Impact of transformational leadership on the person-organization fit of Chinese nurses: The moderating effect of emotional intelligence.

AIMS: To explore the relationships between transformational leadership and person-organization fit, as well as to test the moderating effects of emotional intelligence. DESIGN: A descriptive cross-sectional study design was used to conduct an online questionnaire survey among 326 nurses in Chinese hospitals between March and June 2022. METHODS: Transformational leadership, person-organization fit and emotional intelligence were measured using the Person-Organization Fit Scale, Transformational Leadership Questionnaire and Emotional Intelligence Scale. Hierarchical multiple linear regression models and simple slope analyses were used. RESULTS: Transformational leadership had a significant positive impact on person-organization fit. Furthermore, emotional intelligence had a conditional moderating effect on the relationship between transformational leadership and nurses' person-organization fit. Under a high level of emotional intelligence, transformational leadership had a stronger positive effect on person-organization fit, while under a low level of emotional intelligence, the relationship between the two was not significant. CONCLUSION: Transformational leadership has a positive predictive effect on person-organization fit, but this positive predictive effect is driven by conditional effect. The emotional intelligence of nurses plays a moderating role between them.

Prediction of Male Coronary Artery Bypass Grafting Outcomes Using Body Surface Area Weighted Left Ventricular End-diastolic Diameter: Multicenter Retrospective Cohort Study.

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

Implementation of Prediction Models in the Emergency Department from an Implementation Science Perspective-Determinants, Outcomes, and Real-World Impact: A Scoping Review.

STUDY OBJECTIVE: Prediction models offer a promising form of clinical decision support in the complex and fast-paced environment of the emergency department (ED). Despite significant advancements in model development and validation, implementation of such models in routine clinical practice remains elusive. This scoping review aims to survey the current state of prediction model implementation in the ED and to provide insights on contributing factors and outcomes from an implementation science perspective. METHODS: We searched 4 databases from their inception to May 20, 2022: MEDLINE (through PubMed), Embase, Scopus, and CINAHL. Articles that reported implementation outcomes and/or contextual determinants under the Reach, Effectiveness, Adoption, Implementation Maintenance (RE-AIM)/Practical, Robust, Implementation, and Sustainability Model (PRISM) framework were included. Characteristics of studies, models, and results of the RE-AIM/PRISM domains were summarized narratively. RESULTS: Thirty-six reports on 31 implementations were included. The most common prediction models implemented were early warning scores. The most common implementation strategies used were training stakeholders, infrastructural changes, and using evaluative or iterative strategies. Only one report examined ED patients' perspectives, whereas the rest were focused on the experience of health care workers or organizational stakeholders. Key determinants of successful implementation include strong stakeholder engagement, codevelopment of workflows and implementation strategies, education, and usability. CONCLUSION: Examining ED prediction models from an implementation science perspective can provide valuable insights and help guide future implementations.

Effects of acceptance and commitment therapy on cognitive function: A systematic review.

Cognitive function is essential for daily activities. Acceptance and commitment therapy (ACT) may improve cognitive function by enhancing psychological flexibility, but the underlying mechanism is unknown. This systematic review evaluated the effectiveness of ACT on cognitive function. Seven research databases (PubMed, ProQuest Dissertations and Theses, Web of Science, EBSCOhost, CNKI, Scopus, Wanfang) were searched to collect articles with trials published in English and Chinese. After applying inclusion and exclusion criteria, we identified 12 studies published between 1994 and 2022 that included a combined total of 904 participants. Among the included studies were within-group (N = 3) and randomized controlled trial (RCT, N = 9) study designs. Outcome measures included cognitive scales and behavioral measurements. Of the 12 articles, 10 studies showed improvements in certain domains of cognitive function due indirectly to ACT intervention. We found that the ability of ACT intervention to promote psychological flexibility is due to its transdiagnostic nature. Also, the effects of the ACT intervention were observed in multiple cognitive domains: attention, subjective cognitive function, executive function, and memory. In conclusion, cognitive trainers could consider practicing ACT as part of their strategy to enhance an individual's psychological flexibility and cognitive function.

Exopolysaccharide-producing bacteria enhanced Pb immobilization and influenced the microbiome composition in rhizosphere soil of pakchoi (Brassica chinensis L.).

