MoS2high temperature sensitive element with a single Si3N4protective layer.

Temperature sensors find extensive applications in industrial production, defense, and military sectors. However, conventional temperature sensors are limited to operating temperatures below 200°C and are unsuitable for detecting extremely high temperatures. In this paper, a method for thermal protection of molybdenum disulfide (MoS2) films is proposed and a MoS2 high temperature sensor is prepared. By depositing a monolayer of Si3N4 onto MoS2, not only is the issue of high-temperature oxidation effectively addressed, but also the contamination by impurities that could potentially compromise the performance of MoS2 is prevented. Moreover, the width of the Schottky barrier of metal/MoS2 is reduced by using PECVD deposition of 400 nm Si3N4 to form an ohmic contact, which improves the electrical performance of the device by three orders of magnitude. The sensor exhibits a positive temperature coefficient measurement range of 25 to 550°C, with a maximum temperature coefficient of resistance (TCR) of 0.32%·°C-1. The thermal protection method proposed in this paper provides a new idea for the fabrication of high-temperature sensors, which is expected to be applied in the high-temperature field. .

A Three-Day Prehabilitation Program is Cost-Effective for Preventing Pulmonary Complications after Heart Valve Surgery: A Health Economic Analysis of a Randomized Trial.

Background: While prehabilitation (pre surgical exercise) effectively prevents postoperative pulmonary complications (PPCs), its cost-effectiveness in valve heart disease (VHD) remains unexplored. This study aims to evaluate the cost-effectiveness of a three-day prehabilitation program for reducing PPCs and improving quality adjusted life years (QALYs) in Chinese VHD patients. Methods: A cost-effectiveness analysis was conducted alongside a randomized controlled trial featuring concealed allocation, blinded evaluators, and an intention-to-treat analysis. In total, 165 patients scheduled for elective heart valve surgery at West China Hospital were randomized into intervention and control groups. The intervention group participated in a three-day prehabilitation exercise program supervised by a physiotherapist while the control group received only standard preoperative education. Postoperative hospital costs were audited through the Hospital Information System, and the EuroQol five-dimensional questionnaire was used to provide a 12-month estimation of QALY. Cost and effect differences were calculated through the bootstrapping method, with results presented in cost-effectiveness planes, alongside the associated cost-effectiveness acceptability curve (CEAC). All costs were denominated in Chinese Yuan (CNY) at an average exchange rate of 6.73 CNY per US dollar in 2022. Results: There were no statistically significant differences in postoperative hospital costs (8484 versus 9615 CNY, 95% CI -2403 to 140) or in the estimated QALYs (0.909 versus 0.898, 95% CI -0.013 to 0.034) between the intervention and control groups. However, costs for antibiotics (339 versus 667 CNY, 95% CI -605 to -51), nursing (1021 versus 1200 CNY, 95% CI -330 to -28), and electrocardiograph monitoring (685 versus 929 CNY, 95% CI -421 to -67) were significantly lower in the intervention group than in the control group. The CEAC indicated that the prehabilitation program has a 92.6% and 93% probability of being cost-effective in preventing PPCs and improving QALYs without incurring additional costs. Conclusions: While the three-day prehabilitation program did not significantly improve health-related quality of life, it led to a reduction in postoperative hospital resource utilization. Furthermore, it showed a high probability of being cost-effective in both preventing PPCs and improving QALYs in Chinese patients undergoing valve surgery. Clinical Registration Number: This trial is registered in the Chinese Clinical Trial Registry (URL: https://www.chictr.org.cn/) with the registration identifier ChiCTR2000039671.

Tetramethylpyrazine Analogue T-006 Protects Neuronal and Endothelial Cells Against Oxidative Stress via PI3K/AKT/mTOR and Nrf2 Signaling.

