Joint micrograph denoising and protein localization in cryo-electron microscopy.

Cryo-electron microscopy (cryo-EM) is an imaging technique that allows the visualization of proteins and macromolecular complexes at near-atomic resolution. The low electron doses used to prevent radiation damage to the biological samples result in images where the power of noise is 100 times stronger than that of the signal. Accurate identification of proteins from these low signal-to-noise ratio (SNR) images is a critical task, as the detected positions serve as inputs for the downstream 3D structure determination process. Current methods either fail to identify all true positives or result in many false positives, especially when analyzing images from smaller-sized proteins that exhibit extremely low contrast, or require manual labeling that can take days to complete. Acknowledging the fact that accurate protein identification is dependent upon the visual interpretability of micrographs, we propose a framework that can perform denoising and detection in a joint manner and enable particle localization under extremely low SNR conditions using self-supervised denoising and particle identification from sparsely annotated data. We validate our approach on three challenging single-particle cryo-EM datasets and projection images from one cryo-electron tomography dataset with extremely low SNR, showing that it outperforms existing state-of-the-art methods used for cryo-EM image analysis by a significant margin. We also evaluate the performance of our algorithm under decreasing SNR conditions and show that our method is more robust to noise than competing methods.

Recent trends in extraction, purification, structural characterization, and biological activities evaluation of Perilla frutescens (L.) Britton polysaccharide.

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO­1 pathway activity: Integrating animal experiments and network pharmacology.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti­inflammatory and antioxidant properties. Nuclear factor erythroid­2­related factor 2/heme oxygenase 1 (Nrf2/HO­1) pathway regulates occurrence and development of numerous types of diseases through anti­inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO­1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO­1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL­6, IL­1ß, TNF­α and IL­10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)­1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro­inflammatory cytokines IL­6, IL­1ß and TNF­α and increased anti­inflammatory factor IL­10 expression. Res also restored the decreased protein expression of ZO­1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti­inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO­1. In conclusion, Res treatment activated the Nrf2/HO­1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.

Perturbed liver gene zonation in a mouse model of non-alcoholic steatohepatitis.

Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal hepatic function. Wnt signaling is a master regulator of spatial liver zonation. A perivenous-periportal Wnt activity gradient orchestrates metabolic zonation by activating gene expression in perivenous hepatocytes, while suppressing gene expression in their periportal counterparts. However, the understanding as to the liver gene zonation and zonation regulators in diseases is limited. Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fat accumulation, inflammation, and fibrosis. Here, we investigated the perturbation of liver gene zonation in a mouse NASH model by combining spatial transcriptomics, bulk RNAseq and in situ hybridization. Wnt-target genes represented a major subset of genes showing altered spatial expression in the NASH liver. The altered Wnt-target gene expression levels and zonation spatial patterns were in line with the up regulation of Wnt regulators and the augmentation of Wnt signaling. Particularly, we found that the Wnt activator Rspo3 expression was restricted to the perivenous zone in control liver but expanded to the periportal zone in NASH liver. AAV8-mediated RSPO3 overexpression in controls resulted in zonation changes, and further amplified the disturbed zonation of Wnt-target genes in NASH, similarly Rspo3 knockdown in Rspo3+/- mice resulted in zonation changes of Wnt-target genes in both chow and HFD mouse. Interestingly, there were no impacts on steatosis, inflammation, or fibrosis NASH pathology from RSPO3 overexpression nor Rspo3 knockdown. In summary, our study demonstrated the alteration of Wnt signaling in a mouse NASH model, leading to perturbed liver zonation.

Biochemical characterization, structure-guided mutagenesis, and application of a recombinant D-allulose 3-epimerase from Christensenellaceae bacterium for the biocatalytic production of D-allulose.