Lead (Pb) contamination of planting soils is increasingly serious, leading to harmful effects on soil microflora and food safety. Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms, which are efficient biosorbent materials and has been widely used in wastewater treatment to remove heavy metals. However, the effects and underlying mechanism of EPS-producing marine bacteria on soil metal immobilization, plant growth and health remain unclear. The potential of Pseudoalteromonas agarivorans Hao 2018, a high EPS-producing marine bacterium, to produce EPS in soil filtrate, immobilize Pb, and inhibit its uptake by pakchoi (Brassica chinensis L.) was studied in this work. The effects of strain Hao 2018 on the biomass, quality, and rhizospheric soil bacterial community of pakchoi in Pb-contaminated soil were further investigated. The results showed that Hao 2018 reduced the Pb concentration in soil filtrate (16%-75%), and its EPS production increased in the presence of Pb2+. When compared to the control, Hao 2018 remarkably enhanced pakchoi biomass (10.3%-14.3%), decreased Pb content in edible tissues (14.5%-39.2%) and roots (41.3%-41.9%), and reduced the available Pb content (34.8%-38.1%) in the Pb-contaminated soil. Inoculation with Hao 2018 raised the pH of the soil, the activity of several enzymes (alkaline phosphatase, urease, and dehydrogenase), the nitrogen content (NH4 +-N and NO3 --N), and the pakchoi quality (Vc and soluble protein content), while also raising the relative abundance of bacteria that promote plant growth and immobilize metals, such as Streptomyces and Sphingomonas. In conclusion, Hao 2018 reduced the available Pb in soil and pakchoi Pb absorption by increasing the pH and activity of multiple enzymes and regulating microbiome composition in rhizospheric soil.

The carbon and nitrogen metabolisms of Ardisia quinquegona were altered in different degrees by canopy and understory nitrogen addition in a subtropical forest.

Although effects of atmospheric nitrogen (N) deposition on forest plants have been widely investigated, N interception and absorption effects by forest canopy should not be neglected. Moreover, how N deposition change the molecular biological process of understory dominant plants, which was easily influenced by canopy interception so as to further change physiological performance, remains poorly understood. To assess the effects of N deposition on forest plants, we investigated the effects of understory (UAN) and canopy N addition (CAN) on the transcriptome and physiological properties of Ardisia quinquegona, a dominant subtropical understory plant species in an evergreen broad-leaved forest in China. We identified a total of 7394 differentially expressed genes (DEGs). Three of these genes were found to be co-upregulated in CAN as compared to control (CK) after 3 and 6 h of N addition treatment, while 133 and 3 genes were respectively found to be co-upregulated and co-downregulated in UAN as compared to CK. In addition, highly expressed genes including GP1 (a gene involved in cell wall biosynthesis) and STP9 (sugar transport protein 9) were detected in CAN, which led to elevated photosynthetic capacity and accumulation of protein and amino acid as well as decrease in glucose, sucrose, and starch contents. On the other hand, genes associated with transport, carbon and N metabolism, redox response, protein phosphorylation, cell integrity, and epigenetic regulation mechanism were affected by UAN, resulting in enhanced photosynthetic capacity and carbohydrates and accumulation of protein and amino acid. In conclusion, our results showed that the CAN compared to UAN treatment had less effects on gene regulation and carbon and N metabolism. Canopy interception of N should be considered through CAN treatment to simulate N deposition in nature.

Did lockdown influence bystanders' willingness to perform cardiopulmonary resuscitation? A worldwide registry-based perspective.

AIM: Bystander cardiopulmonary resuscitation (CPR) significantly increases the survival rate after out-of-hospital cardiac arrest. Using population-based registries, we investigated the impact of lockdown due to Covid-19 on the provision of bystander CPR, taking background changes over time into consideration. METHODS: Using a registry network, we invited all registries capable of delivering data from 1. January 2017 to 31. December 2020 to participate in this study. We used negative binominal regression for the analysis of the overall results. We also calculated the rates for bystander CPR. For every participating registry, we analysed the incidence per 100000 inhabitants of bystander CPR and EMS-treated patients using Poisson regression, including time trends. RESULTS: Twenty-six established OHCA registries reported 742 923 cardiac arrest patients over a four-year period covering 1.3 billion person-years. We found large variations in the reported incidence between and within continents. There was an increase in the incidence of bystander CPR of almost 5% per year. The lockdown in March/April 2020 did not impact this trend. The increase in the rate of bystander CPR was also seen when analysing data on a continental level. We found large variations in incidence of bystander CPR before and after lockdown when analysing data on a registry level. CONCLUSION: There was a steady increase in bystander CPR from 2017 to 2020, not associated with an increase in the number of ambulance-treated cardiac arrest patients. We did not find an association between lockdown and bystanders' willingness to start CPR before ambulance arrival, but we found inconsistent patterns of changes between registries.

