Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

Characteristics associated with effectiveness in postoperative delirium research: a systematic review of randomised controlled trials with meta-regression and meta-analysis.

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

The exploration of perioperative hypotension subtypes: a prospective, single cohort, observational pilot study.

Background: Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension. Methods: This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored. Results: Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1-23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury. Conclusion: Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.

Land use and river-lake connectivity: Biodiversity determinants of lake ecosystems.

Lake ecosystems confront escalating challenges to their stability and resilience, most intuitively leading to biodiversity loss, necessitating effective preservation strategies to safeguard aquatic environments. However, the complexity of ecological processes governing lake biodiversity under multi-stressor interactions remains an ongoing concern, primarily due to insufficient long-term bioindicator data, particularly concerning macroinvertebrate biodiversity. Here we utilize a unique, continuous, and in situ biomonitoring dataset spanning from 2011 to 2019 to investigate the spatio-temporal variation of macroinvertebrate communities. We assess the impact of four crucial environmental parameters on Lake Dongting and Lake Taihu, i.e., water quality, hydrology, climate change, and land use. These two systems are representative of lakes with Yangtze-connected and disconnected subtropical floodplains in China. We find an alarming trend of declining taxonomic and functional diversities among macroinvertebrate communities despite improvements in water quality. Primary contributing factors to this decline include persistent anthropogenic pressures, particularly alterations in human land use around the lakes, including intensified nutrient loads and reduced habitat heterogeneity. Notably, river-lake connectivity is pivotal in shaping differential responses to multiple stressors. Our results highlight a strong correlation between biodiversity alterations and land use within a 2-5 km radius and 0.05-2.5 km from the shorelines of Lakes Dongting and Taihu, respectively. These findings highlight the importance of implementing land buffer zones with specific spatial scales to enhance taxonomic and functional diversity, securing essential ecosystem services and enhancing the resilience of crucial lake ecosystems.

Event-Triggered Adaptive Finite-Time Control Using a Fuzzy State Observer for Nonlinear Cyber-Physical Systems Under Deception Attacks.

This article presents a new event-triggered adaptive finite-time control strategy using a fuzzy state observer for a class of nonlinear cyber-physical systems (CPSs) under malicious deception attacks with a more general form. Compared with the traditional assumptions on the deception attacks in the existing results, a more general assumption on deception attacks is given in this article. During the design process, real system states are initially estimated by developing an improved state observer, which effectively addresses the problem of state unavailability. Then, a coordinate transformation technology, in which the estimated states of observer are considered, is presented to stabilize the studied system. By constructing the singularity-free finite time virtual controls, the singularity problem in the traditional finite time design algorithms is cleverly avoided. Furthermore, to minimize communication overhead, a final finite-time controller is established by using a relative threshold event-triggered scheme. The developed event-triggered adaptive finite-time control strategy guarantees that all signals in the closed-loop system are semi-globally bounded in finite time without Zeno behavior. Finally, the correctness of the proposed control strategy is validated through two simulation results.

[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer.

Background: Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear. Methods: Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on. Results: We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo. Conclusion: Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.

Assembly-Dissociation-Reconstruction Synthesis of Covalent Organic Framework Membranes with High Continuity for Efficient CO2 Separation.

Covalent organic frameworks (COFs), at the forefront of porous materials, hold tremendous potential in membrane separation; however, achieving high continuity in COF membranes remains crucial for efficient gas separation. Here, we present a unique approach termed assembly-dissociation-reconstruction for fabricating COF membranes tailored for CO2/N2 separation. A parent COF is designed from two-node aldehyde and three-node amine monomers and dissociated to high-aspect-ratio nanosheets. Subsequently, COF nanosheets are orderly reconstructed into a crack-free membrane by surface reaction under water evaporation. The membrane exhibits high crystallinity, open pores and a strong affinity for CO2 adsorption over N2, resulting in CO2 permeance exceeding 1060 GPU and CO2/N2 selectivity surpassing 30.6. The efficacy of this strategy offers valuable guidance for the precise fabrication of gas-separation membranes.