BACKGROUND: T-006, a novel neuroprotective derivative of tetramethylpyrazine (TMP), exhibits multifunctional neuroprotective properties. T-006 has been shown to improve neurological and behavioral functions in animal models of ischemic stroke and neurodegenerative diseases. The present study aims to further elucidate the mechanisms underlying the protective effects of T-006 against oxidative injuries induced by glutamate or hypoxia. METHODS: Mouse hippocampal HT22 cells were used to evaluate the neuroprotective effects of T-006 against glutamate-induced injuries, while mouse brain endothelial bEnd.3 cells were used to evaluate the cerebrovascular protective effects of T-006 against oxygen-glucose deprivation followed by reperfusion (OGD/R)-induced injuries. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to measure cell viability and oxidative stress. Western blot and immunofluorescence analyses of protein expression were used to study cell signaling pathways. RESULTS: T-006 exhibited significant protective effects in both oxidative injury models. In HT22 cells, T-006 reduced cell death and enhanced antioxidant capacity by upregulating mTOR and nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling. Similarly, in bEnd.3 cells, T-006 reduced oxidative injuries and preserved tight junction integrity through Nrf2/HO-1 upregulation. These effects were inhibited by LY294002, a Phosphoinositide 3-kinase (PI3K) inhibitor. CONCLUSIONS: T-006 may exert its neuroprotective and cerebrovascular protective effects via the regulation of PI3K/AKT-mediated pathways, which facilitate downstream mTOR and Nrf2 signaling, leading to improved cell survival and antioxidant defenses.

Tetramethylpyrazine Nitrone (TBN) Reduces Amyloid ß Deposition in Alzheimer's Disease Models by Modulating APP Expression, BACE1 Activity, and Autophagy Pathways.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with age. A wealth of evidence indicates that the amyloid ß (Aß) aggregates result from dyshomeostasis between Aß production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aß reduction represent a promising strategy for AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with potential for the treatment of AD. Previously, we demonstrated that TBN markedly enhanced cognitive functions and decreased the levels of Aß, APP, BACE 1, and hyperphosphorylated tau in 3×Tg-AD mice. However, the mechanism by which TBN inhibits Aß deposition is still unclear. In this study, we employed APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months, and N2a/APP695swe cells treated with TBN (300 µM) to explore the mechanism of TBN in Aß reduction. Our results indicate that TBN significantly alleviated cognitive impairment and reduced Aß deposition in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway, inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, and decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-ß, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aß levels likely by reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Why nursing students do not report workplace bullying during clinical practice: A mixed methods systematic review.

BACKGROUND: Workplace bullying in clinical nurse education significantly threatens students' well-being and professional development. Despite its prevalence, many incidents go unreported, exacerbating the issue and compromising the quality of care. A significant gap exists in the literature regarding comprehensive mixed-methods systematic reviews on unreported bullying incidents among nursing students. This review aims to address this knowledge gap and propose effective strategies to tackle this pervasive problem. AIM: This mixed-methods systematic review aimed to explore the factors influencing the non-reporting of workplace bullying incidents among nursing students during clinical practice. DESIGN: Mixed-methods systematic review. REVIEW METHODS AND DATA SOURCES: An extensive literature search was conducted across ten databases, including PubMed, Cochrane, Embase, Web of Science, CINAHL, PsycINFO, Scopus, Chinese Biomedical, China National Knowledge Internet, and WANFANG, from database inception to November 1, 2023. Google Scholar and reference lists of included studies were also searched. Studies were selected based on eligibility criteria regarding population, phenomena of interest, and context. Two researchers independently assessed study quality, with disagreements resolved by a third reviewer. Relevant data were extracted and synthesized using the Joanna Briggs Institute's convergent integrated approach, ensuring a comprehensive integration of qualitative and quantitative findings. RESULTS: Twenty-one studies met the inclusion criteria, comprising six qualitative, twelve quantitative, and three mixed-methods studies. Four integrated themes emerged from nursing students' perspectives on reasons for not reporting workplace bullying during clinical practice: (i) fear and concerns related to reporting, (ii) concerns about professional image, (iii) barriers and challenges in reporting, and (iv) perceived ineffectiveness of reporting. CONCLUSIONS: This systematic review provides valuable insights into nursing students' perspectives on the non-reporting of workplace bullying incidents during clinical practice. Understanding these reasons enables stakeholders to collaboratively develop interventions to create a safer and more supportive environment for nursing students, ultimately enhancing quality care and the well-being of healthcare professionals.