Predicting the mortality of patients with cardiogenic shock after coronary artery bypass grafting.

INTRODUCTION: Cardiogenic shock (CS) is a critical condition and the leading cause of mortality after coronary artery bypass grafting (CABG). To define the risk factors for CS in patients who undergo CABG and create a risk-predictive model is crucial. METHODS: In this observational study, we retrospectively evaluated consecutive patients who underwent CABG between January 2018 and October 2022 at Beijing Anzhen Hospital. A total of 496 patients were enrolled and categorized into the training (396 cases) and internal test (100 cases) sets. The variables significantly associated with mortality (p < 0.05) were analyzed using logistic regression analyses. RESULTS: The E/A ratio at admission, postoperative brain natriuretic peptide, postoperative arterial lactate, two or more arrhythmias at the same time after CABG, and carotid artery stenosis at admission were identified as independent prognostic factors for in-hospital mortality after multivariate logistic regression analysis. The CS after CABG score (ACCS) was established and three classes of ACCS, named classes I (ACCS, <20), II (ACCS, 20-30), and III (ACCS, >30), made up the risk model. The ACCS showed better discrimination with an AUROC of 0.937 (95% confidence interval, 0.982-0.892) and calibration with the Hosmer-Lemeshow test (X2 = 5.854 with 8 df; p = 0.664). In addition, tenfold cross-validation demonstrated that the mean misdiagnosis rate was 5.56% and the lowest misdiagnosis rate was 6.38%. CONCLUSION: The ACCS score represents a risk-predictive model for in-hospital mortality of patients with CS after CABG in acute care settings. Patients identified as class III may have a worse prognosis.

The efficacy and safety of SARS-CoV-2 vaccines mRNA1273 and BNT162b2 might be complicated by rampant C-to-U RNA editing.

The SARS-CoV-2 RNA vaccines are smartly designed to increase the synonymous codon usage by introducing multiple U-to-C mutations. This design would elevate the translation efficiency of vaccine RNAs. However, we found evidence to reason that the designed cytidines might be converted to uridines again by C-to-U RNA deamination in host cells. This C-to-U mechanism might be a main factor that affects the efficacy and safety of RNA vaccines.

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson disease using machine learning.

BACKGROUND AND PURPOSE: A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson disease (PD) have been investigated separately. However, there is as yet no study including all of them to assess variable importance. Shapley variable importance cloud (ShapleyVIC) can robustly assess variable importance while accounting for correlation between variables. Objectives of this study were (i) to prioritize the important variables associated with PD-MCI and (ii) to explore new blood biomarkers related to PD-MCI. METHODS: ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables associated with PD-MCI. Relative risk was used to quantify the association of final associated variables and PD-MCI in the final multivariable log-binomial regression model. RESULTS: Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and eight variables were subsequently selected in the final model, indicating fewer years of education, shorter history of hypertension, higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor score, higher levels of triglyceride (TG) and apolipoprotein A1 (ApoA1), and SNCA rs6826785 noncarrier status were associated with increased risk of PD-MCI (p < 0.05). CONCLUSIONS: Our study highlighted the strong association between TG, ApoA1, SNCA rs6826785, and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interest.

Adding heart rate n-variability (HRnV) to clinical assessment potentially improves prediction of serious bacterial infections in young febrile infants at the emergency department: a prospective observational study.

Background: We aim to investigate the utility of heart rate variability (HRV) and heart rate n-variability (HRnV) in addition to vital signs and blood biomarkers, among febrile young infants at risk of serious bacterial infections (SBIs). Methods: We performed a prospective observational study between December 2017 and November 2021 in a tertiary paediatric emergency department (ED). We included febrile infants <90 days old with a temperature ≥38 ℃. We obtained HRV and HRnV parameters via a single lead electrocardiogram. HRV measures beat-to-beat (R-R) oscillation and reflects autonomic nervous system (ANS) regulation. HRnV includes overlapping and non-overlapping R-R intervals and provides additional physiological information. We defined SBIs as meningitis, bacteraemia and urinary tract infections (UTIs). We performed area under curve (AUC) analysis to assess predictive performance. Results: We recruited 330 and analysed 312 infants. The median age was 35.5 days (interquartile range 13.0-61.0); 74/312 infants (23.7%) had SBIs with the most common being UTIs (66/72, 91.7%); 2 infants had co-infections. No patients died and 32/312 (10.3%) received fluid resuscitation. Adding HRV and HRnV to demographics and vital signs at ED triage successively improved the AUC from 0.765 [95% confidence interval (CI): 0.705-0.825] to 0.776 (95% CI: 0.718-0.835) and 0.807 (95% CI: 0.752-0.861) respectively. The final model including demographics, vital signs, HRV, HRnV and blood biomarkers had an AUC of 0.874 (95% CI: 0.828-0.921). Conclusions: Addition of HRV and HRnV to current assessment tools improved the prediction of SBIs among febrile infants at ED triage. We intend to validate our findings and translate them into tools for clinical care in the ED.