Comparative simulations of methanol steam reforming on PdZn alloy using kinetic Monte Carlo and mean-field microkinetic model.

Methanol steam reforming (MSR) is an attractive route for producing clean energy hydrogen. PdZn alloys are extensively studied as potential MSR catalysts for their stability and high CO2 selectivity. Here, we investigated the reaction mechanism using density functional calculations, mean-field microkinetic modeling (MF-MKM), and kinetic Monte Carlo (kMC) simulations. To overcome the over-underestimation of CO2 selectivity by log-kMC, an ads-kMC algorithm is proposed in which the adsorption/desorption rate constants were reduced under certain requirements and the diffusion process was treated by redistributing surface species each time an event occured. The simulations show that the dominant pathway to CO2 at low temperatures is CH3OH → CH3O → CH2O → H2COOH → H2COO → HCOO → CO2. The ads-kMC predicted OH coverage is 2-3 times that of MF-MKM, while they produce similar coverage for other species. Analyses indicate that surface OH promotes the dehydrogenation of CH3OH, CH3O, and H2COOH significantly and plays a key role in the MSR process. The dissociation of water/methanol is the most important rate-limiting/rate-inhibiting step. The CO2 selectivity obtained by the two methods is close to each other and consistent with the experimental trend with temperature. Generally, the ads-kMC results agree with the MF-MKM ones, supporting the previous finding that kMC and MF-MKM predict similar results if the diffusion is very fast and adsorbate interactions are neglected. The present study sheds light on the MSR process on PdZn alloys, and the proposed scheme to overcome the stiff problems in kMC simulations is worthy of being extended to other systems.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

A horizontal and perpendicular interlaminar approach for intrathecal nusinersen injection in patients with spinal muscular atrophy and scoliosis: an observational study.

BACKGROUND: Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture. METHODS: Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed. RESULTS: Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture. CONCLUSIONS: The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.

Hederagenol improves multiple sclerosis by modulating Th17 cell differentiation.

Multiple sclerosis (MS) is a common autoimmune illness that is difficult to treat. The upregulation of Th17 cells is critical in the pathological process of MS. Hederagenol (Hed) has been shown to lower IL-17 levels, although its role in MS pathophysiology is uncertain. In this study, we explore whether Hed could ameliorate MS by modulating Th17 cell differentiation, with the goal of identifying new treatment targets for MS. The experimental autoimmune encephalomyelitis (EAE) mouse model was conducted and Hed was intraperitoneally injected into mice. The weight was recorded and the clinical symptom grade was assessed. Hematoxylin-eosin staining was carried out to determine the extent of inflammation in the spinal cord and liver. The luxol Fast Blue staining was performed to detect the pathological changes in the myelin sheath. Nerve damage was detected using NeuN immunofluorescence staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Immunohistology approaches were used to study alterations in immune cells in the spinal cord. The proportions of T cell subsets in the spleens were analyzed by flow cytometry. RORγt levels were measured using quantitative real-time PCR or Western blot. The activity of the RORγt promoter was analyzed by Chromatin immunoprecipitation. Hed administration reduced the clinical symptom grade of EAE mice, as well as the inflammatory infiltration, demyelination, and cell disorder of the spinal cord, while having no discernible effect on the mouse weight. In addition, Hed treatment significantly reduced the number of T cells, particularly Th17 cells in the spinal cord and spleen-isolated CD4+ T cells. Hed lowered the RORγt levels in spleens and CD4+ T cells and overexpression of RORγt reversed the inhibitory effect of Hed on Th17 differentiation. Hed decreased nerve injury by modulating Th17 differentiation through the RORγt promoter. Hed regulates Th17 differentiation by reducing RORγt promoter activity, which reduces nerve injury and alleviates EAE.

