese respondents' vaccine acceptance decreased from 71.70 to 70.70%, while American respondents' vaccine acceptance increased from 74.69 to 75.81%. The discrete choice experiment showed that American respondents regarded the efficacy of COVID-19 vaccine as the most important attribute, whereas Chinese respondents attached the highest importance to the cost of vaccination. But overall, the COVID-19 vaccine with the higher efficacy, the milder adverse effect, the lower cost, and the longer duration will promote the preference of the public in both countries. Additionally, the public were willing to spend the most money for a reduction in COVID-19 vaccine adverse effect from moderate to very mild (37.476USD for the United States, 140.503USD for China), followed by paying for the 1% improvement in its efficacy and paying for the one-month extension of its duration. Conclusion: Given the impact of social cues on vaccine acceptance, Chinese government should promote reasonable vaccine-related information to improve national vaccination acceptance. Meanwhile, considering the influence of COVID-19 attributes on public preference and willingness to pay, regulating the vaccine pricing, improving the efficacy of the vaccine, reducing its adverse effect, and prolonging the duration of the vaccine works will contribute to vaccine uptake.

Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis.

Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemia‒reperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.

LiNO3-Assisted Succinonitrile-Based Solid-State Electrolyte for Long Cycle Life toward a Li-Metal Anode via an In Situ Thermal Polymerization Method.

Succinonitrile (SN)-based electrolytes have a great potential for the practical application of all-solid-state lithium-metal batteries (ASSLMBs) due to their high room-temperature ionic conductivity, broad electrochemical window, and favorable thermal stability. Nevertheless, the poor mechanical strength and low stability toward Li metal hinder the further application of SN-based electrolytes to ASSLMBs. In this work, the LiNO3-assisted SN-based electrolytes are synthesized via an in situ thermal polymerization method. With this method, the mechanical problem is negligible, and the stability of the electrolyte enhances tremendously toward Li metal due to the addition of LiNO3. The LiNO3-assisted electrolytes exhibit a high ionic conductivity of 1.4 mS cm-1 at 25 °C, a wide electrochemical window (0-4.5 V vs Li+/Li), and excellent interfacial compatibility with Li (stable for over 2000 h at a current density of 0.1 mA cm-1). The LiFePO4/Li cells with the LiNO3-assisted electrolytes present significantly enhanced rate capability and cycling performance compared to the control group. NCM622/Li batteries also exhibit good cycling and rate performances with a voltage range of 3.0 to 4.4 V. Furthermore, ex situ SEM and XPS are employed. A compact interface is observed on Li anode after cycling, and the polymerization of SN is found to be suppressed. This paper will promote the development of practical application of SN-based ASSLMBs.