Pathoclinical associations between panic disorders and the brain-derived neurotrophic factor Val66Met polymorphism: an updated meta-analysis.

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant's association with PD irrespective of the subject's ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.

Effect of drying processes on the occurrence of lipid oxidation-derived 4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal in Spanish mackerel (Scomberomorus niphonius).

In this study, dry-cured Spanish mackerel (Scomberomorus niphonius, DCSM) was prepared via three different methods (hot-air drying, cold-air drying, and sun drying). The content of 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) derived from lipid oxidation in whole processes was investigated by HPLC-MS/MS. The changes in fatty acid composition were detected by GC-MS, and the degree of lipid oxidation was evaluated by the levels of acid values (AV), peroxide values (POV), and thiobarbituric acid-reactive substances (TBARS). The results showed that the drying process significantly accelerated lipid oxidation in DCSM. The contents of HHE and HNE were significantly increased after processing. The content of HHE was higher by 18.44-, 13.45-, and 16.32-folds compared with that of HNE after three different processes, respectively. The HHE and HNE contents fluctuated upward during the hot-air and cold-air drying process. However, the contents of HHE and HNE increased time-dependent during the sun drying process, with the highest values of 86.33 ± 10.54 and 5.29 ± 0.54 mg/kg fish among the three different processes. Besides, there was a significant positive correlation between HHE contents and n-3 fatty acids content in hot-air drying and sun drying processes (Pearson's r = .991/.996), and HNE occurrence was closely related to n-6 fatty acid content in sun drying process (Pearson's r = .989). Regression analysis indicated that the content of HHE and TOTOXTBA values in DCSM showed good linear relationships (R 2 value = .907), which suggested that the content of HHE could be used to estimate the oxidative deterioration of dry-cured fish products.

Acute diffuse peritonitis secondary to a seminal vesicle abscess: A case report.

BACKGROUND: Seminal vesicle abscess (SVA) is the manifestation of a relatively rare urinary system infection. In response to urinary system inflammation, an abscess forms in special locations. However, acute diffuse peritonitis (ADP) induced by SVA is unusual. CASE SUMMARY: We report a case of a left SVA in a male patient complicated with pelvic abscess, ADP, multiple organ dysfunction syndrome, infectious shock, bacteremia, and acute appendiceal extraserous suppurative inflammation as a result of a long-term indwelling urinary catheter. The patient received a course of morinidazole + cefminol antibiotics but showed no obvious relief, so the perineal SVA underwent puncture drainage and abdominal abscess drainage + appendectomy was performed. The operations were successful. After the operation, anti-infection, anti-shock, and nutritional support treatments were continued and various laboratory indicators were regularly reviewed. The patient was discharged from the hospital after recovery. This disease is a challenge for the clinician because of the unusual spreading path of the abscess. Moreover, appropriate intervention and adequate drainage of abdominal and pelvic lesions are necessary, especially when the primary focus cannot be determined. CONCLUSION: The etiology of ADP varies, but acute peritonitis secondary to SVA is very rare. In this patient, the left SVA not only affected the adjacent prostate and bladder but also spread retrogradely through the vas deferens, forming a pelvic abscess in the loose tissues of the extraperitoneal fascia layer. Inflammation involving the peritoneal layer led to ascites and pus accumulation in the abdominal cavity, and appendix involvement led to extraserous suppurative inflammation. In clinical practice, surgeons need to consider the results of various laboratory tests and imaging examinations to make comprehensive judgments involving the diagnosis and treatment plan.

Biodegradable photothermal thermosensitive hydrogels treat osteosarcoma by reprogramming macrophages.

Osteosarcoma is one of the most common malignant tumors in children and tends to occur around the knee. Problems such as recurrence and metastasis are the outcomes of traditional treatment methods. One of the reasons for these issues is the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment. In this study, we designed a biodegradable, injectable, and photothermal hydrogel that functions to reprogram TAMs into classically activated macrophages (M1) based on hydroxypropyl chitin (HPCH), tannic acid and ferric ions (HTA). We found that HTA had better photothermal efficiency than a pure hydrogel; its photothermal repeatability is good and it can be NIR (808 nm) irradiated as needed. In addition, the precooled hydrogel solution can be injected into the tumor and it can rapidly gel in situ. In vitro, HTA with NIR irradiation (HTA + NIR) induced the apoptosis of K7M2 cancer cells. In vivo, the local administration of HTA + NIR exerted photothermal killing of primary tumors and reprogramming of TAMs into M1-type macrophages in the TME. Therefore, the injectable photothermally active antitumor hydrogel has great potential for modulating the TME to treat bone tumors.