D-Allulose has become a promising alternative sweetener due to its unique properties of low caloric content, moderate sweetness, and physiological effects. D-Allulose 3-epimerase (DAEase) is a promising enzyme for D-Allulose production. However, the low catalytic efficiency limited its large-scale industrial applications. To obtain a more effective biocatalyst, a putative DAEase from Christensenellaceae bacterium (CbDAE) was identified and characterized. The recombinant CbDAE exhibited optimum activity at pH 7.5°C and 55°C, retaining more than 60% relative activity from 40°C to 70°C, and the catalytic activity could be significantly increased by Co2+ supplementation. These enzymatic properties of purified CbDAE were compared with other DAEases. CbDAE was also found to possess desirable thermal stability at 55°C with a half-life of 12.4 h. CbDAE performed the highest relative activity towards D-allulose and strong affinity for D-fructose but relatively low catalytic efficiency towards D-fructose. Based on the structure-guided design, the best double-mutation variant G36N/W112E was obtained which reached up to 4.21-fold enhancement of catalytic activity compared with wild-type (WT) CbDAE. The catalytic production of G36N/W112E with 500 g/L D-fructose was at a medium to a higher level among the DAEases in 3.5 h, reducing 40% catalytic reaction time compared to the WT CbDAE. In addition, the G36N/W112E variant was also applied in honey and apple juice for D-allulose conversion. Our research offers an extra biocatalyst for D-allulose production, and the comprehensive report of this enzyme makes it potentially interesting for industrial applications and will aid the development of industrial biocatalysts for D-allulose.

A DNA-based and bifunctional nanomedicine for alleviating multi-organ injury in sepsis under diabetic conditions.

Sepsis, defined as a life-threatening organ dysfunction, is associated with increased mortality in individuals with diabetes mellitus. In sepsis under diabetic conditions (SUDC), the superimposed inflammatory response and excessive production of reactive oxygen species (ROS) can cause severe damage to the kidney and liver, making it challenging to effectively repair multi-organ injury. In this study, we report the development of a DNA-based bifunctional nanomedicine, termed IL10-rDON, generated by assembling interleukin 10 (IL10) with rectangular DNA origami nanostructures (rDON) to address multi-organ dysfunction in SUDC. IL10-rDON was shown to predominantly accumulate in the kidney and liver of diabetic mice in vivo and effectively alleviate inflammatory responses through its anti-inflammatory IL10 component. In addition, the consumption of rDON itself significantly reduced excessive ROS in the liver and kidney. Serum and histological examinations further confirmed that IL10-rDON treatment could effectively improve liver and kidney function, as well as the survival of mice with SUDC. This study demonstrates an attractive antioxidant and anti-inflammatory nanomedicine for addressing acute liver and renal failure. The integration of rDON with therapeutic agents using DNA nanotechnology is a promising strategy for generating multifunctional nanomedicine to treat multi-organ dysfunction and other complicated diseases. STATEMENT OF SIGNIFICANCE: Sepsis under diabetic conditions (SUDC) leads to high mortality due to multiple organ failure such as acute liver and kidney injury. The anti-inflammatory cytokine interleukin 10 (IL10) holds great potential to treat SUDC, while disadvantages of IL-10 such as short half-life, non-specific distribution and lack of antioxidant activities limit its wide clinical applications. In this study, we developed a DNA-based, bifunctional nanomedicine (IL10-rDON) by assembling IL10 with rectangular DNA origami nanostructures (rDON). We found that IL10-rDON preferentially accumulated and sufficiently attenuated the increased levels of ROS and inflammation in the kidney and liver injury sites, and eventually improved the survival rate of mice with SUDC. Our finding provides new insights into the application of DNA-based nanomedicine in treating multi-organ failure.

CD137 Signaling Mediates Pulmonary Artery Endothelial Cell Proliferation Under Hypoxia By Regulating Mitochondrial Dynamics.

Altered mitochondrial dynamics affect pulmonary artery endothelial cells (PAECs) proliferation, contributing to the development of pulmonary hypertension. CD137 signaling promotes mitochondrial fission. We hypothesize CD137 signaling is involved in the excessive proliferation of PAECs. The levels of CD137 protein were increased in the lung tissue of hypoxic mice and hypoxic-stimulated PAECs. Activation of CD137 signal in hypoxic-PAECs upregulated the levels of hypoxia-inducible factor-2α (HIF-2α), glucose transporters type 4, the lactate transporter monocarboxylate transporter 4, key glycolysis rate-limiting enzymes and promoted mitochondrial division; moreover, increased glucose uptake, lactic acid and ATP production and proliferative cells were observed in these PAECs. Whereas, knockdown HIF-2α reversed CD137 signal-mediated effects in PAECs mentioned above. Compared with wild-type mice, the proliferation of PAECs and the percentage of vascular lateral wall thickness decreased in CD137 knockout mice. Together, CD137 signal participated in pulmonary vascular remodeling through the regulation of mitochondrial dynamics dependent on HIF-2α in PAECs.

Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

The effect of music on pain management in preterm infants during daily painful procedures: a systematic review and meta-analysis.

Background: The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of music on pain management in preterm neonates during painful procedures. Methods: The PubMed, Embase, Web of Science, EBSCO and Cochrane Library databases were searched to identify relevant articles published from their inception to September 2023. The study search strategy and all other processes were implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Four RCTs that satisfied the inclusion criteria were included in this meta-analysis. The music group had significantly lower Premature Infant Pain Profile (PIPP) scores during (RR = -1.21; 95% CI = -2.02--0.40, p = 0.0032) and after painful procedures (RR = -0.65; 95% CI = -1.06--0.23, p = 0.002). The music group showed fewer changes in PIPP scores after invasive operations than did the control group (RR = -2.06; 95% CI -3.16--0.96; p = 0.0002). Moreover, our results showed that music improved oxygen saturation during (RR = 3.04, 95% CI = 1.64-4.44, p < 0.0001) and after painful procedures (RR = 3.50, 95% CI = 2.11-4.90, p < 0.00001). However, the change in peak heart rate during and after painful procedures was not statistically significant (RR = -12.14; 95% CI = -29.70-5.41 p = 0.18; RR = -10.41; 95% CI = -22.72-1.90 p = 0.10). Conclusion: In conclusion, this systematic review demonstrated that music interventions are effective for relieving procedural pain in preterm infants. Our results indicate that music can reduce stress levels and improve blood oxygen saturation. Due to the current limitations, large-scale, prospective RCTs should be performed to validate the present results.

Effects of gait adaptation training on augmented reality treadmill for patients with stroke in community ambulation.

Gait adaptability is essential for stroke survivors to achieve efficient and safe community ambulation. However, conventional treadmill rehabilitation is only a repetitive practice of leg movement. This study compared the effects of augmented reality treadmill-based gait adaptation training with regular treadmill programs for patients with stroke. Forty patients with stroke (n = 40) were randomly assigned to the gait adaptation training {n = 20, age: 49.85 [standard deviation (SD) 8.44] years; onset of stroke: 107.80 (SD 48.31) days} and regular training [n = 20, age: 50.75 (SD 8.05) years, onset of stroke: 111.60 (SD 49.62) days] groups. Both groups completed three sessions of training per week for 5 weeks (15 sessions). The primary outcomes were the 10-m walk test and success rate of obstacle avoidance, while secondary outcomes included the Berg balance scale, component timed-up-and-go, and fall rate in a 6-month follow-up period. Assessments were performed before and after the intervention. The paired t-test was applied to compare the differences within groups and independent sample t-test was performed to compare the differences between groups. The 10-m walk test, success rate of obstacle avoidance, Berg balance scale, and component timed-up-and-go all significantly improved in the both groups (P < .001). The success rate of obstacle avoidance [P = .02, 95% confidence interval (CI): -21.07, -1.64], Berg Balance Scale (P = .02, 95% CI: -8.03, -0.67), 'turning around time' (P = .04, 95% CI: 0.08, 2.81), 'stand-to-sit' (P = .03, 95% CI: 0.16, 2.41) and 'total time' (P = .048, 95% CI: 0.04, 10.32) improved significantly in gait adaptation training group after intervention, while the 10-m walk test (P = .09, 95% CI: -0.17, 0.01), timed 'sit-to-stand' (P = .09, 95% CI: -0.14, 2.04), and 'linear walking' (P = .09, 95% CI: -0.27, 3.25) in gait adaptation training group did not show statistical difference compared to the regular training group. Total fall rate during the follow-up period was statistically decreased in the gait adaptation training group (P = .045). Both interventions improved mobility outcomes, with augmented reality treadmill-based gait adaptation indicating greater improvement in obstacle avoidance, balance, turning, and stand-to-sit. Augmented reality treadmill-based gait adaptation training emerges as an effective and promising intervention for patients with stroke in early rehabilitation.

Pachymaran Alleviates Acute Gouty Arthritis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis.