Erythrocyte-Mimicking Nanovesicle Targeting Porphyromonas gingivalis for Periodontitis.

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.

Prediction of Adolescents' Fluid Intelligence Scores based on Deep Learning with Reconstruction Regularization.

Objective: The aim of this study was to develop a predictive model for uncorrected/actual fluid intelligence scores in 9-10 year old children using magnetic resonance T1-weighted imaging. Explore the predictive performance of an autoencoder model based on reconstruction regularization for fluid intelligence in adolescents. Methods: We collected actual fluid intelligence scores and T1-weighted MRIs of 11,534 adolescents who completed baseline tasks from ABCD Data Release 3.0. A total of 148 ROIs were selected and 604 features were proposed by FreeSurfer segmentation. The training and testing sets were divided in a ratio of 7:3. To predict fluid intelligence scores, we used AE, MLP and classic machine learning models, and compared their performance on the test set. In addition, we explored their performance across gender subpopulations. Moreover, we evaluated the importance of features using the SHapley Additive Explain method. Results: The proposed model achieves optimal performance on the test set for predicting actual fluid intelligence scores (PCC = 0.209 ± 0.02, MSE = 105.212 ± 2.53). Results show that autoencoders with refactoring regularization are significantly more effective than MLPs and classical machine learning models. In addition, all models performed better on female adolescents than on male adolescents. Further analysis of relevant characteristics in different populations revealed that this may be related to gender differences in underlying fluid intelligence mechanisms. Conclusions: We construct a weak but stable correlation between brain structural features and raw fluid intelligence using autoencoders. Future research may need to explore ensemble regression strategies utilizing multiple machine learning algorithms on multimodal data in order to improve the predictive performance of fluid intelligence based on neuroimaging features.

Prevalence of involuntary treatment among community-living older persons with dementia: A systematic review.

OBJECTIVE: This systematic review and meta-analysis aimed to ascertain the prevalence of involuntary treatment among community-living older persons with dementia and explore associated factors. METHODS: We comprehensively searched seven electronic databases (PubMed, Embase, Cochrane Library, Web of Science, CINAHL, PsycINFO, and Scopus) from their inception to October 17, 2023, with an update conducted on April 1, 2024. Meta-analysis synthesized prevalence estimates of involuntary treatment and its three subcategories, with 95% confidence intervals. RESULTS: This study included 11 research papers involving 12,136 community-dwelling individuals with cognitive impairment and dementia from 19 countries. The pooled prevalence of involuntary treatment among community-dwelling older persons with dementia was 45.2% (95% CI: 33.7-60.5%). Subcategories included physical restraints (9.8%, 95% CI: 5.1-18.8%), psychotropic medication (19.1%, 95% CI: 13.6-26.9%), and non-consensual care (34.3%, 27.6-42.7%). Factors influencing involuntary treatment were categorized as caregiver-related and care recipient-related. CONCLUSION: This study underscores the prevalent use of involuntary treatment among community-dwelling older persons with dementia, emphasizing its association with specific caregiver and care recipient factors. Addressing these findings underscores the importance of proactive measures and targeted interventions to improve the quality of care for this vulnerable population.

Tetramethylpyrazine nitrone delays the aging process of C. elegans by improving mitochondrial function through the AMPK/mTORC1 signaling pathway.

Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic deterioration of multiple tissues. Among the numerous molecular, cellular, and systemic hallmarks associated with aging, mitochondrial dysfunction is considered one of the pivotal factors that initiates the aging process. During aging, mitochondria undergo varying degrees of damage, resulting in impaired energy production and disruption of the homeostatic regulation of mitochondrial quality control systems, which in turn affects cellular energy metabolism and results in cellular dysfunction, accelerating the aging process. AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) are two central kinase complexes responsible for sensing intracellular nutrient levels, regulating metabolic homeostasis, modulating aging and play a crucial role in maintaining the homeostatic balance of mitochondria. Our previous studies found that the novel compound tetramethylpyrazine nitrone (TBN) can protect mitochondria via the AMPK/mTOR pathway in many animal models, extending healthy lifespan through the Nrf2 signaling pathway in nematodes. Building upon this foundation, we have posited a reasonable hypothesis, TBN can improve mitochondrial function to delay aging by regulating the AMPK/mTORC1 signaling pathway. This study focuses on the C. elegans, exploring the impact and underlying mechanisms of TBN on aging and mitochondrial function (especially the mitochondrial quality control system) during the aging process. The present studies demonstrated that TBN extends lifespan of wild-type nematodes and is associated with the AMPK/mTORC1 signaling pathway. TBN elevated ATP and NAD+ levels in aging nematodes while orchestrating mitochondrial biogenesis and mitophagy. Moreover, TBN was observed to significantly enhance normal activities during aging in C. elegans, such as mobility and pharyngeal pumping, concurrently impeding lipofuscin accumulation that were closely associated with AMPK and mTORC1. This study not only highlights the delayed effects of TBN on aging but also underscores its potential application in strategies aimed at improving mitochondrial function via the AMPK/mTOR pathway in C. elegans.

SLAMF8 Promotes Atherosclerosis by Activating the TLR4 Signaling Pathway in Rheumatoid Arthritis.

Objectives: Rheumatoid Arthritis (RA) can accelerate atherosclerosis (AS) plaque formation. High prevalence of AS has been demonstrated in early-stage RA patients. Therefore, there is an urgent need to investigate what mechanisms and key molecules accelerate AS in RA to improve the management of RA. Methods: We retrieved gene expression data for RA (GSE45291) and atherosclerosis (GSE28829) from Gene Expression Omnibus (GEO). Seventeen key genes were identified, and the top one candidate hub gene was SLAM family member 8 (SLAMF8). To investigate the role of SLAMF8 in AS and RA, U937 cells were differentiated into macrophages using Phorbol 12-myristate 13-acetate (PMA) and further transformed into foam cells by oxidized low-density lipoprotein (ox-LDL) treatment and siRNA was manipulated to knock down SLAMF8. Flow Cytometry was employed to assess cell state. The mRNA and protein expressions of the genes were investigated using western blot and RT-qPCR. Results: SLAMF8 was screened as a key gene by bioinformatic methods. Compared to Mφ, SLAMF8, TLR4 and inflammatory cytokines, tumor necrosis factor α (TNF-α), and Interleukin 6 (IL-6) were noticeably expressed in foam cells. Knockdown of SLAMF8 could remarkably curtail TLR4, TNF-α, and IL-6 protein levels. Antagonizing SLAMF8 could attenuate inflammatory factors and apoptosis of foam cells by inhibiting the TLR4 pathway, thus mitigating the severity of AS in RA. Conclusions: Our work demonstrated that SLAMF8 promoted AS in patients with RA by inducing inflammation and apoptosis of foam cells via TLR4 signaling. Therefore, SLAMF8 could be a possible therapeutic spot for AS in RA patients.

Remote sensing inversion on heavy metal content in salinized soil of Yellow River Delta based on Random Forest Regression-a case study of Gudao Town.