Effects of compatibility of Clostridium butyricum and Bacillus subtilis on growth performance, lipid metabolism, antioxidant status and cecal microflora of broilers during the starter phase.

Objective: This study aimed to determine the effects of compatibility of Clostridium butyricum and Bacillus subtilis on growth performance, lipid metabolism, antioxidant status and cecal microflora of broilers during the starter phase. Methods: A total of 600 1-day-old Ross 308 broilers were randomly divided into two groups with six replicates in each group. Chickens in the control group were fed a basal diet, while chickens in the experimental group were fed a diet supplemented with 2 × 108 CFU/kg of C. butyricum and 1 × 109 CFU/kg of B. subtilis. The experimental period was 21 days. Results: Addition of C. butyricum and B. subtilis significantly increased (p<0.05) the body weight and liver NADP-malic enzyme (NADP-ME) activity of broilers, enhanced (p<0.05) the average daily gain and average daily feed intake of broilers. However, the addition of C. butyricum and B. subtilis did not significantly affect the concentrations of triglyceride and total cholesterol in the serum, the activities of fatty acid synthase and acetyl-CoA carboxylase in the liver, the total antioxidant capacity, glutathione peroxidase activity and malondialdehyde content in the serum and liver. Besides, microbial analysis revealed that supplementation of C. butyricum and B. subtilis increased (p<0.05) the abundance of Firmicutes such as CHKCI001 and Faecalibacterium, decreased (p<0.05) the abundance of Bacteroidota such as Bacteroides and Alistipes. Spearman correlation analysis confirmed that the above cecal microbiota were closely related to the growth performance of broilers (p<0.05). In addition, simultaneous supplementation of C. butyricum and B. subtilis significant affected (p<0.05) 33 different functional pathways such as lipid metabolism and carbohydrate metabolism. This explains the phenomenon of increased growth performance and liver NADP-ME activity in the probiotics group. Conclusion: The compatibility of C. butyricum and B. subtilis could improve the growth of broilers during the starter phase by changing the cecal microflora.

Rotation Culture of Macroalgae Based on Photosynthetic Physiological Characteristics of Algae.

Seaweed farming has made outstanding contributions to food supply and the restoration of the ecological environment despite the limitations in production and ecological effects due to the current intensive farming of single algae species. These limitations can be overcome by selecting suitable algal species based on their physiological characteristics and by constructing a large-scale seaweed rotation model. This study carried out a trial culture in aquaculture sea areas, and performed in situ monitoring of the environmental conditions and physiological characteristics of Saccharina japonica, Hizikia fusiformis, and Gracilariopsis lemaneiformis. Additionally, a comparative analysis of the three macroalgae at different times was conducted to determine their response characteristics to environmental factors. The results showed that: (1) The three macroalgae had varying light tolerance. The effective quantum yield of Hizikia fusiformis and Gracilariopsis lemaneiformis remained unchanged during the changes in light environment, while that of Saccharina japonica first decreased and then recovered. (2) The relative electron transport rates of the three macroalgae were significantly different under different temperature conditions. Hizikia fusiformis and Saccharina japonica exhibited the highest relative electron transport rates (70.45 and 106.75, respectively) in May (20.3 °C). Notably, Gracilariopsis lemaneiformis demonstrated good growth and exhibited the highest relative electron transport rate (93.07) in September (27.5 °C). These findings collectively support the feasibility of establishing a macroalgae rotation model. Based on the combined environmental conditions of the seas in Shandong, Zhejiang, and Fujian, a macroalgae rotation model was proposed. The application of this model in the construction of artificial seaweed farms in marine ranches can provide a stable output of large-scale seaweed production and ecological benefits.

Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1ß levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

Predictive Value of Smoking Index Combined with NT-proBNP for Patients with Pulmonary Hypertension Due to Chronic Lung Disease: A Retrospective Study.

Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity. Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve. Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628). Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.

New insights into dairy management and the prevention and treatment of osteoporosis: The shift from single nutrient to dairy matrix effects-A review.