FESNet: Frequency-Enhanced Saliency Detection Network for Grain Pest Segmentation.

As insect infestation is the leading factor accounting for nutritive and economic losses in stored grains, it is important to detect the presence and number of insects for the sake of taking proper control measures. Inspired by the human visual attention mechanism, we propose a U-net-like frequency-enhanced saliency (FESNet) detection model, resulting in the pixelwise segmentation of grain pests. The frequency clues, as well as the spatial information, are leveraged to enhance the detection performance of small insects from the cluttered grain background. Firstly, we collect a dedicated dataset, GrainPest, with pixel-level annotation after analyzing the image attributes of the existing salient object detection datasets. Secondly, we design a FESNet with the discrete wavelet transformation (DWT) and the discrete cosine transformation (DCT), both involved in the traditional convolution layers. As current salient object detection models will reduce the spatial information with pooling operations in the sequence of encoding stages, a special branch of the discrete wavelet transformation (DWT) is connected to the higher stages to capture accurate spatial information for saliency detection. Then, we introduce the discrete cosine transform (DCT) into the backbone bottlenecks to enhance the channel attention with low-frequency information. Moreover, we also propose a new receptive field block (NRFB) to enlarge the receptive fields by aggregating three atrous convolution features. Finally, in the phase of decoding, we use the high-frequency information and aggregated features together to restore the saliency map. Extensive experiments and ablation studies on our dataset, GrainPest, and open dataset, Salient Objects in Clutter (SOC), demonstrate that the proposed model performs favorably against the state-of-the-art model.

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans.

Naringin (Nar) is a dihydroflavonoid compound, widely found in citrus fruit and used in Chinese herbal medicine. As a phytochemical, it acts as a dietary supplement that can delay aging and prevent aging-related disease, such as obesity and diabetes. However, its exact mechanism remains unclear. In this study, the high-glucose-induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. The mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11%, respectively, by Nar treatment. Oil red O staining revealed a significant reduction in fat accumulation and dFP::LGG-labeled worms showed the promotion of autophagy. Additionally, whole transcriptome sequencing and gene set variation analysis suggested that Nar upregulated the lipid biosynthesis and metabolism pathways, as well as the TGF-ß, Wnt and longevity signaling pathways. Protein-protein interaction (PPI) network analysis identified hub genes in these pathways for further analysis. Mutant worms and RNA interference were used to study mechanisms; the suppression of hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 disabled the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Collectively, our findings indicate that Nar plays an important role in alleviating HGI-aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.

A comparison of low- versus standard-dose bridging alteplase in acute ischemic stroke mechanical thrombectomy using indirect methods.

Background: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. Aims: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. Methods: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT. Primary efficacy outcomes were functional independence and excellent recovery defined as a dichotomized modified Rankin Scale (mRS) 0-2 and 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). Results: We included six RCTs of 2334 AIS patients in this analysis, including one trial using low-dose bridging alteplase (n = 103) and five trials using standard-dose bridging alteplase (n = 1067) against a common comparator (dMT). Indirect comparisons of low- to standard-dose bridging alteplase yielded an odds ratio (OR) of 0.84 (95% CI 0.47-1.50) for 90-day mRS 0-2, 1.18 (95% CI 0.65-2.12) for 90-day mRS 0-1, 1.21 (95% CI 0.44-3.36) for mortality, and 1.11 (95% CI 0.39-3.14) for successful recanalization. There were no significant differences in the odds for sICH (OR 1.05, 95% CI 0.32-3.41) or any ICH (OR 1.71, 95% CI 0.94-3.10) between low- and standard-dose bridging alteplase. Conclusion: Indirect evidence shows that the effects of low- and standard-dose bridging alteplase are similar for key efficacy and safety outcomes. Due to the wide confidence intervals, larger randomized trials comparing low- and standard-dose alteplase bridging therapy are required.

Herpud1 deficiency alleviates homocysteine-induced aortic valve calcification.

OBJECTIVES: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). BACKGROUND: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. METHODS: In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression. RESULTS: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. CONCLUSIONS: These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.