To explore the potential of using the mineral alteration information extracted by remote sensing technology to indirectly estimate the heavy metal content of salinized soil, 23 sampling points were uniformly set up in the town of Gudao in the Yellow River Delta as the research area in 2022. The concentrations of seven heavy metals, Cr, Cu, Pb, Zn, As, Mn and Ni, at the sampling points were determined in laboratory tests. Spectral derivative indices, topographic factors, and mineral alteration information (iron staining, hydroxyl, and carbonate ions) were extracted and screened as modeling factors using Sentinel 2 imagery. An inverse model of heavy metal content was constructed using the random forest algorithm, and the model accuracy was evaluated using the cross-validation method. The results of the study show that: (1) Hydroxyl and carbonate ion alteration can be effectively used for the inversion of soil As and Ni content in this study area. Iron-stained alteration can be used as a modeling factor in the inversion of Cr, Cu, Pb, Zn, and Mn concentrations. (2) The inclusion of alteration information improves the accuracy of heavy metal content inversion. The Cu concentration was verified to be the best predictor, with an RMSE of 3.309, MAPE of 11.072%, and R2 of 0.904, followed by As, Ni, and Zn; the predictive value of Mn, Cr and Pb was average. (3) Based on the results of concentration inversion, the high concentration areas of As, Ni, and Mn are primarily distributed on both sides of the river and around lakes and ponds. The high-concentration areas of Zn were mainly distributed in the farmland areas on both sides of the river. Areas with high concentrations of Cu were mainly distributed in the eastern oil extraction area, both sides of the rivers, and around lakes.

Heavy Metal(oid)s Contamination and Potential Ecological Risk Assessment in Agricultural Soils.

Soil pollution caused by heavy metal(oid)s has generated great concern worldwide due to their toxicity, persistence, and bio-accumulation properties. To assess the baseline data, the heavy metal(oid)s, including manganese (Mn), iron (Fe), Cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), and cadmium (Cd), were evaluated in surface soil samples collected from the farmlands of Grand Forks County, North Dakota. Samples were digested via acid mixture and analyzed via inductively coupled plasma mass spectrometry (ICP MS) analysis to assess the levels, ecological risks, and possible sources. The heavy metal(oid) median levels exhibited the following decreasing trend: Fe > Mn > Zn > Ni > Cr > Cu > Pb > Co > As > Cd > Hg. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested the main lithogenic source for the studied metal(oid)s. Metal(oid) levels in the current investigation, except Mn, are lower than most of the guideline values set by international agencies. The contamination factor (Cf), geo accumulation index (Igeo) and enrichment factor (EF) showed considerable contamination, moderate contamination, and significant enrichment, respectively, for As and Cd on median value basis. Ecological risk factor (Er) results exhibited low ecological risk for all studied metal(oid)s except Cd, which showed considerable ecological risk. The potential ecological risk index (PERI) levels indicated low ecological risk to considerable risk. Overall, the results indicate the accumulation of As and Cd in the study area. The high nutrients of the soils potentially affect their accumulation in crops and impact on consumers' health. This drives the impetus for continued environmental monitoring programs.

Association of periodontitis with gastrointestinal tract disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The bidirectional link of periodontitis (PD) and gastrointestinal tract (GIT) disorders has been investigated in previous epidemiological studies; however, the conclusions still remain controversial. The aim of this study was to comprehensively explore the bidirectional causal effect between PD and various GIT diseases. METHODS: Based on summary-level data of genome-wide association studies (GWASs), a two-sample bidirectional Mendelian randomization (MR) study was undertaken. Single-nucleotide polymorphisms (SNPs) associated with PD or GIT disorders (chronic gastritis [CG], gastric ulcer [GU], duodenal ulcer [DU], gastroesophageal reflux disease [GERD], irritable bowel syndrome [IBS], and diverticular disease of the intestine [DI]) in GWASs were applied as exposure. The primary method employed was the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed to investigate potential pleiotropy. RESULTS: With regard to the investigation of the causality between PD and GIT disorders, the IVW method revealed that there is a causal impact of PD on GU (odds ratio [OR] 1.088; 95% confidence interval [CI], 1.036-1.141; adjusted p = 0.004) and DI (OR 0.938; 95% CI, 0.911-0.965; adjusted p = 0.000). However, no significant genetic liability was observed for the causal effect of PD on CG, DU, GERD, and IBS. Furthermore, the primary analysis did not demonstrate a causal effect of GIT disorders on PD. CONCLUSION: This MR study suggests that PD may be associated with an increased risk of GU and a reduced risk of DI, with possibly limited clinical relevance. Further studies are needed to support the conclusions of this MR study.