Objective: Acute gouty arthritis is the most common rheumatic diseases, and leads to a heavy clinical burden, thereby to explore the treatment effects of pachymaran on acute gouty arthritis and elucidate its mechanism are meaningful. Methods: Eighteen SPF C57BL/6 mice were randomly divided into three groups: the sham group, model group, and pachymaran group (200mg/kg), with 6 mice in each group. The acute gouty arthritis model of mice was established by injecting 0.025 mL sodium urate solution into the right ankle cavity of the mice. The pachymaran group was given 200mg/kg of pachymaran intragastrically, in the sham group and model group were given the same volume of normal saline, respectively, for 7 consecutive days. Blood samples were collected from the orbital venous plexus 1 h after the last administration, all mice were killed, and ankle tissue samples were collected. The pathological changes of mouse ankle synovial tissue were observed by HE staining. The expression levels of IL-1ß and IL-18 inflammatory factors in the serum of mice were determined by ELISA. The ultrastructure of the synovial tissue of the mouse ankle joint was observed by transmission electron microscope. The protein expression levels of NLRP3, ASC, IL-1ß, IL-18, GSDMD, and Caspase-1 in synovial tissue of mouse ankle were detected by Western blot assay. Mouse chondrocytes were cultured and divided into groups I, II, III, and IV. Group I was the control group without any drug intervention. The cells in groups II, III, and IV were stimulated with sodium urate solution (100µg/mL), and groups III and IV were intervened by pachymaran (200µg/mL), among which the NLRP3 agonist Nigericin sodium salt intervened group IV. The expression levels of NLRP3, IL-1ß, GSDMD, and Caspase-1 proteins were detected by Western blot assay, and the apoptosis rate was detected by flow cytometry. Results: Compared with the sham group, the pathological injury of mice ankle synovial tissue in the model group was significantly aggravated, as the membrane was incomplete, mitochondria were swollen, the ridge was unclear or even disappeared, and the pathological injury of mice ankle synovial tissue in the pachymaran group was significantly improved vs model group; the serum levels of IL-1ß and IL-18 were increased in model group vs sham group, and pachymaran decreased these index vs model group; Compared with the sham group, protein expression levels of NLRP3, ASC, IL-1ß, IL-18, GSDMD, and Caspase-1 were significant increased in model group, and pachymaran suppressed these proteins vs model group. The TEM results showed that in model group the wide swelling of mitochondria accompanied by disappearance of mitochondrial cristae vs sham group, and the mitochondrial ridge was slightly damaged, or the mitochondria were only swollen, and the ridge was still clearly visible in pachymaran group. In vitro experiments, Compared with group I, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group II were significantly increased. Compared with group II, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group III were significantly decreased. Compared with group III, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group IV were significantly increased. Conclusion: Pachymaran maintain the structural integrity of joints and alleviate the progression of acute gouty arthritis by inhibiting NLRP3 inflammasome activation and pyroptosis, pachymaran may be used and applied to clinical treatment.

Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

Recent progress in self-healable energy harvesting and storage devices - a future direction for reliable and safe electronics.

Electronic devices with multiple features bring in comfort to the way we live. However, repeated use causes physical as well as chemical degradation reducing their lifetime. The self-healing ability is the most crucial property of natural systems for survival in unexpected situations and variable environments. However, this self-repair property is not possessed by the conventional electronic devices designed today. To expand their lifetime and make them reliable by restoring their mechanical, functional, and electrical properties, self-healing materials are a great go-to option to create robust devices. In this review the intriguing self-healing polymers and fascinating mechanism of self-healable energy harvesting devices such as triboelectric nanogenerators (TENG) and storage devices like supercapacitors and batteries from the aspect of electrodes and electrolytes in the past five years are reviewed. The current challenges, strategies, and perspectives for a smart and sustainable future are also discussed.

Development, Reliability and Validity of the Medication Literacy Scale for Parents of Children with Epilepsy.