Dairy is recognized as a good source of calcium, which is important for preventing osteoporosis. However, the relationship between milk and bone health is more complex than just calcium supplementation. It is unwise to focus solely on observing the effects of a single nutrient. Lactose, proteins, and vitamins in milk, as well as fatty acids, oligosaccharides, and exosomes, all work together with calcium to enhance its bioavailability and utilization efficiency through various mechanisms. We evaluate the roles of dairy nutrients and active ingredients in maintaining bone homeostasis from the perspective of the dairy matrix effects. Special attention is given to threshold effects, synergistic effects, and associations with the gut-bone axis. We also summarize the associations between probiotic/prebiotic milk, low-fat/high-fat milk, lactose-free milk, and fortified milk with a reduced risk of osteoporosis and discuss the potential benefits and controversies of these dairy products. Moreover, we examine the role of dairy products in increasing peak bone mass during adolescence and reducing bone loss in old age. It provides a theoretical reference for the use of dairy products in the accurate prevention and management of osteoporosis and related chronic diseases and offers personalized dietary recommendations for bone health in different populations.

Evaluation of a 12-hole clock model for improving bronchoscopic skills in simulated normal and difficult airways among anesthesia residents: A randomized controlled study.

BACKGROUND: Simulation-based training is used to improve fiberoptic bronchoscopic skills for novices. We developed a nonanatomical task trainer (named 12-hole clock model) that focused on training manipulation of bronchoscopes. The aim of this study was to evaluate the training effect of this model on bronchoscopic skills and learning interests in simulated normal and difficult airways among anesthesia residents. METHODS: Forty-three anesthesia residents without experience in bronchoscopic intubation were randomly divided into control (n = 22) and intervention groups (n = 21). All participants received standard multimedia learning and a baseline test using a normal airway manikin. Then, the control and intervention groups engaged in 60 minutes of training via a traditional airway manikin or the clock model, respectively. After training, the participants completed bronchoscopic performance assessments in simulated normal and difficult airways, as well as an electronic questionnaire related to the course. RESULTS: During training, the total hands-on time of bronchoscopic practice recorded by trainees' themselves was longer in the intervention group than in the control group (1568 ±â€…478 seconds vs 497 ±â€…172 s, P < .0001). Posttraining, the time required to visualize the carina in simulated normal airways was longer in the intervention group than in the control group (22.0 [18.0, 29.0] vs 14.0 [10.8, 18.3], P < .0001), while it was shorter for simulated difficult airways (24.0 [16.0, 32.0] s vs 27.0 [21.0, 35.5] s, P = .0425). The survey results indicated that confidence in bronchoscopic intubation increased in both groups, without significant differences in satisfaction, acceptance, or perceived difficulty between the groups. However, the interest ratings were higher in the intervention group than in the control group. CONCLUSIONS: The 12-hole clock model is a simple and feasible method for improving bronchoscopic skills and promoting interest among trainees. TRIAL REGISTRATION: NCT05327842 at Clinicaltrials.gov.

Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.

Neurodegenerative diseases (NDs) refer to a group of diseases in which slow, continuous cell death is the main pathogenic event in the nervous system. Most NDs are characterized by cognitive dysfunction or progressive motor dysfunction. Treatments of NDs mainly target alleviating symptoms, and most NDs do not have disease-modifying drugs. The pathogenesis of NDs involves inflammation and apoptosis mediated by mitochondrial dysfunction. Dantrolene, approved by the US Food and Drug Administration, acts as a RyRs antagonist for the treatment of malignant hyperthermia, spasticity, neuroleptic syndrome, ecstasy intoxication and exertional heat stroke with tolerable side effects. Recently, dantrolene has also shown therapeutic effects in some NDs. Its neuroprotective mechanisms include the reduction of excitotoxicity, apoptosis and neuroinflammation. In summary, dantrolene can be considered as a potential therapeutic candidate for NDs.