Multifunctional Ultrathin Metasurface with a Low Radar Cross Section and Variable Infrared Emissivity.

The development of stealth devices that are compatible with both infrared (IR) and radar systems remains a significant challenge, as the material properties required for effective IR and radar stealth are often contradictory. In this work, based on an IR electrochromic device (IR-ECD), concepts of metamaterial manipulating electromagnetic waves are applied to develop a multifunctional ultrathin metasurface with a low radar cross section (RCS) and variable infrared emissivity. This paper presents a linear-to-linear polarization conversion metasurface (PCM) designed by hollowing the IR-ECD. In this way, the IR-ECD based on polyaniline (PANI) can also modulate the reflection waves in the microwave band without affecting its features in the infrared region. Thus, the proposed metasurface integrates both microwave stealth and variable infrared emissivity through a single layer. The measured results show that a 10 dB RCS reduction is achieved in the band of 8.46-9.5 GHz, and the infrared emissivity can be adjusted from 0.870 to 0.513 in the infrared stealth band of 8-14 µm. Due to the ultrathin thickness (only 0.081λ0 at 9 GHz), low RCS in the X-band, and variable infrared emissivity, the designed multifunctional stealth metasurface has promising applications on military platforms with various surrounding environments.

Tetramethylpyrazine Nitrone Promotes the Clearance of Alpha-Synuclein via Nrf2-Mediated Ubiquitin-Proteasome System Activation.

Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson's disease (PD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent enhancement of the expression of the 20S proteasome core particles (20S CPs) and regulatory particles (RPs) increases proteasome activity, which can promote α-syn clearance in PD. Activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) may reduce oxidative stress by strongly inducing Nrf2 gene expression. In the present study, tetramethylpyrazine nitrone (TBN), a potent-free radical scavenger, promoted α-syn clearance by the ubiquitin-proteasome system (UPS) in cell models overexpressing the human A53T mutant α-syn. In the α-syn transgenic mice model, TBN improved motor impairment, decreased the products of oxidative damage, and down-regulated the α-syn level in the serum. TBN consistently up-regulated PGC-1α and Nrf2 expression in tested models of PD. Additionally, TBN similarly enhanced the proteasome 20S subunit beta 8 (Psmb8) expression, which is linked to chymotrypsin-like proteasome activity. Furthermore, TBN increased the mRNA levels of both the 11S RPs subunits Pa28αß and a proteasome chaperone, known as the proteasome maturation protein (Pomp). Interestingly, specific siRNA targeting of Nrf2 blocked TBN's effects on Psmb8, Pa28αß, Pomp expression, and α-syn clearance. In conclusion, TBN promotes the clearance of α-syn via Nrf2-mediated UPS activation, and it may serve as a potentially disease-modifying therapeutic agent for PD.

Linking preoperative and early intensive care unit data for prolonged intubation prediction.