Purpose: This study aimed to develop a medication literacy scale for parents of children with epilepsy (MLSPCE) and to test the reliability and validity of the scale. Patients and Methods: The pilot scale was formulated based on the concept of medication literacy, the knowledge-attitude-practice model, and relevant literature reviews. It was formed through two rounds of expert consultations using the Delphi method. A survey of 657 parents of children with epilepsy, who were admitted to the neurology department or examined in the neuro-electrophysiological outpatient department of Guangzhou Women and Children Medical Center, using the pilot scale was conducted from October 2021 to January 2022 to test the reliability and validity of the scale questionnaire. The content validity of the scale questionnaire was assessed by consulting 20 neurology nursing, neurology clinician, and nursing education experts. Numbers, percentages, t-test, correlation analysis, Cronbach's alpha reliability coefficient and factor analysis were used for data analysis. Results: The MLSPCE included 34 items in four dimensions. Ten factors were drawn from the explorative factor analysis, with a cumulative variance contribution rate of 62.32%. The content validity index of each item on the 34-item scale was between 0.81 and 1.0, and the scale-content validity index/ average was 0.97. The correlation coefficient between each item and its dimension was between 0.399 and 0.760, the correlation coefficients between dimensions were between 0.150 and 0.382, and the correlation coefficients between each dimension and the total scale were between 0.390 and 0.845. Differences for all comparisons were statistically significant (P < 0.05). Cronbach's alpha coefficient for the total scale was 0.864, and the split-half reliability of the total scale was 0.923. Conclusion: All the statistical procedures performed in the validity and reliability stages of the study showed that MLSPCE is a valid and reliable tool for measuring medication literacy among Chinese parents of children with epilepsy.

Weakened black carbon trans-boundary transport to the Tibetan Plateau during the COVID-19 pandemic.

The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

Effects of triglyceride glucose (TyG) and TyG-body mass index on sex-based differences in the early-onset heart failure of ST-elevation myocardial infarction.

BACKGROUND AND AIM: Heart failure (HF) is an important complication of ST-elevation myocardial infarction (STEMI), including early- and late-onset HF. This study aimed to investigate the association between insulin resistance (IR)-related parameters triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) index and early-onset HF in STEMI between sexes. METHODS AND RESULTS: This cross-sectional study included patients with STEMI who underwent primary percutaneous coronary intervention (PCI) between January 2016 and September 2022. Patients were divided into tertiles according to TyG/TyG-BMI index levels in males and females. The presence of early-onset HF was compared between tertiles in both sexes. Moreover, patients were stratified according to the tertiles of TyG/Tyg-BMI index. Differences in early-onset HF of STEMI were compared between males and females in each tertile group. 1118 patients were included in this study, 20.3% of whom were females. The incidence rate of early-onset HF was significantly higher in females than in males (29% vs. 14.8%). TyG-BMI index was negatively correlated with early-onset HF. In both females and males, there was no difference in the occurrence of early-onset HF between the highest and lowest TyG/TyG-BMI index groups. Sex disparity was observed in females who had a significantly higher prevalence of early-onset HF than males in each TyG/TyG-BMI index tertile group; however, after adjustment, the differences disappeared. CONCLUSIONS: For patients with STEMI who undergo primary PCI, the incidence of early-onset HF is higher in females than in males. The TyG/TyG-BMI index do not contribute to the difference in early-onset HF between sexes.

Ni Single-Atoms Based Memristors with Ultrafast Speed and Ultralong Data Retention.

Memristor with low-power, high density, and scalability fulfills the requirements of the applications of the new computing system beyond Moore's law. However, there are still nonideal device characteristics observed in the memristor to be solved. The important observation is that retention and speed are correlated parameters of memristor with trade off against each other. The delicately modulating distribution and trapping level of defects in electron migration-based memristor is expected to provide a compromise method to address the contradictory issue of improving both switching speed and retention capability. Here, high-performance memristor based on the structure of ITO/Ni single-atoms (NiSAs/N-C)/Polyvinyl pyrrolidone (PVP)/Au is reported. By utilizing well-distributed trapping sites , small tunneling barriers/distance and high charging energy, the memristor with an ultrafast switching speed of 100 ns, ultralong retention capability of 106  s, a low set voltage (Vset ) of ≈0.7 V, a substantial ON/OFF ration of 103 , and low spatial variation in cycle-to-cycle (500 cycles) and device-to-device characteristics (128 devices) is demonstrated. On the premise of preserving the strengths of a fast switching speed, this memristor exhibits ultralong retention capability comparable to the commercialized flash memory. Finally, a memristor ratioed logic-based combinational memristor array to realize the one-bit full adder is further implemented.