Objectives: Prolonged intubation (PI) is a frequently encountered severe complication among patients following cardiac surgery (CS). Solely concentrating on preoperative data, devoid of sufficient consideration for the ongoing impact of surgical, anesthetic, and cardiopulmonary bypass procedures on subsequent respiratory system function, could potentially compromise the predictive accuracy of disease prognosis. In response to this challenge, we formulated and externally validated an intelligible prediction model tailored for CS patients, leveraging both preoperative information and early intensive care unit (ICU) data to facilitate early prophylaxis for PI. Methods: We conducted a retrospective cohort study, analyzing adult patients who underwent CS and utilizing data from two publicly available ICU databases, namely, the Medical Information Mart for Intensive Care and the eICU Collaborative Research Database. PI was defined as necessitating intubation for over 24 h. The predictive model was constructed using multivariable logistic regression. External validation of the model's predictive performance was conducted, and the findings were elucidated through visualization techniques. Results: The incidence rates of PI in the training, testing, and external validation cohorts were 11.8%, 12.1%, and 17.5%, respectively. We identified 11 predictive factors associated with PI following CS: plateau pressure [odds ratio (OR), 1.133; 95% confidence interval (CI), 1.111-1.157], lactate level (OR, 1.131; 95% CI, 1.067-1.2), Charlson Comorbidity Index (OR, 1.166; 95% CI, 1.115-1.219), Sequential Organ Failure Assessment score (OR, 1.096; 95% CI, 1.061-1.132), central venous pressure (OR, 1.052; 95% CI, 1.033-1.073), anion gap (OR, 1.075; 95% CI, 1.043-1.107), positive end-expiratory pressure (OR, 1.087; 95% CI, 1.047-1.129), vasopressor usage (OR, 1.521; 95% CI, 1.23-1.879), Visual Analog Scale score (OR, 0.928; 95% CI, 0.893-0.964), pH value (OR, 0.757; 95% CI, 0.629-0.913), and blood urea nitrogen level (OR, 1.011; 95% CI, 1.003-1.02). The model exhibited an area under the receiver operating characteristic curve (AUROC) of 0.853 (95% CI, 0.840-0.865) in the training cohort, 0.867 (95% CI, 0.853-0.882) in the testing cohort, and 0.704 (95% CI, 0.679-0.727) in the external validation cohort. Conclusions: Through multicenter internal and external validation, our model, which integrates early ICU data and preoperative information, exhibited outstanding discriminative capability. This integration allows for the accurate assessment of PI risk in the initial phases following CS, facilitating timely interventions to mitigate adverse outcomes.

Ultrastrong to nearly deep-strong magnon-magnon coupling with a high degree of freedom in synthetic antiferromagnets.

Ultrastrong and deep-strong coupling are two coupling regimes rich in intriguing physical phenomena. Recently, hybrid magnonic systems have emerged as promising candidates for exploring these regimes, owing to their unique advantages in quantum engineering. However, because of the relatively weak coupling between magnons and other quasiparticles, ultrastrong coupling is predominantly realized at cryogenic temperatures, while deep-strong coupling remains to be explored. In our work, we achieve both theoretical and experimental realization of room-temperature ultrastrong magnon-magnon coupling in synthetic antiferromagnets with intrinsic asymmetry of magnetic anisotropy. Unlike most ultrastrong coupling systems, where the counter-rotating coupling strength g2 is strictly equal to the co-rotating coupling strength g1, our systems allow for highly tunable g1 and g2. This high degree of freedom also enables the realization of normalized g1 or g2 larger than 0.5. Particularly, our experimental findings reveal that the maximum observed g1 is nearly identical to the bare frequency, with g1/ω0 = 0.963, indicating a close realization of deep-strong coupling within our hybrid magnonic systems. Our results highlight synthetic antiferromagnets as platforms for exploring unconventional ultrastrong and even deep-strong coupling regimes, facilitating the further exploration of quantum phenomena.

Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway.

Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1ß, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.

Association between pulp and periapical disease with type 2 diabetes: A bidirectional Mendelian randomization.

AIM: This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2 diabetes mellitus (T2DM). METHODOLOGY: Summary level data of European-based population genome-wide association studies (GWASs) were employed to undertake this MR study. With the selection of single nucleotide polymorphisms (SNPs) as the instrumental variable, the radial inverse-variance weighted (radial IVW) method with modified second-order weights was applied as the primary method. Additionally, a range of sensitivity analyses were conducted to investigate pleiotropy. Results from different sources of outcome were pooled by meta-analysis with the fixed model. RESULTS: The results of this MR analysis did not suggest a significant impact of pulp and periapical disease on type 2 diabetes (combined OR = 1.04, 95% CI: 1.00-1.07, p = .033) and vice versa (OR = 1.04, 95% CI: 0.96-1.14, p = .329). No significant pleiotropy was detected in the final model after the removal of outliers, demonstrating the reliability of the results in our primary analysis. CONCLUSIONS: With the limitations inherent in the present MR study, there is no significant evidence in either direction to suggest a causal association between pulp and periapical disease and type 2 diabetes mellitus.